GM-free Scotland

June '08 | MON 810 - Is this regulation?

Our attention was recently drawn to worrying scientific doubts about the only GM maize approved for cultivation in Europe.

The investigation we were irresistibly drawn into calls into question, not only the integrity of the GM maize itself, but the integrity of its manufacturers, and the competence of regulators world-wide. There are, no doubt, simple explanations for some of the apparent discrepancies, but the whole evidence is too great to ignore.

The maize is Monsanto's MON 810, 'YieldGard' genetically transformed to kill specific insect pests. Eighteen seed varieties derived from MON 810 were approved for commercial growing in Europe, but Spain is the only country which has adopted the crop on any scale. MON 810 has been the subject of widespread controversy, as several EU member-states have banned it due to environmental safety concerns.

Our story begins in 1996 with Monsanto's petition to the US Department of Agriculture (USDA) for 'non-regulation status' of MON 810. The Company had tried to produce a stacked insect- and herbicide-resistant maize using two separate DNA constructs, both of which included an antibiotic resistance marker gene. However, the only successful transformation was with “1 complete copy of the cry1A(b) (the Bt-toxin) gene and its regulatory sequence”. The latter sequence included a gene to enable expression of the engineered DNA in the maize plant and DNA 'start' and 'stop' signals at the beginning and end of the construct. In the final MON 810 crop developed, the antibiotic resistance marker genes plus their associated bacterial DNA machinery were confirmed absent.

Monsanto describes the protein product of cry1A(b) as “nature identical”, and further, states that the amino-acid sequence (the basic protein structure) generated by the gene is identical to that in the native Bt toxin.

The only other test result reported was on the “continued efficacy of maize line MON 810” confirming that an insecticidally active Cry1A(b) protein was produced by the GM crop, and, that it provided “season long control of European Corn Borer”.

OUR COMMENT

One or two things in Monsanto's petition raised our eyebrows:

  1. The 'nature identical' cry1A(b) gene is later reported to be a 'modified' version of the native gene, the modification being required to improve the expression of this bacterial gene inside a plant.

Does this mean that the cry1A(b) gene inserted is “nature identical” except for the modifications needed for it to function inside a plant cell?

  1. The size of the cry1A(b) DNA engineered for insertion was 3.46 Kb in length. The evidence produced by Monsanto to prove “cry1A(b) gene integrity” shows a DNA of length only 3.1 Kb. Does this mean that the cry1A(b) gene inserted is “nature identical” except for the 0.37 Kb which is missing? Does it mean that the amino-acid sequence produced by the gene is identical except for the bits missing, altered or mis-folded because part of the genetic code is missing?

The USDA, which accepted Monsanto's submission clearly tolerates inconsistent industry submissions.

During 1996-1999, MON 810 received regulatory approval around the world. In the EU, the Health and Consumer Protection Scientific Committee submitted its report on MON 810 in 1998. This largely consists of a repetition of what Monsanto had said to the USDA in 1996. The only proviso seemed to be that the Committee realised Monsanto had only tested for the transfer of whole gene constructs, but the missing genes and their associated DNA were unaccounted for. It, therefore, 'encouraged' the provision of data on the possible presence of fragments of DNA. It assured the Company, however, that “Absence of these data does not prejudice the Committee's overall (favourable) conclusions and opinions.”

The next interesting piece in the jigsaw was a paper submitted for publication in March 2002. The aim of this study was to develop a sensitive and accurate method for quantifying amounts of cry1A(b) gene in unknown samples. In the discussion, it is noted that in MON 810 'the structure of the transgene differs notably from the original (DNA) construct as reported in the safety assessment by Monsanto”. The transgene is later described as 'unique' and 'truncated' while the protein toxin is described as 'partial'.

At the same time, March 2002, a 'Safety Assessment of YieldGard Insect-Protected Corn Event MON 810' was prepared by Monsanto. In this, the “molecular characterisation” of the GM corn has changed subtly from the presence of “1 complete copy of the cry1A(b) gene and its regulatory sequence” to “a single functional copy of the cry1A(b) coding sequence”. The presence, or otherwise, of associated regulatory sequences is not mentioned, although the absence of antibiotic-resistance marker genes is confirmed.

OUR COMMENT The 'functional' DNA is what generates an insecticidal protein: how similar this is compared to anything actually produced by any bacterium in nature becomes a matter of pure conjecture.

By 2003, scientists in Europe got round to looking more closely at the GM crops in our fields derived from MON 810.

A French study found a number of major differences between the actual transformation event and that reported by the company. The first was that the DNA 'stop' signal which marks the end of the gene was missing. This indicates that the protein generated could have extra sections added on and/or have acquired secondary properties. Rather than being lost, the missing section seems to have moved to another location in the genome, where it might disrupt genomic function due to the misplaced 'end-of-gene' signal.

When the location of the novel construct was investigated, the researchers placed it within a known maize gene cluster, but the DNA around the mis-placed 'stop' signal consisted of unidentifiable, scrambled DNA. This would, of course, have unpredictable effects on gene function.

At about the same time as the French study, the Scientific Institute of Public Health in Brussels published its own genetic map of MON 810. They confirmed the absence of the 'stop' signal DNA, and the scrambled DNA at this location. However, the novel construct's location was placed at a different position in the maize gene cluster, and the DNA 'start' signal (a viral promoter sequence) was in a slightly different form from that reported by the French team.

A few more bits of the jigsaw fell into place from an article on MON 810 in the pro-biotech website, agbios.com The date of posting of this isn't given, but the most recent scientific references mentioned are from 2001, with regulatory updates continuing up until 2005. This article mentions the missing 'stop' signal, and a maize-expressed protein about two-thirds of the size of the native bacterial Cry1Ab one. This truncated version is now described as “equivalent” to the insecticidally-active protein core of the native bacterial version. The protein core is rapidly digested in simulated stomach conditions, but unaffected by simulated intestinal conditions. The plant expression of the Cry1A(b) protein was noted as declining over the growing season.

In 2004, farm workers suffering debilitating illnesses after working with one of the strains of maize derived from MON 810 were found to have antibodies to Cry1A(b) protein in their blood. In other words their immune systems were reacting to the Bt toxin.

Fast forward to 2007. A molecular analysis of MON 810 by researchers in India consistently found the 'lost' antibiotic-resistance marker genes and the 'lost' 'stop' signal DNA. An Italian team looked more closely at the scrambled DNA region beside the missing 'stop' signal in two strains of MON 810. They demonstrated the potential for a novel section to be added on to the truncated

Cry1A(b) protein. The nature and size of this extra material was different in each of the two maize strains studied. The scientists commented on the fact that the genomic aberrations don't seem to have interfered with the insecticidal activity of the protein, nor, with the vigor and yield of the crop containing it.

OUR COMMENT

In case you've lost the thread, here's a summary:

The original, complete, copied Bt-toxin gene, cry1A(b), which Monsanto inserted into maize has:

Other changes noted include:

Or, to summarise, the MON 810 we are eating now is not the same as the one approved in 1998.

The toxic Cry1A(b) protein will be rapidly degraded in the mammalian stomach, but if protected from digestion by other dietary or physiological factors, will survive intact in the intestines where we will be intimately exposed to it.

Why does all this matter?

Assuming that all the scientists whose work has been quoted here are competent (and there is no reason to doubt this), MON 810 maize contains an unstable transformation event which can move around, disturbing the nearby genome as it goes, and generate fragments which can disturb the distant genome. It can generate non-uniform proteins with the potential to stimulate the immune system and cause disease. All of these changes are unpredictable. All of these make nonsense of any safety testing carried out in the past.

Neither Monsanto, nor any of our regulators, has been checking for any molecular changes arising during the cross-breeding of MON 810 with other maize strains. This is a serious omission because maize is known to have a high amount of mobile DNA elements, making it prone to genomic rearrangements.

The scientists of the Institute of Science in Society have repeatedly warned regulators about the instability of transgenic DNA in higher plants. If you want to see for yourself how much attention is being paid to them, check out www.i-sis.org.uk/MON810GenomeRearranged.php.

Since France is beginning to wake up and demand that a much wider expertise be applied to GMO approvals, including food safety, farming economy, soil deterioration and effects on other crops, this is a good time to ask for more thorough regulation. Think about adding your voice to ask regulators for ongoing, detailed, molecular tests of all transgenic crop plants, because if MON 810 is as unstable as it appears from the sketchy information presented here, there is no reason why every other GM plant might not be equally so. (Don't accept the silly and insulting reply that the crops wouldn't be approved if they weren't safe, and uniform and stable.)

If you want to see for yourself what one dogged and dedicated French journalist managed to find out about Monsanto, you can buy Marie-Monique Robin's DVD “The World According to Monsanto” online from Arte Boutique, accessible through the Greenpeace website www.greenpeace.org/international/news/monsanto_movie080307.

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