Why GM is Unsafe

 
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Why GM Is Unsafe


(Draft text for GLA briefing)

Mae-Wan Ho, Institute of Science in Society, PO Box 32097, London NW1 0XR, UK www.i-sis.org.uk

I am going to describe how new findings are confirming what we have been telling our government’s scientific advisors for years, that the GM process is inherently uncontrollable and unsafe. But still, they persist in denying and dismissing the evidence.


There must now be a review into the lack of social accountability in publicly funded research and the serious abuse of science and scientific evidence that has allowed GM crops to be grown and GM food to go on sale in our markets that had clear signs of being unsafe.

The government’s own Farm Scale Evaluations reported that two out of three GM crops harm wildlife; the third, glufosinate-tolerant GM maize appeared to do better because the conventional crop was sprayed with the deadly herbicide atrazine that Europe had banned a week before the Report was released. It is really a sin for ACRE to give it a green light.

New data from the United States Department of Agriculture showed that between 1996 and 2003, 550 million acres of GM maize, soybeans and cotton were planted in the US, and overall, the use of herbicides and pesticides increased by about 50 million pounds. GM crops are definitely not good for the environment.

But that’s only scratching the surface.

Cows ate GM maize and died
A farmer in Hesse, Germany, grew Syngenta’s Bt 176 maize and fed them to his cows. Twelve cows died and others had to be slaughtered because of mysterious illnesses. The demonstrators, suspecting a cover-up, are demanding a full investigation from the Robert Koch Institute.

What’s wrong with Bt176?
The chief suspect is the Cry1Ab toxin, which Syngenta claims is in Bt 176. But molecular analysis recently carried out by Belgian government scientists showed it was much more similar to a synthetic crylAc gene. Cry1Ac protein is a potent immunogen, as potent as cholera toxin. Many Bt transgenes are synthetic, including the one in Bt 176. They are often hybrids of multiple toxins, and are unknown and untested for toxicities.
Bt 176 is also the worst GM crop in terms of stability and uniformity. There are multiple transgenic inserts, the number of inserts depending on the source. The transgenic inserts have undergone rampant rearrangements since characterised by the company. Many breakpoints involved cauliflower mosaic virus (CaMV) 35S promoter, of which I shall say more about later.

Most if not all GM crops have the same problems

The problems with Bt 176 are by no means unique; they are common to most, if not all GM crops. New proteins, of untested and unknown toxicities, are being introduced into our food and food web. Just the number of Bt toxins and hybrid toxins created is staggering. Joe Cummins has done a review on this for us recently.

Transgene instability not only compromises agronomic performance, it is a safety issue, as unstable transgenic DNA is more likely to spread uncontrollably by horizontal gene transfer: by jumping into genomes of viruses, bacteria and other cells including our own; in the course of which, creating new viruses and bacteria that causes disease epidemics, spreading drug and antibiotic resistance, and triggering cancer (more about that later).

The problem of instability is so well known that I have called it “the best kept open secret”, because everyone knows about it but agree to say nothing while regulators turned a blind eye for years. Not any more.

Two French laboratories have found that five out of five transgenic lines analysed were unstable, including the T25 maize that’s about to be approved by our government. The transgenic inserts had rearranged and broken up from the structure given in the company’s dossier, and the CaMV 35S promoter was involved in many breakpoints.

Two out of two transgenic inserts analysed for flanking host sequences showed evidence of scrambling. The inserts appeared to show a preference for retrotransposons or jumping genes that could multiply and jump to a different location in the genome or to a different genome. The T25 maize insert was found to be associated with a retrotransposon.

Belgian government scientists, in another study, confirmed the instability of the transgenic lines analysed by the French. But there were small and large discrepancies between the two studies, and the results were different for the same transgenic line depending on the sample. That indicates the transgenic lines are non-uniform besides being unstable, either of which would make them illegal for Europe. We have communicated the findings to the European authorities in advance of the meeting of the Standing Committee of the Foodchain and Animal Health in December 2003. That meeting, rightly, upheld the de facto moratorium on GM in Europe.

CaMV 35S promoter
It is generally not easy to get a foreign gene to express in an organism. And in order to force the organism to express the foreign gene, a very strong promoter has to be used. The promoter is a genetic signal that goes in front of the gene, or the coding sequence, to say to the cell, “start copying here”, just as the terminator placed after the gene is a signal for saying, “stop copying here”. The cauliflower mosaic virus (CaMV) 35S promoter fulfils the role of a very aggressive promoter, and ended up in most, if not all GM crops now commercially grown before some very worrying problems came to light.

In 1999, two laboratories independently confirmed earlier suspicion that the CaMV 35S promoter has a recombination hotspot, which resulted in frequent breaks and rearrangements of the transgenic DNA and other signs of increased transgenic instability.
Joe Cummins was the first to warn against using the CaMV 35S promoter or any viral genes in plants because it had been shown that such viral transgenes in plants could recombine with naturally occurring viruses to generate, in some cases, super-infectious viruses.
We wrote a review drawing attention to the hazards of the promoter calling for all GM crops containing it to be withdrawn. We were viciously attacked and vilified.

We replied to all the scientific criticisms in a paper that was much longer than the original, and our critics never acknowledged it.
In the course of debating with our critics we uncovered even more damning evidence: the CaMV 35S promoter is active in species across the living world: bacteria, fungi, algae, plants, animal and human cells included. Again, our critics never acknowledged this to themselves or to the public.

The hazards of CaMV 35S promoter are summarised in Box 1. As you can see, it substitutes for the promoter of many plant and animal viruses, and may hence activate dormant viruses in the genome or recombine with other viruses to generate super-infectious viruses. Because it is very aggressive and active in animal and human cells, there is a real possibility that it could trigger cancer by making certain oncogenes over-express. The problem is exacerbated, because in some cases, the CaMV 35S promoter contains extra ‘enhancer’ sequences as a further booster.

 

Box 1
Hazards of the CaMV 35S promoter

  • Contains a recombination hotspot that enhances horizontal gene transfer

  • Active in species across the living world, including animal and human cells

  • Substitutes for the promoter of a wide range of plant and animal viruses to give infectious viruses

  • May reactivate dormant viruses in the genome

  • May recombine with other viruses to create super infectious viruses

  • May trigger cancer if inserted into the genome of animal and human cells

 

Some of you may recall the headlines in 2000 on the first success of gene therapy after some 12 years trying. Gene therapy is the genetic modification of human cells, and use methods and constructs very similar to those employed for genetic modification of animals and plants.
The bone-marrow cells from infants suffering from an X-linked Severe Combined Immune Deficiency were genetically modified in a petri-dish, and the transformed cells re-implanted into the patient.
Eleven infants were treated and nine were apparently successful. However, among the nine successes, two developed leukaemia in 2002. It turns out that the GM construct jumped into a gene, that when over-expressed, triggers cancer.

Dead cows in Hesse not an isolated case
Just as the problems of Bt 176 are not unique, the dead cows in Hesse are not an isolated case. Remember what Pusztai & his colleagues found? I am sure he’ll tell you more later. GM potato, engineered with the snowdrop lectin had adverse impacts on practically all organ systems of young rats. Among the most dramatic is that their stomach lining grew twice as thick.

Scientists in Egypt had reported similar though less dramatic results by feeding Bt potato to mice. And a report submitted to the US Food and Drug Administration in the early 1990s showed that Flav Savr GM tomato with an antisense gene to delay ripening fed to rats made holes in the stomach of some of them.

Add to that numerous anecdotes from farmers that wild animals and livestock avoid GM feed and when forced to eat it, failed to thrive.
The significant common factor in all cases is the genetic modification process, and very possibly the CaMV 35S promoter.
These and several other recent scientific findings, described in the next issue of our magazine, Science in Society, are casting grave doubts over the safety of GM food in general, and the fatal flaw may be something in the genetic modification process itself.

Why genetic modification is unsafe
Genetic modification involved chopping and changing the genetic material of organisms to make new combinations and transferring that into the genomes of organisms resulting in so-called genetically modified organisms or GMOs.

An organism such as a maize plant contains tissues made up of cells, Inside each cell is a spherical compartment, the nucleus, which contains a copy of all the maize’s genetic material, or its genome, organised into long thin structures called chromosomes. Unwinding a chromosome gives a very long then thread, chromatin. And if you strip all the proteins from chromatin, you end up with the genetic material or DNA.
Genetic modification used to be called genetic engineering. It was inspired by a very simplistic view of how genes determine the characteristics of organisms: in linear, one-way causal chains, encapsulated by Francis Crick’s Central Dogma of Molecular Biology. Francis Crick shared the Nobel Prize for the double helix structure of DNA with James Watson and Maurice Wilkins.

If things were really that simple, genetic modification would work perfectly every time. Unfortunately, genetics is a hell of a lot more complicated.

The fluid genome
The ‘Fluid Genome’ was a term coined by molecular geneticists sometime between the late 1970s and early 1980s, when a rapid succession of surprising findings blew apart the classical picture that the genome is static and constant, and determines the characteristics of organisms in linear causal chains.

Instead, the genome is dynamic and flexible, responding to multiple levels of feedback from the environment that not only changes the pattern of gene expression but the very structure of genes and the genome. Organisms seem to indulge in a kind of ‘natural genetic engineering’ that’s necessary for survival. You can read the details in my book, Living with the Fluid Genome.

Artificial versus natural genetic engineering
There’s a big difference between the natural process and the artificial genetic engineering done by molecular geneticists however.
Natural genetic engineering appears to be precisely regulated by the organism as a whole, whereas artificial genetic engineering is crude and uncontrollable. I have no time to elaborate on the details. But you can think of it as follows.

The organism has its own dynamic coherence and integrity. It is engaging, as it were, in a dance of life: every gene and protein knows the rules and they are playing musical chairs in the genome.

Along comes a piece of rogue DNA that does not know the rules and does not speak the language, shouting non-stop at the top of its voice, due to its strong CaMV 35S promoter; and it has a tendency to break loose and run amok. That’s the extent of mayhem caused.
This is a summary of why GM is hazardous (Box 2).

 

Box 2
The inherent dangers of genetic modification

  • Creates novel genes and combinations that have never existed, e.g., CaMV 35S promoter used with many transgenes

  • Introduces new products untested for safety into our food and food web, e.g., Bt toxins that include potent immunogens and allergens
  • Process uncontrollable, unreliable and unpredictable

  • Foreign inserts more likely to invade gene-rich regions and transposons

  • Plasmid and other extraneous sequences of unknown safety are often inserted

  • Inserts are frequently rearranged and host genome scrambled

  • Transgenic lines are unstable, which makes quality control impossible

  • Antibiotic resistance genes are routinely used as selective markers and remain in many GM products

  • Greatly enhances the scope and frequency of horizontal gene transfer; newer processes such as DNA shuffling can generate millions of recombinant viruses in a matter of minutes

  • Toolkit for GM essentially the same as that for making biological weapons, but without the stringent safeguards, e.g., lethal virus and bacteria ‘accidentally’ created
  •  

    The most important thing is that GM greatly increases the scope and the frequency of horizontal gene transfer. Some new techniques, called DNA shuffling or molecular breeding can generate millions of recombinant viruses in a matter minutes in the laboratory.

    Finally, the toolkit for GM is actually the same as for making biological weapons: viruses and bacteria that cause diseases. GM could be worse, because if you are creating dangerous biological weapons, or studying dangerous viruses, you take proper precautions. But people are assuming GM is safe, and they don’t take the same precautions, and nasty surprises have already come to light, the ‘accidental’ creation of lethal pathogens in the course of manipulating an apparently harmless mousepox virus, and recently, in trying to make the tuberculosis bacterium less harmful.

    The problem with our government’s scientific advisors that they not only refuse to look at evidence in their own field of molecular genetics, they refuse to look at evidence from other fields.

    In contrast, the Independent Science Panel has not only compiled comprehensive evidence on the problems and hazards of GM, but also on the proven successes of all forms of non-GM sustainable agriculture, which is why we have called our report, The Case for a GM-Free Sustainable World.

    I just came back from Ethiopia, which has a Green as president. The head of the Environment Protection Authority, Tewolde Egziabher, and Sue Edwards, Director of the Institute of Sustainable Development, started a small project in sustainable agriculture in Tigray, the state at the very north of the country in 1996. The results were so good that it rapidly spread, and now 2 000 families are involved. Over a range of agricultural land from wet to very dry, from rich soils to very poor thin soils, farmers found that just by adopting pit composting, which is the traditional way in Ethiopia, they were able to increase yields up to 4-fold, and do better than chemical fertilizers in the overwhelming majority of farms. That is something Londoners can do in their garden while they keep London and Britain GM-Free.

    We need a review on the lack of social accountability of publicly funded science and the serious abuse of science and scientific evidence that has allowed GM crops to be grown and GM food to go on sale in our markets that had clear signs of being unsafe.

     
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