1.The digestive tract as the main target of GM food safety assessment - recent presentation by Dr Arpad Pusztai
2.url for Daily Mail story about chicken deaths in GM maize trial
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1.The digestive tract as the main target of GM food safety assessment
General considerations on the safety evaluation of GM foods

The difficulty of safety evaluation of foods is often used by the biotech industry as an excuse for not performing safety tests for GM foodstuffs. 

As a result, there are "many opinions but few data"1.  No proper human clinical trials [STUDIES WHICH MAY HAVE BEEN DONE BUT NOT PUBLISHED CANNOT BE RETRIEVED FROM THE LITERATURE AND THEREFORE DO NOT EXIST!] and very few animal studies with GM foods have been conducted or published to date2.  The preferred approach of the industry AND THE OECD is to use compositional comparisons between the GM foodstuff and its traditional counterpart.  If these results show no significant differences the two foodstuffs are regarded "substantially equivalent", meaning that the GM- is as safe as the non-GM food.  Regulation today is therefore dependent on this poorly defined non-scientific concept ACCORDING TO WHICH "AD ABSURDUM" A BSE-COW WOULD BE EQUIVALENT TO A HEALTHY COW BECAUSE 99.9999% OF THEIR PROTEIN, FAT, ETC COMPOSITION WAS THE SAME.  THIS IS A CONVENIENT PLOY FOR THE INDUSTRY NOT TO CARRY OUT BIOLOGICAL TESTING.

In genetic modification the transgene is incorporated into the genome of a crop using a vector containing several other genes, promoters, transcription terminators, antibiotic resistance marker - and reporter genes whose action(s) could contribute to the overall effect3.  As DNA does not always break down in the alimentary tract4, it is possible, for example, that functional fragments of the antibiotic resistance marker gene can survive and be taken up by gut bacteria, contributing to the spreading of antibiotic resistance.  The finding that a part (6 to 25%) of a GM plasmid survived exposure to saliva5 for one hour and that plasmid DNA successfully transformed human mouth bacteria supported this idea.  Saliva also contains factors which increased the transformation of bacteria by naked DNA.  Similar results have been obtained using artificial gut preparations6.

IT IS WELL-KNOWN THAT THE PRIMARY AMINO ACID SEQUENCE OF A PROTEIN BUT NOT ITS FOLDING, CONFORMATION AND STABILITY TO PROTEOLYTIC DEGRADATION IN THE GUT IS DETERMINED BY THE NUCLEOTIDE SEQUENCES OF THE DNA CODING FOR THE PROTEIN.   THE SAME DNA EXPRESSED IN A PLANT OR IN A BACTERIA WILL LIKELY YIELD A DIFFERENT PROTEIN BECAUSE AFTER THE DNA IS TRANSCRIBED AND TRANSLATED THE FOLDING AND STABILITY OF THE PROTEIN WILL BE DETERMINED BY THE CELLS OF THE VERY ORGANISM IN WHICH THIS TAKES PLACE. AS EVOLUTIONARILY BACTERIA ARE HUNDREDS OF MILLIONS OF YEARS BEHIND PLANTS THEIR METHODS OF POST-TRANSLATIONAL MODIFICATION IS MUCH SIMPLER AND MORE RESTRICTED THAN THAT OF THE MORE ADVANCED PLANTS. ACCORDINGLY, THE BIOTECH INDUSTRY'S PLOY FOR NOT USING THE TRANSGENIC PROTEIN ISOLATED FROM THE GM PLANT IN THEIR TOXICITY TESTS BUT A RECOMBINANT PROTEIN FROM BACTERIA IS FUNDAMENTALLY FLAWED. INDEED, WE HAVE DEMONSTRATED THAT EVEN TWO CLOSELY RELATED PLANTS EXPRESS THE SAME DNA DIFFERENTLY BY SHOWING THAT WITH THE TRANSFER OF THE DNA OF A STARCH-DEGRADING ENZYME INHIBITOR FROM KIDNEY BEANNS TO GM PEAS THE STABLE BEAN INHIBITOR IS RENDERED SO UNSTABLE AS TO BREAK DOWN IN THE RAT GUT WITHIN MINUTES AFTER CONSUMING DIETS CONTAINING GM PEAS7.

The insertion of transgene(s) into the plant genome may cause significant, indirect and unintended effects on the expression and functionality of the plant's own genes.  More than a single copy may be inserted whose location(s) in the genome (pleiotropic effect) may cause unexpected harmful changes the consequences of which may be severe. Unfortunately, WITHOUT BIOLOGICAL TESTING THE current MAINLY CHEMICAL methods to detect these are inadequate2,8.  In the absence of sound criteria, selection for the desired traits and elimination of the harmful ones is flawed because it is only possible to compare the properties of known constituents but not of unknown components. This equally applies for the newly developed more sophisticated analytical methods (mRNA fingerprinting, proteomics and secondary metabolite profiling)8.

Reliance based solely on chemical analysis is therefore dangerous AND THEREFORE without rigorous toxicological/nutritional investigation of the interactions between the ingested GM foodstuff, the alimentary tract and its bacterial population, it IS impossible to screen for the unintended deleterious health effects.  THUS UNSURPRISINGLY, the most valuable information to date on safety has been provided by those few studies in which the effects of GM foods on the gastrointestinal tract were investigated9.
 
The alimentary tract as target for GM food safety assessment GM tomatoes.  The first and last official safety evaluation of a GM crop, FLAVR SAVRTM tomato, including a 28 day rat feeding trial, carried out for the Food and Drug Administration (FDA) in the USA has never been published, but because of a Court case, it is on the internet10.

Tomatoes are fruits and not foods and therefore cannot support the growth of young animals.  As the nutritional value or potential toxicity of GM tomatoes could not be established by classical nutritional tests a new method was devised in which rats (both males and females) were fed on normal rat chow but they were also given by stomach tubing a daily single dose of tomato homogenates: for the test groups GM- and for the controls non-GM tomatoes.  Because its flawed design the results of the nutritional/toxicological tests have very little scientific validity2.

However, the evaluation by histology of the direct effect of the GM versus non-GM tomatoes on the stomach indicated that there was a possible treatment-related increase in glandular stomach erosion/necrosis in four out of twenty female rats but none in the controls or in male rats.  The numbers increased to seven on re-scoring by an independent pathology panel10.  Even though that in a repeat study the control and GM tomatoes were from different locations and harvests the results supported the original findings.  Despite these clear differences between GM- and non-GM tomatoes, FDA claimed that the stomach lesions had nothing to do with GM tomatoes but occurred spontaneously because rat chow is full of mucolytic agents and because the rats were stressed by restraining them in their cages and by restricting their feed intake even though the same conditions applied to the controls which did not show these symptoms10. So, in a typical manifestation of duplicity the FDA dismissed the significance of the findings instead of widening the scope of the studies to include the histology of the WHOLE digestive tract.  This is the more serious because the dark red pin-point necrotic STOMACH lesions of female rats are termed 'erosion' in human pathology which may have sequelae such as life-endangering haemorrhage in the elderly, particularly on low dosage aspirin to prevent thrombotic events and synergy with GM tomatoes may occur.  The rats in this study were models for humans and therefore the pathology findings ought to have been put in this human context, particularly as seven out of forty rats eating GM tomatoes died within two weeks and the nature of these deaths was not specified nor were they shown to be unrelated to the ingestion of GM tomatoes and investigated further.  In a very curious outcome, after the completion of these GM tomato studies the FDA has never again required the nutritional/toxicological testing of any other GM food.  GM potatoes expressing Bacillus thuringiensis toxin (Bt-toxin potatoes).  An interesting electron microscopy histology study was carried out on the lower part (ileum) of the small intestine of mice fed with potatoes tran!  sformed with a Bacillus thuringiensis var. kurstaki CryI toxin gene. As a control, the effect of the toxin itself was also investigated11.

 Although there were flaws in the experimental design of this important study2, the results showed that both the delta endotoxin and, to a lesser extent the Bt-potato, caused the disruption, swelling and multinucleation of the gut surface cells and increased their self-degradation. This underlined the authors' recommendations that "thorough tests of these new types of genetically engineered crops must be made to avoid the risks before marketing".  This study has once for all established that, contrary to general belief, the Bt CryI toxin does not break down in the gut11 but binds to its surface and can induce major immune effects12.  Despite the importance of these findings, this study is never referred to in official pro-GM reference lists.

GM potatoes expressing GNA, snowdrop (Galanthus nivalis) bulb lectin. The publication3 of the results of our histology study of the entire digestive tract of rats fed GM potatoes expressing GNA was attacked by pro-GM scientists and politicians alike13. However, none of the criticisms were based on published evidence but were personal opinions8,13 which were fully answered14.      Groups of young, rapidly growing rats were strictly pair-fed with different raw or boiled potato diets containing the same amount of protein and energy for 10 days.  The test diets contained GM potatoes while the control diets contained the same amount of parental line non-GM potatoes  alone or supplemented with GNA at the same concentration as expressed in the GM potatoes. Microscopic examination of fixed and stained samples of stomach, small intestine (jejunum and ileum), and large intestine (caecum and colon) showed proliferative growth of most parts of the digestive tract by the GM potato diet that was not observed in the control groups.  This was most striking in the small intestine of rats fed with raw GM potatoes but some effects were also seen when the rats were fed with boiled potato diets.  This, and the accompanying stimulation of the gut immune system was not caused by GNA, THE TRANSGENE PRODUCT but was probably due to some so far unknown DIRECT effects of other parts of the genetic construct used for the transformation or THE EFFECTS OF THEIR INSERTION INTO THE POTATO GENOME BY MODULATING THE FUNCTION OF THE GENES OF THE POTATO (PLEITROPIC EFFECT) OR the genetic transformation itself.  The results again underlined the need that the effects on the gut structure and metabolism of all GM crop LINES should be thoroughly investigated case-by-case as a part of the regulatory process before their release into the human food chain.

Transgene survival in humans.  The only human study with GM foods to establish whether the antibiotic resistance marker gene survives in the gut and whether it is taken up by gut bacteria is so far unpublished but its results can be found on the British Food Standards Agency's (FSA) website15 who initiated and funded the study.  It was shown that in the digesta of seven ileostomy patients (people whose large intestine has been surgically removed and replaced with with an external pouch joined to the lower end of their small intestine) given a single meal containing GM soya, variable but measurable amounts of the full length transgene construct survived and that in three patients this was highly significant. Thus, transgenic DNA survives not only in mice4 or in artificial guts6 but also in humans and can be taken up by gut bacteria.  However, the FSA report misrepresented these findings by stating that "... the study findings showed that small fragments of GM DNA survived in the gut of three people taking part in the study" while the data in the study actually showed that these were not fragments but measurable amounts of the full length transgene.  WITH THIS the FSA IN FACT FALSIFIED the results OF THEIR OWN SCIENTISTS BY ASSERTING THAT THEY had no biological significance because the surviving transgenes were only small non-functional fragments which could not have transformed the bacteria and make them antibiotic resistant.  The FSA's suggestion that BECAUSE the VIRUS PROMOTER USED IN GM SOYA DOES NOT FUNCTION IN BACTERIA IT WOULD BE IMPOSSIBLE FOR THE BACTERIA in the human gut TO TAKE UP THE TRANSGENE CONSTRUCT, IS SIMILARLY UNTRUE.  The FSA's assertion that GM soya is harmless because their scientists could not find transgenic DNA in the faeces of normal human subjects has little relevance because it is the physiological effects of the transgene(s) and their products ON THE GUT during their passage through the digestive tract what is important and not what is left after the digesta has voided the body. [THIS  FSA STUDY IS THE ONLY STUDY THAT PROVIDES DIRECT EXPERIMENTAL EVIDENCE THAT BACTERIA IN THE HUMAN GUT DOES TAKE UP A FULLY FUNCTIONAL TRANSGENE CONSTRUCT - ALL OTHER REFERENCES GIVE ONLY INDIRECT EVIDENCE FOR THIS OR SUGGEST THIS; IT IS IMPORTANT TO SEPARATE PROVEN FACTS FROM SPECULATION!]  It was also curious that the FSA used GM soya to establish whether the antibiotic resistance marker gene could be passed on to human gut bacteria when this is one of the few GM foodcrops which do not contain such a marker gene.

Conclusions 
This brief overview of GM food regulation demonstrated two important major points.  Thus, even these few examples have indicated that methods based on the striking biological effects of the transgenic DNA and proteins on the gastrointestinal tract could be developed into potentially powerful tools WHICH COULD THE BE USED TOGETHER WITH OTHERS in GM food risk analysis.  The second important conclusion is that the FSA's, FDA's AND OTHER regulatory authorities' dismissal of legitimate scientific evidence questioning the safety of GM foods makes it clear that their main concern is to promote GM technology and not to present unbiased information to the general public.  Moreover, when they find it difficult to dismiss the results suggesting that the GM food may be deleterious for the consumer, the authorities either try to keep this information from the public1 or massage15 or corrupt13 the damning evidence.  It is all the more curious why it is that the pro-GM scientific and political establishments are unable to understand that people can see through such manipulations and just make their resolve even stronger in demanding a GM food regulatory system which is open, transparent and inclusive.  OF COURSE, IT IS POSSIBLE THAT THEY ARE JUST SIMPLY AFRAID TO ACCEED TO THIS DEMAND FOR THE FEAR THAT THE RESULTS OF UNBIASED STUDIES MIGHT NOT ONLY SHOW HOW UNNECESSARY GM FOODS ARE BUT ALSO HOW DANGEROUS. WE HAVE TO REMIND OUR POLITICIANS THAT THE ABSENCE OF EVIDENCE OF HARM CANNOT BE REGARDED AS EVIDENCE FOR THE SAFETY OF GM FOODS PARTICULARLY IN THE ABSENCE OF SAFETY STUDIES.
   
References
1. Domingo JL, Science 288, 1748-1749 (2000).
2. Pusztai A,
http://www.actionbioscience.org/biotech/pusztai.html (2001)
3.   Ewen SWB, Pusztai A, The Lancet 354, 1353-1354 (1999).
4.   Schubbert R et al, Molecules, Genes and Genetics 259, 569-576 (1998).
5.   Mercer DK et al, Applied and Environmental Microbiology 65, 6-10 (1999).
6.   MacKenzie D, New Scientist, 30 January 1999
7.   Pusztai A et al,  Journal of Nutrition  129, 1597-1603 (1999). 
8.   Kuiper HA et al, The Plant Journal 27, 503-528 (2001).
9.   Pusztai A, Nutrition and Health 16, 73-84 (2002).
10.   Alliance for Biointegrity website,
http://www.biointegrity.org (1998).
11.  Fares NH, El-Sayed AK, Natural
Toxins 6, 219-233 (1999).
12. Vazquez-Padron RI et al, Biochemical and
Biophysical Research Communications 271, 54-      58 (2000).
13.  Kuiper HA et al, The Lancet 354, 1315-1316 (1999).
14.  Ewen SWB, Pusztai A, The Lancet 354, 1727-1728 (1999).
15.  FSA website,
http://www.food.gov.uk/science/sciencetopics/gmfoods/gm_reports   -
Reports       GO10008 (2002).
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"For the sake of a continent threatened by famine, I urge the European governments to end their opposition to biotechnology. We should encourage the spread of safe, effective biotechnology to win the fight against global hunger." - George W. Bush
http://reuters.com/newsArticle.jhtml?type=topNews&storyID=2974214
This is the man who torpedoed Chirac's proposal to ban the dumping of subsidised farm produce in African markets.
http://news.independent.co.uk/world/politics/story.jsp?story=41156
http://politics.guardian.co.uk/columnist/story/0,9321,969259,00.html
This is the man in charge of the world's stingiest aid budget
http://www.guardian.co.uk/g8/story/0,13365,967654,00.html
And whose aid promises are misleading.
http://story.news.yahoo.com/news?tmpl=story&u=/oneworld/20030522/wl_oneworld
/118151053610546
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Dangers of GM chicken feed
http://www.femail.co.uk/pages/standard/article.html?in_article_id=186115&in_page_id=194

EXCERPT: Alarming safety doubts have been raised about GM maize after a feeding trial in which death rates among chickens doubled.  Twice as many birds fed GM maize died during the 42-day Canadian trial compared with those on conventional diets.  And when it was over, the birds fed GM maize varied widely in size.  But far from raising concerns, the trial was used to back up an application to grow the new crop in Britain.