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    Genetically Modified Organisms and risks associated with GeneticallyModified Organisms

    Genetically modified organisms (GMOs) can be defined as organisms in which

    the genetic material (DNA) has been altered in a way that does not occur naturally.The technology is often called modern biotechnology or gene technology,sometimes also recombinant DNA technology or genetic engineering. It allowsselected individual genes to be transferred from one organism into another, alsobetween non-related species.

    GM foods are developed and marketed because there is some perceivedadvantage either to the producer or consumer of these foods. This is meant totranslate into a product with a lower price, greater benefit (in terms of durability ornutritional value) or both. Initially GM seed developers wanted their products to beaccepted by producers so have concentrated on innovations that farmers (and the

    food industry more generally) would appreciate.The initial objective for developing plants based on GM organisms was to improvecrop protection. The GM crops currently on the market are mainly aimed at anincreased level of crop protection through the introduction of resistance againstplant diseases caused by insects or viruses or through increased tolerancetowards herbicides.

    Insect resistance is achieved by incorporating into the food plant the gene fortoxin production from the bacterium Bacillus thuringiensis (BT). This toxin iscurrently used as a conventional insecticide in agriculture and is safe for humanconsumption. GM crops that permanently produce this toxin have been shown to

    require lower quantities of insecticides in specific situations, e.g. where pestpressure is high.

    Virus resistance is achieved through the introduction of a gene from certainviruses which cause disease in plants. Virus resistance makes plants lesssusceptible to diseases caused by such viruses, resulting in higher crop yields.

    Herbicide tolerance is achieved through the introduction of a gene from abacterium conveying resistance to some herbicides. In situations where weedpressure is high, the use of such crops has resulted in a reduction in the quantity ofthe herbicides used.

    Some risks associated with GMOs:

    The safety assessment of GM foods generally investigates: (a) direct health effects(toxicity), (b) tendencies to provoke allergic reaction (allergenicity); (c) specificcomponents thought to have nutritional or toxic properties; (d) the stability of theinserted gene; (e) nutritional effects associated with genetic modification; and (f)any unintended effects which could result from the gene insertion.

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    While theoretical discussions have covered a broad range of aspects, the threemain issues debated are tendencies to provoke allergic reaction (allergenicity),gene transfer and outcrossing.

    Allergenicity. As a matter of principle, the transfer of genes from commonly

    allergenic foods is discouraged unless it can be demonstrated that the proteinproduct of the transferred gene is not allergenic. While traditionally developedfoods are not generally tested for allergenicity, protocols for tests for GM foodshave been evaluated by the Food and Agriculture Organization of the UnitedNations (FAO) and WHO. No allergic effects have been found relative to GM foodscurrently on the market.

    Gene transfer. Gene transfer from GM foods to cells of the body or to bacteria inthe gastrointestinal tract would cause concern if the transferred genetic materialadversely affects human health. This would be particularly relevant if antibioticresistance genes, used in creating GMOs, were to be transferred. Although the

    probability of transfer is low, the use of technology without antibiotic resistancegenes has been encouraged by a recent FAO/WHO expert panel.

    Outcrossing. The movement of genes from GM plants into conventional crops orrelated species in the wild (referred to as outcrossing), as well as the mixing ofcrops derived from conventional seeds with those grown using GM crops, mayhave an indirect effect on food safety and food security. This risk is real, as wasshown when traces of a maize type which was only approved for feed useappeared in maize products for human consumption in the United States of

    America. Several countries have adopted strategies to reduce mixing, including aclear separation of the fields within which GM crops and conventional crops are

    grown.

    Feasibility and methods for post-marketing monitoring of GM food products,for the continued surveillance of the safety of GM food products, are underdiscussion.

    Safety tests on commercial GM crops:

    GM tomatoes: The first and only safety evaluation of a GM crop, the FLAVRSAVRTM tomato, was commissioned by Calgene, as required by the FDA. This GMtomato was produced by inserting kanr genes into a tomato by an antisense GM

    method. The test has not been peer-reviewed or published but is on the internet.The results claim there were no significant alterations in total protein, vitamins andmineral contents and in toxic glycoalkaloids. Therefore, the GM and parenttomatoes were deemed to be substantially equivalent.

    In acute toxicity studies with male/female rats, which were tube-fed homogenizedGM tomatoes, toxic effects were claimed to be absent. In addition, it wasconcluded that mean body and organ weights, weight gains, food consumption and

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    clinical chemistry or blood parameters were not significantly different between GM-fed and control groups. However:

    Some rats died within a few weeks after eating GM tomatoes.

    The unacceptably wide range of rat starting weights (18% to 23%)invalidated these findings. No histology on the intestines was done even though stomach sections

    showed mild/moderate erosive/necrotic lesions in up to seven out of twentyfemale rats but none in the controls. However, these were considered to beof no importance, although in humans they could lead to life-endangeringhemorrhage, particularly in the elderly who use aspirin to preventthrombosis.

    Seven out of forty rats on GM tomatoes died within two weeks for unstatedreasons.

    These studies were poorly designed and therefore the conclusion that

    FLAVR SAVR

    TM

    tomatoes were safe does not rest on good science,questioning the validity of the FDAs decision that no toxicological testing ofother GM foods will in future be required.

    GM potatoes: In a short feeding study to establish the safety of GM potatoesexpressing the soybean glycinin gene, rats were daily force-fed with 2 g of GM orcontrol potatoes/kg body weight. Although no differences in growth, feed intake,blood cell count and composition and organ weights between the groups wasfound, the potato intake of the animals was too low and unclear, whether thepotatoes were raw or boiled.

    Toxins were found in mice after eating GM potatoes.

    Feeding mice with potatoes transformed with a Bacillus thuringiensis var. kurstakiCry1 toxin gene or the toxin itself was shown to have caused villus epithelial cellhypertrophy and multinucleation, disrupted microvilli, mitochondrial degeneration,increased numbers of lysosomes and autophagic vacuoles and activation of cryptPaneth cells. The results showed that despite claims to the contrary, CryI toxin wasstable in the mouse gut and therefore GM crops expressing it need to be subjectedto thorough teststo avoid the risks before marketing.

    GM maize: Two lines of Chardon LL herbicide-resistant GM maize expressing the

    gene of Phosphinothricin Acetyltransferase Enzyme (PAT-PROTEIN) before andafter ensiling showed significant differences in fat and carbohydrate contentscompared with non-GM maize and were therefore substantially different. Toxicitytests were only performed with the PAT-PROTEIN even though with this theunpredictable effects of the gene transfer or the vector or gene insertion could notbe demonstrated or excluded. The design of these experiments was also flawedbecause:

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    Rats ability to digest was decreased after eating GM corn.

    The starting weight of the rats varied by more than 20% and individual feedintakes were not monitored.

    Feed conversion efficiency on PAT-PROTEIN was significantly reduced.

    Urine output increased and several clinical parameters were also different. The weight and histology of the digestive tract (and pancreas) was not

    measured.

    Thus, GM maize expressing PAT-PROTEIN may present unacceptable healthrisks.

    Future of GMOs:

    Future GM organisms are likely to include plants with improved disease or droughtresistance, crops with increased nutrient levels, fish species with enhanced growth

    characteristics and plants or animals producing pharmaceutically importantproteins such as vaccines. At the international level, the response to newdevelopments can be found in the expert consultations organized by FAO andWHO in 2000 and 2001, and the subsequent work of the Codex ad hoc Task Forceon Foods Derived from Biotechnology. This work has resulted in an improved andharmonized framework for the risk assessment of GM foods in general. Specificquestions, such as the evaluation of allergenicity of GM foods or the safety offoods derived from GM microorganisms, have been covered and an expertconsultation organized by FAO and WHO will focus on foods derived from GManimals in 2003.

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    References:

    Alliance for Biointegritywebsite: http://www.biointegrity.org(1998), includingCalgene FLAVR SAVRTM tomato report, pp. 1-604; International Research andDevelopment Corp. first test report, pp. 1736-1738; Conclusions of the expertpanel regarding the safety of the FLAVR SAVRTM tomato, ENVIRON, Arlington VA,

    USA pp. 2355-2382; Four week oral (intubation) toxicity study in rats by IRDC, pp.2895-3000.

    Redenbaugh, K., Hatt, W., Martineau, B, Kramer, M., Sheehy, R., Sanders, R.,Houck, C. and Emlay, D. (1992) A case study of the FLAVR SAVRTM tomato. In:Safety Assessment of Genetically Engineered Fruits and Vegetables. CRC Press,Inc. Boca Raton.

    Hashimoto, W., Momma, K., Yoon, H.J., Ozawa, S., Ohkawa, Y., Ishige, T., Kito,M., Utsumi, S. and Murata, K. (1999) Safety assessment of transgenic potatoeswith soybean glycinin by feeding studies in rats. Bioscience Biotechnology

    Biochemistry63, 1942-1946.

    Fares, N.H. and El-Sayed, A.K. (1998) Fine structural changes in the ileum of micefed on delta-endotoxin-treated potatoes and transgenic potatoes. Natural Toxins 6,219-233.

    Websites:

    1.www.who.int/foodsafety/publications/biotech/20questions/en

    2. http://www.actionbioscience.org/biotech/pusztai.html

    3. http://www.nature.com/embor/journal/v5/n1s/full/7400231.html

    http://www.biointegrity.org/http://www.biointegrity.org/http://www.actionbioscience.org/biotech/pusztai.htmlhttp://www.nature.com/embor/journal/v5/n1s/full/7400231.htmlhttp://www.biointegrity.org/http://www.actionbioscience.org/biotech/pusztai.htmlhttp://www.nature.com/embor/journal/v5/n1s/full/7400231.html

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