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Genetically Modified Foods

By Amy Porter,2014-09-19 19:05
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    Genetically Modified Foods: Are They a Risk to Human/Animal Health?

    Arpad Pusztai

    An ActionBioscience.org original article

    ?en español

    articlehighlights

    Genetically modified (GM) crops and food are being grown and consumed by the public, even though:

    ; there is little scientific study about their health risks

    ; safety test technology is inadequate to assess potential harm

    ; they can carry unpredictable toxins

    ; they may increase the risk of allergenic reactions

    June 2001

    Scarcity of safety tests

    Soybeans were genetically engineered to make them herbicide resistant. Photo: Scott Bauer. How can the public make informed decisions about genetically modified (GM) foods when there is so little information about its safety? The lack of data is due to a number of reasons, including:

    Information is scarce about health hazards, such as toxicity in genetically modified (GM) crops.

    ; It‟s more difficult to evaluate the safety of crop-derived foods than individual chemical,

    drug, or food additives. Crop foods are more complex and their composition varies according to differences in growth and agronomic conditions.

; Publications on GM food toxicity are scarce. An article in Sciencemagazine said it all:

    1“Health Risks of Genetically Modified Foods: Many Opinions but Few Data”. In fact, no

    peer-reviewed publications of clinical studies on the human health effects of GM food exist. Even animal studies are few and far between.

    ; The preferred approach of the industry has been to use compositional comparisons between GM and non-GM crops. When they are not significantly different the two are regarded as “substantially equivalent”, and therefore the GM food crop is regarded as safe as its conventional counterpart. This ensures that GM crops can be patented without animal testing. However, substantial equivalence is an unscientific concept that has never been properly defined and there are no legally binding rules on how to

    2establish it.

    GM foods may cause bacteria to become resistant to antibiotics.

    They can also produce allergies.

    When food-crops are genetically modified, (“genetically modified” food is a misnomer!) one or more genes are incorporated into the crop‟s genome using a vector containing several other genes, including as a minimum, viral promoters, transcription terminators, antibiotic resistance marker genes and reporter genes. Data on the safety of these are scarce even though they can affect the safety of the GM crop. For example:

    3,4; DNA does not always fully break down in the alimentary tract. Gut bacteria can take

    up genes and GM plasmids5 and this opens up the possibility of the spread of antibiotic resistance.

    ; Insertion of genes into the genome can also result in unintended effects, which need to be reduced/eliminated by selection, since some of the ways the inserted genes express themselves in the host or the way they affect the functioning of the crop‟s own genes are unpredictable. This may lead to the development of unknown toxic/allergenic components, which we cannot analyze for and seriously limiting the selection criteria. Current testing methods need radical improvements.

    Currently, toxicity in food is tested by chemical analysis of macro/micro nutrients and known toxins. To rely solely on this method is at best inadequate and, at worst, dangerous. Better diagnostic methods are needed, such as mRNA fingerprinting,

    6proteomics and secondary metabolite profiling. However, consuming even minor

    constituents with high biological activity may have major effects on the gut and body‟s

    metabolism, which can only be revealed from animal studies. Thus novel toxicological/nutritional methods are urgently needed to screen for harmful consequences on human/animal health and to pinpoint these before allowing a GM crop

    7into the food chain.

    Safety tests on commercial GM crops

    GM tomatoes: The first and only safety evaluation of a GM crop, the FLAVR

    TMSAVR tomato, was commissioned by Calgene, as required by the FDA. This GM tomato was produced by inserting kanr genes into a tomato by an „antisense‟ GM method. The

    8test has not been peer-reviewed or published but is on the internet. The results claim

    there were no significant alterations in total protein, vitamins and mineral contents and

    9in toxic glycoalkaloids. Therefore, the GM and parent tomatoes were deemed to be “substantially equivalent.”

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

    none in the controls. However, these were considered to be of no importance, although

    in humans they could lead to life-endangering hemorrhage, particularly in the elderly

    who use aspirin to prevent thrombosis.

    ; Seven out of forty rats on GM tomatoes died within two weeks for unstated reasons. ; These studies were poorly designed and therefore the conclusion that FLAVR

    TMSAVR tomatoes were safe does not rest on good science, questioning the validity of

    the FDA‟s decision that no toxicological testing of other GM foods will in future be

    required.

    GM maize: Two lines of Chardon LL herbicide-resistant GM maize expressing the gene of Phosphinothricin Acetyltransferase Enzyme (PAT-PROTEIN) before and after ensiling showed significant differences in fat and carbohydrate contents compared with non-GM maize and were therefore substantially different. Toxicity tests were only performed with the PAT-PROTEIN even though with this the unpredictable effects of the gene transfer or the vector or gene insertion could not be demonstrated or excluded. The design of these experiments was also flawed because:

    Rats’ ability to digest was decreased after eating GM corn.

    ; The starting weight of the rats varied by more than ?20% and individual feed intakes

    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 health risks. Compositional studies

    Allergen content increased when soybeans were genetically modified.

    GM soybeans: To make soybeans herbicide resistant, the gene of

    5-enolpyruvylshikimate-3-phosphate synthase from Agrobacterium was used. Safety

    tests claim the GM variety to be “substantially equivalent” to conventional

    10soybeans. The same was claimed for GTS (glyphosate-resistant soybeans) sprayed

    11with this herbicide. However, several significant differences between the GM and

    10control lines were recorded and the statistical method used was flawed because:

    ; Instead of comparing the amounts of components in a large number of samples of each individual GTS with its appropriate parent line grown side-by-side and harvested at the same time, the authors compared samples from different locations and harvest times. ; There were also differences in the contents of natural isoflavones (genistein, etc.) with

    12potential importance for health.

    ; Additionally, the trypsin inhibitor (a major allergen) content was significantly increased

    10in GTS.

    Because of this, and the large variability (? 10% or more), the lines could not be regarded as “substantially equivalent.”

    GM potatoes: There is only one peer-reviewed publication on GM potatoes that express

    13the soybean glycinin gene. However, the expression level was very low and no

    improvements in the protein content or amino acid profile were obtained. GM rice: The kind that expresses soybean glycinin gene (40-50 mg glycinin/g protein)

    14has been developed and is claimed to contain 20% more protein. However, the

    increased protein content was probably due to a decrease in moisture rather than true increase in protein putting a question mark over the significance of this GM crop. The toxin level of GM cotton is unpredictable.

    GM cotton: Several lines of GM cotton plants have been developed using a gene from Bacillus thuringiensis subsp. kurstaki providing increased protection against major

    lepidopteran pests. The lines were claimed to be “substantially equivalent” to parent

    15lines in levels of macronutrients and gossypol, cyclopropenoid fatty acids and aflatoxin levels were less than those in conventional seeds. However, because of the use of inappropriate statistics it is questionable whether the GM and non-GM lines were truly

    equivalent, particularly as environmental stresses could have unpredictable effects on

    16antinutrient/toxin levels.

    Nutritional/toxicological studies

    17Herbicide-resistant soybean: Studies have been conducted on the feeding value and

    18possible toxicity for rats, broiler chickens, catfish and dairy cows of two GM lines of glyphosate-resistant soybean (GTS). The growth, feed conversion efficiency, catfish fillet composition, broiler breast muscle and fat pad weights and milk production, rumen fermentation and digestibilities in cows were claimed to be similar for GTS and non-GTS. However:

    ; These experiments were poorly designed since the high dietary protein concentration

    and the low inclusion level of GTS could have masked any GM effect.

    ; No individual feed intakes, body or organ weights were given and no histology was

    performed, except some qualitative microscopy on the pancreas.

    ; The feeding value of the two GTS lines was not substantially equivalent either because

    the rats grew significantly better on one of the GTS lines than on the other. ; The experiment with broiler chicken was a commercial and not a scientific study. ; The catfish experiment showed again that the feeding value of one of the GTS lines was

    superior to the other.

    ; Milk production and performance of lactating cows also showed significant differences

    between cows fed GM and non-GM feeds.

    ; Moreover, testing of the safety of 5-enolpyruvylshikimate-3-phosphate synthase

    18which renders soybeans glyphosate-resistant was irrelevant because in the gavage

    studies an E. coli recombinant and not the GTS product was used. Their effects could

    be different as the differences in post-translational modification could have impaired

    their stability to gut proteolysis.

    Thus, the claim that the feeding value of GTS and non-GTS lines was substantially equivalent is at best premature.

    Rats had meager weight gain when fed GM soybeans.

    19In a separate study it was claimed that rats and mice which were fed 30% toasted GTS or non-GTS in their diet had no significant differences in nutritional performance, organ

    weights, histopathology and production of IgE and IgG antibodies. However, under the unphysiological basically, starvation conditions of these experiments when, instead

    of the normal daily growth of 5-8 g per day, the rats grew less than 0.3 g and mice not at all, no valid conclusions could be drawn.

    GM corn: One broiler chicken feeding study with rations containing transgenic Event 176

    20derived Bt corn (Novartis) has been published. However, the results of this trial are

    more relevant to commercial than academic scientific studies.

    GM peas: The nutritional value of diets containing GM peas expressing bean alpha-amylase inhibitor when fed to rats for 10 days at two different (30% or 65%)

    21dietary inclusions, was shown to be similar to that of parent-line peas.

    GM peas seem to have no harmful effects on animals but that doesn’t mean they are safe for humans.

    ; Even at 65% level the difference was small mainly because the alpha-amylase inhibitor expressed in the peas was quickly digested in the rat gut and its antinutritive effect abolished. Unfortunately no gut histology was done or lymphocyte responsiveness measured.

    ; Although some organ weights, mainly the caecum and pancreas were different, those of others were remarkably similar suggesting that GM peas may be used in the diets of farm animals at low/moderate levels if their progress was carefully monitored. However, to establish its safety for humans a more rigorous specific risk assessment will have to be carried out with several GM lines. This should include:

    ; An initial nutritional/toxicological testing on laboratory animals

    ; If no harmful effects are then detected, it should be followed by clinical, double-blind, placebo-type tests with human volunteers, keeping in mind that any possible harmful effects would be particularly serious with the young, old, and disabled. A protocol for such testing was given at the OECD conference in Edinburgh, February

    222000 and subsequently published.

    GM potatoes: In a short feeding study to establish the safety of GM potatoes expressing the soybean glycinin gene, rats were daily force-fed with 2 g of GM or control

    23potatoes/kg body weight. Although no differences in growth, feed intake, blood cell count and composition and organ weights between the groups was found, the potato intake of the animals was too low and unclear, whether the potatoes were raw or boiled. Toxins were found in mice after eating GM potatoes.

Feeding mice with potatoes transformed with a Bacillus thuringiensis var.kurstaki Cry1

    24toxin gene or the toxin itself was shown to have caused villus epithelial cell

    hypertrophy and multinucleation, disrupted microvilli, mitochondrial degeneration, increased numbers of lysosomes and autophagic vacuoles and activation of crypt Paneth cells. The results showed that despite claims to the contrary, CryI toxin was stable in the mouse gut and therefore GM crops expressing it need to be subjected to “thorough

    24tests…to avoid the risks before marketing.

    When the health risks of GM potatoes were revealed in some studies, a debate ensued.

    In another study, young, growing rats were pair-fed on iso-proteinic and iso-caloric

    balanced diets containing raw or boiled non-GM potatoes and GM potatoes with the

    25snowdrop (Galanthus nivalis) bulb lectin (GNA) gene. The results showed that the

    mucosal thickness of the stomach and the crypt length of the intestines of rats fed GM potatoes was significantly increased. Most of these effects were due to the insertion of the construct and not to GNA which had been been pre-selected as a non-mitotic lectin

    26unable to induce hyperplastic intestinal growth and epithelial T lymphocyte infiltration.

    Although there is controversy about the tests, most of the adverse comments on this Lancet paper were personal, non-peer reviewed opinions and, as such, of limited scientific value. The findings, on the other hand, were published in a peer-reviewed

    257publication and the criticism replied to. The work, however, has not been repeated

    nor results contradicted and it is therefore imperative that the effects on the gut structure and metabolism of all other GM crops developed using similar techniques and genetic vectors should be thoroughly investigated before their release into the food chain.

    GM tomatoes: This study with a GM tomato expressing B. thuringiensis toxin CRYIA(b)

    gene was published in a book and not in a peer-reviewed journal. However, its importance was underlined by the immunocytochemical demonstration of in

    vitro binding of Bt toxin to the caecum/colon from humans and rhesus

    27monkeys. Although in vivo the Bt toxin was not bound by the rat gut, this was possibly due to the authors‟ use of recombinant Bt toxin.

    Allergenicity studies

    One of the major health concerns with GM food is its potential to increase allergies and anaphylaxis in humans eating unlabeled GM foodstuffs.

    Allergies are a major concern with GM food, especially if ingredients are not labeled in packaged food.

    ; When the gene is from a crop of known allergenicity, it is easy to establish whether the GM food is allergenic usingin vitrotests, such as RAST or immunoblotting, with sera

    from individuals sensitised to the original crop. This was demonstrated in GM soybeans

    28expressing the brasil nut 2 S protein or in GM potatoes expressing cod protein

    29genes.

    ; It is also relatively easy to assess whether genetic engineering affected the potency of

    30endogenous allergens. Some farm workers exposed toB. thuringiensis pesticide

    were shown to have developed skin sensitization and IgE antibodies to the Bt spore extract. With their sera it may now therefore be possible to test for the allergenic

    31potential of GM crops expressing Bt toxin. It is all the more important because Bt

    toxin Cry1Ac has recently been shown to be a potent oral/nasal antigen and

    32adjuvant.

    There are no reliable ways to test GM foods for allergies.

    Assessment of the allergenicity of a GM foodcrop, however, is difficult when the gene is transferred from a source not eaten before or with unknown allergenicity or on gene transfer/insertion a new allergen or adjuvant is developed or the expression of a minor allergen is increased. Unfortunately, while there are good animal models for nutritional/toxicological testing, no such models exist for allergenicity testing. ; Presently only indirect and rather scientifically unsound methods, such as finding SHORT sequence homologies (at least 8 contiguous amino acids) to any of the about 200 known allergens, are used for the assessment of allergenicity.

    ; The decision-tree type of indirect approach based on factors (such as size and stability)

    33of the transgenically expressed protein is even more unsound, particularly as its

    34stability to gut proteolysis is assessed by an in vitro (simulated) testing instead ofin

    vivo(human/animal) testing and this is fundamentally wrong. The concept that most allergens are abundant proteins is also misleading because for example Gad c 1, the

    29major allergen in codfish, is not a predominant protein.

    ; However, when the gene responsible for the allergenicity is known, such as the gene of the alpha-amylase/trypsin inhibitors/allergens in rice, cloning and sequencing opens

    35the way for reducing their level by antisense RNA strategy.

    Thus, in the absence of reliable methods for allergenicity testing, it is at present impossible to definitely establish whether a new GM crop is allergenic or not before its release into the human/animal food/feed chain.

    In conclusion

    We need more and better testing methods before making GM foods available for human consumption.

    1One has to agree with the piece in Science that there are many opinions but scarce data

    on the potential health risks of GM food crops, even though these should have been tested for and eliminated before their introduction. Our present data base is woefully inadequate. Moreover, the scientific quality of what has been published is, in most instances not up to expected standards. If, as claimed, our future is dependent on the success of the promise of genetic modification delivering wholesome, plentiful, more nutritious and safe GM foods, the inescapable conclusion of this review is that the present crude method of genetic modification has so far not delivered these benefits and the promise of a superior second generation is still in the future. Although it is argued by some that small differences between GM and non-GM crops have little biological meaning, it is clear that most GM and parental line crops fall short of the definition of “substantial equivalence.” In any case, this crude, poorly defined and unscientific concept outlived its possible previous usefulness and we need novel methods and concepts to probe into the compositional, nutritional/toxicological and metabolic differences between GM and conventional crops and into the safety of the genetic techniques used in developing GM crops if we want to put this technology on a proper scientific foundation and allay the fears of the general public. We need more science,

    6,7not less.

    Why is genetically modified evil? Many things are genetically modified for the better. Plants are sprayed with a hormone specific to it’s species to create seedless fruit. Do you run from seedless grapes? Most other types of genetic modification involves taking a gene from an animal that is something like mosquito resistant, and putting it into the plant, thus eliminating the need for pesticide. Look things up before you open your ignorant mouth. You can eat inorganic fruit all you want, the pesticide won’t kill you.

    Genetically modified crops are the most rigorously scrutinized foods in America, regulated by the EPA, USDA, and the FDA. Genetic modification merely allows crops to produce higher yields while thriving in conditions it would be unable to naturally. It’s not like scientists are fiddling with the ―be more poisonous‖ gene.

    It’s wonderful that America has such an overabundance of food that you can afford to RUN!!!! from GM foods, but they are a matter of life or death in countries where that is not the case.

    Also, unless you’re eating nothing but wild berries picked off a hidden bush in a secret forest on an alternate-dimension Earth, everything you eat has been modified over time through human selection and modification.

    Genetically modified is not bad and a cursory knowledge of genetic history will show that most cultivated produce has been genetically modified pretty much since plant-grafting was developed centuries ago.

    Many people tend to associate genetically modified with steroid and chemical enhancement which couldn’t be further from the truth.

    The difference between a GM food and a conventional (or organic) food is the gene make-up, which as the end result produces a protein which in almost all

    cases (for the purposes of GM food) acts as an enzyme, changing one chemical into another. Now, the word ―chemical‖ does have some harsh connotations in the English language, but since we’ve put semantics aside I’ll continue to use it and point out that all of the genes added to GM food have to come from natural products (i.e. scientists do not create genes for a specific purpose out of nothing, it must come from a specific animal). I’m sure you’re already aware of that and I’m sorry to go over it again, but it’s a nice reminder that GM food is not purely science-fiction this food is still natural and is just the product in the next step of artificial selection the same kind of selection that led to the organic foods you love so much. This next step, however, lets developers have more control over the outcome so people don’t have to sacrifice flavor for fruit that last in storage longer, for example.

    Genetic modification mainly tries to do the following: increase yields, increase storage length and reduce bruising, and reduce pesticide use. And as long as there’s no plastic in your apple, all of the genes in it came from living things nature created.

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