7 Foods To Stop Consuming Today

If just one quarter of developed nations would stop consuming the following seven foods, the incidence of obesity and preventable disease would drop more than 50 percent.

1. Wheat
There are many health risks associated with the consumption of wheat.
Mainstream nutrition rarely focuses on all the crippling effects of wheat such as neurological impairment, dementia, heart disease, cataracts, diabetes, arthritis and visceral fat accumulation, not to mention the full range of intolerances and bloating now experienced by millions of people.

2. Soy
If you stop 10 strangers on the street and ask them if soy is health food, most will probably say yes, of course, everyone knows soy is healthy. However many people are now realizing how toxic soy really is.  Even so, the public’s perception of soy as health food got a boost from the FDA with a rule that permits soy beverages, soy-based cheese substitutes, and soy-based butter substitutes which are all toxins.

3. Corn
The second most genetically modified crop after soy is corn. According to one study, three varieties of Monsanto’s GM corn – Mon 863, insecticide-producing Mon 810, and Roundup herbicide-absorbing NK 603 – are approved for consumption by US, European and several other national food safety authorities.

4. Processed Foods
Eating too many processed foods with high sodium levels contributed to 2.3 million deaths from heart attacks, strokes and other heart-related diseases throughout the world in 2010, representing 15 percent of all deaths due to these causes, according to research presented at the American Heart Association’s Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions.

5. Refined Grains/Flour
Most refined grains and flours are also courtesy of Monsanto and GMO. Do you realize how much power one company can have over the foundation of the world’s food supply? Without stiff competition, Monsanto could raise its seed prices at will, which in turn could raise the cost of everything from animal feed to wheat bread and cookies. Stop eating them!

6. Conventional/Processed Meats
Conventional meat meaning factory farmed and processed meat meaning any meat preserved by smoking or adding chemical preservatives or refined salt.

Most meat eaters may be unaware that more than 70% of all beef and chicken in the United States, Canada and other countries is being treated with poisonous carbon monoxide gas. It can make seriously decayed meat look fresh for weeks. The meat industry continues to allow this toxic gas injection into many of the meat products people consume on a daily basis.

7. Conventional Dairy
Some studies have linked high intakes of dairy to increased risk of cancer. But others have found no connection, and even a reduced risk. The question is, which ones are unbiased studies and which ones are sponsored by the dairy industry?

US scientists suspect this is because milk and other dairy foods contain the hormone oestrogen, which encourages tumour growth.

Breakfast:
Try a smoothie for breakfast filled with fresh and frozen fruits, add some chia seeds and green your smoothie with kale, spirulina or spinach. Add a scoop of almond butter. Need more protein? Mix in some hemp protein powder or raw sprouted protein powder. Still hungry? Have some nuts, pumpkin seeds or some dates with coconut butter.

Lunch:
Need a sandwich for lunch? How about egg salad? Try sprouted Ezekiel bread (now available at many grocery retailers). Use organic eggs, hardboiled (cook them to perfection using this method). Mayo recipe on that link as well. Add the mayo with some finely chopped celery and red pepper. Add a pinch of pepper and you have a healthy great tasting sandwich.

Dinner:
Make yourself a beautiful large salad with a high quality olive oil and mix in your favorite greens and veggies. Shavings of some raw unpasteurized Parmesan cheese is always a nice addition along with olives and walnuts. This is a wonderful meal that should keep most satisfied until bed time. If it doesn’t, have another hemp protein smoothie, on the lighter side with minimal fruits, but add celery and cucumber with a pinch of ginger and some honey.

Full article

Advertisements

The GMO Cover-Up

Agriculture Secretary Tom Vilsack was getting lots of appreciative applause and head nods from the packed hall at the Community Food Security Coalition conference today, held in Des Moines, Iowa. He described the USDA’s plans to improve school nutrition, support local food systems, and work with the Justice Department to review the impact of corporate agribusiness on small farmers. But then, with time for only one more question, I was handed the microphone.

“Mr. Secretary, may I ask a tough question on GMOs?”

He said yes.

“The American Academy of Environmental Medicine this year said that genetically modified foods, according to animal studies, are causally linked to accelerated aging, dysfunctional immune regulation, organ damage, gastrointestinal distress, and immune system damage. A study came out by the Union of Concerned Scientists confirming what we all know, that genetically modified crops, on average, reduce yield. A USDA report from 2006 showed that farmers don’t actually increase income from GMOs, but many actually lose income. And for the last several years, the United States has been forced to spend $3-$5 billion per year to prop up the prices of the GM crops no one wants.
“When you were appointed Secretary of Agriculture, many of our mutual friends—I live in Iowa and was proud to have you as our governor—assured me that you have an open mind and are very reasonable and forward thinking. And so I was very excited that you had taken this position as Secretary of Agriculture. And I’m wondering, have you ever heard this information? Where do you get your information about GMOs? And are you willing to take a delegation in D.C. to give you this hard evidence about how GMOs have actually failed us, that they’ve been put onto the market long before the science is ready, and it’s time to put it back into the laboratory until they’ve done their homework.”

Read entire article here.

Genetically modified crops safety assessments: present limits and possible improvements

Gilles-Eric Séralini1*, Robin Mesnage1, Emilie Clair1, Steeve Gress1, Joël S de Vendômois2 and Dominique Cellier3

* Corresponding author: Gilles-Eric Séralini criigen@unicaen.fr

1 Laboratory of Biochemistry – IBFA, University of Caen, Esplanade de la Paix, 14032 Caen, Cedex, France
2 CRIIGEN, Paris, France
3 University of Rouen LITIS EA 4108, 76821 Mont-Saint-Aignan, France

Environmental Sciences Europe 2011, 23:10                                      doi:10.1186/2190-4715-23-10

The electronic version of this article is the complete one and can be found online at: http://www.enveurope.com/content/23/1/10

Received: 17 January 2011
Accepted: 1 March 2011
Published: 1 March 2011

© 2011 Séralini et al; licensee Springer.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

We reviewed 19 studies of mammals fed with commercialized genetically modified soybean and maize which represent, per trait and plant, more than 80% of all environmental genetically modified organisms (GMOs) cultivated on a large scale, after they were modified to tolerate or produce a pesticide. We have also obtained the raw data of 90-day-long rat tests following court actions or official requests. The data obtained include biochemical blood and urine parameters of mammals eating GMOs with numerous organ weights and histopathology findings.

Methods

We have thoroughly reviewed these tests from a statistical and a biological point of view. Some of these tests used controversial protocols which are discussed and statistically significant results that were considered as not being biologically meaningful by regulatory authorities, thus raising the question of their interpretations.

Results

Several convergent data appear to indicate liver and kidney problems as end points of GMO diet effects in the above-mentioned experiments. This was confirmed by our meta-analysis of all the in vivo studies published, which revealed that the kidneys were particularly affected, concentrating 43.5% of all disrupted parameters in males, whereas the liver was more specifically disrupted in females (30.8% of all disrupted parameters).

Conclusions

The 90-day-long tests are insufficient to evaluate chronic toxicity, and the signs highlighted in the kidneys and livers could be the onset of chronic diseases. However, no minimal length for the tests is yet obligatory for any of the GMOs cultivated on a large scale, and this is socially unacceptable in terms of consumer health protection. We are suggesting that the studies should be improved and prolonged, as well as being made compulsory, and that the sexual hormones should be assessed too, and moreover, reproductive and multigenerational studies ought to be conducted too.

Background, aim, and scope

Recently, an ongoing debate on international regulation has been taking place on the capacity to predict and avoid adverse effects on health and the environment for new products and novel food/feed (GMOs, chemicals, pesticides, nanoparticles, etc.). The health risk assessments are often, but not always, based on the study of blood analyses of mammals eating these products in subchronic tests, and more rarely in chronic tests. In particular, in the case of GMOs, the number and nature of parameters assessed, the length of the necessary tests, the statistics used and their interpretations are the subject of controversies, especially in the application of Organization of Economic Cooperation and Development (OECD) norms. Confusion is perceived even in regulatory agencies, as in the European Food Safety Authority (EFSA) GMO panel working group and its guidelines. Doubt has arisen on the role and necessity of animal feeding trials in safety and nutritional assessments of GM plants and derived food and feed [1]. Based on the literature data, EFSA first admitted (p. S33) that for other tests than GMOs: “For 70% (57 of 81) of the studies evaluated, all toxicological findings in the 2-year tests were seen in or predicted by the 3-month subchronic tests”. Moreover, they also indicated (p. S60) that “to detect effects on reproduction or development […] testing of the whole food and feed beyond a 90-day rodent feeding study may be needed.” We fully agree with these assumptions. This is why we think that in order to protect large populations from unintended effects of novel food or feed, imported or cultivated crops on a large scale, chronic 2-year and reproductive and developmental tests are crucial. However, they have never been requested by EFSA for commercial edible crops. We therefore wish to underline that in contrast with the statements of EFSA, all commercialized GMOs have indeed been released without such tests being carried out, and as it was the case recently with maize stacked events without 90-day in vivo mammalian tests being conducted. GM stacked events have the cumulated characteristics of first generation of GMOs (herbicide tolerance and insecticide production), which are mostly obtained by hybridization. For instance, Smarstax maize contains two genes for herbicide tolerance and six genes for insecticide production. In fact, this contradictory possibility was already highlighted in the same review by EFSA (p. S60), when substantial equivalence studies and other analyses were performed: “animal feeding trials with rodents […] adds little if anything […], and is not recommended.” This is why, in this work we will analyze and review deficiencies in GMO safety assessments, not only performed by biotech companies, but also by regulatory agencies.

We will focus on the results of available 90-day feeding trials (or more) with commercialized GMOs, in the light of modern scientific knowledge. We also suggest here an alternative to conventional feeding trials, to understand the biological significance of statistical differences. This approach will make it possible to avoid both false negative and false positive results in order to improve safety assessments of agricultural GMOs before their commercialization for cultivation and food/feed use and imports.

Overview of the safety studies of GMOs performed on mammals

Our experience in scientific committees for the assessment of environmental and health risks of GMOs and in biological, biostatistical research, and medicine, as well as in the research relative to side effects [26] allowed us to review and criticize mammalian feeding trials with GMOs and make new proposals. Mammalian feeding trials have been usually but not always performed for regulatory purposes in order to obtain authorizations or commercialization for GM plant-derived foods or feed. They may have been published in the scientific literature afterwards; however, without public access to the raw data.

We have obtained, following court actions or official requests, the raw data of several 28- or 90-day-long safety tests carried out on rats. The thing we did was to thoroughly review the longest tests from both a biostatistical and a biological point of view. Such studies often analyze the biochemical blood and urine parameters of mammals eating GMOs, together with numerous organ weights and histopathology. We have focused our review on commercialized GMOs which have been cultivated in significant amounts throughout the world since 1994 (Table 1). We observe and emphasize that all the events in Table 1 correspond to soybean and maize which constitute 83% of the commercialized GMOs, whilst other GMOs not displayed in the table, but still commercialized, are canola or cotton. However, they are not usually directly consumed [7]. Only Sakamoto’s and Malatesta’s studies have been more than 90 days long (104 weeks and 240 days with blood analyses in Japanese for the first one). Moreover, such tests are not obligatory yet for all GMOs. No detailed blood analysis is available for Malatesta’s study, as it mostly includes histochemistry at the ultrastructural level; moreover, the latter tests have not been used to obtain the commercial release by the firm. However, this work has been performed by researchers independent from the GMO industry; it is an important element to take into account for an objective interpretation of the facts, as pointed out in the case of the risk assessments conducted by regulatory agencies with Bisphenol A. For instance in the latter case, it was observed that none of the industry-funded studies showed adverse effects of Bisphenol A, whereas 90% of government-funded studies showed hazards at various levels and various doses [8]. However, regulatory agencies still continue to refer only to industry-funded studies because they are supposed to follow OECD norms, even if such standards are not always appropriate for the detection of environmental hazards [9]. In this paper, Myers et al. showed that hundreds of laboratory animals and cell culture studies were rejected by regulatory authorities because they did not follow the Good Laboratory Practices (GLP). The Food and Drug Administration and EFSA have based their final decision on two industry-funded studies, claiming that they were superior to the others because they followed GLP. Yet, GLP are based on ancient paradigms. They have serious conceptual and methodological flaws, and do not take into account the latest knowledge in environmental sciences. For example, in the case of Bisphenol A assessment, the animal models used are known to be insensitive to estrogen (CD-1 mouse). Also, assays and protocols in some OECD guidelines are out of date and insensitive. It is obvious that new product assessments should be based on adapted studies using state-of-the-art experiments. The significant gap between scientific knowledge and regulations should be filled also in the case of GMOs [9]. Therefore, some tests presented here show controversial results or statistically significant results that were not considered as biologically significant by EFSA, raising the question of their interpretation.

Table 1. Review of the longest chronic or subchronic toxicity studies in mammals fed with commercialized GM soybean and maize representing more than 80% of edible GMOs (2010).

First of all, the data indicating no biological significance of statistical effects in comparison to controls have been published mostly by companies from 2004 onwards, and at least 10 years after these GMOs were first commercialized round the world. This is a matter of grave concern. Moreover, only three events were tested for more than 90-days in feeding experiments or on more than one generation. This method was not performed by industries which conducted 90-day tests (with blood and organ analyses), but it was in some cases only. However, a 90-day period is considered as insufficient to evaluate chronic toxicity [1,5]. All these commercialized cultivated GMOs have been modified to contain pesticides, either through herbicide tolerance or by producing insecticides, or both, and could therefore be considered as “pesticide plants.” Almost all GMOs only encode these two traits despite claims of numerous other traits. For instance, Roundup ready crops have been modified in order to become insensitive to glyphosate. This chemical together with adjuvants in formulations constitutes a potent herbicide. It has been used for many years as a weed killer by blocking aromatic amino acid synthesis by inhibition of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Most Roundup ready plants have been modified thanks to the insertion of a mutated EPSPS gene coding for a mutated enzyme, which is not inhibited by glyphosate. Therefore, GM plants exposed to glyphosate-based herbicides such as Roundup do not specifically degrade glyphosate. They can even accumulate Roundup residues throughout their life, even if they excrete most of such residues. Glyphosate and its main metabolite AMPA (with its own toxicity) are found in GMOs on a regular and regulatory basis [10,11]. Therefore, such residues are absorbed by people eating most GM plants (as around 80% of these plants are Roundup tolerant). On the other hand, about 20% of the other GMOs do synthesize new insecticide proteins through the insertion of mutated genes derived from Bacillus thuringiensis (Bt).

Usually, pesticides are tested over a period of 2 years on a mammal, and this quite often highlights side effects. Additionally, unintended effects of the genetic modification itself cannot be excluded, as direct or indirect consequences of insertional mutagenesis, creating possible unintended metabolic effects. For instance, in the MON810 maize, the insertion of the transgene in the ubiquitine ligase gene caused a complex recombination event, leading to the synthesis of new RNA products encoding unknown proteins [12]. Thus, genetic modifications can induce global changes in the genomic, transcriptomic, proteomic, or metabolomic profiles of the host. The frequency of such events in comparison to classical hybridization is by nature unpredictable. In addition, in a plant producing a Cry1Ab-modified toxin, a metabolomic study [13] revealed that the transgene introduced indirectly 50% changes in osmolytes and branched amino acids.

Review of statistical effects after GMO consumption

Some GMOs (Roundup tolerant and MON863) affect the body weight increase at least in one sex [2,14]. It is a parameter considered as a very good predictor of side effects in various organs. Several convergent factors appear to indicate liver and kidney problems as end points of GMO diet effects in these experiments [2,5,15,16]. This was confirmed by our meta-analysis of all in vivo studies published on this particular topic (Table 2). The kidneys are particularly affected, concentrating 42% of all parameters disrupted in males. However, other organs may be affected too, such as the heart and spleen, or blood cells [5].

Table 2. Meta-analysis of statistical differences with appropriate controls in feeding trials

Liver parameters

For one of the longest independent tests performed, a GM herbicide-tolerant soybean available on the market was used to feed mice. It caused the development of irregular hepatocyte nuclei, more nuclear pores, numerous small fibrillar centers, and abundant dense fibrillar components, indicating increased metabolic rates [17]. It was hypothesized that the herbicide residues could be responsible for that because this particular GM plant can absorb the chemicals to which it was rendered tolerant. Such chemicals may be involved in the above-mentioned pathological features. This became even clearer when Roundup residues provoked similar features in rat hepatic cells directly in vitro [18]. The reversibility observed in some instances for these parameters in vivo [19] might be explained by the heterogeneity of the herbicide residues in the feed [20]. Anyway, these are specific parameters of ultrastructural dysfunction, and the relevance is clear. The liver is reacting. The Roundup residues have been also shown to be toxic for human placental, embryonic, and umbilical cord cells [2123]. This was also the case for hepatic human cell lines in a comparable manner, inducing nuclei and membrane changes, apoptosis and necrosis [24].

The other major GMO trait has to do with the mutated (mBt) insecticidal peptidic toxins produced by transgenes in plants. In this case, some studies with maize confirmed histopathological changes in the liver and the kidneys of rats after GM feed consumption. Such changes consist in congestion, cell nucleus border changes, and severe granular degeneration in the liver [16]. Similarly, in the MON810 studies, a significantly lower albumin/globulin ratio indicated a change in hepatic metabolism of 33% of GM-fed male rats (according to EFSA opinion on MON810 and [5]). Taken together, the results indicate potential adverse effects in hepatic metabolism. The insecticide produced by MON810 could also induce liver reactions, like many other pesticides. Of course, the mCry1Ab and other mBt (mutated Bt toxins derived from native Bacillus thuringiensis toxins) in GMOs are proteic toxins; however, these are modified at the level of their amino acid sequence by biotechnologies and introduced by artificial vectors, thus these could be considered as xenobiotics (i.e., a molecule foreign to life). The liver together with the kidneys are the major reactive organs in case of food chronic intoxication.

Kidney parameters

In the NK603 study, statistically significant strong urine ionic disturbances and kidney markers could be explained by renal leakage [5], which is well correlated with the effects of glyphosate-based herbicides (like Roundup) observed on embryonic kidney cells [23]. This does not exclude metabolic effects indirectly due to insertional mutagenesis linked to the plant transformation. Roundup adjuvants even stabilize glyphosate and allow its penetration into cells, which in turn inhibit estrogen synthesis as a side effect, cytochrome P450 aromatase inhibition [21]. This phenomenon changes the androgen/estrogen ratio and may at least, in part, explain differential impacts in both sexes.

Kidney dysfunctions are observed with mBt maize producing mutated insecticides such as in MON863. For instance, we quote the initial EFSA report: “Individual kidney weights of male rats fed with the 33% MON863 diet were statistically significantly lower compared to those of animals on control diets”, “small increases in the incidences of focal inflammation and tubular regenerative changes in the kidneys of 33% MON863 males.” This was confirmed by the company tests [25] and another counter analysis revealed disrupted biochemical markers typical of kidney filtration or function problems [2]. The first effects were not always but sometimes greater than the ones with non-isogenic maize (called reference lines), which contain different salts, lipids, or sugars. Moreover, both results described are different between males and females; this is quite usual in liver or kidney pesticide reactions. These facts do not exclude that such effects can be considered as treatment-related. Other studies also confirmed effects on kidneys. Tubular degeneration and not statistically significant enlargement in parietal layer of Bowman’s capsules were also observed with GM maize fed rats [16].

Last but not least, a total of around 9% of parameters were disrupted in a meta-analysis (Table 2). This is twice as much as what could be obtained by chance only (generally considered as 5%). Surprisingly, 43.5% of significant different parameters were concentrated in male kidneys for all commercialized GMOs, even if only around 25% of the total parameters measured were kidney-related. If the differences had been distributed by chance in the organs, not significantly more than 25% differences would have been found in the kidney. Even if our own counter analysis is removed from the calculation, showing numerous kidney dysfunctions [2], around 32% of disturbances are still noticed in kidneys.

Discussion

Need for chronic tests and other tests

Chronic toxicity tests (both with males and females) and reproductive tests with pregnant females and then with the developing progeny over several generations (none of these steps exist at present) are called as a whole the Toxotest approach (or Risk management test, see “Details on the new suggested Toxotest approach”). This could address the long-term physiological or pathological relevance of the previous observations. The physiological interpretations of 90-day-based effects are otherwise somewhat limited. These studies should be complementary to the present regulations or the Safotest and the sentinel test suggested by EFSA [1]. The Toxotest could provide evidence of carcinogenic, developmental, hormonal, neural, and reproductive potential dysfunctions, as it does for pesticides or drugs. Additionally, it is obvious that the 90-day-long trials on mature animals performed today cannot scientifically replace the sensitivity of developmental tests on neonates. A good example is the gene imprinting by drugs that will be revealed only at maturity; this is an important subject of current research, and many findings have been reported for some chemicals such as bisphenol A [26,27]. Even transgenerational effects occur after epigenetic imprinting by a pesticide [28]. These effects cannot be detected by classical 90-day feeding trials and will be visible after many decades by epidemiology in humans if any, as illustrated in the case of diethylstilbestrol, which induced female genital cancers among other problems in the second generation [29]. The F3 multigenerational study for a GMO (Table 1) was too rarely performed. This is why, because of the number of parameters disrupted in adult mammals within 90 days, the new experiments should be systematically performed to protect the health of billions of people that could consume directly or indirectly these transformed products.

The acute toxicity approach (less than a month of investigations on rodents with high doses) may give effects which are more proportional to the dose, as it might correspond to a rapid poisoning of the animals, generally with force-fed experiments. However, for many pesticide studies in the scientific literature, some long-term side effects of pesticides at environmental doses are described, which are not apparent in short-term experiments [30]. Classical toxicology is quite often based on the concept of revealing linear dose-responses as defined by Paracelsus, which generally fails to evidence U or J curves observed after hormonal sex-specific disruptions. Moreover, the effects of mixtures are also neglected in long-term studies, when supposed active principles of pesticides are not assessed with their adjuvants, which also are present as residues in GMOs. Such pesticides may have the capacity to disrupt the “cell web”, i.e., to interfere with a signaling pathway, and this could be unspecific. For instance Roundup is known to disrupt the EPSPS in plants, but is also known to interact with the mammalian ubiquist reductase [21] common and essential to cytochromes P450, a wide class of detoxification enzymes. The so-called Roundup active principle, glyphosate, acts in combination with adjuvants to increase glyphosate-mediated toxicity[21,31], and this may apply to other environmental pollutants [22]. Moreover, all new metabolites in edible Roundup ready GMOs, as acetyl-glyphosate for the new GAT GMOs, have not been assessed for their chronic toxicity [11], and we consider this as a major oversight in the present regulations.

Therefore, as xenobiotic effects are complex, the determination of their toxic effects cannot be determined using a single method, but rather converging pieces of evidence. In GMO risk assessment, the protocols must be optimized to detect side effects, in particular for herbicide-treated GM plants. These cannot be reduced to GM assessment on one side and herbicide residues with any diet on the other side, but unfortunately this has been the case, and this approach has been promoted up to now by regulatory authorities.

In fact, it is impossible, within only 13 weeks, to conclude about the kind of pathology that could be induced by pesticide GMOs and whether it is a major pathology or a minor one. It is therefore necessary to prolong the tests, as suggested by EFSA, since at least one third of chronic effects visible with chemicals are usually new in comparison to the ones highlighted in subchronic studies [1]. The so-called Toxotests, which are supposed to include the studies of chronic pathologies in particular, should be performed on three mammalian species, with at least one non-rodent, similar to the type of rodents used for pesticides and drugs. However, the chronic feeding tests for GMOs cannot be based on the no observed adverse effect level, nor on the lowest observed adverse effect level approach, as in classical toxicology. There are several reasons for that. There is not only one chemical, but also several unknown metabolites and components, in Roundup tolerant varieties for instance, and therefore toxicity is enhanced thanks to the fact that they are mixed together. There is also no possibility of increasing the doses of GMOs in an equilibrated diet over an acceptable level. The diets should be rather representative of an equilibrated diet with GMOs like it could be the case in a real population in America. To prolong 90-day subchronic tests with three normal doses of GM in the diet (11%, 22%, 33% for instance) is the solution.

Sex- or dose-specific pathological effects are common

When there is a low or environmental dose impregnation of the feed (with a pesticide GM plant for instance), the chronic effects could be more differentiated according to the sex, the physiological status, the age, or the number of intakes over such and such a period of time in the case of a drug. These parameters (chronic intake, age of exposure, etc.) are more decisive for pathologies like cancers, than the actual quantity of toxin ingested in one intake. This is in part because the liver, kidney, and other cytochrome P450-rich organs are concerned for long-term metabolism and detoxification, and this phenomenon is hormone dependent. It is also due to the process of carcinogenesis or hormone-sensitive programming of cells [32]. The liver for instance is a sex differentiated organ as far as its enzymatic equipment is concerned [4]. An effect in subchronic or chronic tests cannot be disregarded on the rationale that it is not linear to the dose (or dose-related) or not comparable in genders. This would not be scientifically acceptable. However, this reasoning was adopted both by companies and EFSA for several GMOs, as underlined by Doull et al. [33]. Indeed, most xenobiotics or pollutants may have non-linear effects, and/or may have sex- and age-specific impacts.

One of the pivotal requirements for regulators nowadays, in order to interpret a significant difference as biologically relevant, is to observe a linear dose-response. This allows them to deduce a causality. However, this dose-response cannot be studied with only two points, which is nonetheless the case for all major commercial GMOs today, which are given in the diet in 11% and 33% concentrations only, in subchronic tests. This is true overall if no preliminary data has been obtained to choose the given doses, which is the case in regulatory files. As we have already emphasized, most of pathological and endocrine effects in environmental health are not directly proportional to the dose, and they have a differential threshold of sensitivity in both sexes [34]. This is, for instance, the case with carcinogenesis and endocrine disruption.

Improving the knowledge on impacts of modified Bt toxins

One of the interpretations of the side effects observed (Tables 1 and 2) would be that the insecticide toxins in maize lines may have more pleiotropic or specific actions than originally supposed. The toxins could generate particular metabolites, either in the GM plant or in the animals fed with it. The Bt toxins in GMOs are new and modified, truncated, or chimerical in order to change their activities/solubility in comparison to wild Bt. For instance, there is at least a 40% difference between the toxin in Bt176 and its wild counterpart [10]. None of the modified Bt toxins have been authorized separately for food or feed, neither has the wild Bt, and neither have they been tested by themselves on animal or human health to date. Even if some studies were performed, the receptors have not been cloned and the signaling pathways have not been identified as yet, nor required for authorizations, and the metabolism of these proteins in mammals are unknown [35]. Thus, the argument about “safe use history” of the wild Bt protein (not designed for direct consumption, in contrast to several GMOs) cannot, on a sound scientific basis, be used for direct authorizations of the above-cited GM corns, overall without in vivo chronic toxicity tests (or Toxotest approach), as it is requested for a pesticide. Some improvements may even be included with regard to pesticide legislation, since these human modified toxins considered as xenobiotics are continuously produced by the plants devoted to consumption.

The proteins usually compared (modified Bt toxins and wild ones) are not identical, and the tests on human cells of Bt proteins are not performed nor are they requested by authorities. Their stability has been assessed in vitro, and GM insecticide toxins are never fully digested in vivo [36]. If some consumers suffer from stomach problems or ulcers, the new toxins will possibly act differently; the digestion in children could be affected too; however, these GMOs could be eaten anywhere and all proteins are never fully decomposed in amino acids by the digestive tract.

Details on the new suggested Toxotest approach

The suggested Toxotest would basically include an extension of the existing 90-day tests, but with at least three doses plus controls (0%, 11%, 22%, 33% GMOs for instance; today the equilibrated diets tested contain 0%, 11%, and 33% GMOs in the best regulatory tests). The purpose would be to characterize scientifically the dose-response approach. The latter cannot be taken seriously with only two GM doses. The final goal is the best health protection for the population without really possible clinical trials, in our case for practical and ethical reasons. There is also no epidemiological follow-up for lack of traceability and labeling in GM-producing American countries. In addition, the fact that the Toxotest includes the best possible toxicological approach will also be in favor of the biotechnology economy and the European Community because it is more expensive to address an issue concerning a whole population afterwards, rather than to work with laboratory animals beforehand; it is also more ethical to work on rats and other mammalian experiments, in order to get the relevant information, rather than to give pesticide plants directly to humans on a long-term basis.

As previously underlined, the health effects such as those suggested in Table 2 (if any, are revealed by adapted studies, such as Safotests or Toxotests), could only be due to two possibilities:

Firstly, the side effects may be directly or indirectly due to a pesticide residue and/or its metabolites. The direct effect is about the pesticide effect on the consumer, and the indirect one is about a metabolism disruption that it has provoked within the plant first. This could not be visible by a detailed compositional analysis, such as the one performed to be assessed by a substantial equivalence study. This concept is not a well-defined one (how many cultivations of crops, over how many years, under which climate, and to measure what precise parameters).

Secondly, the pathological signs may be due to the genetic transformation itself, its method provoking either insertional mutagenesis or a new metabolism by genetic interference. This is the reason why separating intended effects (the direct genetic trait consequence itself) from unintended effects (linked to biotechnology, e.g., insertional mutagenesis), such as spiking the control diet with the purified toxin in the Toxotest approach, is clearly inadequate. It could work in the case of a direct action of the toxin in mammals, but conversely one could not conclude, between an insertional mutagenesis and a specific metabolic action in the plant due to the toxin. However, this is more a research question about the mode of genesis of an effect on health, and new research avenues could be, for instance, to compare the GM diet with or without herbicide treatment in long-term tests with the isogenic control diet including herbicide residues added. This is only necessary for the understanding of the potential signs of toxicity and not for a conclusion of the Safotest or the Toxotest, which would rather suggest, if positive, excluding immediately the corresponding GMO from food and feed.

Improvement of statistical analysis

A serious experimental design is based on a proper choice of the groups, with only one question studied per experiment if possible, and balanced sample sizes. In several authorized GMOs, the sample sizes appear inadequate in 90 days: ten animals per group for the measurement of biochemical parameters out of 20, as performed by the major stakeholders, and accepted by EFSA for MON863, MON810, or NK603 for instance. This is too limited a size to ensure that parametric statistical methods used by the company are reliable. Moreover, an important discrepancy between GMO-treated rats (40 measured out of 80) and the total number of animals (400) renders more difficult the evidencing of relevant effects, and confusion factors are brought in at the same time with six different reference diets in addition to the two normal control groups as performed in three commercialized GMOs at least [5,6]. This introduces new uncontrolled sources of variability about the effects of the diets and new unnecessary questions not relevant to the GMO safety. The representation of a standard diet with multiple sources could have been studied with only one control group of the same size than the GMO group, eating a mix of six different regular non-GM diets.

Several questions have been raised by companies and authorities as well as comments on statistically significant effects that would supposedly not be biologically meaningful. A subjective part is introduced at this level because it is necessary to take into account the context and the general and detailed knowledge of toxicology and endocrine disruption, as EFSA underlines. This might be highly expert dependent. This is why, to avoid or prevent any misunderstanding, we suggest, in addition to a new statistical approach based on classical methods, to analyze the 90-day tests, even with control and reference diets called the “SSC method” (according to the initials of the authors in [2]).

Briefly, following the necessity to model and analyze the growth curves, multivariate data analysis and data mining of all parameters can be used to correlate, cluster, and select meaningful variables. This kind of approach is not performed at all today. Thereafter, the detailed comparison between GM-treated and control groups, fed with the near isogenic line (because the real isogenic line does not often exists anymore), will necessarily be followed by the study of specific diet effects, when there are non-substantially equivalent diets for reference groups. For that purpose, the controls will be first compared using multivariate inference with reference groups, and thereafter, similarly GMO-treated groups with reference groups. The significant differences linked to the GMO and/or the composition of the diet will be classified according to organ and function. The results will appear more clearly than with the simple statistics accepted today by the authorities (that is, comparison of the highest GM dose group with the mean value of all six control groups), and will reveal in addition new information, as it can be demonstrated.

As recommended by EFSA, an appropriate and relevant statistical analysis is crucial. It should follow the following series of steps, allowing the use of several methods depending on the questions raised:

• Obtaining and modeling the growth curves and feed consumption, assessed by non-linear regression, validation, and statistical comparisons in order to test if the curves are significantly different, thus taking into account individual variability. This necessitates the use of time series analysis, selection models, and non-parametric tests, Akaike Information Criteria and related methods. Water consumption should also be an important factor to follow-up and therefore better understand kidney and urine data.

• The study of dose-response predictions using non-linear regression should be the goal, but the only two doses generally used in these tests do not make it possible to evidence linearity as we indicated. Moreover, in the cases where there are not dose-related trends or relationships using the two doses mentioned, the absence of linear dose-response curves cannot be a reason to neglect the effects. For instance, as previously cited, U or J curves may be characteristic of endocrine effects [37], and spiky irregular curves may be detected in carcinogenesis.

• Simultaneous analysis of all observed variables: multivariate data analysis, principal component analysis, correlations analysis, factorial analysis and clustering

• Multivariate comparisons of the different variables: hypothesis testing, multiple ways ANOVA, MANOVA, and others to determinate if the groups differ relative to the different questions: specific GMO effect or diet effect per se. To evidence a detail, when comparing two mean values, SEM should be calculated to determine confidence intervals; however, SD have been used up to now by the company for MON863 and NK603 files for instance.

Apart from empirical curves in some instances, ANOVA and univariate hypothesis testing only the GMO effect, none of the other statistical approaches is currently used nor requested by the authorities.

Human tests and post-market monitoring

For the record, it must be said that very few tests on humans have been carried out up to now. Moreover, epidemiological studies are not feasible in America, since there is no organized traceability of GMOs anywhere on the continent, where, by far, most of edible GMOs are cultivated (97%). As a consequence, a post-market monitoring (PMM) is offered to the population. The Cartagena Biosafety Protocol identifying GMOs at the borders of a country has now been signed by over 150 countries, including the member states of the European Union. PMM may have some value in detecting unexpected adverse effects. It could therefore be considered as a routine need. This approach makes it possible to collect information related to risk management. It can be relied upon as a technique for monitoring adverse events or other health outcomes related to the consumption of GM plant-derived foods, provided that the Toxotest approach, together with the SSC method, should have already been applied. The PMM should be linked with the possibility of detecting allergenicity reactions to GMOs in routine medicine, thanks to the very same routine cutaneous tests that should be developed prior to large-scale commercialization. A screening of serum banks of patients with allergies could be also put forward in order to search for antibodies against the main GMOs and not only their transgenic proteins, since they may induce secondary allergenic metabolites in the plant not visible in the substantial equivalence study.

The traceability of products from animals fed on GMOs is also crucial. The reason for this is because they can develop chronic diseases which are not utterly known today. Such possible diseases could be linked to the hepatorenal toxicity observed in some GMO-related cases (Table 1).

Moreover, labeling animals fed on GMOs is therefore necessary because some pesticide residues linked to GMOs could pass into the food chain and also because nobody would want to eat disabled or physiologically modified animals after long-term GMOs ingestion, even if pesticides residues or DNA fragments are not toxic nor transmitted by themselves.

Conclusion

Transcriptomics, proteomics and other related methods are not ready yet for routine use in the laboratories, and moreover they may be inappropriate for studying toxicity in animals, and could not in any way replace in vivo studies with all the physiological and biochemical parameters that are measured with organs weight, appearance, and histology. By contrast, afterwards, new approaches could well help to explain pathological results or action mechanisms of pesticides present in the GM plants or GM-fed animals, if found.

To obtain the transparency of raw data (including rat blood analyses) for toxicological tests, maintained illegally confidential, is crucial. It has also become crucial to apply objective criteria of interpretation like the criteria described here: sex-specific side effects or non-linear ones. Such data can be put online on the EFSA website with a view to provide a fuller review to the wider scientific community, and in order to better inform the citizen to make biotechnologies more socially acceptable. Since fundamental research is published on a regular basis, it should be the same for this kind of applied research on long-term health effects, as suggested by the CE/2001/18 and the corresponding 1829/2003 regulations.

We can conclude, from the regulatory tests performed today, that it is unacceptable to submit 500 million Europeans and several billions of consumers worldwide to the new pesticide GM-derived foods or feed, this being done without more controls (if any) than the only 3-month-long toxicological tests and using only one mammalian species, especially since there is growing evidence of concern (Tables 1 and 2). This is why we propose to improve the protocol of the 90-day studies to 2-year studies with mature rats, using the Toxotest approach, which should be rendered obligatory, and including sexual hormones assessment too. The reproductive, developmental, and transgenerational studies should also be performed. The new SSC statistical method of analysis is proposed in addition. This should not be optional if the plant is designed to contain a pesticide (as it is the case for more than 99% of cultivated commercialized GMOs), whilst for others, depending on the inserted trait, a case-by-case approach in the method to study toxicity will be necessary.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

GES designed and coordinated the review. RM participated in the drafting of the manuscript and final version. EC, SG, JSV and DC helped the writing, compiling the literature, revising in details and proofreading the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We thank the CRIIGEN scientific committee for helpful discussions and structural support, as well as the Risk Pole (MRSH-CNRS, University of Caen, France). We acknowledge the French Ministry of Research for financial support and the Regional Council of Basse-Normandie. We are grateful to Herrade Hemmerdinger for the English revision of this manuscript.

References

  1. EFSA: Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials. Food Chem Toxicol 2008, 46:S2-70. OpenURL
  2. Séralini GE, Cellier D, Spiroux J: New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity. Arch Environ Contam Toxicol 2007, 52:596-602. PubMed Abstract | Publisher Full Text OpenURL
  3. Séralini G-E: Comment on Transgenic aubergines put on ice. Naturenews 2009. OpenURL
  4. Séralini GE, Spiroux J, Cellier D, Sultan C, Buiatti M, Gallagher L, Antoniou M, Dronamraju KR: How subchronic and chronic health effects can be neglected for GMOs, pesticides or chemicals. Int J Biol Sci 2009, 5:438-443. PubMed Abstract | PubMed Central Full Text OpenURL
  5. Spiroux J, Roullier F, Cellier D, Séralini GE: A comparison of the effects of three GM corn varieties on mammalian health. Int J Biol Sci 2009, 5:706-726. PubMed Abstract | PubMed Central Full Text OpenURL
  6. Spiroux J, Cellier D, Vélot C, Clair E, Mesnage R, Séralini GE: Debate on GMOs health risks after statistical findings in regulatory tests. Int J Biol Sci 2010, 6:590-598. PubMed Abstract | PubMed Central Full Text OpenURL
  7. James C: Global Status of Commercialized Biotech/GM Crops. ISAAA Brief 41 2009. OpenURL
  8. Vom Saal FS, Hughes C: An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect 2005, 113:926-933. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  9. Myers JP, vom Saal FS, Akingbemi BT, Arizono K, Belcher S, Colborn T, Chahoud I, Crain DA, Farabollini F, Guillette LJ Jr, Hassold T, Ho SM, Hunt PA, Iguchi T, Jobling S, Kanno J, Laufer H, Marcus M, McLachlan JA, Nadal A, Oehlmann J, Olea N, Palanza P, Parmigiani S, Rubin BS, Schoenfelder G, Sonnenschein C, Soto AM, Talsness CE, Taylor JA, Vandenberg LN, Vandenbergh JG, Vogel S, Watson CS, Welshons WV, Zoeller RT: Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: the case of bisphenol A. Environ Health Perspect 2009, 117:309-315. PubMed Abstract | PubMed Central Full Text OpenURL
  10. Séralini G-E: Ces OGM qui changent le monde. France: Flammarion; 2004. OpenURL
  11. EFSA: Modification of the residue definition of glyphosate in genetically modified maize grain and soybeans, and in products of animal origin on request from the European Commission. EFSA Journal 2009, 7:42. OpenURL
  12. Rosati A, Bogani P, Santarlasci A, Buiatti M: Characterisation of 3′ transgene insertion site and derived mRNAs in MON810 YieldGard maize. Plant Mol Biol 2008, 67:271-81. PubMed Abstract | Publisher Full Text OpenURL
  13. Manetti C, Bianchetti C, Casciani L, Castro C, Di Cocco ME, Miccheli A, Motto M, Conti F: A metabonomic study of transgenic maize (Zea mays) seeds revealed variations in osmolytes and branched amino acids. J Exp Bot 2006, 57:2613-2625. PubMed Abstract | Publisher Full Text OpenURL
  14. Zhu Y, Li D, Wang F, Yin J, Jin H: Nutritional assessment and fate of DNA of soybean meal from roundup ready or conventional soybeans using rats. Arch Anim Nutr 2004, 58:295-310. PubMed Abstract | Publisher Full Text OpenURL
  15. Vecchio L, Cisterna B, Malatesta M, Martin TE, Biggiogera M: Ultrastructural analysis of testes from mice fed on genetically modified soybean. Eur J Histochem 2004, 48:448-454. PubMed Abstract OpenURL
  16. Kilic A, Akay MT: A three generation study with genetically modified Bt corn in rats: biochemical and histopathological investigation. Food Chem Toxicol 2008, 46:1164-1170. PubMed Abstract | Publisher Full Text OpenURL
  17. Malatesta M, Caporaloni C, Gavaudan S, Rocchi MB, Serafini S, Tiberi C, Gazzanelli G: Ultrastructural morphometrical and immunocytochemical analyses of hepatocyte nuclei from mice fed on genetically modified soybean. Cell Struct Funct 2002, 27:173-180. PubMed Abstract | Publisher Full Text OpenURL
  18. Malatesta M, Perdoni F, Santin G, Battistelli S, Muller S, Biggiogera M: Hepatoma tissue culture (HTC) cells as a model for investigating the effects of low concentrations of herbicide on cell structure and function. Toxicol In Vitro 2008, 22:1853-1860. PubMed Abstract | Publisher Full Text OpenURL
  19. Malatesta M, Tiberi C, Baldelli B, Battistelli S, Manuali E, Biggiogera M: Reversibility of hepatocyte nuclear modifications in mice fed on genetically modified soybean. Eur J Histochem 2005, 49:237-242. PubMed Abstract OpenURL
  20. Arregui MC, Lenardon A, Sanchez D, Maitre MI, Scotta R, Enrique S: Monitoring glyphosate residues in transgenic glyphosate-resistant soybean. Pest Manag Sci 2004, 60:163-166. PubMed Abstract | Publisher Full Text OpenURL
  21. Richard S, Moslemi S, Sipahutar H, Benachour N, Séralini GE: Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ Health Perspect 2005, 113:716-720. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  22. Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Séralini GE: Time- and dose-dependent effects of roundup on human embryonic and placental cells. Arch Environ Contam Toxicol 2007, 53:126-133. PubMed Abstract | Publisher Full Text OpenURL
  23. Benachour N, Séralini GE: Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem Res Toxicol 2009, 22:97-105. PubMed Abstract | Publisher Full Text OpenURL
  24. Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Séralini GE: Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology 2009, 262:184-191. PubMed Abstract | Publisher Full Text OpenURL
  25. Hammond B, Lemen J, Dudek R, Ward D, Jiang C, Nemeth M, Burns J: Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn. Food Chem Toxicol 2006, 44:147-160. PubMed Abstract | Publisher Full Text OpenURL
  26. Braniste V, Jouault A, Gaultier E, Polizzi A, Buisson-Brenac C, Leveque M, Martin PG, Theodorou V, Fioramonti J, Houdeau E: Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci USA 2009, 107:448-453. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  27. Braun JM, Yolton K, Dietrich KN, Hornung R, Ye X, Calafat AM, Lanphear BP: Prenatal bisphenol A exposure and early childhood behavior. Environ Health Perspect 2009, 117:1945-1952. PubMed Abstract | PubMed Central Full Text OpenURL
  28. Anway MD, Cupp AS, Uzumcu M, Skinner MK: Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005, 308:1466-1469. PubMed Abstract | Publisher Full Text OpenURL
  29. Wise LA, Palmer JR, Rowlings K, Kaufman RH, Herbst AL, Noller KL, Titus-Ernstoff L, Troisi R, Hatch EE, Robboy SJ: Risk of benign gynecologic tumors in relation to prenatal diethylstilbestrol exposure. Obstet Gynecol 2005, 105:167-173. PubMed Abstract | Publisher Full Text OpenURL
  30. Hernandez AF, Casado I, Pena G, Gil F, Villanueva E, Pla A: Low level of exposure to pesticides leads to lung dysfunction in occupationally exposed subjects. Inhal Toxicol 2008, 20:839-849. PubMed Abstract | Publisher Full Text OpenURL
  31. Benachour N, Moslemi S, Sipahutar H, Séralini GE: Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination. Toxicol Appl Pharmacol 2007, 222:129-140. PubMed Abstract | Publisher Full Text OpenURL
  32. Melnick R, Lucier G, Wolfe M, Hall R, Stancel G, Prins G, Gallo M, Reuhl K, Ho SM, Brown T, Moore J, Leakey J, Haseman J, Kohn M: Summary of the National Toxicology Program’s report of the endocrine disruptors low-dose peer review. Environ Health Perspect 2002, 110:427-431. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  33. Doull J, Gaylor D, Greim HA, Lovell DP, Lynch B, Munro IC: Report of an Expert Panel on the reanalysis by of a 90-day study conducted by Monsanto in support of the safety of a genetically modified corn variety (MON 863). Food Chem Toxicol 2007, 45(11):2073-85. PubMed Abstract | Publisher Full Text OpenURL
  34. Goldsmith JR, Kordysh E: Why dose-response relationships are often non-linear and some consequences. J Expo Anal Environ Epidemiol 1993, 3:259-276. PubMed Abstract OpenURL
  35. Then C: Risk assessment of toxins derived from Bacillus thuringiensis-synergism, efficacy, and selectivity. Environ Sci Pollut Res Int 2010, 17:791-797. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  36. Paul V, Guertler P, Wiedemann S, Meyer HH: Degradation of Cry1Ab protein from genetically modified maize (MON810) in relation to total dietary feed proteins in dairy cow digestion. Transgenic Res 2010, 19(4):683-689. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  37. Andrade AJ, Grande SW, Talsness CE, Grote K, Chahoud I: A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity. Toxicology 2006, 227:185-192. PubMed Abstract | Publisher Full Text OpenURL
  38. Malatesta M, Caporaloni C, Rossi L, Battistelli S, Rocchi MB, Tonucci F, Gazzanelli G: Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean. J Anat 2002, 201:409-415. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
  39. Malatesta M, Biggiogera M, Manuali E, Rocchi MB, Baldelli B, Gazzanelli G: Fine structural analyses of pancreatic acinar cell nuclei from mice fed on genetically modified soybean. Eur J Histochem 2003, 47:385-388. PubMed Abstract OpenURL
  40. Appenzeller LM, Munley SM, Hoban D, Sykes GP, Malley LA, Delaney B: Subchronic feeding study of herbicide-tolerant soybean DP-356O43-5 in Sprague-Dawley rats. Food Chem Toxicol 2008, 46:2201-2213. PubMed Abstract | Publisher Full Text OpenURL
  41. Sakamoto Y, Tada Y, Fukumori N, Tayama K, Ando H, Takahashi H, Kubo Y, Nagasawa A, Yano N, Yuzawa K, Ogata A: A 104-week feeding study of genetically modified soybeans in f344 rats. Shokuhin Eiseigaku Zasshi 2008, 49:272-282. PubMed Abstract | Publisher Full Text OpenURL
  42. Appenzeller LM, Munley SM, Hoban D, Sykes GP, Malley LA, Delaney B: Subchronic feeding study of grain from herbicide-tolerant maize DP-O9814O-6 in Sprague-Dawley rats. Food Chem Toxicol 2009, 47:2269-2280. PubMed Abstract | Publisher Full Text OpenURL
  43. Hammond B, Dudek R, Lemen J, Nemeth M: Results of a 13 week safety assurance study with rats fed grain from glyphosate tolerant corn. Food Chem Toxicol 2004, 42:1003-1014. PubMed Abstract | Publisher Full Text OpenURL
  44. Hammond BG, Dudek R, Lemen JK, Nemeth MA: Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn. Food Chem Toxicol 2006, 44:1092-1099. PubMed Abstract | Publisher Full Text OpenURL
  45. MacKenzie SA, Lamb I, Schmidt J, Deege L, Morrisey MJ, Harper M, Layton RJ, Prochaska LM, Sanders C, Locke M, Mattsson JL, Fuentes A, Delaney B: Thirteen week feeding study with transgenic maize grain containing event DAS-O15O7-1 in Sprague-Dawley rats. Food Chem Toxicol 2007, 45:551-562. PubMed Abstract | Publisher Full Text OpenURL
  46. He XY, Huang KL, Li X, Qin W, Delaney B, Luo YB: Comparison of grain from corn rootworm resistant transgenic DAS-59122-7 maize with non-transgenic maize grain in a 90-day feeding study in Sprague-Dawley rats. Food Chem Toxicol 2008, 46:1994-2002. PubMed Abstract | Publisher Full Text OpenURL
  47. Malley LA, Everds NE, Reynolds J, Mann PC, Lamb I, Rood T, Schmidt J, Layton RJ, Prochaska LM, Hinds M, Locke M, Chui CF, Claussen F, Mattsson JL, Delaney B: Subchronic feeding study of DAS-59122-7 maize grain in Sprague-Dawley rats. Food Chem Toxicol 2007, 45:1277-1292. PubMed Abstract | Publisher Full Text OpenURL
  48. Appenzeller LM, Malley L, Mackenzie SA, Hoban D, Delaney B: Subchronic feeding study with genetically modified stacked trait lepidopteran and coleopteran resistant (DAS-O15O7-1xDAS-59122-7) maize grain in Sprague-Dawley rats. Food Chem Toxicol 2009, 47:1512-1520. PubMed Abstract | Publisher Full Text OpenURL

 

The Institute for Responsible Technology – FAQ on GMO

 

What’s a GMO?

A GMO (genetically modified organism) is the result of a laboratory process of taking genes from one species and inserting them into another in an attempt to obtain a desired trait or characteristic, hence they are also known as transgenic organisms. This process may be called either Genetic Engineering (GE) or Genetic Modification (GM); they are one and the same.

But haven’t growers been grafting trees, breeding animals, and hybridizing seeds for years?

Genetic engineering is completely different from traditional breeding and carries unique risks.

In traditional breeding it is possible to mate a pig with another pig to get a new variety, but is not possible to mate a pig with a potato or a mouse. Even when species that may seem to be closely related do succeed in breeding, the offspring are usually infertile�a horse, for example, can mate with a donkey, but the offspring (a mule) is sterile.

With genetic engineering, scientists can breach species barriers set up by nature. For example, they have spliced fish genes into tomatoes. The results are plants (or animals) with traits that would be virtually impossible to obtain with natural processes, such as crossbreeding or grafting.

What combinations have been tried?

It is now possible for plants to be engineered with genes taken from bacteria, viruses, insects, animals or even humans. Scientists have worked on some interesting combinations:

  • Spider genes were inserted into goat DNA, in hopes that the goat milk would contain spider web protein for use in bulletproof vests.
  • Cow genes turned pigskins into cowhides.
  • Jellyfish genes lit up pigs’ noses in the dark.
  • Arctic fish genes gave tomatoes and strawberries tolerance to frost.
  • Potatoes that glowed in the dark when they needed watering.
  • Human genes were inserted into corn to produce spermicide.

Current field trials include:

  • Corn engineered with human genes (Dow)
  • Sugarcane engineered with human genes (Hawaii Agriculture Research Center)
  • Corn engineered with jellyfish genes (Stanford University)
  • Tobacco engineered with lettuce genes (University of Hawaii)
  • Rice engineered with human genes (Applied Phytologics)
  • Corn engineered with hepatitis virus genes (Prodigene)

DNA Double HelixWhat is a gene?

Every plant and animal is made of cells, each of which has a center called a nucleus. Inside every nucleus there are strings of DNA, half of which is normally inherited from the mother and half from the father. Short sequences of DNA are called genes. These genes operate in complex networks that are finely regulated to enable the processes of living organisms to happen in the right place and at the right time.

How is genetic engineering done?

Because living organisms have natural barriers to protect themselves against the introduction of DNA from a different species, genetic engineers have to find ways to force the DNA from one organism into another. These methods include:

  • Using viruses or bacteria to “infect” animal or plant cells with the new DNA.
  • Coating DNA onto tiny metal pellets, and firing it with a special gun into the cells.
  • Injecting the new DNA into fertilized eggs with a very fine needle.
  • Using electric shocks to create holes in the membrane covering sperm, and then forcing the new DNA into the sperm through these holes.

Is genetic engineering precise?

The technology of genetic engineering is currently very crude. It is not possible to insert a new gene with any accuracy, and the transfer of new genes can disrupt the finely controlled network of DNA in an organism.

Current understanding of the way in which DNA works is extremely limited, and any change to the DNA of an organism at any point can have side effects that are impossible to predict or control. The new gene could, for example, alter chemical reactions within the cell or disturb cell functions. This could lead to instability, the creation of new toxins or allergens, and changes in nutritional value.

Does the biotech industry hold any promise?

Genetic modification of plants is not the only biotechnology. The study of DNA does hold promise for many potential applications, including medicine. However, the current technology of GM foods is based on obsolete information and theory, and is prone to dangerous side effects. Economic interests have pushed it onto the market too soon.

Moreover, molecular marker technologies�so called Marker Assisted Selection (MAS) used with conventional breeding shows much promise for developing improved crop varieties, without the potentially dangerous side effects of direct genetic modification.

GMOs in Foods:

What kinds of traits have been added to food crops?

Although there are attempts to increase nutritional benefits or productivity, the two main traits that have been added to date are herbicide tolerance and the ability of the plant to produce its own pesticide. These results have no health benefit, only economic benefit.

Herbicide tolerance lets the farmer spray weed-killer directly on the crop without killing it.

Crops such as Bt cotton produce pesticides inside the plant. This kills or deters insects, saving the farmer from having to spray pesticides. The plants themselves are toxic, and not just to insects. Farmers in India, who let their sheep graze on Bt cotton plants after the harvest, saw thousands of sheep die!

Why do genetically engineered foods have antibiotic resistant genes in them?

The techniques used to transfer genes have a very low success rate, so the genetic engineers attach “marker genes” that are resistant to antibiotics to help them to find out which cells have taken up the new DNA. These marker genes are resistant to antibiotics that are commonly used in human and veterinary medicine. Some scientists believe that eating GE food containing these marker genes could encourage gut bacteria to develop antibiotic resistance.

What are the problems created through genetic engineering of food and crops?

Genetic engineers continually encounter unintended side effects � GM plants create toxins, react to weather differently, contain too much or too little nutrients, become diseased or malfunction and die. When foreign genes are inserted, dormant genes may be activated or the functioning of genes altered, creating new or unknown proteins, or increasing or decreasing the output of existing proteins inside the plant. The effects of consuming these new combinations of proteins are unknown.

What foods are GM?

Currently commercialized GM crops in the U.S. include soy (94%), cotton (90%), canola (90%), sugar beets (95%), corn (88%), Hawaiian papaya (more than 50%), zucchini and yellow squash (over 24,000 acres).

What are other sources of GMOs?

Products derived from the above, including oils from all four, soy protein, soy lecithin, cornstarch, corn syrup and high fructose corn syrup among others. Also:

  • meat, eggs, and dairy products from animals that have eaten GM feed (and the majority of the GM corn and soy is used for feed);
  • dairy products from cows injected with rbGH (a GM hormone);
  • food additives, enzymes, flavorings, and processing agents, including the sweetener aspartame (NutraSweet�) and rennet used to make hard cheeses; and
  • honey and bee pollen that may have GM sources of pollen.

The Health Dangers:

What are the potential dangers of eating GM foods?

There are a number of dangers that broadly fall into the categories of potential toxins, allergens, carcinogens, new diseases, antibiotic resistant diseases, and nutritional problems.

Viewall 65 health risks of GM foods, excerpted from Jeffrey Smith’s comprehensive book Genetic Roulette: The Documented Health Risks of Genetically Engineered Foods.

Hasn’t research shown GM foods to be safe?

No. The only feeding study done with humans showed that GMOs survived inside the stomach of the people eating GMO food. No follow-up studies were done.

Various feeding studies in animals have resulted in potentially pre-cancerous cell growth, damaged immune systems, smaller brains, livers, and testicles, partial atrophy or increased density of the liver, odd shaped cell nuclei and other unexplained anomalies, false pregnancies and higher death rates.

But aren’t the plants chemically the same, whether or not they are GM?

Most tests can’t determine the differences at the level of the DNA. And, even if they appear to be the same, eyewitness reports from all over North American describe how several types of animals, including cows, pigs, geese, elk, deer, squirrels, and rats, when given a choice, avoid eating GM foods.

Haven’t people been eating GM foods without any ill effect?

The biotech industry says that millions have been eating GM foods without ill effect. This is misleading. No one monitors human health impacts of GM foods. If the foods were creating health problems in the US population, it might take years or decades before we identified the cause.

What indications are there that GM foods are causing problems?

Soon after GM soy was introduced to the UK, soy allergies skyrocketed by 50 percent.

In March 2001, the Center for Disease Control reported that food is responsible for twice the number of illnesses in the U.S. compared to estimates just seven years earlier. This increase roughly corresponds to the period when Americans have been eating GM food.

Without follow-up tests, which neither the industry or government are doing, we can’t be absolutely sure if genetic engineering was the cause.

What about GM hormones in milk?

Milk from rBGH-treated cows contains an increased amount of the hormone IGF-1, which is one of the highest risk factors associated with breast and prostate cancer, but no one is tracking this in relation to cancer rates.

Why do genetically engineered foods have antibiotic resistant genes in them?

The techniques used to transfer genes have a very low success rate, so the genetic engineers attach “marker genes” that are resistant to antibiotics to help them to find out which cells have taken up the new DNA. That way scientist can then douse the experimental GMO in antibiotics and if it lives, they have successful altered the genes. The marker genes are resistant to antibiotics that are commonly used in human and veterinary medicine. Some scientists believe that eating GE food containing these marker genes could encourage gut bacteria to develop antibiotic resistance.

But is there any documented instance of adverse effects of GMOs on people?

One epidemic was rare, serious, and fast acting, and therefore more easily discovered. Called EMS, it was traced to a GM brand of the food supplement L-tryptophan. In the 1980’s, the contaminated brand killed about 100 Americans and caused sickness or disability in about 5,000-10,000 others.

Why are children particularly susceptible to the effects of GM foods?

Children face the greatest risk from the potential dangers of GM foods for the same reasons that they also face the greatest risk from other hazards like pesticides and radiation, these include:

  • Young, fast-developing bodies are influenced most.
  • Children are more susceptible to allergies.
  • Children are more susceptible to problems with milk.
  • Children are more susceptible to nutritional problems.
  • Children are in danger from antibiotic resistant diseases.

How dangerous, or potentially dangerous, are GM foods relative to other food dangers, e.g., pesticides, irradiation, additives, preservatives?

Since so little research has been done on the safety of GM foods, it is not possible to rank its risks. Unlike the others, GM crops persist in the environment, and may continue to pose risks to health for centuries.

In addition, transfer of transgenes to gut bacteria may present long-term chronic exposure, since the foreign protein may continued to be produced inside of us after we no longer consume the GM food.

Dangers to the environment and traditional agriculture:

What is the effect of growing GM crops on the environment?

Studies have shown that pesticide-producing crops contaminate nearby streams, possibly affecting aquatic life. They may harm beneficial insects too.

As weeds adapt to herbicides, they develop resistance and evolve into what are called “super weeds.”When that happens, herbicide use increases and the benefits of herbicide resistant crops are diminished, if not lost.

Can the growing of GM crops effect nearby crops?

Pollen from GM crops can contaminate nearby crops of the same type, except for soy, which does not cross-pollinate. In fact, virtually all heritage varieties of corn in Mexico (the origin of all corn) have been found to have some contamination. Canola and cotton also cross-pollinate.

Why is there an effort to create GM-free agricultural zones?

Using identity preservation (IP), farmers keep crop varieties separate from others to meet purity requirements of their buyers. Contamination is a key challenge to IP growers. Unwanted varieties may cross-pollinate or get mixed up in the seed, harvest equipment, or during storage and transport.

Some farm regions create entire zones that exclude unwanted varieties, where all the farms, and if possible all collection and distribution points, only handle approved grain.

Have any local efforts in the US been successful?

There are local efforts throughout the U.S. that are raising public awareness, changing laws, and creating commitments to non-GM ingredients. Most notably, voters in Mendocino and Marin Counties in California passed a ballot initiative to ban GM crops.

Officials in Trinity County and Arcata, California have passed ordinances banning the outdoor cultivation of GM crops as well. But since then, a California law was passed prohibiting this type of local initiative.

In March 2008, voters at the Montville, Maine, annual town meeting overwhelmingly passed a binding ordinance banning the cultivation of GM crops in their community.

Is it possible that organically grown crops can be infected by GM genes?

Yes. Organic standards do not allow the use of GM seeds and therefore steps are taken to try to prevent contamination. Tests are not required, although some vigilant organic companies require them. According to the organic standards, contamination by cross-pollination is not disallowed, but some companies reject contaminated product above some small amount such as 0.1%.

Organic canola farmers in Canada sued biotech companies, since cross-pollination has made it impossible for them to grow organic, non-GM canola.

Is the Natural Foods Industry doing something to insure the purity of its products?

Right now there are efforts underway for an industry wide clean up of foods labeled organic and non-GMO. A handful of noble companies took it upon themselves to ensure that consumers could rest assured that their organic and non-GMO foods are truly free of modified genes. They established The Non-GMO Project, which has created an industry-wide consensus-based set of standards and a third-party verification process with testing for GMO content.

Companies began to enroll their products in the spring of 2008 and the first “non-GMO” seals for companies who fully comply with the protocols will be issued in 2009.

Government Regulation:

Hasn’t the FDA said that GM foods are safe?

The biotech industry claims that the FDA has thoroughly evaluated GM foods and found them safe. This is untrue. The FDA does not require safety studies. Instead, if the makers of the GM foods claim that they are safe, the agency has no further questions.

Didn’t the scientists at the FDA study GM foods themselves?

No. The FDA relies solely on information supplied by the biotech companies.

What kind of information did the companies provide?

Calgene, the makers of the first GM crop, the FlavrSavr tomato, was the only company to submit detailed raw data from animal feeding studies to the FDA. The rest provide only summaries and conclusions. Industry research can be rigged; data often is omitted or distorted.

In the FlavrSavr tests, lab rats refused to eat the tomatoes and had to be force-fed. Several developed stomach lesions, and seven of forty died within two weeks. Still, the tomato was approved, but has since been taken off the market.

Based on the information that was supplied, did the FDA scientist have concerns?

Agency scientists did warn that GM foods might create toxins, allergies, nutritional problems, and new diseases that might be difficult to identify. Internal FDA memos reveal that the scientists urged their superiors to require long-term safety testing to catch these hard-to-detect side effects.

What did the FDA do about these concerns?

Nothing was done that would protect consumers. In fact, in the case of genetically modified bovine growth hormone, some FDA scientists who expressed concerns were harassed, stripped of responsibilities, or fired. The remaining whistleblowers had to write an anonymous letter to Congress complaining of fraud and conflict of interest at the agency

How could the government approve dangerous foods?

A close examination reveals that industry manipulation and political collusion � not sound science � was the driving force.

The FDA official in charge ignored all warnings of the FDA staff scientists. The official, a former outside attorney for Monsanto, was a political appointee specifically to a new FDA post on GM policy, and left shortly after to become vice president at Monsanto.

Why aren’t foods with GMOs at least labeled here?

The same political influence and money that got them past the FDA has prevented any labeling laws from being passed. However, President Obama had indicated support for labeling laws during his campaign.

So do the biotech companies always get everything they want?

No. The biotech companies have fallen far short of their goals due to consumer resistance. The GM potatoes and tomatoes were taken off the market, and other GM crops, although approved, were never commercialized.

Concerned consumers in Europe were able to get major companies to commit to eliminate GMOs within one week. This was done with only a small percentage of the overall population. Businesses do not want to lose even a portion of their customer base. Everyone can vote with his or her pocketbook!

In 1998 the industry tried to get the USDA to let GM products pass as organic. During the public comment period, the Department received over 275,000 irate letters of protest from citizens, a public response unprecedented in the USDA’s history. Thanks to this public protest, GM products cannot be labeled organic in the USA.

Around the World

What about in neighboring countries?

In Canada, government scientists also complained that they were being pressured to approve the GM hormone, which is injected into cows to increase milk supply. They were concerned about human health impacts. They testified that the drugs maker, Monsanto, offered them a bribe of $1-2 million to approve it. They also reported that documents were stolen from a locked file cabinet in a government office.

Mexico has resisted GMOs, but contamination has still occurred.

Other stories of pressure, bribes, and threatened whistleblowers are reported through the history of GM foods and their approval, research, and promotion around the world.

What is happening with GM foods in the rest of the world?

All over the world, regions and even nations are demanding an end to GM crop cultivation. Twenty-two countries in Europe have regions wanting to be GM-free. States in Australia, regions in New Zealand and Brazil, the countries of Venezuela, Zambia, Sudan, Angola, and others, all want to be GM-free. Thus, world markets are shrinking.

In 2009, Germany joined France, Hungary, Italy, Greece, Austria, Poland and Romania in banning Monsanto’s Mon 810 GM corn because of its documented hazards to biodiversity and human health. In 2007 over three million Italians signed a petition, declaring their opposition to GM crops in their country. In Europe over 175 regions and over 4,500 municipalities have declared themselves GM-free zones. In Spain alone this includes over 50 municipalities and regions like Asturias, the Canary Islands and the Basque country.

Europe has greater rejection of GMOs due to a more balanced reporting by their press on the health and environmental dangers. In Europe, at least 174 regions, more than 4,500 councils and local governments have declared themselves GM free.

Have any GM foods been banned?

The rules of the World Trade Organization (which the US and other 150 countries are members of) explicitly prohibit countries from banning GM products. Therefore, countries that ban them do so at great risk. If this weren’t the case, no doubt many countries would already have done so.

Some countries have banned GM crops entirely or not approved certain GM crops that are approved elsewhere.

In the US, GM wheat was not approved when wheat farmers banded together because they were concerned that contamination would seriously hurt exports. So the reason was economic, not safety.

Source