Right, and this is exactly why real scientists- the ones in Europe and Australia and South America, completely oppose GMOs. Maybe this farmer needs to read up on how so-called American “research” was funded by the same companies- liike Monsanto- who have been destroying the environment for YEARS and have an ugly track record when it comes to genocide-causing pesticides- like Agent Orange and Dioxin- which they are using again on GMO crops and dumping PCBs and Mercury on small town America. When the regulatory bodies in America are run by the very same people who worked for Monsanto (cough, Michael Taylor, cough) and when the deadly trio of Monsanto-Dow-Bayer team up to create an heribicide that caused 500,000 birth defects (cough, Agent Orange, cough) and these same pesticides have been directly linked to cancer, birth defects and autism as per recent studies coming out of Stanford, then you know that real science- the one not funded by the corruptive influence of agribusiness (much like how tobacco company doctors said tobacco was “safe”)- is against these nonthinking sheep.

The American Medical Association agrees

GMOs should be safety tested – AMA

Thursday, 21 June 2012 12:07

NOTE: U.S. regulators rely almost exclusively on information provided by GM crop developers like Monsanto on an entirely voluntary basis, and those data are not normally published in journals or subjected to peer review. This is why many critics regard U.S. regulation of GM foods as a rubber-stamp approval process that does nothing to ensure the safety of GM foods.

The American Medical Association’s stance echoes what the British medical journal The Lancet said in an editorial more than a decade ago, “Governments should never have allowed these products into the food chain without insisting on rigorous testing for effects on health.”
http://bangmfood.org/quotes/24-quotes/29-regulatory-breakdown


GMOs should be safety tested before they hit the market says AMA
Monica Eng
Chicago Tribune, 20 June 2012
http://www.chicagotribune.com/features/food/stew/chi-gmos-should-be-safety-tested-before-they-hit-the-market-says-ama-20120619,0,4405082.story

The American Medical Association called for mandatory pre-market safety testing of genetically engineered foods as part of a revised policy voted on at the AMA’s meeting in Chicago Tuesday.

Currently biotech companies are simply encouraged to engage in a voluntary safety consultation with the Food and Drug Administration before releasing a product onto the market.

Some activists concerned about foods made with genetically modified organisms, or GMOs, had hoped the association would have gone so far as to support mandatory labeling of genetically engineered foods. But some still view the policy change as a major breakthrough.

“We applaud the AMA for taking the lead to help ensure a safe and adequate food supply,” said Anne Dietrich of the Truth In Labeling Campaign, which advocates labeling of genetically engineered foods. When Monsanto Co., the world’s largest biotech seed company, testified Sunday at the AMA committee hearing on the policy, its representative did not raise any objections to the mandatory safety assessment provision.

On Tuesday, however, Monsanto spokesman Tom Helscher would not say whether or not the company supports mandatory pre-market testing, only that the current voluntary consultation process “is working,” he wrote to the Tribune. “All of Monsanto’s biotech products, and to our knowledge all those of other companies, go through the FDA consultation process, which provides a stringent safety assessment of biotech crops before they are placed on the market.”

The AMA’s Dr. Patrice Harris said the testing provision was aimed at addressing public interests and ensuring public health.

“Recognizing the public’s interest in the safety of bioengineered foods, the new policy also supports mandatory FDA pre-market systemic safety assessments of these foods as a preventive measure to ensure the health of the public,” Harris said in a statement. “We also urge the FDA to remain alert to new data on the health consequences of bioengineered foods.”

Tuesday afternoon FDA officials would not say whether the department supported mandatory testing. “New foods have an obligation under the Federal Food, Drug & Cosmetic Act to ensure that the foods they offer consumers are safe and in compliance with applicable legal requirements,” the agency said. “In meeting their legal obligation, firms do conduct premarket safety testing.”

The agency was referring to testing manufacturers commission for their own use. Critics, however, argue that independent testing overseen by regulatory authorities often produces different results than testing paid for by the manufacturer.

After the policy was announced Tuesday, Consumers Union senior scientist Michael Hansen released a statement saying: “We wholeheartedly commend AMA for coming out in support of mandatory pre-market safety assessment of (genetically engineered) foods, but are disappointed that AMA did not also support mandatory labeling. … Studies in the scientific literature have suggested that genetic engineering could introduce new food allergens, increase the levels of known allergens, raise or lower nutrient levels and have adverse effects on the animals that eat such foods.”

Just Label It, the national campaign for the labeling of genetically engineered foods (www.justlabelit.org), issued a statement saying “just the fact that the AMA even considered this measure is a significant win for the vast majority (91%) of Americans (see the Mellman Poll findings) who believe they have the right to know about the foods they eat and feed their families — a fundamental right already enjoyed by citizens in more than 50 countries worldwide, including all of Europe, Japan, Russia and China.”

Groundbreaking Study Links Monsanto’s Glyphosate To Cancer | Collective-Evolution http://t.co/HQa8vL1fxZ Groundbreaking Study Links Monsanto’s Glyphosate To Cancer collective-evolution.com Glyphosate is a major component of Monsanto’s Roundup herbicide. It was created and manufactured on a mass scale by Monsanto and is one of the most widely used herbicides in the world. A number of scientific studies
Groundbreaking Study Links Monsanto’s Glyphosate To Cancer http://www.collective-evolution.com Glyphosate is a major component of Monsanto’s Roundup herbicide. It was created and manufactured on a mass scale by Monsanto and is one of the most widely used herbicides in the world. A number of scientific studies surrounding glyphosate have shed light on the danger it posses to the human body. A…
3:42pm Alex Henry Monsanto GM maize may face Europe ban after French study links to cancer : http://t.co/3Dt1IirMJJ Monsanto GM maize may face Europe ban after French study links to cancer rfi.my FRANCE – France will ask for a Europe-wide ban on a genetically modified maize developed by US agribusiness Monsanto if the findings of tests made public Wednesday prove to be true. The study found…
Monsanto GM maize may face Europe ban after French study links to cancer http://www.english.rfi.fr FRANCE – France will ask for a Europe-wide ban on a genetically modified maize developed by US agribusiness Monsanto if the findings of tests made public Wednesday prove to be true. The study found…
3:42pm Alex Henry Corn Flakes With a Side of Cancer:http://t.co/bjHcMX3PQ3 via @PolicyMic Corn Flakes With a Side of Cancer: Why America Should Pay Attention to France’s GMO Research policymic.com Research in France reveals that GMOs have devastating health effects and can lead to cancer. Prop. 37, California’s GMO labeling bill, is an opportunity
Corn Flakes With a Side of Cancer: Why America Should Pay Attention to France’s GMO Research http://www.policymic.com Research in France reveals that GMOs have devastating health effects and can lead to cancer. Prop. 37, California’s GMO labeling bill, is an opportunity that should not be wasted.
3:42pm Alex Henry Peru Passes Monumental Ten-Year Ban on Genetically Modified Foods http://t.co/THMJOg41Rk via @naturalsociety Peru Passes Ten-Year Ban on Genetically Modified Foods naturalsociety.com In an act of defiance against biotech companies like Monsanto, Peru has officially passed a law banning genetically modified ingredients.
Peru Passes Ten-Year Ban on Genetically Modified Foods naturalsociety.com In an act of defiance against biotech companies like Monsanto, Peru has officially passed a law banning genetically modified ingredients.
3:43pm Alex Henry GMO Crops Require More Pesticides, Create Resistant Insects http://t.co/dgWT6KOXtA via @naturalsociety GMO Crops Require More Pesticides, Create Resistant Insects naturalsociety.com Genetically modified crops are not only devastating to your health, but they are also wreaking havoc on the environment.
GMO Crops Require More Pesticides, Create Resistant Insects naturalsociety.com Genetically modified crops are not only devastating to your health, but they are also wreaking havoc on the environment.
3:43pm Alex Henry France Maintains Key Ban on Monsanto’s GMO Maize Crops http://t.co/i9LknUk4fh via @naturalsociety France Maintains Key Ban on Monsanto’s GMO Maize Crops naturalsociety.com France has upheld a decision to ban Monsanto’s GMO maize crops, the last remaining GMO allowed within Europe.
France Maintains Key Ban on Monsanto’s GMO Maize Crops naturalsociety.com France has upheld a decision to ban Monsanto’s GMO maize crops, the last remaining GMO allowed within Europe.
3:43pm Alex Henry Italy to Ban Monsanto GMO Corn with 80% Public Support http://t.co/bgzBNK8QMZ via @naturalsociety Italy to Ban Monsanto GMO Corn with 80% Public Support naturalsociety.com Italy is moving to ban one of Monsanto’s genetically modified corn maize crops, and 80 percent of the public is supporting the ban on GMOs.
Italy to Ban Monsanto GMO Corn with 80% Public Support naturalsociety.com Italy is moving to ban one of Monsanto’s genetically modified corn maize crops, and 80 percent of the public is supporting the ban on GMOs.
3:44pm Alex Henry Greenpeace Tells the FDA: Stop Misleading the Public About GMOs http://t.co/gCToLKWuFh via @naturalsociety Greenpeace Tells the FDA: Stop Misleading the Public About GMOs naturalsociety.com Greenpeace is speaking up for the general public, by telling the Food and Drug Administration (FDA) that they have no right to claim that GMOs are safe.
3:44pm Alex Henry Groundbreaking New Study Links GMO to Leukemia: When Will Monsanto Stop Lying to Us? http://t.co/SzI94pYFQc via @naturalsociety Groundbreaking New Study Links GMO to Leukemia naturalsociety.com A recent and concerning study shows the potential ‘leukemogenic’ properties of the Bt toxin biopesticides used in almost all GMO foods. GMOs are dangerous. Unlike your article that you posted which was published in a magazine which owns major stocks in Monsanto and by a writer who has always been biased, all of these are scientific studies and it’s why GMOs are now banned throughout Europe and starting to become labeled even here- Connecticut just passed a labelling law and New York is next! Monsanto doesn’t want labeling because they dont want people to know what’s in their food just like they didn’t want anyone to know about the PCBs and Mercury they were putting in the ground water of Anniston, Alabama for over 40 years! And this guy Henry Miller works for the FDA? Please. Both the FDA and USDA have been exposed countless times for letting companies like Monsanto go unregulated because the people who work for them (cough Michael Taylor cough) also work for that company- or used to. How stupid does this man think we are that he thinks he can hoodwink us? There’s a reason these so-called “conventional” GMO products are being outlawed throughout Europe, Asia and South America and we’re finally starting to label them here. Because the company behind them hides its research (and for good reason) and whenever unbiased scientific research is done, it shows exactly how the chemicals GMOs are treated with increase the likelihood of everything from leukemia to autism to birth defects. There is plenty of research even on the government’s own NIH website showing this, the above is just a small inkling of what I was able to find in a few minutes. So when you talk to a real scientist, that isn’t in the pay of the big corporations, a Monsanto lackey, you’ll here the truth. But you wont hear the truth from Henry Miller, because he wouldn’t know the truth if it slapped him in the face.

http://​www.ncbi.nlm.nih.gov/pmc/​articles/PMC2952409/

Abstract

We summarize the major points of international debate on health risk studies for the main commercialized edible GMOs. These GMOs are soy, maize and oilseed rape designed to contain new pesticide residues since they have been modified to be herbicide-tolerant (mostly to Roundup) or to produce mutated Bt toxins. The debated alimentary chronic risks may come from unpredictable insertional mutagenesis effects, metabolic effects, or from the new pesticide residues. The most detailed regulatory tests on the GMOs are three-month long feeding trials of laboratory rats, which are biochemically assessed. The tests are not compulsory, and are not independently conducted. The test data and the corresponding results are kept in secret by the companies. Our previous analyses of regulatory raw data at these levels, taking the representative examples of three GM maize NK 603, MON 810, and MON 863 led us to conclude that hepatorenal toxicities were possible, and that longer testing was necessary. Our study was criticized by the company developing the GMOs in question and the regulatory bodies, mainly on the divergent biological interpretations of statistically significant biochemical and physiological effects. We present the scientific reasons for the crucially different biological interpretations and also highlight the shortcomings in the experimental protocols designed by the company. The debate implies an enormous responsibility towards public health and is essential due to nonexistent traceability or epidemiological studies in the GMO-producing countries.
Keywords: GMOs, Health risks, Pesticides, Regulatory toxicology, Animal testsDebate on GMOs Health Risks after Statistical Findings in Regulatory Tests
http://www.ncbi.nlm.nih.gov
We summarize the major points of international debate on health risk studies for…See More

http://​www.ncbi.nlm.nih.gov/​pubmed/17356802

Arch Environ Contam Toxicol. 2007 May;52(4):596-602. Epub 2007 Mar 13.
New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity.
Séralini GE, Cellier D, de Vendomois JS.
Source
Committee for Independent Information and Research on Genetic Engineering CRIIGEN, Paris, France. criigen@unicaen.fr
Abstract
Health risk assessment of genetically modified organisms (GMOs) cultivated for food or feed is under debate throughout the world, and very little data have been published on mid- or long-term toxicological studies with mammals. One of these studies performed under the responsibility of Monsanto Company with a transgenic corn MON863 has been subjected to questions from regulatory reviewers in Europe, where it was finally approved in 2005. This necessitated a new assessment of kidney pathological findings, and the results remained controversial. An Appeal Court action in Germany (Münster) allowed public access in June 2005 to all the crude data from this 90-day rat-feeding study. We independently re-analyzed these data. Appropriate statistics were added, such as a multivariate analysis of the growth curves, and for biochemical parameters comparisons between GMO-treated rats and the controls fed with an equivalent normal diet, and separately with six reference diets with different compositions. We observed that after the consumption of MON863, rats showed slight but dose-related significant variations in growth for both sexes, resulting in 3.3% decrease in weight for males and 3.7% increase for females. Chemistry measurements reveal signs of hepatorenal toxicity, marked also by differential sensitivities in males and females. Triglycerides increased by 24-40% in females (either at week 14, dose 11% or at week 5, dose 33%, respectively); urine phosphorus and sodium excretions diminished in males by 31-35% (week 14, dose 33%) for the most important results significantly linked to the treatment in comparison to seven diets tested. Longer experiments are essential in order to indicate the real nature and extent of the possible pathology; with the present data it cannot be concluded that GM corn MON863 is a safe product.

PMID:

17356802

http://pubs.acs.org/doi/abs/10.1021/tx1001749?journalCode=crtoec

Tell EPA to Reject the Use of Toxic 2,4-D Herbicide for Dow Chemical’s “Agent Orange” GE Crops

EPA is deciding whether to allow the use of the herbicide 2,4-D for Dow Chemical’s genetically engineered “Agent Orange” corn and soybeans. Tell EPA to deny approval for these additional uses of toxic 2,4-D.

The Environmental Protection Agency has just opened a public comment period on the approval of the use of toxic 2,4-D specifically for Dow’s GE corn and soybeans. EPA is timing their approval process with that of USDA, with both agencies proposing approval of the Dow Agent Orange, GE crop system.

Dow Chemical, the same company that brought us Dursban, Napalm, and Agent Orange, is now in the food business and is pushing for an unprecedented government approval: genetically engineered (GE) versions of corn, soybeans and cotton that are designed to survive repeated dousing with 2,4-D, half of the highly toxic chemical mixture Agent Orange.

Agent Orange was the chemical defoliant used by the U.S. in Vietnam, and it caused lasting environmental damage as well as many serious medical conditions in both American veterans and the Vietnamese.

Tell EPA, USDA, and President Obama to stop Dow Chemical’s “Agent Orange” crops!

Wide scale use of Roundup with Roundup Ready GE crops has already led to an epidemic of resistant weeds, and the next step in the chemical arms race is 2,4-D — a chemical linked to major health problems including cancer, Parkinson’s disease, endocrine disruption, and reproductive problems. Industry tests show that 2,4-D is contaminated with dioxins—often referred to as the most toxic substances known to science.

EPA has reported that 2,4-D is the seventh largest source of dioxins in the U.S. Dioxin contamination in the rivers and soil around Dow Chemical’s headquarters in Midland, Michigan has led to the highest dioxin levels ever found by the EPA in fish, and has been linked to increased breast cancer rates in the contaminated areas.

EPA’s approval would lead to a massive increase in the use of this toxic, dioxin-contaminated herbicide on our farms!

If approved, Dow’s “Agent Orange” crops will trigger a large increase in 2,4-D use–and our exposure to this toxic herbicide—yet the government has completely failed to investigate the harms such increased use would cause. This is part of a growing problem, an escalating chemical arms race going on across America’s heartland.

Dow Chemical is hyping GE 2,4-D corn, soy and cotton as the “solution” to Roundup-resistant weeds caused by GE Roundup Ready crops. But by driving up 2,4-D use, Dow’s crops will generate even more intractable weeds resistant to 2,4-D and other herbicides. This GE crop system ensures a toxic spiral of ever-increasing chemical use on our land and food, which benefits no one but Dow.

Tell the government to reject Dow Chemical’s “Agent Orange” crops and the toxic chemicals they rely on!

SHARE THIS

For more information:

CFS’s Dow Campaign website: http://www.dow-watch.org

EPA’s Environmental Risk Assessment of Proposed Label for Enlist (2,4-D Choline Salt), New Uses on Soybean with DAS 68416-4 (2,4-D Tolerant) and Enlist (2,4-D + Glyphosate Tolerant) Corn and Field Corn: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0195

USDA’s draft environmental impact statement: http://www.aphis.usda.gov/brs/aphisdocs/24d_deis.pdf

CFS factsheet, “Agent Orange” Corn: The Next Stage in the Chemical Arms Race”: http://www.centerforfoodsafety.org/files/agent-orange-crops_fact-sheet_22481.pdf

CFS report, “Going Backwards: Dow’s 2,4-D-Resistant Crops and a More Toxic Future”: http://www.centerforfoodsafety.org/files/fsr_24-d.pdf

http://www.facebook.com/l.php?u=http%3A%2F%2Fwww.examiner.com%2Farticle%2Fmounting-evidence-that-gmo-crops-can-cause-infertility-and-birth-defects&h=TAQF4gASA

http://www.seattleorganicrestaurants.com/vegan-whole-foods/gmo-harms-dangers/

http://www.policymic.com/articles/15889/french-gmo-research-finds-monsanto-corn-causes-cancer-america-should-pay-attention_

http://www.english.rfi.fr/americas/20120920-monsanto-gm-maize-may-face-europe-ban-after-french-study-links-cancer

http://www.collective-evolution.com/2013/06/14/groundbreaking-study-links-monsantos-glyphosate-to-cancer/

http://www.collective-evolution.com/2013/06/14/groundbreaking-study-links-monsantos-glyphosate-to-cancer/

http://pubs.acs.org/doi/abs/10.1021/tx1001749?journalCode=crtoec

ttp://www.davidicke.com/headlines/47833-gmo-pesticides-linked-to-birth-defects-disruption-of-male-hormones-cancer-

http://www.english.rfi.fr/americas/20120920-monsanto-gm-maize-may-face-europe-ban-after-french-study-links-cancer

http://www.policymic.com/articles/15889/french-gmo-research-finds-monsanto-corn-causes-cancer-america-should-pay-attention_

http://www.policymic.com/profiles/21102/kaylin-greene

http://www.sciencedirect.com/science/article/pii/S0278691512005637

http://www.sciencedirect.com/science/article/pii/S0278691512008149

Answers to critics: Why there is a long term toxicity due to a Roundup-tolerant genetically modified maize and to a Roundup herbicide
Gilles-Eric Séralinia, , , Robin Mesnagea, Nicolas Defargea, Steeve Gressa, Didier Hennequinc, Emilie Claira, Manuela Malatestab, Joël Spiroux de Vendômoisa
Show more
DOI: 10.1016/j.fct.2012.11.007
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Under a Creative Commons license
Refers To
Lúcia de Souza, Leila Macedo Oda
Letter to the editor
Food and Chemical Toxicology, Volume 53, March 2013, Page 440
PDF (211 K)
Open Access
Abstract
Our recent work (Séralini et al., 2012) remains to date the most detailed study involving the life-long consumption of an agricultural genetically modified organism (GMO). This is true especially for NK603 maize for which only a 90-day test for commercial release was previously conducted using the same rat strain (Hammond et al., 2004). It is also the first long term detailed research on mammals exposed to a highly diluted pesticide in its total formulation with adjuvants. This may explain why 75% of our first criticisms arising within a week, among publishing authors, come from plant biologists, some developing patents on GMOs, even if it was a toxicological paper on mammals, and from Monsanto Company who owns both the NK603 GM maize and Roundup herbicide (R). Our study has limits like any one, and here we carefully answer to all criticisms from agencies, consultants and scientists, that were sent to the Editor or to ourselves. At this level, a full debate is biased if the toxicity tests on mammals of NK603 and R obtained by Monsanto Company remain confidential and thus unavailable in an electronic format for the whole scientific community to conduct independent scrutiny of the raw data. In our article, the conclusions of long-term NK603 and Roundup toxicities came from the statistically highly discriminant findings at the biochemical level in treated groups in comparison to controls, because these findings do correspond in an blinded analysis to the pathologies observed in organs, that were in turn linked to the deaths by anatomopathologists. GM NK603 and R cannot be regarded as safe to date.

Keywords
GMO; Roundup; NK603; Rat; Glyphosate-based herbicides; Endocrine disrupting effects; Answers to critics
1. Introduction
Our recent publication of research evaluating the long term toxicity of a NK603 Roundup-tolerant genetically modified (GM) maize and of a Roundup (R) herbicide (Séralini et al., 2012) has provoked numerous positive and negative reactions throughout the world. This is the way science moves forward and here we provide a response to this intense debate. Our work is the most detailed study involving the life-long consumption of an agricultural genetically modified organism (GMO), and especially on NK603 for which only a 90-day safety test was previously conducted and using the same rat strain (Hammond et al., 2004). It is also the first long term detailed research on mammals exposed to a highly diluted pesticide in its total formulation with adjuvants. These adjuvants help to stabilize the active principles of pesticides, and promote a better penetration into organisms, and thus more side-effects. R is the most widely used herbicide in the world, which we tested from levels arising in tap water. Indeed in our study, its active principle glyphosate (G) was not studied alone, contrasting with the long term experiments conducted by the manufacturer as part of its application for regulatory approval. As such, the debate in question here is at the cornerstone of science and regulatory issues on this topic. This fact has major economic ramifications for the development of such products, which can explain the severe comments posted within hours of our publication becoming available online. This may explain why 75% of our first criticisms arising within a week, among publishing authors, come from plant biologists, some developing patents on GMOs, even if it was a toxicological paper on mammals, and from Monsanto Company who owns both the NK603 GM maize and R herbicide.

We must firstly focus on science. Our work is a research study; it has not a direct regulatory purpose and should not be considered as a final point in knowing the toxicological effects of NK603 and R. This is a first step in the iterative investigation of the long-term health effects on mammals of these commercial products that should be replicated independently, as well as on developing mammals. It has limits like any study, and here we carefully answer to all criticisms from agencies, consultants and scientists, that were sent to the Editor of Food & Chemical Toxicology or to ourselves. These challenged our results and the validity of our protocol, some letters even requested the withdrawal of the publication from the journal. All remarks and answers are summarized in Table 1 and with some explanatory details given below.

Table 1.
Summary of criticisms and responses on Séralini et al. long-term NK603 GM maize and Roundup toxicity rat study.
Criticisms Answers
Relevance of the scientific context
No scientific context This study addresses biological interpretations of early signs of toxicity in biochemistry after 90-day feeding trials (Spiroux de Vendomois et al., 2010)
OECD guidelines not respected No guidelines exist for GMO animal studies. Protocol based and adapted from OECD 408 and 452
Protocol not adapted to tumor findings This is not a carcinogenesis study, but a long term full toxicological study
GLP violation because of amendments Research protocols not adapted to GLP agreement because of amendments. The experiment was conducted under a GLP environment and conditions
History of flaw by the authors which are not toxicologists. Previous studies of the group rejected More than 26 international scientific peer reviewed papers by the team with the lead author on the topic in the last 5 years, and 11 in toxicological journals on the same period only in PubMed. One author, Malatesta, has also published on GMO/pesticide health risks. None of the papers was considered as flawed by the scientific community. Regulatory agencies or Monsanto are not scientific peer reviewed journal systems
Lack of signs in 90 days Statistical differences in biochemical parameters of liver and kidney function recognized by both industry and agencies
Not the first long term study First chronic investigation with NK603 GM maize; others of two years in farm animals are not over the entire lifespan; the most detailed study for all agricultural GMOs and a formulated pesticide

Originality and limits of the experimental design
Choice of the rat strain (sensitivity to mammary tumors and nephropathies in males) Necessity to have sensitive strains, recommended by the US National Toxicology Program (King-Herbert et al. 2010). Rats and mice have been preferred experimental models because of their susceptibility to tumor induction (OECD guidelines) Relevant comparisons to controls in this work
Number of rats per group OECD 408 (90-day toxicity study) 10 animals per group OECD 452 (Chronic toxicity study) 20 animals per group but at least 10 animals per group are studied for hematological and clinical biochemical function
Missing data: diet composition and process, PCR analysis of batches, contaminants (mycotoxins, pesticides), storage (R in water, BPA, feed), isogenic line, culture conditions Normally included in GLP environment studies. No possibility to detail all these data in this scientific study in this journal – in process of publication. Diet equilibrated for substantial equivalence between GMO and the closest isogenic line and other compounds. Other points detailed in the text
No blinding, not the knowledge to interpret tumors, no morphometric analyses, no use of PETO codes, no classification Independent and blinded analysis by GLP performed by professional regulatory anatomopathologists. Nature of most frequent tumors in Fig. 3 legend and results. A professional report for each rat indicates the cause of mortality
R formulations are different Depends on the country
Controls not sufficient (number of rats per group, 4 groups 11 and 22%, no drinking water control group) Number of rats approved in guidelines, best in the world at this level of details for these products. All the animals have eaten 33% of maize and substantially equivalent diets. Only R treated rats had received R in water
No reference groups, no lab historical data Reference groups add irrelevant variability with non-substantially equivalent diets; historical data contain diets not controlled for pesticides and GMOs, thus not relevant
Ad Libitum feeding In accordance to guidelines and usual practices
Diurnal variations All samplings were taken at the same time

Focus on statistics
Not enough statistical power
No Kaplan Meier’s curves
Variability expected by chance
Only raw data in Figs. 1–3 and Table 2 Statistics do not tell the truth, but may help in understanding results. The biological interpretations and the crossing of methodologies are the key. Enough and high statistical power for OPLS-DA, and this is why raw data only were presented in Figs. 1 and 2 and Table 2; no statistical power of Kaplan Meier’s analyses for a conclusion demonstrating effects or no effects.
No means and standard deviations in Table 3 OPLS-DA is not a method to compare mean differences which were presented for understanding of biochemical measurements with highly discriminant parameters in bold

Pertinence of the results
Missing data (Behavioral studies, ophthalmology, microbiology in feces and in infectious nodules, G in tissues, body and organ weights, feed and water consumptions, transgene in tissues, time effects) All measures cannot be presented in one paper and will be the subject of other publications. The other analyses are not relevant for the conclusions presented
No isoflavones in maize Testing the diets for phytoestrogens is relevant because the equilibrated diet (non-GM) contains other components
Phenolic acids in the normal range Used as biomarkers indicative of change in the metabolism of the GMO. This does not exclude the presence of unknown toxic compounds
No incidence / severity Lack of histopathology data Taken into account as indicated in the legend of Table 2 which consists in a summary of the most relevant data
Endocrine disruption not sufficiently supported Convergent body of evidence stemming from mammary tumors, pituitary dysfunctions, histopathology and sex hormone biochemistry
Wilm’s tumors are only of genetic origin Promotion by pesticide exposure is plausible and as evidenced by gestational exposure described in the literature
Feeding state explains glycogen in electron microscopy No difference in feed consumption; experience in the domain by M. Malatesta
Pictures of control rat not shown Rats representative of each group shown, controls do not present tumors in majority during the experiment, pictures non necessary

Discussion: findings in regard with the contradictory hypotheses
R is not a sex endocrine disruptor This is still true at a regulatory but not at a scientific research level. R endocrine disrupting properties are described in vivo and in vitro (references in the text). Regulatory classification should be in process
G is not toxic in two-year tests G is never used alone in agriculture, but in formulations with G far more toxic than G alone; G tests are not relevant, we used R
G is close in structure to amino acids and surfactant exposure is as soap exposure This is not supported by the scientific literature; the structural and activity comparisons are not scientifically relevant to predict with certainty toxicological effects or safety
No effects on farm animals and in human population of the USA No epidemiology, no life-long experimental studies; farms animals are generally killed too young to show development of long term diseases. No traceability and labeling of GMOs in USA, no epidemiological survey can be performed
Sakamoto et al. 2008 not reported This study does not use the same GMO (soy vs maize) and neither the same strain of rat. No effect for GM soy in F344 rats is claimed but does not imply the same for NK603 GM maize in SD rats
Raw data expected for our study Raw data also expected for regulatory accepted tests for this GMO and this pesticide to scientifically discuss details

Ethical issues and deontology
Maize illicitly grown Not at all; grown and imported with appropriate authorizations
Animal welfare problems, a veterinarian would not authorize such tumor development The work follows GLP conditions. All rats followed by veterinarians on the site, applying the rules of the ethical committee and guidelines
Conflicts of interests No conflict for us. Conflicts of interests for companies testing their own products
Role of funders See acknowledgments, funders identified. No interference in study or results; confidential up to the embargo
Publication released before for journalists Everything was released on the same day (September 19th), in accordance with the conditions set by the FCT editorial board.
Confidentiality agreement unusual The confidentiality of the work is a usual practice before embargo
The authors should alert agencies from the end of experiment instead of waiting for a publication The publication and reviewing of the work is the guarantee of quality with no interference
Table options
At this level, a full debate is biased if the toxicity tests on mammals of NK603 and R obtained by Monsanto Company remain confidential and thus unavailable for the scientific community to conduct independent scrutiny of their raw data. This is why, after several exchanges, we requested again from the European Food Safety Agency (EFSA) on September 20th and October 18th 2012 the release on a public website of the raw data on health risks on the basis of which commercialization of these products was granted, in particular results from the longest study of NK603 and Roundup on mammals (Hammond et al., 2004). We ask for a free and transparent exchange of scientific findings, mainly when these are related to public health and environmental risks (Schreider et al., 2010). Examination of industry raw data previously evidenced divergence of regulatory decisions from scientific evidence underestimating toxicological features of G (Antoniou et al., 2012). We recall that the tests on rats are usually considered as a model for mammalian health before clinical trials (for example for pharmaceuticals) or for a direct market release (for novel food and feed, pesticides or chemicals). Moreover, tests on rats are also models for environmental risk assessment, since they are models for other wildlife mammals. The public release of these raw data will reveal if significant differences observed between test and control groups in both studies are coherent and if the statistics are of sufficient power in both cases, thereby allowing the design of appropriate follow-up experiments by others, perhaps through a publically discussed and agreed protocol.

2. Relevance of the scientific context
Some remarks emphasize a lack of context, claiming that the study was performed for non-scientific reasons. The establishment of this protocol was however the consequence of an intense debate about the biological relevance of numerous statistically significant differences compared to controls revealed and admitted to in 90-day feeding studies with agricultural GMOs (Spiroux de Vendomois et al., 2010). This is highly controversial, with companies and regulatory agencies having refuted findings, which were validated by a peer reviewed process in international journals (EFSA, 2007 and Séralini et al., 2007). Indeed, regulatory agencies such as EFSA appear to have their own criteria to judge the biological relevance of research findings (Doull et al., 2007), which is markedly at odds with some recent knowledge. This includes cases of sex specific non-linear endocrine disruptions, which were not admitted to as valid at a regulatory level although accepted at a scientific research level (Myers et al., 2009b). In order to overcome the divergence in biological interpretation of early signs of toxicity in blood biochemistry for GMOs, one solution was to prolong 90-day feeding tests to chronic periods. We therefore chose the R tolerant NK603 GM maize because R tolerance is the trait present in approximately 80% of agricultural GMOs (James, 2011) and because statistical differences in the 90-day feeding trial with this maize were admitted to by both the petitioner and regulatory agencies (EFSA, 2009).

3. Originality and limits of the experimental design
Due to the economic and regulatory issues of this topic, it is not surprising that our research study was confounded with pre-commercial regulatory assessments. This is why the most common criticism questions the following of Organization for Economic Co-operation and Development (OECD) guidelines. However, no guidelines exist for GMO toxicity studies in vivo, which are still not mandatory. Published reviews have confirmed that most of the studies conducted to date did not follow specific guidelines or were contradictory (Domingo, 2007 and Domingo and Giné Bordonaba, 2011). We compared our design (Table 1 of Séralini et al., 2012) to Hammond et al. (2004) inspired from OECD guideline 408 for chemicals. We have replicated, extended and thus improved the experiments conducted by Hammond and colleagues (Hammond et al., 2004) by measuring outcomes from 3 instead of 2 feed doses and more crucially for a period 8 times longer in duration (90-days vs 2 years), with 11 blood and urine measures of around 50 parameters, 34 organs instead of 17, etc., in order to ascertain if the statistical findings (observed at 90 days; Hammond et al., 2004), were biologically relevant or not in the long term. We thus biochemically measured 10 rats per sex per group as performed by Monsanto. Even for a study of up to two years, we had no reason to monitor biochemical effects on more than 10 animals per sex per group as this is the number recommended in OECD guideline 452 for chronic toxicity testing (OECD 1981 was in application when the study started in 2008), even if 20 animals per group or more are possible.

The purpose of the addition of R treated groups was not to assess R long term carcinogenesis, which needs to follow OECD 453 guideline with at least 50 rats per sex per group (even if 10 rats are then still measured at a biochemical level). The aim of our study was to test R under similar conditions to the GM maize in order to try and understand if residues of R in the feed could explain the possible pathologies that may arise. There were two main potential sources of harm tested in our study: (i) effects from the GM maize itself, treated or not with R, and (ii) herbicide residues alone in drinking water, using 3 doses for each treatment. We recall that the initial investigation published by Hammond and colleagues (Hammond et al., 2004) used 2 doses for each treatment group despite that fact that 3 doses are recommended by OECD guideline 408, which they reported to have followed.

In addition, one of the criteria for biological relevance employed by Monsanto and other critics of our study is the linearity or lack thereof in response to the dose. Such a dose–response relationship cannot be claimed from a trial using only 2 doses of test material as employed in the initial NK603 assessment (Hammond et al., 2004). We therefore find it surprising that the relevance of Monsanto’s and the agencies’ conclusion of safety was not challenged due to such protocol insufficiencies. A recent review of the literature is often cited as a proof of the safety of GMO consumption on a long-term basis (Snell et al., 2012). However, of the 24 studies they evaluated, only 2 are long-term on rodents, since a 2 year feeding period with pigs or cows do not constitute a life-long experiments. The 2 rodent studies quoted by Snell and colleagues are from Sakamoto et al. (2008) where not all rats fed transgenic soy were analyzed, and Malatesta et al. (2008a) in mice fed again GM soy, which showed at an electronic microscopy level effects of this product on hepatic function. Moreover, of the 24 studies cited, 16 did not mention the use of the closest isogenic non-GM line as a control, many did not describe the methods in detail, and contained additional deficiencies (Snell et al., 2012). However, all these studies were accepted as proof of safety regardless of the inadequacies highlighted here. It would appear that conclusions of safety seem to need fewer requirements than conclusions of toxicity. However, scientifically it is easier to conclude an outcome of toxicity than safety. This was not the first time regulatory agencies used such double standards to minimize independent research findings in regard to industry findings (Hilbeck et al., 2012 and Myers et al., 2009a). Our control groups were also questioned and this needs some clarification. Some claimed that controls are lacking for all 4 test groups (GMO+R and GMO alone at 11% and 22%). We compared all treated groups to the control group containing 33% of the closest available isogenic maize, as all diets were equilibrated to 33% maize; that is, for example the 11% GM maize diet was supplemented with non-GM control maize to reach 33%. More accurately the closest available isogenic line was the DKC2675 variety compared to the DKC2978 GM maize (NK603). Regulatory agencies also questioned the conditions under which the maize was grown. One R treatment was applied 4 months before harvest. Fungicides were applied similarly. We were unable to use the same R formulation in the field (Canada) and in the drinking water of the rats (France) because authorized formulations vary between nations. The diet was nutritionally equilibrated from substantially equivalent maize and was then checked by PCR for GMO content. A major concern was the potential presence of mycotoxins. Fumonisin B1 and B2, zearalenone, deoxynivalenol (DON), nivalenol, 3-acetyl-DON, 15-acetyl-DON, fusarenone X, T2 toxin, HT2 toxin and diacetoxyscirpenol were all under recommended limits in food/feed used in this study. We did not present details of each of these substances when no particular changes affecting the understanding of the results were noticed.

As a research protocol, Good Laboratory Practice (GLP, OECD, 1997; 2004/10/EC regulation) was followed, meaning that housing conditions, manufacturing process, diet composition and storage, stability of solutions and dietary contaminants were assessed by approved laboratories. Anatomopathology was performed in a blind manner (without knowing the treatments) by professional anatomopathologists approved for regulatory purposes. An electronic chip was inserted in each rat for identification. However, the technicians employed for the care and sampling of the animals did not know either the nature of the diets or the drinking water prepared independently, or which was the control group. The cages housing the animals were moved within holding rooms regularly and similarly for all animals. The blood (1 mL) and urine samples were coded and the measurement of biochemical parameters also blind, as were the decisions of euthanasia to avoid suffering in accordance with precise regulatory ethical rules (hemorrhages, impossibility to drink and eat, large tumors over 25% body weight because they provoke mortality). All the animals were monitored during the experiment by professional veterinarians. The statistical analysis was also undertaken on coded groups. However, we have made research amendments adding additional analyses (tissue and biochemical parameters) adapted to the findings in order to improve the understanding of the pathologies, thus we are only in a GLP environment. Generally, it is standard practice that a regulatory agency does not take note of research studies because they are not conducted under GLP conditions (Myers et al., 2009a). By its very nature, a research protocol is rarely compatible with GLP agreements. GLP agreement is a good tool to normalize regulatory assessment but research studies need a greater degree of freedom, in test protocols, models, etc.

4. Rat strain
We would like to explain the choice of the strain of rat. This is another redundant remark made by critics of our study design. We recall that OECD norms (408, 452 and 453) are not prescriptive for the strain of rat to be used. Sprague Dawley (SD) rats are subject to spontaneous neoplasms and this property is supposed to invalidate them being used as a model for carcinogenesis. However, on the contrary, the fact that the SD strain develops tumors, hence has led to it is preferentially used by some agencies such as for the National Toxicology Program using it for 2-year carcinogenicity and other long-term studies (King-Herbert et al., 2010). Indeed, it would be a non-sense to study pathologies in a strain insensitive to tumor formation. Long-term OECD guideline 452 even states that rats and mice have been preferred as experimental model systems because of their susceptibility to tumor induction. The same reasoning is used for chronic progressive nephropathies (CPN) developed by SD rats. The fact that the strain developed spontaneous CPN with age (Hard and Khan, 2004) does not invalidate the model as we looked at the difference in the chronology, age, number and severity of CPN in comparison to controls.

To assess the biological relevance of results, many authors make comparisons with historical data of control rats, either within the laboratory or the breeding company from which animals are sourced. However, this clearly greatly enhances control variability and heightens the risk of false negative findings (Cuffe, 2011). It is now established that this concept should be used with caution. There are several reasons for this. Control diets for rats are generally not monitored, neither for pesticides (Hayes, 2004), nor for chemicals leaching from cages or other environmental sources (Howdeshell et al., 2003). This artificially enhances background effects. The supplier even recognizes that their historical data come from rats potentially fed GMOs since this was not controlled for (Harlan communication), except in our experiment. Thus, it was not appropriate for us to use historical control data. This is also the reason why we did not use reference groups fed different non-substantially equivalent diets, as they increase the standard deviation of the control groups, hiding differential effects due to treatments.

Many non-relevant remarks have also been noticed. Among others, some criticized the use of ad libitum feed to explain the increase of tumor incidence. Guidelines on the design and conduct of chronic toxicity studies state that rodents should be fed and watered ad libitum (OECD, Guidance Document No. 116). The hormonal imbalances were criticized to be due to diurnal or cyclic variations. However, sampling was performed at the same time each day in the morning.

5. Focus on statistical analytical methods and outcomes
Statistics do not tell the truth, but may assist in our understanding of experimental outcomes. The biological interpretations and the crossing of methodologies are the key (Cooper and Kavlock, 1997). We have applied the most modern statistical methods (OPLS-DA, see below) for multivariate data analysis of approximately 50 parameters measured 11 times for 200 rats. This allowed, in a blinded manner, to obtain results significantly discriminant at 99% confidence levels. These discriminant biochemical markers were, for example in the case of sexual hormones (at 95% for females at month 15), when the differences in hormone-dependent tumor incidence with the control group began. Disability in pituitary function was characteristic of this second most affected organ as certified independently by the pathologists in a blinded manner in treated female groups in comparison to controls. Such a disturbance in hormonal function is known to elicit mammary tumors in rats with the pituitary being a target of endocrine disrupting chemicals (Wozniak et al., 2005). The pathologists employed in our study explained that most of the mortality in females resulted from tumors, which led to euthanasia independently of the grade of cancer. This is why we did not detail the grade of tumors in our research but with the cancerous nature of the major tumor growths described in our study (Fig. 3 legend and results section (Par. 3.2)). These observations together with microscopic analysis reinforced our conclusions.

We believe all this was more pertinent than the study of statistically non-powerful Kaplan–Meiers’ curves on survival (because of the groups of 10 animals per sex dying progressively) that cannot allow any conclusion on mortality linked or not to the treatment. Taking into account these limits, we decided to be simply factual in our presentation and thus describe the chronology and incidence of tumors and deaths. In comparison, statisticians from agencies could evaluate the power of the statistical analyses of the tests conducted by Hammond et al. (2004), which gave a score of safety, and that were used for market release. For us, the power of statistics used in Hammond et al. (2004) is extremely low to conclude to safety.

In our study, case PLS-regression (Projections to Latent Structures by means of partial least squares) is of particular relevance because, unlike conventional multivariate data analytical methods, it can analyze data sets with variables more numerous than observations, which can be strongly correlated (Wold et al., 2001). In the case of Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) there is separation between the inter-group variation (represented on the predictive component) and the intra-group variation (variability of the samples, represented on the first Y-orthogonal components). OPLS-DA is thus not an appropriate method with which to compare mean differences. However, for providing biochemical understanding, we have presented and highlighted those in Table 3 of our study, with highly discriminant parameters in bold text. OPLS-DA renders it possible to identify which variables are responsible for the separation of the groups. For instance, we also indicate in Fig. 5B that estradiol and testosterone are significantly discriminant at 95% confidence levels in some groups (not at 99% like other parameters presented).

Moreover, the SIMCA-P (V12) software (UMETRICS AB Umea, Sweden) for the multivariate analysis of biochemical data uses a method of validation of models, which is a k-fold cross-validation. The Q2(Y) parameter which measures the predictive ability of the models is calculated according to this cross-validation method. Only valid models with a satisfactory predictive quality Q2 index were retained for the selection of the discriminant variables (bold in figures, Table 3). Furthermore, all models retained are significant (CV-ANOVA test with p-value <5%). One of the authors of our paper (D.H.) previously used this method and published their results in international peer-reviewed journals ( Ledauphin et al., 2010, Malzert-Freon et al., 2010a and Malzert-Freon et al., 2010b).

6. Pertinence of the results
The first major criticisms that were raised concerned the results and their format of presentation. A scientific publication is by necessity limited in figures/tables and only shows the data necessary to understand and discuss the conclusions. This is why behavioral studies, ophthalmology, microbiology in feces and in infectious nodules, G in tissues, body and organ weights, feed and water consumptions, transgene in tissues, time effects will be the subject of future publications. The inclusion of these data at this stage would neither add to the main message nor would it improve the understanding of this first publication. Indeed, the peer review process has controlled the logic of the body of data presented. Additional sets of results were included in the revision of the manuscript in response to issues raised by the reviewers prior to publication.

The second major criticism of the results is that we attached too much importance to findings related to mortality and tumor relative to their scientific significance. We are aware of the limitations of these findings as discussed above in relation to the statistical analysis undertaken. The body of evidence for our conclusions comes from the converging methodologies and data (see Focus on Statistics). The variability in rates of mortality can indeed, if looked at in isolation, arise in principle by chance. However, statistical analysis for Figs. 1 and 2 is not of sufficient power to conclude that this is the case or the contrary. This is why we have presented the raw data for these sets of observations. For instance, males presented up to 4 times (2 times of the mean) more large palpable tumors than controls, similarly to that observed in female animals. As these observations may represent a potential risk for the human population, this cannot simply be disregarded so rapidly with non-potent statistics. This is also why we emphasized statistically discriminant biochemical effects at the 15th month, when most of animals were still alive (in treated groups 90% males, 94% females, and 100% controls). The significantly discriminant biochemical markers disrupted do correspond to the organic markers linked to the pathologies in a blinded analysis for the pathologists, who in turn linked that to the deaths. The two nephroblastomas in GMO fed groups linked to premature deaths was criticized for bringing confusion to the results, because these tumors are often of embryonic and/or genetic origin. However, these tumors are also known to be promoted by pesticide exposure (Fear et al., 1998).

The summary of the major histopathological findings in Table 2 was subject to the same criticisms. In fact, we indicated the severities of the CPN and only marked or severe CPN were shown. Indeed, elderly rats are subject to CPN and taking into account all CPN could hide interesting and important differences. The power of statistics may be discussed as for Figs. 1 and 2. However, all these data need to be seen in the context of all the significant results presented in the paper, as previously underlined.

For the findings obtained from the electron microscopy analysis, it is important to compare our results with those reported previously. Several studies have shown ultrastructural abnormalities in the liver of mice fed with GM soy (Malatesta et al., 2002) and that this structural disturbance was reproduced by adding the herbicide R directly to rat hepatocytes (Malatesta et al., 2008b). We thus wanted to test if the same disruptions can be seen in the liver of the rats in our experiment. This was indeed the case, and furthermore these observations conform with ours and others published in vitro effects of R (Gasnier et al., 2010 and Gasnier et al., 2011). Glycogen dispersion or appearance in lakes found by electron microscopy was attributed to the feeding state by some critics. However, differences in feed consumption were not observed during the course of our study. Not only appearance of glycogen in lakes was noticed, but also a reduced rate of transcription of mRNA and rRNA, which is not normally known to be due to the feeding state, but rather to a toxic insult. Ultrastructural patterns revealed by of electron microscopy were coherent with an increase in detoxifying activity in liver, and this is corroborated by differences in cytochrome enzyme activities.

A major gap in some toxicological assessments is the lack of measurements investigating endocrine disrupting effects (Birnbaum, 2012). As noted previously, the central dogma in toxicology is that effects vary linearly to dose. This is true for standard poison intoxication. However, toxins with endocrine disruptive properties can give response curves that are U, inverted U or J in shape and are frequently observed in the case of exposure to environmental pollutants (Vandenberg et al., 2012). Endocrine disturbance is supported by observations in human (Gasnier et al., 2009) and rat testicular cells for R residues (Clair et al., 2012). In our study it is demonstrated by statistically significant sex hormone imbalances and disabled pituitary function. Moreover, doses varied from 50 ng/L to 2.5 g/L of glyphosate in R; that is, a factor 50 million, from which we cannot expect linear effects with such a wide range of doses tested, characteristic of the range of different kinds of environmental exposures (tap water, GM food and feed, diluted agricultural use). The kidneys and liver are also sensitive to endocrine disruptors. As the two major detoxifying organs, containing cytochrome P450 or other enzymes involved in xenobiotic or sex steroid metabolism, they often react with steroid sex hormone and related compounds (Pascussi et al., 2008).

Last but not least, we have identified phenolic acids as potential biomarkers of metabolic disturbances in the GM diet. We have also measured isoflavones in the diet even though maize does not produce these compounds. Rats indeed did not eat only maize but also other plants in an equilibrated diet. Even OECD 452 guidelines on chronic toxicity ask for testing phytoestrogen content of the diet. Importantly, decrease in phenolic acids is a good indicator of change in the metabolism of the GMO that could in turn lead to a reduced protection against the pathologies observed in the animals fed the NK603 GM maize. However, this does not exclude the possibility of other toxic effects of the GMO alone, which have not been identified in the experiment.

7. Discussion
7.1. Findings in regard with the contradictory hypotheses
Critics have claimed that no argument exists for R to be a sex hormone endocrine disruptor, which is based on a review by Williams et al. (2000), where most of the studies cover G effects alone and not R. We wish to draw attention again to the fact that G is never used as such, but in formulations with other substances allowing toxicity, both of target and non-target species. This is extensively described for G-based herbicides, but also for other pesticides (Eddleston et al., 2012). This is why, in our opinion, all discussion of our study referring to testing of G alone is not relevant. Furthermore, we find it incomprehensible that non-scientific assertions justify R innocuousness by the structural homology of G with non-toxic amino acids. In addition adjuvants in the R formulation cannot be judged harmless by a comparison of their activity to soap. There is no scientific basis to use these assertions to predict with certainty toxicological effects or safety. The fact that G alone is neither a carcinogen nor an endocrine disruptor in regulatory tests is not a proof of the safety of whole R formulations, especially when some formulations contained toxic compounds (Cox, 2004). The unexpected finding of new active principles with human cell toxicity capabilities in G-based herbicides has challenged the relevance of testing G alone as the active principle in R (Mesnage et al., 2012). R has already been demonstrated to be an endocrine disruptor in vivo (Dallegrave et al., 2007, Oliveira et al., 2007, Romano et al., 2010 and Romano et al., 2012) with the underlying mechanism understood in vitro.

Several studies have shown significant endocrine disrupting effects of R, such as decrease in progesterone production, decreased levels of Steroidogenic Acute Regulatory (StAR) mRNA production in MA-10 mouse Leydig cells (Walsh et al., 2000), decrease in aromatase mRNA and activity levels in JEG3 cells and placental and equine testicular microsomes (Richard et al., 2005 and Benachour et al., 2007), inhibition of transcriptional activities of androgens and of both α- and β-estrogen receptors in cells (Gasnier et al., 2009), and a decrease in testosterone production in rat Leydig cells (Clair et al., 2012). All these studies reinforce the biological relevance of our findings.

Some critics have emphasized that no adverse effects have been reported on either farm animals or in the human population of the USA who have consumed an unknown mixture GMO crop derived food. Such claims are scientifically unsound for the following reasons. First, it is important to note that there have been neither epidemiological studies of the human population nor monitoring of farm animals in an attempt to correlate any ill-health observed with the consumption of a given GM crop. Second, it should be recalled that farm animals are not reared to live for the entire duration of their natural lifespan, and thus usually do not live long enough to develop long-term chronic diseases, which contrasts with the rats in our life-long experiment. If any studies in lactating cows are conducted, biological analyses performed are far less complete than those done in regulatory tests using rodents including in our study. Third, as there is no labeling of GMO food and feed in the USA, the amount consumed is unknown, and no “control group” exists. Thus, without a clear traceability or labeling, no epidemiological survey can be performed.

7.2. Ethical issues
Many critics argue against our refusal to release all the raw data generated in our study. This is a very unusual request when we clearly stated that we plan several other papers out of this data set. Our study was not performed for regulatory purposes. However, due to the social impact and for full scientific understanding of the potential risks associated NK603 GM maize and R, we will release our raw data if the regulatory agencies that have taken industry data into account in their approval of their products also release the data pertinent for environmental and health risk assessments, in particular their longest toxicological tests on mammals, as we have indicated in our correspondence with EFSA. As a first step to this end, we have communicated the raw data underlying the data presented in Figs. 1 and 2 to the French food safety agency (ANSES), and answered their questions on experimental design and results, including analysis of food composition and mycotoxin content, etc.

Most of the criticisms on the topic of ethical conduct relate to animal welfare, some thinking that we overpassed the threshold in size of tumors above which animals should be euthanized, with the purpose of taking shocking photographs. However, it should be recalled that in a GLP environment, animal welfare is of major concern and that we fully respected the threshold in tumor size before euthanasia. Pictures of every animal and organ were taken. We presented those related to the most observed pathologies, including those of a microscopic nature, for illustrative purposes in Fig. 3, with rats representative of each group.

Some critics raised concerns about the role of the funders of this work, and possible conflicts of interest. Of course, the funders neither played a role in the design and conduct of the experiment, and nor in its interpretation. The data remained confidential to the funders. We recall that in the regulatory assessment of GMOs, chemicals and medicines, tests are conducted by the applying companies themselves, often in their own laboratories. As a result, conflicts of interest exist in these cases. These are even not claimed by authors from the company defending the safety of the tested products (Hammond et al., 2012). Our study does not aim to request commercialization of a new product. In contrast, we wanted to estimate the health risk of these products. It is the most detailed test conducted to date that is also independent from biotechnology and pesticide companies. We encourage others to replicate such chronic experiments, with greater statistical power. What is now urgently required is for the burden of proof to be obtained experimentally by studies conducted independent from industry. This was recommended by regulatory agencies in France that have assessed our work, even though their objective is more to regulate products than to review research. GM NK603 and R cannot be regarded as safe to date.

Conflict of Interest
The authors declare that there are no conflicts of interest.

Acknowledgments
We would like to acknowledge again our funders as already stated in our original publication (FPH, CERES, Ministry of Research, CRIIGEN structural help). We warmly thank also fellowships for S.G. (Léa Nature, Nature Vivante), and all supports, constructive and positive comments coming from almost 300 scientists from more than 33 countries from 5 continents (November 2012).

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Yannick Chenet, a French winegrower, died after contracting leukemia, becoming the first farmer to have his illness officially linked to the pesticides he used for years on his crops. He is among 40 or so farmers in France whose illnesses have now been officially linked to their profession and the pesticides they have sprayed on the land. More than a quarter of the roughly 220,000 tons of pesticides used in Europe per year is sprayed onto French soil.

Yannick started working at 14 or 15 years of age and, like many children around the world, has been heavily exposed to pesticides and many other noxious chemicals. In April 2004, he inadvertently breathed in noxious fumes from his agricultural spraying machine without a mask on. Immediately admitted to hospital, he fell into a coma. Since then his illness continues to affect his kidneys and nervous system and he has again fallen into comas on several occasions.

Research by the European Union claims pesticides used on
fruits, vegetables and cereals harms fetuses and young
children. Since pesticides attack the brains of insects, experts
insist they're also "very likely" to damage human brains.

Dramatic deficits in brain function are seen in rural children with long-term exposure to pesticides compared with children not similarly exposed. Contamination has been documented in many studies from populations around the world, with breastmilk containing concentrations of lindane, heptachlor, benzene hexachloride, aldrin and endrin all above limits established by the U.N. Food and Agricultural Organization.

According to pediatrician Philip Landrigan of Mount Sinai Medical Center, we should have "very important concerns about the toxic effects of pesticides on children's nervous systems." Bernard Weiss of the Department of Environmental Medicine at the University of Rochester School of Medicine and Dentistry stated, "It doesn't seem a surprise that you would see an effect, knowing what we know about pesticides and the elevated vulnerability of the developing brain."

According to Dr. Maryse Bouchard, "Pesticides act on a set of brain chemicals closely related to those involved in ADHD."

Children face higher risks from pesticides than adults and need greater protection against these chemicals, particularly in developing countries, according to a joint report published by FAO, the U.N. Environment Programme (UNEP) and the World Health Organization (WHO). Children who were exposed to organophosphate pesticides while still in their mother's womb were more likely to develop attention disorders years later, according to researchers at the University of California, Berkeley's School of Public Health.

Findings published in the journal Environmental Health Perspectives (EHP) examine the influence of prenatal organophosphate exposure on the later development of attention problems. The researchers found that prenatal levels of organophosphate metabolites were significantly linked to attention problems at age five, with the effects apparently stronger among boys. The organophosphate family of chemicals damages the nervous system (which includes the brain), so scientists are particularly concerned about children's exposure because their bodies are still developing. Chlorpyrifos is one of the many insecticides in this chemical family.

Different researchers at Harvard University have also associated greater exposure to organophosphate pesticides in school-aged children with higher rates of attention deficit hyperactivity disorder (ADHD) symptoms.

"These studies provide a growing body of evidence that organophosphate pesticide exposure can impact human neurodevelopment, particularly among children," said the study's principal investigator, Brenda Eskenazi, UC Berkeley professor of epidemiology and of maternal and child health. "We were especially interested in prenatal exposure because that is the period when a baby's nervous system is developing the most."

Reduce and Eliminate Exposure with Organic Food
President Obama's Cancer Panel recommends consumers choose food grown without chemical fertilizers or pesticides, antibiotics and growth hormones to decrease exposure to environmental chemicals that can increase the risk of cancer.

The journal Pediatrics published a study that concludes that children exposed to organophosphate pesticides at levels common among America's children are more likely to develop attention deficit hyperactivity disorder (ADHD), a disorder becoming more and more common in today's children. Researchers at Emory University [1] have found that switching children to an organic diet provides a "dramatic and immediate protective effect" against exposures to two organophosphate pesticides that are commonly used in U.S. agricultural production – malathion and chlorpyrifos. The results were published in the September 2005 issue of the scientific journal Environmental Health Perspectives.

"Immediately after substituting organic food items for the children's normal diets, the concentration of the organophosphorus pesticides found in their bodies decreased substantially to non-detectable levels until the conventional diets were re-introduced," says Dr. Lu, an assistant professor in the department of environmental and occupational health, Rollins School of Public Health, Emory University.

Twenty-three elementary-school-age children participated in a 15-day study that was divided into three parts. First the children ate their usual diet of conventionally-grown food for three days. Then they were switched to organically-grown substitutes for five days. For the final seven days, they were switched back to conventional food. The organic substitutes were mainly fruits, vegetables, juices and grain products (such as wheat) because these foods are often contaminated with organophosphates. Urine samples were collected twice a day for each child. Researchers tested the urine for signs of pesticides.

In the case of two organophosphate insecticides – malathion and chlorpyrifos – the results were startling. Signs of these two chemicals were found in the urine in the first part of the study. Almost immediately after the children switched to an organic diet, these chemicals could not be detected. The chemicals showed up again when the children switched back to their normal diet.

The researchers said, "We were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agriculture."

Danger Warning
A tractor sprays pesticides on a food crop. A new UC Berkeley study finds a linkbetween prenatal exposure to pesticides and attention problems at age 5.

Pesticides are widely used for many purposes, including home, garden, commercial, and agricultural pest control. Thus, the potential for some degree of exposure to these chemicals is great. In general, pesticides can enter the body through the lungs, the mouth, and the skin. Of course, each class of pesticide will differ somewhat in the specific way it is absorbed. Recent studies have shown that young children may be at particularly increased risk of pesticide exposure for several reasons:

Their tendency to explore their environment with their mouths
Their closeness to the ground
Their increased time playing outdoors.

Kids may be exposed to pesticides in the following ways:

In Food:

The diet is clearly an important potential route of pesticides exposure in children and adults.

The small amounts of pesticides present on our food are called pesticide residues. Both adults and children consume these residues regularly to some degree.

Children's diets are relatively higher in fruits and vegetables than adults. Thus, they may be at increased risk of exposure from their diet.

According to the National Research Council, differences in diet between children and adults are responsible for most of the differences in the possible health effects of pesticides.

Children and infants tend to eat fewer types of foods and eat more processed foods than adults (infant formula, baby food, etc.). There is very little current evidence about the amount of pesticide residues in processed foods. However, the limited available evidence shows that processed foods in general may actually have fewer residues than unprocessed foods.

In the Home:

It is estimated that over 90% of U.S. homes use some form of pesticide.

In fact, most toxic pesticide exposure in humans occurs from misuse or accidents in the setting of the home or garden.

Infants may be exposed to pesticides in household dust by skin contact, breathing, and eating of the dust.

One study has found that pesticide residues may remain on toys, pillows, and other surfaces for up to two weeks after the house has been sprayed for bugs.

In Drinking Water:

Since children consume more water than any other substance, the water supply is clearly an important possible route of exposure to environmental chemicals.

Several scientific studies have examined the relative amounts of various pesticides in the drinking water supply in different parts of the country. Except in a few areas where dramatic pesticide contamination has occurred, most studies have concluded that the levels of pesticide in the drinking water supply in the U.S. is extremely low.

Outside the Home:

This category would include school, playground, daycare, and commercial settings.

These settings are probably not as important as the home in terms of pesticide exposure to children. However, exposure is possible in these settings especially if there has been recent pesticide application.

In Agricultural Settings:

Agricultural settings may be a risk factor for pesticide exposure in children, especially when one or both parents are agricultural workers.

Children may be exposed while playing in fields sprayed with agricultural pesticides.

Also, pesticide residues may be tracked into the home by parents who are agricultural workers.

One study looked at specific activities that might increase the chances of exposure to children of agricultural workers. These include, a delay in changing clothing after spraying pesticides, mixing pesticide-contaminated clothing with the family wash, applying pesticides within 50 yards of the well.

It is important to remember that some of the pesticides used in agriculture may still remain on the fruits and vegetables in the supermarket.

After trucking across the high plains for five hours, and casting my eyes over perhaps 100,000 acres or more of winter's still deathly gray industrial farmland, I came face to face with the newly famous Dr. Don M. Huber in the cave-dark meeting room of the Black Horse Inn just outside the American Heartland village of Creighton, Nebraska.

On the morning of March 24, along with about 80 farmers and Extension agents, I listened as Huber discoursed with erudition and eloquence upon industrial farming practices that may be impacting nearly every morsel of food produced on the planet, and that subsequently may also be having staggeringly serious health consequences for plants, animals, and human beings.

Huber is emeritus soil scientist of Purdue University, and a retired U.S. Army Colonel who served as an intelligence analyst, for 41 years, active and reserves. In Nebraska, he stood ramrod straight for three hours with no notes and spoke with an astonishing depth and range of knowledge on crucial, controversial matters of soil science, genetic engineering, and the profound impact of the widely used herbicide glyphosate upon soil and plants, and ultimately upon the health of animals and human beings.

Dressed in a conservative dark suit and tie, Huber set the stage for his presentation by observing that he has been married for 52 years, and has 11 children, 36 grandchildren, and a great-grandchild on the way. He then began his formal talk framed by a PowerPoint slide bearing a Biblical quote: "All flesh is grass." – Isaiah 4:6. With this he emphasized the foundational reality that the biotech grains we eat, as well as the biotech grains eaten by cows, hogs, and chickens, are grown in vast herbicide-treated fields.

For the domineering giants of industrial agriculture – multinational corporations, universities, and governments – Huber's assertions about the impact of glyphosate, and the mounting scientific questions about GMO crops, may be as significant and disrupting as Martin Luther's "heretical" act in 1517. That's when Luther nailed his 95 theses to the door of the Castle Church in Wittenberg, Germany to challenge the systemic problems in the almighty institutions of his era.

Luther disputed the claim that spiritual forgiveness from sins could be legitimately sold for money. Huber and other researchers say they are accumulating evidence that – along with the 2010 report of the U.S. President's Cancer panel which bluntly blames chemicals for the staggering prevalence of cancers – raises profoundly challenging questions about the chemical and genetic-engineering practices of industrial agriculture. The challenge, if it holds up, has implications not just for agricultural institutions, but also for the primary food chain serving the Earth's population.

Not an altogether new controversy, the complex matters of industrial agriculture, genetic engineering and the far-flung use of herbicides has been ominously and exponentially accentuated in the last year by virtue of its ominous context: last summer's epic oil catastrophe in the Gulf of Mexico, the nation-ripping 9.0 earthquake in Japan earlier this month, with its subsequent tsunami and nuclear meltdown which is contaminating the nation's water and food chain, in combination with the statistical reality that on our planet of nearly seven billion people, over a billion human beings – one of every six of us – is hungry.

All of this was brought into prominent public focus – both sharp and fuzzy – in January of this year by the unlikely matter of alfalfa.

Challenges to the Web of Life

The seminar with Dr. Huber, sponsored by Knox County Extension and the Center for Rural Affairs, commenced on a somber note. The moderator announced that Terry Gompert, 66, a veteran Extension educator and respected advocate for sustainable agriculture, and a man who had played a key role in organizing the conference, had just suffered a massive heart attack. A moment of silence followed before Dr. Huber began his presentation. Mr. Gompert died on March 25, the day after the conference he organized.

At the conference, Huber's talk was highly technical, yet he had easy command of voluminous technical detail. For many, it must have sounded like an alien language as he spun out the esoteric terms: zwitterion, desorbtion, translocation, rhizosphere, meristemic, speudomanads, microbiocidae, bradyrhizobium, shikimate, and more.

Huber spoke about a range of key factors involved in plant growth, including sunlight, water, temperature, genetics, and nutrients taken up from the soil. "Any change in any of these factors impacts all the factors," he said. "No one element acts alone, but all are part of a system…When you change one thing," he said, "everything else in the web of life changes in relationship."

That brought him to the subject of glyphosate, the most widely used herbicide, most commonly recognized in the product named Roundup®. Because it is so widely used, Huber said, it is having a profound impact upon mega millions of farm acres around the world. More than 155 million acres of cropland were treated with glyphosate during the 2008 growing season, and even more by now. Subsequently, Huber said, this chemical is having a sweeping impact on the food chain.

http://thecalloftheland.wordpress.com/2011/03/29/latter-day-luther-nails-troubling-thesis-to-gm-farm-food-citadels/

After trucking across the high plains for five hours, and casting my eyes over perhaps 100,000 acres or more of winter’s still deathly gray industrial farmland, I came face to face with the newly famous Dr. Don M. Huber in the cave-dark meeting room of the Black Horse Inn just outside the American Heartland village of Creighton, Nebraska.

On the morning of March 24, along with about 80 farmers and Extension agents, I listened as Huber discoursed with erudition and eloquence upon industrial farming practices that may be impacting nearly every morsel of food produced on the planet, and that subsequently may also be having staggeringly serious health consequences for plants, animals, and human beings.

Huber is emeritus soil scientist of Purdue University, and a retired U.S. Army Colonel who served as an intelligence analyst, for 41 years, active and reserves. In Nebraska, he stood ramrod straight for three hours with no notes and spoke with an astonishing depth and range of knowledge on crucial, controversial matters of soil science, genetic engineering, and the profound impact of the widely used herbicide glyphosate upon soil and plants, and ultimately upon the health of animals and human beings.

Dressed in a conservative dark suit and tie, Huber set the stage for his presentation by observing that he has been married for 52 years, and has 11 children, 36 grandchildren, and a great-grandchild on the way. He then began his formal talk framed by a PowerPoint slide bearing a Biblical quote: “All flesh is grass.” – Isaiah 4:6. With this he emphasized the foundational reality that the biotech grains we eat, as well as the biotech grains eaten by cows, hogs, and chickens, are grown in vast herbicide-treated fields.

Martin Luther nails his theses to the church door.

For the domineering giants of industrial agriculture — multinational corporations, universities, and governments — Huber’s assertions about the impact of glyphosate, and the mounting scientific questions about GMO crops, may be as significant and disrupting as Martin Luther’s “heretical” act in 1517. That’s when Luther nailed his 95 theses to the door of the Castle Church in Wittenberg, Germany to challenge the systemic problems in the almighty institutions of his era.

Luther disputed the claim that spiritual forgiveness from sins could be legitimately sold for money. Huber and other researchers say they are accumulating evidence that — along with the 2010 report of the U.S. President’s Cancer panel which bluntly blames chemicals for the staggering prevalence of cancers — raises profoundly challenging questions about the chemical and genetic-engineering practices of industrial agriculture. The challenge, if it holds up, has implications not just for agricultural institutions, but also for the primary food chain serving the Earth’s population.

Not an altogether new controversy, the complex matters of industrial agriculture, genetic engineering and the far-flung use of herbicides has been ominously and exponentially accentuated in the last year by virtue of its ominous context: last summer’s epic oil catastrophe in the Gulf of Mexico, the nation-ripping 9.0 earthquake in Japan earlier this month, with its subsequent tsunami and nuclear meltdown which is contaminating the nation’s water and food chain, in combination with the statistical reality that on our planet of nearly seven billion people, over a billion human beings — one of every six of us — is hungry.

All of this was brought into prominent public focus — both sharp and fuzzy — in January of this year by the unlikely matter of alfalfa.

Challenges to the Web of Life

The seminar with Dr. Huber, sponsored by Knox County Extension and the Center for Rural Affairs, commenced on a somber note. The moderator announced that Terry Gompert, 66, a veteran Extension educator and respected advocate for sustainable agriculture, and a man who had played a key role in organizing the conference, had just suffered a massive heart attack. A moment of silence followed before Dr. Huber began his presentation. Mr. Gompert died on March 25, the day after the conference.

Dr. Huber discusses food and safety concerns at the Black Horse Inn, Creighton, Nebraska. (Photo by S. McFadden)

At the conference, Huber’s talk was highly technical, yet he had easy command of voluminous detail. For many in the audience, it must have sounded like an alien language as he spun out the esoteric terms: zwitterion, desorbtion, translocation, rhizosphere, meristemic, speudomanads, microbiocidae, bradyrhizobium, shikimate, and more.

Huber spoke about a range of key factors involved in plant growth, including sunlight, water, temperature, genetics, and nutrients taken up from the soil. “Any change in any of these factors impacts all the factors,” he said. “No one element acts alone, but all are part of a system.”

“When you change one thing,” he said, “everything else in the web of life changes in relationship.”

That brought him to the subject of glyphosate, the most widely used herbicide around the world, and a chemical most commonly recognized in the product named Roundup®. Because it is so widely used, Huber said, it is having a profound impact upon mega millions of farm acres around the world. More than 155 million acres of cropland were treated with glyphosate during the 2008 growing season, and even more by now. Subsequently, Huber said, this chemical is having a sweeping impact on the food chain.

He asserted that glyphosate compromises plant defense mechanisms and thereby increases their susceptibility to disease. He said that it reduces the availability and uptake of essential nutrients, and that it increases the virulence of pathogens that attack plants. Ultimately, Huber said, all of these factors reduce crop vigor and yield (Yield Drag).

Most dramatically, Huber reported on what he described as a newly discovered pathogen. While the pathogen is not new to the environment, Huber said, it is new to science. This pathogen apparently increases in soil treated with glyphosate, he said, and is then taken up by plants, later transmitted to animals via their feed, and onward to human beings by the plants and meat they consume. The pathogen is extraordinarily small. It can be observed only via an electron microscope operating at 38,000 power of magnification. The pathogen has yet to be phenotyped (descrubed) or named, though that work is almost complete, Huber said. He specified that all the research and data would be published in a matter of weeks.

Huber warned that ignoring these emerging realities may have dire consequences for agriculture such as rendering soils infertile, crops non-productive, and plants less nutritious. He said it could also, and apparently already is, compromising the health and well-being of animals and humans.

The Stratosphere of Controversy

Alfalafa

What propelled Huber, glyphosate and biotech crops into the stratosphere of public attention earlier this year was a pending decision on alfalfa (hay) by the US Department of Agriculture (USDA). The “queen of forages,” alfalfa is the principal feedstock for the dairy industry. The USDA was being asked to approve unrestricted use of genetically engineered alfalfa seeds, which could result in as many as 20 million more acres of land being sprayed with up to 23 million more pounds of toxic herbicides each year.

Because alfalfa is pollinated by bees that fly and cross-pollinate between fields many miles apart, the biotech crop will inevitably contaminate natural and organic alfalfa varieties.

Dr. Huber wrote a letter to USDA Secretary Tom Vilsack asking for a delay in making the decision, and for the resources to do further research. In his letter, Huber raised questions about the safety of glyphosate. Huber’s letter also warned of the new pathogen, apparently related to the use of glyphosate, which appears to significantly impact the health of plants, animals, and probably human beings. He said laboratory tests have confirmed the presence of the organism in pigs, cattle and other livestock fed these crops, and that they have experienced sterility, spontaneous abortions, and infertility.

“I believe the threat we are facing from this pathogen is unique and of a high-risk status,” Huber wrote. “In layman’s terms, it should be treated as an emergency.” Vilsack set Huber’s letter aside for later consideration, and on January 27 he authorized the unrestricted commercial cultivation of genetically modified alfalfa. Immediately thereafter, the Center for Food Safety and Earthjustice filed a lawsuit against the USDA, charging that the agency’s approval of genetically engineered alfalfa was unlawful.

While Huber’s letter of warning was not intended for public consumption, it was leaked and immediately went viral on the Internet. In a matter of days Huber became a lightning rod, attracting intense attention from both the scientific community, and the general public, which is understandably concerned about the genetically engineered food it has never wanted and — since GM food is unlabeled — never been able to identify. The prospect of a new and virulent pathogen sweeping through the food chain was profoundly unsettling

Meanwhile, researchers were deeply upset that they were not first notified by Huber of the new pathogen — as is customary — before the matter became public knowledge. They felt they had been blindsided. Huber says that his letter to USDA Secretary Vilsack was leaked, and thus its publication was not his doing.

Huber became the focus of tremendous pushback. His message of urgent concern and the need for delay until more research was completed was unwelcome in many corporate and university citadels, and was deemed heresy by some vested in the multi-billion dollar industry of GMO crops.

The biggest beef researchers have with Huber — who is well known in his field as a member of the American Phytopathological Society and as part of the USDA National Plant Disease Recovery System – is that he has not yet made data available for scientific scrutiny. Many researchers, including some at Purdue, say Huber’s data and hypotheses, when studied, are not likely to hold up to peer review, and that in general his allegations are exaggerated.

When contacted for comment on Huber’s concerns, Monsanto, maker of Roundup ® (glyphosate) and producer of Roundup Ready® seeds, sent a link to a host of professional criticisms of Huber’s work as well as to their official corporate statement: “Independent field studies and lab tests by multiple U.S. universities and by Monsanto prior to, and in response to, these allegations,” the statement reads in part, “do not corroborate his claims.”

Consequences

Glyphosate is a particularly strong broad-spectrum toxin with the power to kill many kinds of plants that have been designated as weeds. As a chelator, or binder, glyphosate changes the physiology and thereby makes plants susceptible to plant pathogens. Roundup Ready® plants are tolerant of glyphosate because technology inserts a new gene. While the RR plants do not die after the toxic herbicide is sprayed over farm fields, the plants do suffer a reduced efficiency in some crucial regards, according to some researchers, changing the nutrient balance in plants. When that change occurs, all subsequent relationships — including the diet of livestock and humans — is changed.

The extensive use of glyphosate and the rapid, widespread use of GM crops resistant to it, have intensified the deficiencies of essential micronutrients, and some macronutrients. This is leading, Huber argues, to weaker and more disease-prone plants, animals, and people. In his presentation, he offered a list of about 40 diseases that, he says, tend to increase in farm fields where glyphosate is used. Those plant diseases include Sun Scald, Leaf Chlorosis, Tomato Wilt, Apple Canker, Barley Root Rot, Bean Root Rot, Wheat Take All, Wheat Head Scab, Wheat Glume, and Grape Black Goo.

Subsequently, he hypothesized, the decrease in nutrients and the increase in the new pathogen in food lead to empty calories, which likely explains increases in allergies, and chronic diseases such as Parkinson’s and Alzheimer’s.

The list of diseases that Huber suspects may be affected by glyphosate and the new pathogen is, he said, increasing as growers and pathologists recognize the cause-effect relationship:
o Increase in cancers of the liver, thyroid, kidneys, tests, and skin melanomas.
o Increase in allergic reactions in general, and an increase of up to 50% in soybean allergies in the USA in the last three years.
o Increase on an epidemic-scale in the incidence of Alzheimer’s disease, perhaps as much as 9,000% over the last 30 years. Specialists say they expect the incidence of Alzhiemer’s to spike far higher over the next four years.
o Increase in the incidence of Parkinson’s disease, which researchers say, is being provoked in part by the factor of chemical pesticides.

What Has Changed?

As if it were a mantra, during his three-hour talk Dr. Huber often raised a rhetorical question: What has changed? If all of these troubling conditions are on the rise for plants, animals and humans in recent years, then what has changed to bring it about?

The most apparent change, he answered, is that glyphosate and genetically engineered plants are out widely in the world. According to Huber, farm animals, including cattle, pigs, horses and chickens that are fed GM crops grown on glyphosate-treated fields have shown an alarming increase in sterility, spontaneous abortions, and stillbirths. By way of anecdotal evidence, he said he gets two to three communications a week from farmers and veterinarians about this troubling phenomenon. “We can no longer ignore the increase in livestock infertility, stillbirths, and spontaneous abortions over the last three to four years,” he said.

GMO feed grown on glyphosate treated fields tends to irritate the stomach of livestock, such that many farm animals are fed daily rations of bicarbonate of soda in an attempt to sooth their stomach lining. Huber showed a slide bearing images of dissected hog stomachs; one from a hog fed GMO feed and the other conventional feed. The GMO hog had a rudely inflamed mass of stomach and intestinal tissue.

A handout from Dr. Huber that was made available at the Nebraska seminar cited 117 peer-reviewed scientific studies that raise serious questions about the impact of glyphosate. These studies have reached critical mass, Huber said, and they could no longer be discounted or ignored. Yet, there are also a substantial number of studies stating that glyphosate and GMO crops are safe and ought to be the cause of no concern.

What Is this Stuff?

Glyphosate is the most used herbicide in the USA. Every year, 5 to 8 million pounds are used on lawns and yards, and another 85 to 90 million pounds are used in agriculture. It is a broad-spectrum systemic herbicide used to kill weeds, especially weeds known to compete with crops grown widely across the Midwest. Initially sold by Monsanto in the 1970s under the trade name Roundup®, its U.S. patent expired in 2000, and thus glyphosate is now marketed in the U.S. and worldwide in different solution strengths under various trade names. Because these products may contain other ingredients, they may have different effects.

Glyphosate inhibits a key enzyme that is involved in the synthesis of amino acids in the plant. Many fungi and bacteria also have this same pathway. Aromatic amino acids in plants are the building blocks for many of their defense compounds.

Some crops have been genetically engineered to be resistant to it (i.e., Roundup Ready®). Such crops allow farmers to use glyphosate as a post-emergence herbicide against both broadleaf and cereal weeds, but the development of similar resistance in some weed species is emerging as a costly problem.

Glyphosate kills plants by interfering with the synthesis of the amino acids which are used by the plant as building blocks in for growth and for defense against disease and insects. Plants that are genetically engineered to tolerate the glyphosate contain a gene that provides an alternative pathway for nutrients that is not blocked by the glyphosate herbicide. But this duplicate pathway requires energy from the plant that could be used for yield, thus many GMO crops experience Yield Drag – a reduction in yield.

Huber had several recommendations for growers, especially a much more judicious use of glyphosate, as small a dose as possible. He said farmers also need to provide supplementary nutrients to counteract its effects and thereby to restore plant resistance to toxins and diseases.

He mentioned that there are other herbicide products on the market, but they are more specific to particular weeds and degrade more swiftly, whereas glyphosate is broad spectrum and thus kills many types of weeds, and also endures for a longer span of time in the soil and plants.

“Slow down,” Huber said. “It takes time to restore soil biota if a field has been treated with glyphosate. We have 30 years of accumulated damage, so it may take some time to remediate all of this.”

“There are a lot of serious questions about the impacts of glyphosate that we need answers for in order to continue using this technology,” he continued. “I don’t believe we can ignore these questions any more if we want to ensure a safe, sustainable food supply and abundant crop production.”

Primary Realities

In his presentation at the Black Horse Inn Huber was convincing in his demeanor, encyclopedic in his knowledge, precise and eloquent in his delivery. Late in the morning as he spoke of the fertility and yield issues, the complications for farmers, and the increased prevalence of disease, his eyes momentarily welled up with tears. Then as he concluded his talk he received a standing ovation from the assembly of about 80 Nebraska farmers and Extension staff.

Still, Huber’s personal integrity and his positive reception, at least at the Black Horse Inn, may be of small consequence in the face of a tsunami of criticism arising from the citadels of corporations and universities. None of that will be resolved until the data he and others have gathered passes peer review.

The primary realities in the GM and glyphosate debates are corporate avidity, scientific uncertainty, and overwhelming public disapproval. Many peer-reviewed articles suggest that biotech crops and foods are harmless; many suggest otherwise. The jury is still out. However, as Huber was arguing, the number of published articles showing that glyphosate and the biotech crops grown in its chemical soup cause harm to livestock is rising rapidly.

Studies showing the public has little taste for genetically engineered foods, and especially not for unlabeled and thus unidentifiable genetically engineered foods, remain convincing. According to reports from Food & Water Watch, 90% of Americans want GM foods labeled, and 91% say the FDA should not allow genetically modified pigs, chicken and cattle into the food supply. To date, the main parties keen about promoting unlabeled GM foods, and their herbicidal aides, are multinational corporations and their investors.

“Before we jump off the cliff,” Huber said, “we need to have more research done. It takes a lot to reverse the problems.” Many observers would argue, convincingly, that we have already jumped off the cliff.

Huber sought just $25,000 to do sequencing to establish the phenotype of the newly identified pathogen, and then to name it. But no government, university, or corporation would provide that relatively paltry amount of money. Finally, a private individual came forward and made the money available. Then the lab that was originally keen to do the phenotyping backed out. The issue had become a hot potato and they did not want the controversy. Still, Huber persevered, and he said they should have the phenotype established, and then be able to name the pathogen, in a matter of weeks.

“Let me emphasize that all of this is not a calamity,” Huber said, surprisingly, near the end of his talk. “Agriculture is the most critical infrastructure for any society. American agriculture has undergone a revolution and it will continue to progress.

“Still, I saw no reason to rush into the critical alfalfa decision and to thereby cause so many more acres to be treated with glyphosate,” he said. “Why take a chance until we get the answers? Research needs to be done…There is lots of new data that needs to be considered, lots of new studies that cannot be ignored.”

http://www.organicconsumers.org/articles/article_22875.cfm

Monsanto is Poisoning Us All: Famous Scientist, Don Huber Exposes Hazards of Monsanto's Roundup Herbicide
Latter-Day Luther Nails Troubling Thesis to GM Farm & Food Citadels
By Steven McFadden
Latter-Day Luther Nails Troubling Thesis to GM Farm & Food Citadels, March 29, 2011
Straight to the Source

For related articles and more information, please visit OCA's Genetic Engineering page, and our Millions Against Monsanto page.

AG CHEMICAL AND CROP NUTRIENT INTERACTIONS – CURRENT UPDATE

Don M. Huber, Emeritus Professor, Purdue University

ABSTRACT: Micronutrients are regulators, inhibitors and activators of physiological processes, and plants provide a primary dietary source of these elements for animals and people. Micronutrient deficiency symptoms are often indistinct (“hidden hunger”) and commonly ascribed to other causes such as drought, extreme temperatures, soil pH, etc. The sporadic nature of distinct visual symptoms, except under severe deficiency conditions, has resulted in a reluctance of many producers to remediate micronutrient deficiency. Lost yield, reduced quality, and increased disease are the unfortunate consequences of untreated micronutrient deficiency. The shift to less tillage, herbicide resistant crops and extensive application of glyphosate has significantly changed nutrient availability and plant efficiency for a number of essential plant nutrients. Some of these changes are through direct toxicity of glyphosate while others are more indirect through changes in soil organisms important for nutrient access, availability, or plant uptake. Compensation for these effects on nutrition can maintain optimum crop production efficiency, maximize yield, improve disease resistance, increase nutritional value, and insure food and feed safety.

INTRODUCTION

Thirty+ years ago, U.S. agriculture started a conversion to a monochemical herbicide program focused around glyphosate (Roundup®). The near simultaneous shift from conventional tillage to no-till or minimum tillage stimulated this conversion and the introduction of genetically modified crops tolerant to glyphosate. The introduction of genetically modified (Roundup Ready®) crops has greatly increased the volume and scope of glyphosate usage, and conversion of major segments of crop production to a monochemical herbicide strategy. Interactions of glyphosate with plant nutrition and increased disease have been previously over looked, but become more obvious each year as glyphosate residual effects become more apparent

The extensive use of glyphosate, and the rapid adoption of genetically modified glyphosate-tolerant crops such as soybean, corn, cotton, canola, sugar beets, and alfalfa; with their greatly increased application of glyphosate for simplified weed control, have intensified deficiencies of numerous essential micronutrients and some macronutrients. Additive nutrient inefficiency of the Roundup Ready® (RR) gene and glyphosate herbicide increase the need for micronutrient remediation, and established soil and tissue levels for nutrients considered sufficient for specific crop production may be inadequate indicators in a less nutrient efficient glyphosate weed management program.

Understanding glyphosate’s mode of action and impact of the RR gene, indicate strategies to offset negative impacts of this monochemical system on plant nutrition and its predisposition to disease. A basic consideration in this regard should be a much more judicious use of glyphosate. Glyphosate damage is often attributed to other causes such as drought, cool soils, deep seeding, high temperatures, crop residues, water fluctuations, etc. Table X provides some of the common symptoms of drift and residual glyphosate damage to crops. This paper is an update of information on nutrient and disease interactions affected by glyphosate and the RR gene(s), and includes recently published research in the European Journal of Agronomy and other international scientific publications.

UNDERSTANDING GLYPHOSATE

Glyphosate (N-(phosphomonomethyl)glycine) is a strong metal chelator and was first patented as such by Stauffer Chemical Co. in 1964 (U.S. Patent No. 3,160,632). Metal chelates are used extensively in agriculture to increase solubility or uptake of essential micronutrients that are essential for plant physiological processes. They are also used as herbicides and other biocides (nitrification inhibitors, fungicides, plant growth regulators, etc.) where they immobilize specific metal co-factors (Cu, Fe, Mn, Ni, Zn) essential for enzyme activity. In contrast to some compounds that chelate with a single or few metal species, glyphosate is a broadspectrum chelator with both macro and micronutrients (Ca, Mg, Cu, Fe, Mn, Ni, Zn). It is this strong, broadspectrum chelating ability that also makes glyphosate a broad-spectrum herbicide and a potent antimicrobial agent since the function of numerous essential enzymes is affected (Ganson and Jensen, 1988).

Primary emphasis in understanding glyphosate’s herbicidal activity has been on inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) at the start of the Shikimate physiological pathway for secondary metabolism. This enzyme requires reduced FMN as a co-factor (catalyst) whose reduction requires manganese (Mn). Thus, by immobilizing Mn by chelation, glyphosate denies the availability of reduced FMN for the EPSPS enzyme. It also can affect up to 25 other plant enzymes that require Mn as a co-factor and numerous other enzymes in both primary and secondary metabolism that require other metal co-factors (Co, Cu, Fe, Mg, Ni, Zn). Several of these enzymes also function with Mn in the Shikimate pathway that is responsible for plant responses to stress and defense against pathogens (amino acids, hormones, lignin, phytoalexins, flavenoids, phenols, etc.). By inhibiting enzymes in the Shikimate pathway, a plant becomes highly susceptible to various ubiquitous soilborne pathogens (Fusarium, Pythium, Phytophthora, Rhizoctonia, etc.). It is this pathogenic activity that actually kills the plant as “the herbicidal mode of action” (Johal and Rahe, 1984; Levesque and Rahe, 1992, Johal and Huber, 2009). If glyphosate is not translocated to the roots because of stem boring insects or other disruption of the vascular system, aerial parts of the plant may be stunted, but the plant is not killed.

Recognizing that glyphosate is a strong chelator to immobilize essential plant micronutrients provides an understanding for the various non-herbicidal and herbicidal effects of glyphosate. Glyphosate is a phloem-mobile, systemic chemical in plants that accumulates in meristematic tissues (root, shoot tip, reproductive, legume nodules) and is released into the rhizosphere through root exudation (from RR as well as non-RR plants) or mineralization of treated plant residues. Degradation of glyphosate in most soils is slow or non-existent since it is not ‘biodegradable’ and is primarily by microbial co-metabolism when it does occur. Although glyphosate can be rapidly immobilized in soil (also spray tank mixtures, and plants) through chelation with various cat-ions (Ca, Mg, Cu, Fe, Mn, Ni, Zn), it is not readily degraded and can accumulate for years (in both soils and perennial plants). Very limited degradation may be a “safety” feature with glyphosate since most degradation products are toxic to normal as well as RR plants. Phosphorus fertilizers can desorb accumulated glyphosate that is immobilized in soil to damage and reduce the physiological efficiency of subsequent crops. Some of the observed affects of glyphosate are presented in table 1.

TABLE 1. Some things we know about glyphosate that influence plant nutrition and disease.

1. Glyphosate is a strong metal chelator (for Ca, Co, Cu, Fe, Mn, Mg, Ni, Zn) – in the spray tank, in soil and in plants.

2. It is rapidly absorbed by roots, stems, and leaves, and moves systemically throughout the plant (normal and RR).

3. Accumulates in meristematic tissues (root, shoot, legume nodules, and reproductive sites) of normal and RR plants.

4. Inhibits EPSPS in the Shikimate metabolic pathway and many other plant essential enzymes.

5. Increases susceptibility to drought and disease.

6. Non-specific herbicidal activity (broad-spectrum weed control).

7. Some of the applied glyphosate is exuded from roots into soil.

8. Immobilized in soil by chelating with soil cat-ions (Ca, Co, Cu, Fe, Mg, Mn, Ni, Zn).

9. Persists and accumulates in soil and plants for extended periods (years) – it is not ‘biodegradable,’ but is rapidly immobilized by chelation generally.

10. Desorbed from soil particles by phosphorus and is available for root uptake by all plants.

11. Toxic to soil organisms that facilitate nutrient access, availability, or absorption of nutrients.

12. Inhibits the uptake and translocation of Fe, Mn, and Zn at very low, non-herbicidal rates.

13. Stimulates soilborne pathogenic and other soil microbes to reduce nutrient availability.

14. Reduces secondary cell wall formation and lignin in RR and non-RR plants.

15. Inhibits nitrogen fixation by chelating Ni for ureide synthesis and is toxic to Rhizoiaceae.

16. Reduces physiological availability and concentration of Ca, Cu, Fe, K, Mg, Mn, and Zn in plant tissues and seed.

17. Residual soil activity can damage plants through root uptake.

18. Increases mycotoxins in stems, straw, grain, and fruit.

19. Reduces photosynthesis (CO2 fixation).

20. Causes fruit (bud) drop and other hormonal effects.

21. Accumulates in food and feed products to enter the food chain as an item of food safety.

UNDERSTANDING THE ROUNDUP READY® GENE

Plants genetically engineered for glyphosate-tolerance contain the Roundup Ready® gene(s) that provide an alternate EPSPS pathway (EPSPS-II) that is not blocked by glyphosate. The purpose of these gene inserts is to provide herbicidal selectivity so glyphosate can be applied directly to these plants rather than only for preplant applications. As an additional physiological mechanism, activity of this duplicate pathway requires energy from the plant that could be used for yield. The RR genes are ‘silent’ in meristematic tissues where glyphosate accumulates so that these rapidly metabolizing tissues are not provided an active alternative EPSPS pathway to counter the physiological effects of glyphosate’s inhibition of EPSPS. Meristematic tissues also are areas of high physiologic activity requiring a higher availability of the essential micronutrients needed for cell division and growth that glyphosate immobilizes by chelation.

Residual glyphosate in RR plant tissues can immobilize Fe, Mn, Zn or other nutrients applied as foliar amendments for 8-35 days after it has been applied. This reduces the availability of micronutrients required for photosynthesis, disease resistance, and other critical physiological functions.The presence of the RR gene(s) reduces nutrient uptake and physiological efficiency and may account for some of the ‘yield drag’ reported for RR crops when compared with the ‘normal’ isolines from which they were derived. Reduced physiological efficiency from the RR gene is also reflected in reduced water use efficiency (WUE) and increased drought stress (table 2).

It should be recognized that:

1. There is nothing in the glyphosate-tolerant plant that operates on the glyphosate applied to the plant.

2. All the technology does is insert an alternative enzyme (EPSPS-II) that is not blocked by glyphosate in mature tissue.

3. When glyphosate enters the plant, it is not selective; it chelates with a host of elements influencing nutrient availability, disease resistance, and the plant’s other physiological functions.

4. Glyphosate is present for the life of the plant or until it is exuded into soil or groundwater through the roots. Degradation products are toxic to RR and non-RR plants.

TABLE 2. Some things we know about the glyphosate-tolerance (RR) gene(s).

1. Provides selective herbicidal activity for glyphosate.

2. Inserts an alternative EPSPS pathway that is not sensitive to glyphosate action in mature tissue.

3. Reduces the plant’s physiological efficiency of Fe, Mn, Ni, Zn, etc.

4. Inactive (silent) in meristematic tissues (root and shoot tips, legume root nodules, and reproductive tissues).

5. Reduces nutrient uptake and efficiency.

6. Increases drought stress.

7. Reduces N-fixation.

8. Lowers seed nutrient content.

9. Transferred in pollen to plants, and from degrading plant tissues to microbes.

10. Generally causes a yield ‘drag’ compared with near-isogenic normal plants from which it was derived.

11. Has greatly increased the application of glyphosate.

12. Permanent in plants once it is introduced.

INTERACTIONS OF GLYPHOSATE WITH PLANT NUTRITION

Glyphosate can affect nutrient efficiency in the plant by chelating essential nutrient co-factors after application since there is many times more ‘free’ glyphosate in the plant than all of the unbound cat-ions. Chelation of Mn and other micronutrients after application of glyphosate is frequently observed as a ‘flashing’ or yellowing that persists until the plant can ‘resupply’ the immobilized nutrients. The duration of ‘flashing’ is correlated with the availability of micronutrients in soil. Symptom remission indicates a resumption of physiological processes, but is not an indicator of plant nutrient sufficiency since micronutrient deficiencies are commonly referred to as ‘hidden hunger.’ As a strong nutrient chelator, glyphosate can reduce physiological efficiency by immobilizing elements required as components, co-factors or regulators of physiological functions at very low rates. Thus, plant uptake and or translocation of Fe, Mn and Zn are drastically reduced (up to 80 %) by commonly observed ‘drift’ rates of glyphosate (<1/40 the herbicidal rate). This is reflected in reduced physiological efficiency, lower mineral nutrient levels in vegetative and reproductive tissues, and increased susceptibility to disease. Microbial and plant production of siderophores and ferric reductase in root exudates under nutrient stress are inhibited by glyphosate to exacerbate plant nutrient stress common in low-available micronutrient soils.

Glyphosate is not readily degraded in soil and can probably accumulate for many years chelated with soil cat-ions. Degradation products of glyphosate are as damaging to RR crops as to non-RR crops. Persistence and accumulation of glyphosate in perennial plants, soil, and root meristems, can significantly reduce root growth and the development of nutrient absorptive tissue of RR as well as non-RR plants to further impair nutrient uptake and efficiency. Impaired root uptake not only reduces the availability of specific nutrients, but also affects the natural ability of plants to compensate for low levels of many other nutrients. Glyphosate also reduces nutrient uptake from soil indirectly through its toxicity to many soil microorganisms responsible for increasing the availability and access to nutrients through mineralization, reduction, symbiosis, etc.

Degradation of plant tissues through growth, necrosis, or mineralization of residues can release accumulated glyphosate from meristematic tissues in toxic concentrations to plants. The most damaging time to plant wheat in ryegrass ‘burned down’ by glyphosate is two weeks after glyphosate application to correspond with the release of accumulated glyphosate from decomposing meristematic tissues. This is contrasted with the need to delay seeding of winter wheat for 2-3 weeks after a regular weed burn-down’ to permit time for immobilization of glyphosate from root exudates and direct application through chelation with soil cat-ions. The Roundup® label for Israel lists recommended waiting times before planting a susceptible crop on that soil.

One of the benefits of crop rotation is an increased availability of nutrients for a subsequent crop in the rotation. The high level of available Mn (130 ppm) after a normal corn crop is not observed after glyphosate-treated RR corn. The lower nutrient availability after specific RR crop sequences may need to be compensated for through micronutrient application in order to optimize yield and reduce disease in a subsequent crop.

THE INFLUENCE OF GLYPHOSATE ON SOIL ORGANISMS IMPORTANT FOR ACCESS, MINERALIZATION, SOLUBILIZATION, AND FIXATION OF ESSENTIAL PLANT NUTRIENTS

Glyphosate is a potent microbiocide and is toxic to earthworms, mycorrhizae (P & Zn uptake), reducing microbes that convert insoluble soil oxides to plant available forms (Mn and Fe, Pseudomonads, Bacillus, etc.), nitrogen-fixing organisms (Bradyrhizobium, Rhizobium), and organisms involved in the ‘natural,’ biological control of soilborne diseases that reduce root uptake of nutrients. Although glyphosate contact with these organisms is limited by rapid chelation-immobilization when applied on fallow soil; glyphosate in root exudates, or from decaying weed tissues or RR plants, contacts these organisms in their most active ecological habitat throughout the rhizosphere. It is not uncommon to see Cu, Fe, Mg, Mn, Ni, and Zn deficiencies intensify and show in soils that were once considered fully sufficient for these nutrients. Increasing the supply and availability of Co, Cu, Fe, Mg, Mn, Ni, and Zn have reduced some of the deleterious effects of glyphosate on these organisms and increased crop yields.

In contrast to microbial toxicity, glyphosate in soil and root exudates stimulates oxidative soil microbes that reduce nutrient availability by decreasing their solubility for plant uptake, immobilize nutrients such as K in microbial sinks to deny availability for plants, and deny access to soil nutrients through pathogenic activity. Plant pathogens stimulated by glyphosate (table 3) include ubiquitous bacterial and fungal root, crown, and stalk rotting fungi; vascular colonizing organisms that disrupt nutrient transport to cause wilt and die-back; and root nibblers that impair access or uptake of soil nutrients.

TABLE 3. Some plant pathogens stimulated by glyphosate.

Botryospheara dothidea Gaeumannomyces graminis

Corynespora cassicola Magnaporthe grisea

Fusarium species Marasmius spp.

F. avenaceum Monosporascus cannonbalus

F. graminearum Myrothecium verucaria

F. oxysporum f.sp. cubense Phaeomoniella chlamydospora

F. oxysporum f.sp. (canola) Phytophthora spp.

F. oxysporum f.sp. glycines Pythium spp.

F. oxysporum f.sp. vasinfectum Rhizoctonia solani

F. solani f.sp. glycines Septoria nodorum

F. solani f.sp. phaseoli Thielaviopsis bassicola

F. solani f.sp. pisi Xylella fastidiosa

Clavibacter michiganensis subsp. nebraskensis (Goss’ wilt)

HERBICIDAL MODE OF ACTION OF GLYPHOSATE

As a strong metal micronutrient chelator, glyphosate inhibits activity of EPSPS and other enzymes in the Shikimate metabolic pathway responsible for plant resistance to various pathogens. Plant death is through greatly increased plant susceptibility of non-RR plants to common soilborne fungi such as Fusarium, Rhizoctonia, Pythium, Phytophthora, etc. that are also stimulated by glyphosate (Johal and Rahe, 1984; Levesque and Rahe, 1992; Johal and Huber, 2009). It is very difficult to kill a plant in sterile soil by merely shutting down the Shikimate pathway (secondary metabolism) unless soilborne pathogens are also present. It is the increased susceptibility to soilborne pathogens, and increased virulence of the pathogens, that actually kills the plants after applying glyphosate. Disease resistance in plants is manifest through various active and passive physiological mechanisms requiring micronutrients. Those metabolic pathways producing secondary anti-microbial compounds (phytoalexins, flavenoids, etc.), pathogen inhibiting amino acids and peptides, hormones involved in cicatrisation (walling off pathogens), callusing, and disease escape mechanisms can all be compromised by glyphosate chelation of micronutrient co-factors critical for enzyme function. Genetic modification of plants for glyphosate tolerance partially restores Shikimate pathway function to provide a selective herbicidal effect.

INTERACTIONS OF GLYPHOSATE WITH PLANT DISEASE

Micronutrients are the regulators, activators, and inhibitors of plant defense mechanisms that provide resistance to stress and disease. Chelation of these nutrients by glyphosate compromises plant defenses and increases pathogenesis to increase the severity of many abiotic (bark cracking, nutrient deficiencies) as well as infectious diseases of both RR and non-RR plants in the crop production system (table 4). Many of these diseases are referred to as ‘emerging’ or reemerging’ diseases because they rarely caused economic losses in the past, or were effectively controlled through management practices.

Non-infectious (Abiotic) Diseases: Research at Ohio State University has shown that bark cracking, sunscald, and winter-kill of trees and perennial ornamentals is caused by glyphosate used for under-story weed control, and that glyphosate can accumulate for 8-10 years in perennial plants. This accumulation of glyphosate can be from the inadvertent uptake of glyphosate from contact with bark (drift) or by root uptake from glyphosate in weed root exudates in soil. Severe glyphosate damage to trees adjacent to stumps of cut trees treated with glyphosate (to prevent sprouting in an effort to eradicate citrus greening or CVC) can occur through root translocation and exudation several years after tree removal.

Infectious Diseases: Increased severity of the take-all root and crown rot of cereals (Gaeumannomyces graminis) after prior glyphosate usage has been observed for over 20 years and take-all is now a ‘reemerging’ disease in many wheat producing areas of the world where glyphosate is used for weed control prior to cereal planting. A related disease of cereals, and the cause of rice blast (Magnaporthe grisea), is becoming very severe in Brazil and is especially severe when wheat follows a RR crop in the rotation. Like take-all and Fusarium root rot, this soilborne pathogen also infects wheat and barley roots, and is a concern for U.S. cereal production.

Fusarium species causing head scab are common root and crown rot pathogens of cereals everywhere; however, Fusarium head scab (FHB) has generally been a serious disease of wheat and barley only in warm temperate regions of the U.S. With the extensive use of glyphosate, it is now of epidemic proportions and prevalent throughout most of the cereal producing areas of North America. Canadian research has shown that the application of glyphosate one or more times in the three years previous to planting wheat was the most important agronomic factor associated with high FHB in wheat, with a 75 % increase in FHB for all crops and a 122 % increase for crops under minimum-till where more glyphosate is used. The most severe FHB occurs where a RR crop precedes wheat in the rotation for the same reason. Glyphosate altered plant physiology (carbon and nitrogen metabolism) increasing susceptibility of wheat and barley to FHB and increased toxin production, is also associated with a transient tolerance of wheat and soybeans to rust diseases.

The increased FHB with glyphosate results in a dramatic increase in tricothecene (deoxynivalenol, nivalenol, ‘vomitoxins’) and estrogenic (zaeralenone) mycotoxins in grain; however, the high concentrations of mycotoxin in grain are not always associated with Fusarium infection of kernels. Quite often overlooked is the increase in root and crown rot by FHB Fusaria with glyphosate and the production of mycotoxins in root and crown tissues with subsequent translocation to stems, chaff and grain. Caution has been expressed in using straw and chaff as bedding for pigs or roughage for cattle because of mycotoxin levels that far exceeded clinically significant levels for infertility and toxicity. This also poses a health and safety concern for grain entering the food chain for humans. The list of diseases affected by glyphosate (see reference No. 18) is increasing as growers and pathologists recognize the cause-effect relationship.

SPECIAL NUTRIENT CONSIDERATIONS IN A GLYPHOSATE-DOMINANT WEED MANAGEMENT ECOLOGICAL SYSTEM

There are two things that should be understood in order to remediate nutrient deficiencies in a glyphosate usage program: 1) the effects of glyphosate on nutrient availability and function and 2) the effect of the RR gene on nutrient efficiency. With this understanding, there are four objectives for fertilization in a glyphosate environment – all of which indicate a more judicious use of glyphosate as part of the remediation process. These four objectives are to:

1. Provide adequate nutrient availability for full functional sufficiency to compensate for glyphosate and RR reduced availability or physiological efficiency of micronutrients (esp. Mn and Zn but also Cu, Fe, Ni).

2. Detoxify residual glyphosate in meristematic and other tissues, in root exudates, and in soil by adding appropriate elements for chelation with the residual glyphosate.

3. Restore soil microbial activity to enhance nutrient availability, supply, and balance that are inhibited by residual glyphosate in soil and glyphosate in root exudates.

4. Increase plant resistance to root infecting and reemerging diseases through physiological plant defense mechanisms dependent on the Shikimate, amino acid, and other pathways that are compromised by micronutrient inefficiency in a glyphosate environment.

Meeting Nutrient Sufficiency: Extensive research has shown that increased levels and availability of micronutrients such as Mn, Zn, Cu, Fe, Ni, etc can compensate for reduced nutrient efficiency and the inefficiency of RR crops. This need may not be manifest in high fertility or nutrient toxic soils for a few years after moving to a predominantly monochemical strategy. The timing for correcting micronutrient deficiencies is generally more critical for cereal plants (barley, corn, wheat) than for legumes in order to prevent irreversible yield and/or quality loss. Nutrient sufficiency levels from soil and tissue analysis that are considered adequate for non-GM crops may need to be increased for RR crops to be at full physiological sufficiency. Since residual ‘free’ glyphosate in RR plant tissues can immobilize most regular sources of foliar-applied micronutrients for 8-15 days, and thereby reduce the future availability of these materials, it may be best to apply some micronutrients 1-2 weeks after glyphosate is applied to RR crops.

The expense of an additional trip across the field for foliar application frequently deters micronutrient fertilization for optimum crop yield and quality. There are newly available micronutrient formulations (nutrient phosphites) that maintain plant availability without impacting herbicidal activity of the glyphosate in a tank-mix, and plants have responded well from these micronutrient-glyphosate mixes. Simultaneous application of some micronutrients with glyphosate might provide an efficient means to overcome deficiencies in low fertility soils, as well as mitigate the reduced physiological efficiency inherent with the glyphosate-tolerant gene and glyphosate immobilization of essential nutrients in the plant.

Under severe micronutrient deficiency conditions, selecting seed high in nutrient content or a micronutrient seed treatment to provide early nutrient sufficiency, establish a well-developed root system, and insure a vigorous seedling plant with increased tolerance to glyphosate applied later, has been beneficial even though excess nutrient applied at this time may be immobilized by glyphosate from root exudates and not available for subsequent plant uptake. Micronutrients such as Mn are not efficiently broadcast applied to soil for plant uptake because of microbial immobilization to non-available oxidized Mn, but could be applied in a band or to seed or foliage.

Detoxifying Residual Glyphosate: Some nutrients are relatively immobile in plant tissues (Ca, Mn) so that a combination of micronutrients may be more beneficial than any individual one to chelate with residual glyphosate and ‘detoxify’ it in meristematic and mature tissues. Thus, foliar application of Mn could remediate for glyphosate immobilization of the nutrient; however, it may be more effective when applied in combination with the more mobile Zn to detoxify sequestered glyphosate in meristematic tissues even though Zn levels may appear sufficient. Gypsum applied in the seed row has shown some promise for detoxifying glyphosate from root exudates since Ca is a good chelator with glyphosate (one of the reasons that ammonium sulfate is recommended in spray solutions with hard water is to prevent chelation with Ca and Mg which would inhibit herbicidal activity).

Although bioremediation of accumulating glyphosate in soil may be possible in the future, initial degradation products of glyphosate are toxic to both RR and non-RR plants. This is an area that needs greater effort since the application of phosphorus fertilizers can desorb immobilized glyphosate to be toxic to plants through root uptake. Micronutrient seed treatment can provide some detoxification during seed germination, and stimulate vigor and root growth to enhance recovery from later glyphosate applications.

Biological Remediation: The selection and use of plants for glyphosate-tolerance that have greater nutrient efficiency for uptake or physiological function has improved the performance of some RR crops, and further improvements are possible in this area. Enhancing soil microbial activity to increase nutrient availability and plant uptake has been possible through seed inoculation, environmental modification to favor certain groups of organisms, and implementation of various management practices. There are many organisms that have been used to promote plant growth, with the most recognized being legume inoculants (Rhizobia, Bradyrhizobia species); however, glyphosate is toxic to these beneficial microorganisms. Continued use of glyphosate in a cereal-legume rotation has greatly reduced the population of these organisms in soil so that annual inoculation of legume seed is frequently recommended.

Biological remediation to compensate for glyphosate’s impact on soil organisms important in nutrient cycles may be possible if the remediating organism is also glyphosate-tolerant and capable of over coming the soils natural biological buffering capacity. This would be especially important for nitrogen-fixing, mycorrhizae, and mineral reducing organisms, but will be of limited benefit unless the introduced organisms are also tolerant of glyphosate. Modification of the soil biological environment through tillage, crop sequence, or other cultural management practices might also be a viable way to stimulate the desired soil biological activity.

Increasing Plant Resistance to Stress and Root-Infecting Pathogens: Maintaining plant health is a basic requirement for crop yield and quality. Plant tolerance to stress and many pathogens is dependent on a full sufficiency of micronutrients to maintain physiological processes mediated through the Shikimate or other pathways that are compromised in a glyphosate environment. Sequential application(s) of specific micronutrients (esp. Ca, Cu, Fe, Mn, Zn) may be required to compensate for those nutrients physiologically lost through glyphosate chelation. Breeding for increased nutrient efficiency and disease resistance will be an important contributor to this objective.

SUMMARY

Glyphosate is a strong, broad-spectrum nutrient chelator that inhibits plant enzymes responsible for disease resistance so that plants succumb from pathogenic attack. This also predisposes RR and non-RR plants to other pathogens. The introduction of such an intense mineral chelator as glyphosate into the food chain through accumulation in feed, forage, and food, and root exudation into ground water, could pose significant health concerns for animals and humans and needs further evaluation. Chelation immobilization of such essential elements as Ca (bone), Fe (blood), Mn, Zn (liver, kidney), Cu, Mg (brain) could directly inhibit vital functions and predispose to disease. The lower mineral nutrient content of feeds and forage from a glyphosate-intense weed management program can generally be compensated for through mineral supplementation. The various interactions of glyphosate with nutrition are represented in the following schematic:

Table X. Some symptoms of glyphosate damage to non-target plants.

1. Micronutrient (and often some macronutrient) deficiency

2. Low vigor, slow growth, stunting

3. Leaf chlorosis (yellowing) – complete or between the veins

4. Leaf mottling with or without necrotic spots

5. Leaf distortion – small, curling, strap-like, wrinkling, or ‘mouse ear’

6. Abnormal bud break, stem proliferation – witches broom

7. Retarded, slow regrowth after cutting or running (alfalfa, perennial plants)

8. Lower yields, lower mineral value – vegetative parts and reproductive (grain, seeds)

9. Early fruit, bud, or leaf drop

10. Early maturity, death before physiological maturity, tip die-back

11. Predisposition to infectious diseases and extended infection/susceptible period– numerous

12. Predisposition to insect damage

13. Induced abiotic diseases – drought, winter kill, sun scald, bark cracking (perennial plants)

14. Root stunting, inefficient N-fixation and uptake

15. Poor root nodulation in legumes

Proceedings Fluid Fertilizer Forum, Scottsdale, AZ February 14-16, 2010. Vol. 27. Fluid Fertilizer Foundation, Manhattan, KS.

DOWNLOAD FULL PAPER HERE INCLUDING REFERENCES

Also: Some Selected References on Glyphosate

http://www.greenpasture.org/utility/showArticle/index.cfm?objectID=7213

http://www.naturalnews.com/031362_pesticides_cancer.html

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