Straight to the point with this title. Though authored in the very first days of the year, this stuff does not have an expiration date (unlike the millions of pounds of food our civilization wastes annually). So lets begin.
2016 yielded yet another study on genetically modified corn. Or more accurately, Monsanto’s NK603.
Lets see what the findings are now. Even before I start, I bet I know their answer to the question posed by the title of the article.
A unique new study published in December 2016 in the scientific journal Nature has used molecular profiles to reveal major differences in composition between a GMO corn and its non-GMO parent. These findings question industry and regulatory position of “substantial equivalence” and have serious safety implications.
The peer-reviewed study led by Dr. Michael Antoniou at King’s College London describes the effects of the process of genetic engineering on the composition of a genetically modified Roundup-resistant GMO corn variety, NK603.
“Our study clearly shows that the GM transformation process results in profound compositional differences in NK603, demonstrating that this GMO corn is not substantially equivalent to its non-GMO counterpart,” Dr. Antoniou said. “The marked increase in putrescine and especially cadaverine is a concern since these substances are potentially toxic, being reported as enhancers of the effects of histamine, thus heightening allergic reactions and both have been implicated in the formation of carcinogenic nitrosamines with nitrite in meat products. Our results call for a more thorough evaluation of the safety of NK603 corn consumption on a long-term basis.”
Overall, the findings of this study disprove industry and regulatory agency claims that NK603 is “substantially equivalent” to its non-GMO counterpart and suggest that a more thorough evaluation of the safety of consuming products derived from this GMO corn on a long term basis should be undertaken.
First off, some chemistry.
Putrescine (butane-1,4-diamine) and cadaverine (pentane-1,5-diamine) are foul-smelling compounds produced when amino acids decompose in decaying animals. They are also found in small amounts in living cells. Putrescine is formed by the decarboxylation of ornithine and arginine; cadaverine by the decarboxylation of lysine
Putrescine is a four carbon diamine produced during tissue decomposition by the decarboxylation of amino acids. Polyamines, including putrescine, may act as growth factors that promote cell division; however, putrescine is toxic at high doses.
Already, 2 things are clear. Its apparent why these 2 chemicals could be useful in the context of bio engineering. But it is also apparent why they have a significant “BOO!” factor attached to them.
On that “Boo!” factor . . .
Biogenic amines and polyamines have been reported in variety of foods, such as fish, meat, cheese, vegetables, and wines, and are described as organic bases with aliphatic, aromatic, and heterocyclic structures (Lorenzo and others 2007).
Polyamines, such as putrescine, cadaverine, agmatine, spermine, and spermidine, are naturally present in food and are involved in growth and cell proliferation (Hernandez-Jover and others 1997; Kalac 2009; Kim and others 2009). These amines in the presence of nitrites can be potential carcinogens when converted to nitrosamines (Kim and others 2009). Nitrosamines from polyamines may not necessarily pose a health risk as toxicity is reached only after consumption of large amounts, more than expected in a daily meal (Kalac 2009).
The aromatic biogenic amines, tyramine, and 2-phenylethylamine have been reported to be initiators of dietary-induced migraine and hypertensive crisis (Stratton and others 1991). Tyramine, 2- phenylethylamine, and putrescine are versoactive amines and increase blood pressure that can lead to heart failure or brain hemorrhage (Til and others 1997; Kalac 2009; Mohan and others 2009).
Boo indeed. Ill never eat anything again.
Oral toxicity levels for putrescine, spermine, and spermidine are 2000, 600, and 600 ppm, respectively. The acute toxicity level for tyramine and cadaverine is greater than 2000 ppm. The no observed adverse effect level (NOAEL) is 2000 ppm for tyramine, putrescine, and cadaverine; 1000 ppm for spermidine; and 200 ppm for spermine (Til and others 1997). Tyramine alone at high levels can cause an intoxication known as the cheese reaction, which has similar symptoms to histamine poisoning.
Fortunately for us (at least in the developed world), this is primarily a problem of food spoilage (and as such, can be kept generally at bay with careful food handling procedures).
The formation of biogenic amines is associated with food spoilage, suggests poor hygienic practices, and may therefore indicate other food safety issues. Any attempts to control biogenic amines must take into account the factors leading to the formation of the biogenic amine and ensure other food safety issues are not being overlooked.
Now, onto the research itself.
The objective of this investigation was to obtain a deeper understanding of the biology of the NK603 GM maize by molecular profiling (proteomics and metabolomics) in order to gain insight into its substantial equivalence classification. We began by undertaking an unsupervised exploratory analysis of variance structure. We integrated metabolome and proteome profiles of the NK603, cultivated either with or without Roundup, and its isogenic counterpart, into a two-step multiple co-inertia analysis (MCIA) process.
The transgenic feed samples NK603 and NK603+Roundup are separated from the non-transgenic control (Isogenic) along the first component (horizontal axis). This clustering accounts for most of the variation (percentage of explained variance of 56.7%). The NK603 maize sprayed with Roundup separates from the unsprayed NK603 maize on the second component (vertical axis, percentage of explained variance of 16.6%).
I feel ya.
I know this is pertinent. I want to understand. But all that comes to mind is . . . meta-prota-WHAT?!
Fortunately for scientific illiterates like me, the study authors are merciful. They provided a diagram. We may not be able to comprehend it, but at least we can see it!
(A) The first two axes of MCIA represent metabolome and proteomic datasets. Different shapes represent the different variables which are connected by lines, the length of these lines is proportional to the divergence between the data. Lines for each sample are joined at a common point at which the covariance derived from the MCIA analysis is maximal. (B) Pseudo-eigenvalue space showing the percentage of variance explained by each of the MCIA component. Each barplot represents the absolute eigenvalues. (C) Protein or metabolites (colored dots) are projected on a 2-dimensional space. In this panel, a protein or a metabolite that is particularly highly expressed in a maize variety will be located on the direction of this variety. (D) Pseudo-eigenvalues space of all datasets, indicating how much variance of an eigenvalue is contributed by the proteome or the metabolome for cultivations 1 and 2.
What comes next is a little bit more clear cut (a little . . .) , and another graph.
We next conducted a statistical evaluation of the biological differences resulting from the GM transformation process, as well as from the spraying of Roundup, by pairwise comparisons in order to identify proteins and metabolites associated with possible metabolic alterations. The list of proteins and metabolites having their levels significantly disturbed is given in Additional files 5 and 6, respectively. Figure 3 shows the statistical significance of differential protein/metabolite levels by volcano plots along with respective fold changes. While only one protein is newly produced as a result of the transgene insertion, a total of 117 proteins and 91 metabolites have been altered in maize by the genetic transformation process and insertion of the EPSPS-CP4 cassette (Isogenic vs NK603 panel, Fig. 3). One protein (B4G0K5) and 31 metabolites had their expression significantly altered by the spraying of the Roundup pesticide (NK603 vs NK603+Roundup (R) panel, Fig. 3).
Volcano plots show the log 2 fold changes and the −log10 adjusted p-values in protein or metabolite level induced by the GM transformation process (isogenic vs NK603, isogenic vs NK603 + R) or by the pesticide spraying (NK603 vs NK603 + R). Data were selected at the cut off values adj-p < 0.05 and fold change >1.5. Red dots represent protein or metabolites having their level significantly altered in the different samples.
And next, the the meat. Or Corn, as is stands.
The most pronounced differences between the NK603 GM maize and its isogenic counterpart mostly consisted of an increase in the amounts of numerous polyamines. The levels of N-acetyl-cadaverine (2.9-fold), N-acetylputrescine (1.8-fold), putrescine (2.7-fold) and cadaverine (28-fold) were increased in NK603. The metabolome profile also highlighted an impairment of energy metabolism. While metabolites from the first part of the TCA cycle had their levels increased (α-ketoglutarate by 1.65-fold and citrate by 1.49-fold), metabolites from the second part of the TCA cycle had their levels decreased (malate by 0.59-fold, fumarate by 0.60-fold, succinate by 0.80-fold). Additionally, while proteins associated with glycolysis were overexpressed, carbohydrate metabolism is depleted in several metabolites (glucuronate by 0.63-fold, glucose 1-phosphate by 0.56-fold, maltohexaose by 0.28-fold, maltopentaose by 0.51-fold). Differences due to the pesticide spray were subtle: phenylpropanoid such as 4-hydroxycinnamate (0.63-fold), ferulate (0.59-fold) and sinapate (2.9-fold) were significantly changed. While alterations of the shikimate pathway were not detected, intermediates from aromatic amino acid metabolism (PEP derived) had their level increased (phenyllactate by 1.60-fold, phenylpyruvate by 2.71-fold, N-acetylphenylalanine by 2.24-fold and xanthurenate by 1.82-fold).
And the part that has the Eco-based fake news sites in a gay ole tizzy.
In this report we present the first multi-omics analysis of GM NK603 maize compared to a near isogenic non-GM counterpart. Based on analysis conducted by the developer Monsanto Company, NK603 maize was scored as ‘substantially equivalent’ to its isogenic control, which was a major contributor to this product being granted market approval for animal and human consumption in the European Union, United States, Brazil and several other nations. Although NK603 had comparable nutritional and compositional profiles when originally accessed by the developer company upon registration of their product, our analysis at a detailed, in-depth molecular profiling level shows that NK603 grains, with or without Roundup spraying during cultivation, are not equivalent to isogenic non-transgenic control samples.
The concept of substantial equivalence has long being used in safety testing of GMO crops, but the term and the concept has no clear definition35. In 1993 the Organization for Economic Co-operation and Development (OECD) stated that the “concept of substantial equivalence embodies the idea that existing organisms used as food, or as a source of food, can be used as the basis for comparison when assessing the safety of human consumption of a food or food component that has been modified or is new”36. The vagueness of this term generates conflict among stakeholders to determine which compositional differences are sufficient to declare a GMO as non-substantially equivalent. However, the Codex Alimentarius Commission37 makes it clear that a safety assessment of a new food based on the concept of substantial equivalence “does not imply absolute safety of the new product; rather, it focuses on assessing the safety of any identified differences so that the safety of the new product can be considered relative to its conventional counterpart.” Thus, the concept of substantial equivalence should not be used as a proof of safety.
However, it could be used as a first tier in risk assessment to detect any unintended effects of the GM transformation process. Unintended effects can be understood as the effects that go beyond the primary expected effects of the genetic modification, and represent statistically significant differences in the GMO compared with an appropriate control38. Unintended effects during transgenesis include rearrangements, insertion, or deletions during the genetic transformation or during the tissue culture stages of GMO development39,40. A comprehensive characterization of the GM plant at the molecular level could facilitate identification of unintended effects in GMO crops and could be used as a complementary analytical tool to existing safety assessment procedures41,42,43,44.
In general, our study design further highlights the importance of restricting comparison to the GMO crop and non-GMO isogenic comparator and cultivation of the two at the same location and season when the objective is to evaluate the effect of the GM transformation process. This is obligatory in order to reduce effects on plant metabolism arising from differing environmental conditions, which can make it difficult to attribute differences that are observed to the procedure of transgenesis.
In general, our study design further highlights the importance of restricting comparison to the GMO crop and non-GMO isogenic comparator and cultivation of the two at the same location and season when the objective is to evaluate the effect of the GM transformation process. This is obligatory in order to reduce effects on plant metabolism arising from differing environmental conditions, which can make it difficult to attribute differences that are observed to the procedure of transgenesis. However, even though our experimental design takes into account the effect of the growing season, further experiments made under different environmental conditions would be needed to determine the full range of effects of the GM transformation process on NK603 phenotype. Indeed, virtually all traits are influenced by genotype–environment interactions. Neither genetic differences nor environmental variations alone can account for the production of a particular phenotypic variation.
Going back to the original article that brought me here, there is not much else really to cover (its essentially an overview of the study. AKA what I just finished plowing though). But there is one thing that sticks out. Both in its absence from the paper I just finished with, and in the familiarity of the name associated with it.
5. Rats fed this GMO corn over 2 years presented signs of a higher incidence of liver and kidney damage (Séralini et al., Environmental Sciences Europe, 26:14) compared with controls.
Ah yes, this asshole. Gilles-Eric Séralini.
Bowing to scientists’ near-universal scorn, the journal Food and Chemical Toxicology today fulfilled its threat to retract a controversial paper claiming that a genetically modified (GM) maize causes serious disease in rats, after the authors refused to withdraw it.
The paper, from a research group led by Gilles-Eric Séralini, a molecular biologist at the University of Caen, France, and published in 20121, showed “no evidence of fraud or intentional misrepresentation of the data”, said a statement from Elsevier, which publishes the journal. But the small number and type of animals used in the study mean that “no definitive conclusions can be reached”. The known high incidence of tumours in the Sprague–Dawley strain of rat ”cannot be excluded as the cause of the higher mortality and incidence observed in the treated groups”, it added.
Today’s move came as no surprise. Earlier this month, the journal’s editor-in-chief Wallace Hayes threatened retraction if Séralini refused to withdraw the paper. Elsevier retracted the paper shortly after a press conference in Brussels this morning, in which Séralini protested his innocence.
And there is more. Butthurt brings out the tinfoil.
He and his team stand by their results, and allege that the retraction derives from the journal’s editorial appointment of biologist Richard Goodman, who previously worked for biotechnology giant Monsanto for seven years.
“The magazine reviewed our paper more than any other,” says co-author and physician Joël Spiroux de Vendômois, who is also president of the Paris-based Committee for Research and Independent Information on Genetic Engineering (CRIIGEN), which collaborated in the study. The retraction is “a public-health scandal”, he says.
The study found that rats fed for two years with Monsanto’s glyphosate-resistant NK603 maize (corn) developed many more tumours and died earlier than controls. It also found that the rats developed tumours when glyphosate (Roundup), the herbicide used with GM maize, was added to their drinking water. (See ‘Rat study sparks GM furore‘).
And now, why it matters.
At the 28 November press conference, Corinne Lepage, a Member of the European Parliament and former French environment minister, said that Séralini’s paper asked “good questions about the long-term toxicity of GMOs [GM organisms] and the Roundup herbicide”. Retraction of the paper “will not make these questions disappear”, added Lepage, who is also a co-founder of CRIIGEN.
To conclude, this article is not bad, considering the source and the topic. Not entirely fake news. However, the rat part was an interesting addition. One that was not utilized in the main referenced study. Because it was debunked.
I agree that these findings should indeed trigger more study. Study of these things should be constant anyways (if for nothing else, to try and calm the GMO hysteria).