GMOsHealth & Disease

New GMO Studies Demonstrate ‘Substantial Non-Equivalence’

Studies document substantial differences of GM maize and GM soybean from their conventional non-GM counterparts, exposing a permissive regulatory regime that has failed miserably in protecting public health and biodiversity.

by Dr Eva Sirinathsinghji

A fully referenced and illustrated version of this article is posted on ISIS members website and is otherwise available for download here.

Several new studies carried out by scientists independent of the biotech industry are showing up glaring differences between GMOs and their non-GMO counterparts. This makes a mockery of the regulatory principle of ‘Substantial Equivalence’ which has facilitated approvals of GMOs with practically no protection for public health and the environment [1] (see [2] The Principle of Substantial equivalence is Unscientific and Arbitrary, ISIS news).

The principle of ‘Substantial Equivalence’

The concept of ‘Substantial Equivalence’ was first introduced in 1993 by the Organisation for Economic Development (OECD), an international economic and trade organisation, not a public health body. The principle states that if a new food is found to be substantially equivalent to an already existing food product, it can be treated the same way as the existing product with respect to safety. This concept has greatly benefited the trade of GM produce, allowing it to effectively bypass regulatory requirements that would apply to novel food and other products including novel chemical compounds, pharmaceuticals, pesticides and food additives, all of which require a range of toxicological tests and can be subject to legal limitations on safe consumption/intake.

Regulatory agencies including the US Food and Drug Administration, the Canadian Food Inspection Agency and Japan’s Ministry of Health and Welfare, generally base their GM food safety regulations on substantial equivalence.

There are many good reasons for consumers to feel unprotected by these regulatory policies, not least because the principle itself is designed to be as flexible and open to interpretation for the approval of just about any and every GMO submitted. In practice, the principle allows the comparison of a GM line to any existing variety within the same species, and even to an abstract entity made up of ingredients from a collection of species. This means that a GM variety can have all the worst traits of many different varieties and still be deemed substantially equivalent [1, 2]. Traits used for comparisons are also based solely on gross and insensitive chemical compositional tests such as levels of carbohydrate, protein and sugars. This process cannot even begin to tackle safety issues. Ironically, for the GMOs to be patentable as they are, a clear novelty, i.e., a difference or non-substantial equivalence is indeed required.

Independent assessments of substantial equivalence have shown how this ill-defined practice is not only inadequate but untrustworthy [3- 5], and the new studies most clearly confirm this.

Studies in Egypt showed substantial non-equivalence and toxicity for GM corn

In April 2013, an Egyptian publication led by Professor El-Sayed Shaltout at Alexandria University found that Monsanto’s 810 Corn (Ajeeb-YG®), modified to express the insecticidal Bt Cry1Ab gene, has increased total protein, crude fat, crude fibre & total saccharides and decreased starch content compared with non-GM Ajeeb corn. Abnormal levels of certain amino acids, fatty acids and elements were also recorded [6]. These compositional differences only gave the merest hint of the toxicity of the GM corn revealed in previous male rat feeding studies conducted by the same team documenting a wide range of organ and tissue abnormalities [7, 8]. Liver cells displayed vacuolation and fatty degeneration. The kidneys had congested blood vessels and dilation of renal tubules. The testes showed signs of necrosis and desquamation of spermatogoneal germ cells lining the seminiferous tubules. The spleens were congested with slight lymphocytic depletion. The small intestines showed hyperplasia and hyperactivation of mucous secretory glands, with necrosis of intestinal villi. Most certainly, the GM corn was not substantially equivalent to non-GM corn.

GM and non-GM soybeans not substantially equivalent

A more recent study led by Thomas Bøhn at the Norwegian Centre for Biosafety [9] tested 31 batches of whole soybeans from Iowa, US in three categories: 1) GM glyphosate-tolerant soy; 2) unmodified soy cultivated using conventional “chemical” regime and 3) unmodified organically cultivated soy. The three groups were analysed for chemical contamination (organochlorine, organophosphorus, pyrethroides, PCBs, glyphosate and AMPA (aminomethylphosponic acid – the major degradation product of glyphosate) based on the list of pesticide brand names used by the farmers) as well as nutritional content. Testing pesticide levels is important as substantial equivalence assessments for GM glyphosate-tolerant soy were not previously done with herbicide residue in the crop despite common knowledge that glyphosate is actually taken into the plant, and also alters the metabolism and biochemistry, and hence the chemical composition of crops. Any assessment of its equivalence is obviously irrelevant when glyphosate is not included.

The results couldn’t be clearer. As shown in Figure 1, glyphosate and AMPA were only present in GM soy samples and not at all in conventional non-GM and organic varieties. In the GM-soy samples, the concentration of AMPA (mean concentration = 5.74 mg/kg) was on average nearly twice as high as glyphosate (3.26 mg/kg). Other herbicides were detected: Fluazifop-P a selective phenoxy herbicide, was found at a concentration of 0.078 mg/kg in one of the GM-soy samples, malathion was found at a concentration of 0.02 mg/kg in one of the conventional soy samples and Dieldrin was found at a concentration of 0.002 mg/kg in one of the organic soy samples. No other residues were detected. Additional testing for pesticide residues in pooled samples of GM, conventional and organic soybeans showed trace-levels of Alpha-endosulfane, Trans-nonachlor and Trans-chlordane, all close to the detection limit of 0.05 µg/kg and in all soy types. Dieldrin was also found in very low levels with 0.51, 0.45 and 0.6 µg/kg in GM, conventional and organic soybeans, respectively.

Figure 1 Gyphosate and its metabolite AMPA present only in GM soy

The researchers looked at chemical composition of the soy samples including composition of protein, fat and sugar content, as well as individual amino acids, vitamins, fatty acids and elements. Organic soy samples show significant differences from both GM and conventional non-GM soybean samples, with higher and lower levels of protein and saturated fats respectively, plus significant differences in levels of total as well as individual levels of amino acids, vitamins, and minerals. A further statistical multivariate analysis of the compositional results found without exception that each individual soybean sample could be discriminated statistically into their respective agricultural background, even excluding the data on glyphosate/AMPA levels. The organic soybean was nutritionally superior to both conventionally grown non-GM soybean and GM soybean.

Profiling technologies for biosafety analyses

Profiling technologies, such as proteomics, allow the simultaneous measurement and comparison of thousands of plant components, in this case proteins, without prior knowledge of their identity. These methods are now being employed by independent scientists to provide a more thorough, unbiased and global profile of GM crop composition for risk assessment.

A new study conducted in Brazil by Agapito-Tenfen and colleagues at the Federal University of Santa Catarina is an example of this type of analysis, with global protein expression analysed in GM MON810 compared with the non-GM maize control grown in two different environmental conditions. Analysis of the total leaf-derived proteome showed 32 differentially expressed proteins (out of an average 458 and 643 detected proteins for each condition) between GM and non-GM maize with most of them involved in carbohydrate metabolism, stress response as well as genetic information processing such as post-translational modification of newly made proteins [10]. Sixteen proteins were differentially expressed between GM and non-GM maize at each of the two growing locations (Campos Novos and Chapecó). In Campos Novos, the experiment found 8 proteins detectable only in the GM samples, the remaining 8 were absent in the GM samples. In Chapecó, there were seven proteins exclusive to GM plants and seven to non-GM plants. 2 proteins showed quantitative differences in expression. For example, glyceraldehydes 3-phosphate degydrogenase (GAPDH) and fructose-biphosphate, ferredoxin-NAPD was exclusive to GM plants in Capos Novos and relate directly to energy metabolism. When it comes to carbohydrate metabolism, this is consistent with previous studies that found increased sugar levels in MON810 plants, with up 14, 7 and 1.8-fold increases in glucose, fructose and sucrose respectively [11]. Indeed, maize plants go through many developmental stages in their leaves that exclusively rely on carbohydrate metabolism. Further, transgenes with high constitutive promoters have been shown to have a high energetic cost e.g. cauliflower mosaic virus 35S promoter [12, 13], which the authors speculate may cause a problem for transgenic plants.

Stress response genes e.g. those related to glutathione metabolism (glyoxylase 1 and IN2-1), peroxidises and pathogenesis-related protein were expressed only in non-GM plants. It was also revealed that 2-cysteine peroxiredoxin BAS1 (2-CP) proteins are over-expressed in GM plants from both locations. Peroxidases are of great importance for eliminating H2O2 resulting from oxidative phosphorylation.

Four genetic information processing proteins were differentially expressed. Two of these were only present in GM plants from Campos Novos, the adenine phosphoribosyl transferase (APT), and the ATP-dependent Clp protease ATP-binding subunit ClpA (Clp-ClpA). APT works on adenine salvage in plants, while Clp-ClpA proteases exert unfoldase activity, playing a key role in regulating the availability of certain short-lived regulatory proteins. Chaperonin protein and S-adenosylmethionine synthetase 1 were upregulated in non-GM plants. S-adenosylmethionine synthetase 1 is involved in transmethylation of proteins, nucleic acids, polysaccharides and fatty acids. Interestingly, many of these genetic information processing proteins are directly related to gene expression control.

This study is the first of its kind to use such technologies to assess how both the environment and genotype can influence plant composition in Brazil and highlights the routine profiling analyses now widely available for proteins, transcripts and metabolites that are still not required by governments for regulatory approval as they should be.

Of further note in this study is the effect of environmental conditions on the composition of crops. GM proponents often argue that other factors such as environmental conditions as well as hybrid varieties determine the composition and physiology of a plant but genetic modification can influence such conditions. Indeed, the environment did cause variation in composition of the crops, but interestingly, it appeared that the GM maize protein expression profile was more affected by the environment.

To conclude, the numerous differences demonstrated between GM varieties and their non-GM counterpart may well impact consumer health and biodiversity, and clearly exposes the substantial equivalence principle as pseudoscience. In reality, genetic modification causes very real and substantial, unpredictable and uncontrollable changes in the host genome including mutations, and rearrangements as well as new transcripts and proteins. Further, glyphosate and GM crops have already been shown to cause damage to both health and the environment in many independent studies (see [14] Ban GMOs Now, ISIS special report). This is now fully confirmed in the new studies.

Further Reading:


  1. What you’re saying is that the GM Soy test which you espouse as a proof of ‘substantial difference’ had for one of it’s test parameters an organic soy bean that had no pesticide applied to it whatsoever, and yet a non-organic pesticide was still detected in the sample? Huh? Are you trying to shoot yourself in the foot. Who in the world would take that test seriously, when you just pointed out that there was a contamination in your samples?

    GM; bad! GM science; really bad! GM regulation; really really bad; GM companies, evil!
    I’m with you all the way there, but you can’t fight their shitty science with your own. If you are to make a convincing argument, please at least make it air-tight first.

    1. The fact remains that pesticides and herbicides are blown around by the wind and are now in the water supply, contaminating fields that are “organic.” I buy organic because it means that there is LESS of these substances on my food, not because I think that they are absolutely clean of them. Once these things have been released into the environment, there is no way to have any products that are absolutely free of them that are raised within the same region.

      1. Don’t get me wrong Tara, I too prefer eating things that haven’t been deliberately modified to be adapted to and then deliberately sprayed by poisons. That is not a very appealing food source to me at all. But the point here is that if anyone is to prove scientifically that there is something wrong with these GMO’s (and not the poisons themselves) then any experiment that is conceived to test that hypothesis must be performed in 100% controlled laboratory conditions. If the experiment cannot guarantee perfectly controlled conditions then any contamination that occurs becomes an uncontrolled variable which invalidates any results of the test. Which means you can no longer prove beyond a doubt that the problem is the GMO alone. It is as simple as that.

        1. So Phillip. Are you saying that since we’ve reached a point where everything is already contaminated, there is no way to prove the GM crops are more or less healtheir than non GM crops? Isn’t this the same approach the tobacco giants took in the past by making it impossible for anyone to prove their lung cancer was due to smoking, because the air we all breathe is contaminated.

    2. Maybe you aren’t aware that pesticides can stay in the soil for *decades*, which means that land transitioned to organic can be contaminated for a long time. I think the point of that study was to test soybeans that were actually being put into the food supply–you know, real-world sources and applications. Those kinds of tests should definitely be done so that we can see how the GMOs are truly holding up and testing out in reality.

      That an organic crop was contaminated by a conventional pesticide only means that the land has been poisoned at some point in its life–directly or by drift. If anything, this should be a lesson to Big Ag trolls and lackeys that their pesticides DO persist much longer than they’re willing to admit to anyone.

  2. You fundamentally misunderstand “substantial equivalence.” This doctrine is how new plants are tested: they assume that a new variety is substantially equivalent to the parent variety and then test for differences.

    1. Well, James, maybe they shouldn’t automatically ASSume that the plants are “substantially equivalent”. And maybe we shouldn’t put too much faith in a word and definition that was made up by an economic and trade organization rather than by scientists and farmers…

  3. Sorry, the definition was coined by scientists at a conference. And you would surely agree that if I breed a new corn variety, you’d like to know how it differs from previous corn varieties. That should catch anything: allergens, poisons, whatever.

    1. Well, obviously, they didn’t catch everything or they buried what they didn’t want publicly known–or they simply didn’t do enough testing.

  4. Since this article does not give any links to the actual papers, it is difficult to evaluate its assertions. It sounds like the article refers to the discredited and withdrawn Seralini paper. The paper by Bohn has been crticised here: I’d like to read the Brazilian paper, though, as it sounds interesting. Do you have a link?

      1. None of these are peer-reviewed studies in scientific journals. I am sure some exist since they are referenced above, and I would to read them.

        1. Hi James. The links I provided were articles showing how Seralini’s study was not “discredited”.

          If you want references for the article above, please see the links at the very top, where it says: “A fully referenced and illustrated version of this article is posted on ISIS members website and is otherwise available for download here.”

  5. Since it seems I have to pay to see that paper, I guess I wont’ see it. Wayne Parrott’s group deconstructed Seralini’s paper here: and in fact, it was discredited by 6 French science organizations within 24 hours of its publication. The main problems were small sample sizes and the use of S-D rats which get tumors anyway if given access to all the food they want for 2 years. And most of the rats in that paper got tumors whether fed GM or not. It was simply inconclusive at best.

    1. I’ve seen a lot of articles like that you linked to, which is why I put up the links above for you. At least read the first one (“the stats stand up”).

      But, if you want to discuss further, I would ask why we would possibly want GMOs in the first place? Please consider that GMOs are born out of the symptoms of industrial agriculture (i.e. trying to find ways to persevere with a system that isn’t working, and is only doing damage to people and place). Taking a ‘systemic’ approach to a healthier path is not only critical, but it entirely does away with any ‘need’ for GMOs (which are a ‘solution looking for a problem’). Please consider:

      No ‘techno-fix’ will solve the massive problems we’re facing in soil erosion and depletion, soil and water pollution (agri-chemicals and fertilisers), water wastage, peak oil (equating to peak food if we don’t change systems fast), etc. etc. GMOs have no answers for these things – but rather just further entrench and capitalise on a failing agricultural model. Biologically, chemical-intensive farming can only be a finite endeavour. I studied soil science myself.

      A couple more for good measure:

    2. Yes, James…like so many other scientific papers and journals, you unfortunately do have to pay to have access.

      The Seralini study has *not* been discredited by anyone that matters; only by the biotech industry and their lackeys. The same rats were used in some of Monsanto’s own safety studies, and they also had small sample sizes–PLUS they only did 3 month studies. This study was much more thorough and indicative of life-long feeding habits. Do you think biotech intends for people to eat GMOs for only a few years of their lives? Lol. From cradle to grave is more like it. Aside from that, inconclusive studies are accepted in the journals *all the time*, and they are used as an initiation into more research that should be done. There’s no reason for that paper to have been retracted, as hundreds of scientists around the world have pointed out….

  6. But this is not a link to a legitimate peer-reviewed journal as far as I know. Certainly it is not to be found in PubMed. Any scientist reading the Seralini paper would find numerous technical problems, and most of those who ave criticized are academic scientists, not those in industrial positions. Calling people “lackeys” is not conducive to reasonable discussion, however. So Monsanto did 3 month studies and that is OK, but Seralini used the same rats for a much longer study where they were guaranteed to develop tumors and that is good science? If his paper is so persuasive, why has Seralini not submitted to another journal? That would be his best line of defense.

    1. I could care less if the biotech trolls don’t like the truth (that they are essentially “lackeys” for the industry). The truth *does* hurt sometimes, doesn’t it?

      I like how you’ve turned things around. That’s typical. I can’t tell you how many times I’ve seen that maneuver. It’s okay for the industry to use a certain type of rat, but it’s not okay for other scientists to use it? How convenient.

      Those that forced the retraction admitted that the only reason they did so was because the results were inconclusive…and I’ve already pointed out that many other studies are still on the record even though their results are also inconclusive.

      There’s really nothing you can say here that will change the facts, so you’re wasting your breath/time. Not everyone is as gullible as the GM-industry would like…

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