Roundup-Tolerant Maize, Mesnage, et. al

My notes (Alice) on a GMO study involving feed corn:

Roundup-tolerant Maize, Mesnage, et. al

Mesnage, R. et al. An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process. Sci. Rep. 6, 37855; doi: 10.1038/srep37855 (2016).

First, the authors established background and history, materials and methods, like in any good study. The entire study is available at this Nature citation:

Study

It’s long and technical, so I have pulled out some parts I thought were most relevant.  Here’s part of the Discussion section. I highlighted some significant parts. All the technical citations can be found in the article in Nature.

The maize kernels analysed in this study were previously used to feed laboratory animals that formed part of a chronic (2 year) study looking at potential toxic effects arising from the consumption of this NK603 Roundup-tolerant GM maize. A dry feed was formulated to contain 11%, 22%, or 33% of NK603 maize, cultivated either with or without Roundup application, or 33% of the near isogenic variety. Sprague Dawley rats fed for two years on these diets presented blood/urine biochemical changes indicative of an increased incidence of liver and kidney structure and functional pathology in the NK603-containing diet groups compared to non-GM controls51. Standard biochemical compositional analysis revealed no particular differences between the different maize types tested51. Metabolic disturbances observed in our study may help to understand the negative health effects suggested after the chronic consumption of this GM maize. Alterations in concentrations of metabolites in grains might be directly related to pathogenic effects due to some active compounds that are known to be toxic52. For instance, a soybean glycoprotein allergen (Gly m Bd 28 K fragment) was also found overexpressed in a proteomic study of Roundup Ready GM soybean seeds (MSOY 7575 RR event)13. In our study, cadaverin levels were significantly increased (Log2FC 4.81 for NK603 and 5.31 for NK603+Roundup). Cadaverin plays important roles in lysine biosynthesis53 and also glutathione metabolism54. Other similar biogenic amines, such as N-acetyl-cadaverine, N-acetylputrescine and putrescine were also found to be present at higher levels in NK603 in our investigation. Different polyamines have been reported to have different effects, which depend on various factors such as age, tissue or disease status55. In certain contexts some of these polyamines have been found to be protective whereas in other situations they can be a cause of toxicity. On the one hand, toxicological effects such as nausea, headaches, rashes and changes in blood pressure are provoked by the consumption of foods with high concentrations of polyamines56. Putrescine and cadaverine have been reported as potentiators of the effects of histamine, and both have been implicated in the formation of carcinogenic nitrosamines with nitrite in meat products57. On the other hand, certain polyamines can also have beneficial anti-inflammatory effects and have been found to be beneficial during aging in some rodent model systems58. Noticeably, these polyamines were not measured in the first compositional analysis of NK603 maize performed for regulatory purposes32. Overall, whether the increased levels of cadaverine and putrescine found in the NK603 maize samples can account for the signs of potential negative health effects upon its consumption by rats, as implied by the blood/urine biochemical analysis33, needs to be further analyzed in experiments using more quantitative methods.

And here is part of the Conclusion section --

This study is the first and most detailed multi-omics (multi-disciplinary statistical) characterization of a widely commercialized GMO crop and its isogenic (not genetically modified) counterpart. In conclusion, our integrative statistical and bioinformatics analysis allowed us to suggest a mechanistic link between the proteome and metabolome alterations observed and the insertion of a particular transgene. The transformation process and the resulting expression of a transgenic protein cause a general disturbance in the GM plant and it is clear that NK603 maize is markedly different from its non-GM isogenic line at the proteome and metabolome levels. In addition, our data correlates with previous studies, which observed higher amounts of ROS that act as free-radicals promoting oxidative stress in those transgenic plant materials. We also confirm a metabolic imbalance in energy and carbohydrate metabolism. Although a clear mechanistic link between alterations in the GM feed and the possible health effects following long-term consumption of this product remains to be established, the evidence we present clearly shows that NK603 and non-GM isogenic maize are not substantially equivalent and the nutritional quality of GM feed might be hampered by metabolic imbalances related to plant energy and stress metabolism.

The way I read this is that they didn’t study how it happens, but that although everyday lab analysis of GM corn vs non-GM corn suggests they have the same protein, fat, fiber, etc. content, there are important and provable differences in how they were metabolized by the rats in this 2-year study.

The study’s length was also significant. Most GM studies last around 90 days, not long enough for long term effects to show up.

There were concern about the levels of putrescine and cadaverine in the corn as well. Love those names, right? They are toxic compounds from the breakdown of amino acids. Think “putrid,” and “cadaver,” and that is what they smell like.

My take on this is that there are indeed significant differences in GM and Non-GM corn that are not apparent in the simple analyses upon which the regulatory industry bases its judgment.

It’s just my opinion, worth what you paid for it, as my grandfather used to say.

Alice