Findings contradict reassuring reports on GM products, say researchers

Rats fed GM Bt corn MON810 for only 90 days suffered serious damage to the surface mucous membranes of the jejunum (part of the small intestine), according to a new study.[1]

The type of corn fed to the rats was MON810: Ajeeb YG, a GM version of Ajeeb, a locally adapted variety of corn grown in Egypt. MON810: Ajeeb YG was developed by Monsanto for the Egyptian market. The GM-fed rats ate a diet containing 30% of MON810: Ajeeb YG corn. Control rats were fed the same amount of non-GM corn.

In the GM-fed rats, some areas of the villi – finger-like structures in the intestine that absorb nutrients from food – were damaged. They were distorted and flattened, with some cells joined together. The damage can clearly be seen in the images included in the study. The crypts (mucosal glands) were disrupted and blood vessels were congested. Signs of inflammation – white blood cell infiltration – were seen around areas of damage. In addition, the cells of the intestinal lining were abnormal in structure.

Other signs of damage included increased shedding of mucosal cells, increased numbers of mucous-secreting goblet cells, and higher rates of division of cells lining the crypts.

The study, conducted by Marwa Ibrahim, MD and Ebtsam Okasha of the Faculty of Medicine at Tanta University, Egypt, was published in the journal Experimental and Toxicologic Pathology (abstract below).

The researchers concluded that “consumption of GM-corn profoundly alters the jejunal histological [microscopic] structure”. They added, “Results from the current study could show that in spite of the assuring reports on GM products, GM corn has profoundly altered the histological structure of the jejunal mucosa at many levels and revealed several alarming signs, as the proliferative and eroded hemorrhagic lesions in addition to several ultrastructural alterations described here for the first time for jejunum under GM corn influence.”

The researchers called for more research to clarify the mechanisms through which the MON810: Ajeeb YG corn exercised this effect. Possible mechanisms include a direct damaging effect on the jejunal mucosa by the Bt toxin (Cry1Ab) present in the GM corn, akin to what takes place in the gut of target pests, or an indirect effect via disruption of the gut bacteria. Either mechanism could lead to the gut mucosa structural changes seen.

What does the study tell us?

The findings of this study are dramatic and significant. However, certain limitations need to be acknowledged. These include the fact that the control corn was not the isogenic non-GM parent variety (Ajeeb), but an unidentified non-GM corn used in formulating standard laboratory diets.[2]

In addition, there was no assessment for the presence of toxic contaminants such as mycotoxins and pesticide residues in the different diets.[2] Both types of contamination could potentially cause ill health effects.

For all these reasons, it is not possible to definitively attribute the harm suffered by the GM-fed rats to the GM process, including the Bt toxin. But the results strongly suggest that this may be the cause. That’s especially the case when this study is placed in the context of previous investigations of toxic effects from the consumption of the same GM MON810: Ajeeb YG corn.

Earlier studies

Two earlier rat feeding studies by Egyptian scientists on the same GM corn, MON810: Ajeeb YG, showed harm in the GM-fed animals. In these cases, the comparator was the appropriate non-GM parent variety Ajeeb, so the ill effects shown in the rats were due to the GM process.

In the first study, rats fed the MON810: Ajeeb YG for 45 and 91 days showed differences in organ and body weights and in blood biochemistry, compared with rats fed the non-GM Ajeeb parent variety grown side-by-side under the same conditions. The authors noted that the changes could indicate “potential adverse health/toxic effects”, which needed further investigation.[3]

In the second study, histopathological (microscopic) investigations by the same group of researchers found toxic effects in multiple organs in the rats fed the GM MON810: Ajeeb YG Bt corn for 91 days. Effects included abnormalities and fatty degeneration of liver cells, congestion of blood vessels in kidneys, and excessive growth and necrosis (death) of the intestinal villi. Examination of the testes revealed necrosis and desquamation (shedding) of the spermatogonial cells that are the foundation of sperm cells and thus of male fertility.[4]

It is significant that the findings of the second study, namely cell abnormalities, congestion of blood vessels, and damage to the intestinal villi were also found in the new study by Ibrahim and Okasha.

Correct comparator

It can be difficult or even impossible for researchers to access the proper materials for an animal feeding study on GM crops: namely the GM crop variety under investigation and the non-GM parent variety grown under the same conditions. This is because GMO developer companies have often not made these materials available to independent researchers.[5]

However, the fact that the correct comparator was used in the two earlier Egyptian studies suggests that theoretically at least, it should be possible for other researchers to access the non-GM parent variety, Ajeeb, as the comparator for any study of MON810: Ajeeb YG corn.

No obvious ill health in GM-fed rats

Ibrahim and Okasha noted that there were no obvious signs of ill health or altered behaviour in the GM-fed rats. This is perhaps not surprising, given the relatively short 90-day duration of this feeding study. Nonetheless, the animals were sick, as revealed by the histopathological examination of the gut tissues, with the findings clearly suggesting that a long-term feeding study of 2 years or more should be conducted to ascertain if the intestinal mucosa lesions found would eventually lead to overt ill-health.

Moreover, the results of this study are a clear signal that all animal feeding trials with GM foods used to justify regulatory approvals must include histopathological investigations. Currently this is not required or routinely practised.

EU Commission wants to see MON810 corn grown in Europe

The new study appears at a time when the EU Commission wants to see MON810 corn approved for cultivation in Europe in time for the 2017 growing season. Two other types of insecticidal GM Bt corn, DuPont Pioneer’s 1507 and Syngenta’s Bt11, are also being considered. EU Member States are expected to vote on this issue on 9 December.*

However, the totality of the evidence on MON810 corn shows it should not be grown more widely but on the contrary should be recalled from the market. And all GM crops should be subjected to proper testing before commercialization. That includes detailed “omics” analyses to reveal unintended changes in gene expression, proteins and metabolites, as well as long-term animal feeding trials.
 
Notes

1. Ibrahim MAA, Okasha EF. Effect of genetically modified corn on the jejunal mucosa of adult male albino rat. Experimental and Toxicologic Pathology 2016;68(2016):579–588. https://www.ncbi.nlm.nih.gov/pubmed/27769625
2. Email communication with the authors.
3. Gab-Alla AA, El-Shamei ZS, Shatta AA, Moussa EA, Rayan AM. Morphological and biochemical changes in male rats fed on genetically modified corn (Ajeeb YG). J Am Sci. 2012;8(9):1117–1123.
4. El-Shamei ZS, Gab-Alla AA, Shatta AA, Moussa EA, Rayan AM. Histopathological changes in some organs of male rats fed on genetically modified corn (Ajeeb YG). J Am Sci. 2012;8(10):684–696.
5. Waltz E. Under wraps – Are the crop industry's strong-arm tactics and close-fisted attitude to sharing seeds holding back independent research and undermining public acceptance of transgenic crops? Nature Biotechnology 2009;27(10):880–882. http://www.nature.com/nbt/journal/v27/n10/full/nbt1009-880.html

Report by Claire Robinson

Update 24 Nov 2016, 16:35 hrs GMT: We've just heard that the vote on the three GM corn varieties proposed for cultivation in Europe has been postponed again, to 17 January 2017.
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Effect of genetically modified corn on the jejunal mucosa of adult male albino rat
Marwa A.A. Ibrahim, MD*, Ebtsam F. Okasha
Experimental and Toxicologic Pathology 68 (2016) 579–588
https://www.ncbi.nlm.nih.gov/pubmed/27769625

Genetically modified (GM) plants expressing insecticidal traits offer a new strategy for crop protection. GM-corn contains Bacillus thuringiensis (Bt) genes producing delta endotoxins in the whole plant. Diet can influence the characteristics of the gastrointestinal tract altering its function and structure. The aim of this study was to evaluate the effect of GM-corn on the histological structure of jejunal mucosa of adult male albino rat using different histological, immunohistochemical and morphometrical methods. Twenty adult male albino rats were divided into two equal groups; control and GM-corn fed group administered with 30% GM-corn for 90 days. Specimens from the jejunum were processed for light and electron microscopy. Immunohistochemical study was carried out using antibody against proliferating cell nuclear antigen (PCNA). Different morphometrical parameters were assessed. Specimens from GM corn fed group showed different forms of structural changes. Focal destruction and loss of the villi leaving denuded mucosal surface alternating with stratified areas were observed, while some crypts appeared totally disrupted. Congested blood capillaries and focal infiltration with mononuclear cells were detected. Significant upregulation of PCNA expression, increase in number of goblet cells and a significant increase in both villous height and crypt depth were detected. Marked ultrastructural changes of some enterocytes with focal loss of the microvillous border were observed. Some enterocytes had vacuolated cytoplasm, swollen mitochondria with disrupted cristae and dilated rough endoplasmic reticulum (rER). Some cells had dark irregular nuclei with abnormally clumped chromatin. It could be concluded that consumption of GM-corn profoundly alters the jejunal histological structure.