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A new study shows that low doses of Bt biopesticide CryA1b as well as the glyphosate herbicide, Roundup, kill human kidney cells. The Bt biopesticide conferring insect resistance and the glyphosate tolerance trait tied to the use of glyphosate herbicides account for almost all the GM crops grown worldwide. Bt crops already constitute 39 % of globally cultivated genetically modified (GM) crops, yet this is the first study that provides evidence on the toxicity of Bt protein in human cells.

This work comes at a time when the French environment and agricultural ministers are seeking an EU-wide ban of Monsanto's MON810 Bt corn variety that is already outlawed in Hungary, Austria, Germany, Greece, and Luxembourg. The EU commission approved this crop in 2009, concluding that it "is as safe as its conventional counterpart with respect to potential effects on human and animal health". In response to their publication the research team raised questions about the safety assessment procedure stating that their findings were a "surprising outcome and this risk was somehow overlooked" in past assessments of such crops[1].

The research team led by Gilles-Eric Séralini at the University of Caen, France, is already well-known for their investigations on the endocrine disrupting effects of glyphosate herbicides (see[2] Glyphosate Kills Rat Testis Cells, SiS 54). The researchers tested the effects of Cry1Ab and Cry1Ac proteins as well as their combined effects with the herbicide Roundup on the human kidney cell line HEK293[3]. Humans are exposed to hundreds of chemicals in a day, and their combined effects need to be understood. This is particularly important when considering the new generation of 'stacked' genetically modified (GM) crops now on the market, which carry multiple resistance genes for Bt toxins and glyphosate tolerance together.

Experiments were performed to assess both cell death and cell membrane integrity, as the pesticidal activity of Bt toxins results from creating pores in the membrane of cells in the insect gut. Cell death was measured using three parameters: 1) mitochondrial succinate dehydrogenase enzyme activity as a general cell death marker, 2) activity of the membrane-bound enzyme adenylate kinase (AK) to assess membrane integrity as a marker of necrotic cell death and 3) caspase 3/7 activity, as a marker of apoptosis (programmed cell death). They found that Cry1Ab caused cell death at concentrations of 100 parts per million (ppm), according to mitochondrial succinate dehydrogenase activity. The membrane-bound enzyme adenylate kinase (AK) goes up in activity when the membrane disintegrates and releases the enzyme into the culture medium. Cry1Ab at 100 ppm induced a 2-fold increase in AK activity. No effects were seen with Cry1Ac.

No increase in caspase 3/7 activity was observed with either Cry1Ab or Cry1Ac, suggesting that necrosis as opposed to apoptosis is the mechanism whereby Cry1Ab kills the cells.

Séralini's team also assessed the effects of Roundup alone on the human kidney cells. Glyphosate at 57.2ppm (the LC50) that killed half of the cell population - 200 times below agricultural use - caused a 15-fold increase in AK activity and 6.7-fold increase in caspase 3/7 activity.

Interestingly, when Roundup was tested in combination with the Bt toxin, there was only one statistically significant effect: the increase in caspase 3/7 activity induced by 57.2 ppm glyphosate was halved in the presence of 10ppm of both Cry1Ab and Cry1Ac. There was also a non-significant trend of reduced AK leakage. The authors speculated that Bt proteins may affect the bioavailability of Roundup, thus delaying its apoptotic effects. The combined effects were not investigated in terms of glyphosate's other known interactions with the cellular biochemistry such as endocrine disruptions. Further studies are needed to understand the combined effects of stacked herbicides and pesticides on the human body.

This study indicates that Bt toxins are not inert on human cells, and may indeed be toxic. As Bt toxins are produced by bacterial species existing naturally in the wild, and are used for organic agriculture, inadequate safety assessments were involved in the approval of Bt crops. Bacterial spores used in organic spraying could be washed away, but the Bt proteins are part and parcel of the GM crops. Furthermore, the Bt proteins in GM crops have been modified from those naturally produced, and the effects of these modification have not been addressed.

Bt crops have previously been shown to induce hepatorenal abnormalities in rat feeding studies[4] as well as immune responses that may be responsible for allergies observed in farmers and factory workers handling Bt crops, affecting the eyes, skin and the respiratory tract (see[5] (More illnesses linked to Bt crops, SiS30). Reduced fertility in mice fed Bt maize has also been reported(see[6] GM Maize Reduces Fertility & Deregulates Genes in Mice, SiS41). These studies, along with the observation that Bt protein is present in the blood of pregnant women and their babies makes it an urgent matter for the health impacts of Bt proteins in GM crops to be thoroughly investigated along with the known effects on the environment and non-target species (see[7] Bt Crops Failures & Hazards, SiS 53).

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