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Sci Tech    H1'ed 10/31/13

How Monsanto and Friends Put the Frankenstein in Frankenfoods

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by John Moffett

Frankenfoods sounds like a catchy way to cast doubts on the safety of genetically modified foods, but does the analogy with Mary Shelley's Frankenstein really apply? Let's take a look, and start with a report from 2012 where researchers at the European Food Safety Authority (EFSA) disclosed that unintentionally introduced viral genes were found in genetically modified plant varieties. The scientific reasons behind why unintended viral genes were introduced into genetically modified plants lend support to the concerns voiced by many around the world that this technology is not being used wisely, or for the benefit of consumers.

Genetically modified organisms (GMO), also known as transgenic organisms, are generated in the lab by introducing genes from unrelated organisms (for example bacteria or viruses) into a plant or animal in order to add a trait not normally found in that plant or animal. This new trait is conferred on the transgenic organism because genes provide the code required to synthesize a specific protein that when present, gives the organism that specific new trait. GMO technology allows humans to bypass the species barrier to transferring genes from one organism to another. However, scientists can't just put a foreign gene into a plant or animal and have it work because that new gene will not be activated or "turned on." The gene would just sit there, doing nothing. In order to mark the gene as one that should be active, the gene must be associated with a so-called promoter gene sequence that is placed at the front of the gene that is going to be inserted (known as a "transgene"). Think of the promoter gene as a "go" signal for making the new protein encoded by the transgene.

So the basic idea is that you can't just stick a gene, let's say a bacterial gene that provides plants with the ability to resist being killed by the herbicide Roundup, into a plant and have it work. First you need to find a powerful promoter gene sequence that will mark your transgene as very active, thus leading the plant to make many copies the bacterial protein. When you insert the gene promoter plus the transgene into your plant species you will get a plant variety that produces lots of the foreign protein and, in the case of "Roundup ready" plants, confer Roundup resistance on that new transgenic plant.

This is where the story about many GMO crop varieties gets a bit Frankenfood-ish. What the European Food Safety Authority researchers found was that Monsanto and other GMO companies have been using several versions of a virus gene promoter to get their transgenes to work in plants. The viral gene promoter comes from the cauliflower mosaic virus, a virus that infects plants such as broccoli and cauliflower. The promoter is known in the industry as P35S (the 35S gene promoter). P35S is the viral gene promoter used in 54 out of 86 transgenic plant varieties authorized in the US. The actual promoter region of the gene is relatively small, but all of the versions used in transgenic plant production in the US are larger than the required promoter region. This means that unwanted portions of the viral genome have been introduced into the plants, along with the viral promoter and transgene. The unintended portion of the gene that was inserted along with the 35S promoter is known as "Gene VI," which codes for a viral protein known as P6, and virtually all plant varieties created with this promoter could potentially contain some portions of the P6 viral protein.

It is not publically known if any Gene VI products (portions of the P6 protein) are produced in specific varieties of GMO crops that use the cauliflower mosaic virus gene promoter, however it is quite likely that the responsible corporations know. The fact that researchers at these large corporations are using genetic engineering tools that are carrying this level of baggage suggests a low quality of scientific rigor. It is very likely that the mentality was to get products to market ASAP, rather than to be careful about how they got there.

This is probably information that Monsanto, Pioneer and other GMO companies would prefer you to not to think about. The European Food Safety Authority researchers looked for similarities between the portions of the P6 viral protein that might be expressed in GMO plants and known food allergens and toxins. They did not find any matches, but that doesn't mean there aren't any potential problems with regard to the human food supply and health.

A key point here is that the viral gene promoter and its unintended gene VI tag-along are rarely discussed, but it is far from certain that there are no negative, unintended consequences. Nonetheless, this didn't stop some like David Kroll at Forbes magazine from declaring that GMO opponents shouldn't "freak out" about viral genes artificially put in their food, because he says the viral gene itself won't hurt us.

That completely misses the point that the viral gene might have negative effects on the plants before we eat them, or might produce peptides in the plants that can have harmful effects on animals or humans that eat them.

There are several questions that should have been answered before these plants were approved for human or livestock and poultry consumption, including 1) are any portions of Gene VI translated into polypeptides in the transgenic plants?, 2) does the 35S promoter sequence alter the expression of any other proteins or peptides in the plant genome?, and 3) do any measurable compositional changes occur in the transgenic plants that would indicate that they are inherently different from plant varieties produced by standard breeding techniques? From my own area of research I can say that it is clear that at least one transgenic plant variety has substantial changes in its constituents as compared with standard varieties.

"Corn Event 98140," sounding like something straight out of a Twilight Zone episode, is a GMO made by Pioneer. This is a relatively new version of a Roundup ready corn that uses a different method of conferring Roundup resistance to transgenic plants. The active ingredient in Roundup is a chemical called glyphosate, so Roundup ready plants are "glyphosate resistant." Rather than inserting a bacterial gene that would confer resistance to glyphosate as was done by Monsanto, researchers at Pioneer engineered a non-natural enzyme that would metabolically alter the glyphosate by making it into acetyl-glyphosate, thus preventing Roundup from killing the plants.

This is where the research from our laboratory intersects with Corn Event 98140. Our research focuses on a brain enzyme (called an acetyltransferase) that is similar to the artificial enzyme that was engineered into Corn Event 98140. The brain enzyme that we have focused on acetylates the amino acid aspartate, to produce N-acetyl-aspartate (NAA), one of the most concentrated chemicals in the human brain, whereas the Pioneer engineered enzyme acetylates glyphosate, the active ingredient in Roundup herbicide, to produce acetyl-glyphosate. One of the unintended consequences of inserting the gene for this engineered enzyme into corn plants is that the plants don't just acetylate the glyphosate that is sprayed all over them, they acetylate lots of other things too, including the amino acid aspartate. So that means Corn Event 98140 contains high levels of the brain chemical NAA, and a number of other acetylated compounds that are normally not found, or found at only very low levels in naturally bred corn varieties. NAA is not harmful to eat, but that is not the point.

Corn Event 98140 is a different plant - one which produces many different metabolites than those found in normal corn. The other unintended consequences in this food plant variety are basically unknown, or perhaps known only to Pioneer researchers and management. For example, uncontrolled acetylation of proteins can have many unintended consequences. Protein acetylation alters protein function, and in the case of gene-associated proteins such as histones, acetylation alters the way genes are expressed in cells. Research into whether any proteins, especially histone proteins associated with gene activation, are hyper-acetylated or hypo-acetylated in plants such as Corn Event 98140 should have been done long before this product was approved for use.

In addition to the artificial acetyltransferase transgene, Pioneer researchers also inserted a second transgene into Corn Event 98140, in order to confer resistance to another class of herbicides, making this particular corn variety highly artificial, and likely to have many unintended traits in addition to the ones already reported. Adding multiple genes to a GMO is called "gene stacking" which is certain to exacerbate unintended consequences. Considering the highly artificial nature of Corn Event 98140 and the obvious differences in composition from normal corn, much more research should have been conducted before this product could be used for human or animal consumption. When livestock and poultry are fed continuous diets of herbicide laden crops and crop products, the animals will bio-accumulate any toxins in their meat presenting a potentially greater risk to human health than the crops themselves.

The simple fact of the matter is that GMO plants like Corn Event 98140 are different from their natural counterparts in various ways including; 1) they may contain viral genes for proteins that were not intended to be incorporated into the plants (for example, portions of Gene VI), 2) they may include artificially created genes which make artificial proteins that could have unintended consequences, for example producing an array of acetylated compounds not normally found in natural plant varieties, and 3) the possibility that protein function could be altered, for example by altered acetylation, thus changing the plant's physiology and composition in unknown ways.

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John R. Moffett PhD is a research neuroscientist in the Washington, DC area. Dr. Moffett's main area of research focuses on the brain metabolite N-acetylaspartate, and an associated genetic disorder known as Canavan disease.

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