Rickinreallife's picture
Dr. Michael Antoniou et.al wrote an open letter to Dr. Megan Clark, Chief Executive CSIRO opposing conduct of human trials to test the efficacy of genetically engineered wheat to have lower glycemic index, that included this claim “There is a large body of evidence that shows that GM crop / food production is highly prone to inadvertent and unpredictable pleiotropic effects, which can result in health damaging effects when GM food products are fed to animals.” The letter cited the following to support this statement: 1. Pusztai A. and Bardocz S. (2006). GMO in animal nutrition: potential benefits and risks. In: Biology of Nutrition in Growing Animals, eds. R. Mosenthin, J. Zentek and T. Zebrowska, Elsevier Limited, pp. 513-540. 2. Schubert D.R. (2008) The problem with nutritionally enhanced plants. J Med Food. 11: 601-605. and 3. Dona A. and Arvanitoyannis I.S. (2009) Health Risks of Genetically Modified Foods. Crit Rev Food Sci Nutr., 49: 164–175. How long has science been aware of the concept of pleiotropic effects and how is an assessment of potential pleiotropic effects incorporated into the regulatory approval process?

A:Expert Answer

RickInRealLife, the best part about pleiotropic effects is that they are pleiotropic! If there was something inadvertent happening that was seriously affecting the physiology, development or metabolism of the plant – it would stick out like a sore, well, leaf. 

 

The claims that there are some unintended glossed-over issues are great to generate an alarmist response, but don't hold much weight in reality.  The idea is predicated on the possibility that gene inserted (the "transgene") may land in a place where it has some role in eliminating a resident gene's function or perhaps increasing it.  That COULD happen. It DOES happen.... but is it something we need to worry about?

 

Certainly we need to know if something collateral happens.  The first indicator might be that the plant itself would never develop or would have severe problems.  Remember, they harbor the transgene and their cells share a lot of similarities with ours. If there was a problem, you'd see it.

 

Today our tools are extremely sensitive.  If the insertion of the transgene had an effect on gene expression (a super sensitive process), we could figure it out in a few days using a process of RNAseq.  Changes in proteins could be visualized with proteomics and metabolic techniques could show changes there.  Basically, if there was a pleiotropic effect, or even a minor collateral one, science would find it!

 

Remember, these genes are engineered into elite backgrounds that are highly productive on their own.  The big co's are going to be darn sure that the inserted gene will not compromise the genetic integrity of the plant, or its safety for those consuming it.

 

But just to give you something to think about... if Antoniou and others fear effects of a transgene, imagine how much sleep they'd lose if they learned about transposable elements.  Transposable elements are natural "jumping" sequences found in massive numbers in many plant genomes.  They move, reinsert, wreck, create, and remodel genes and genomes all the time.  If you see a problem come up in a GM plant it is much more likely that a natural jumping gene did it long before the transgene did!

 

In the end it is an outdated argument.  Today's tools are so sensitive that anything detracting from the safety or quality of the final product would be recognized and eliminated – in the unlikely event that it happened at all.

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Andrew Kniss's picture

You also may be interested in this recent review article: http://www.ncbi.nlm.nih.gov/pubmed/23457026

In a nutshell, herbicide resistance genes can be introduced both by genetic engineering and by conventional breeding techniques. Darmency reviewed the available literature and found that pleiotropic effects were actually more likely to be observed where conventional breeding techniques were used, but could be found in both GE and conventionally bred varieties.

Rickinreallife's picture

Can you define pleitropic effects?

Rickinreallife's picture

Mr. Folta -- I appreciate your answer and had prior to asking the question a layman's understanding that modifying the genetic information of a plant by whatever means, crossbreeding, mutigenisis, transgenic insertion, etc. could potentially alter the plant in unintended ways, and even understand that GE techniques are probably less likely to result in unintended alteration of gene function and expression than other techniques, and we are even more likely to detect any such changes if they do occur through GE development processes and regulation . I also understand that no matter what the method utilized to alter the genetic endowment of plants, breeders are likely to eliminate plants that exhibit undesirable pleiotropic effects in the testing and analysis of plants that occurs prior to marketing and perhaps even prior to submitting for regulatory approval in the case of GE. Thus, if adverse pleiotropic effects did occur, they would probably be abandoned or backcrossed out anyway.

My question was trying to get at to what extent the regulatory process requires entities to identify and document any such alterations, such as in the comparison of the genome of the ge plant to parent or isolene phenotypes, or in the profiling and analysis of any change in protein expression in the harvested portion of the plant, including any novel proteins or accenting or suppression of familiar proteins. You mention that the tools available to us today enable us to detect unwanted pleiotropic events. Could you desribe what those tools are and how analysis for pleiotropic issues is are used in the regulatory process.

One of the persistent inferences of those opposed to altering the genetic endowment of plants through genetic engineering techniques is that the the ge process, as opposed to other processes, somehow is like a vampire bite, that although the resultant variety looks and functions similarly, there has been some type of insidious transformation of the nature of the plant into some artificial, zombie like replica of a non ge version. I am not buying that voodoo, but I do concede that some unintended alterations in gene function and regulation (that does not necessarily rely on paranormal explanations) could occur in the GE process. A prominent anti-gmo argument is that nature and genetics is complex beyond current scientific competency to understand, let alone control and thus we are playing the sorcerers apprentice, potentially unleashing unpredictable consequences. I am just looking for confirmation that science is much more capable than opponents would represent, and that the regulatory system utilizes these competencies.

Lisa's picture

I think this is an excellent exchange of questions and answers. After reading them, my question remains: are we actually using the methods named in order to determine what unwanted changes may have occurred? We know that both conventional and GE breeding cause many genetic alterations. But those which are prone to create unwanted effects are more likely to occur in certain types of GE, or in mutagenesis.
Dr. Folta says:
"Changes in proteins could be visualized with proteomics and metabolic techniques could show changes there."

But is this actually done? My understanding of regulations says that it doesn't require such comparison between parent and GE plant, and that such testing is very expensive. More importantly, although we can gain a lot of information about changes that happen by using these testing methods, we don't yet know how to interpret the information we gain. We've seen that GE crops have had changes realized only after commercialization , often in response to environmental stressors. So, I guess I basically disagree with Dr. Folta's assessment of this situation of unwanted changes in GE plants.

Summation: does deregulation require proteonomic and metabolic assessment of the GE plant?

Rickinreallife's picture

LISA, I would agree with you that this is the area where I believe responsible, legitimate questions can be raised. "Has the gene insertion event or other direct tinkering with the genome made possible through genetic engineering caused collateral effects on gene expression and regulation elsewhere in the plant?" is a valid question. As omics tools become more perfected, this perhaps gives us a means to answer that question, or at least greatly reduce the area of uncertainty.

Subsequent to asking this question, I have kept my eyes open for research articles that explore this very question. I conclude as you do that at this point, the omics analysis methods might be prohibitively costly to be used as a routine regulatory assessment, and as you mention, how to interpret the results is problematic. What is normal metabolic activity, gene expression, protein content? Suppose we test new products that have ge insertion events as part of their genetic endowment and we find that ge A consistently produces more of metabolite X than a non-ge isolene A grown right next to it. What does that tell us. But, what if both ge A and isolene A have less of metabolite X than the indigenous cultivars grown in Mexico, which are assumed safe. I could take seeds from an organically grown heirloom tomato variety originally grown in California and plant some seeds in California and other of the seeds in northern Minnesota -- the change in soils, climate, growing season stress are likely to result in significant differences in the gene expressions and regulationsm, metabolic parameters even though the genetics were identical. Do we declare the tomatoes grown in Minnesota a hazard?

FYI, in case you hadn't come across them, here are two actual primary research articles and one metanalysis of several studies examining the question of whether genetic engineering itself appear to have significant or material changes more than or distinct from other forms of genetic manipulation.

"Compositional differences between near-isogenic GM and conventional maize hybrids are associated with backcrossing practices in conventional breeding" http://onlinelibrary.wiley.com/doi/10.1111/pbi.12248/abstract;jsessionid..., "A comparative analysis of insertional effects in genetically engineered plants: considerations for pre-market assessments" http://link.springer.com/article/10.1007/s11248-014-9843-7/fulltext.html... Evaluation of Genetically Engineered Crops Using Transcriptomic, Proteomic, and Metabolomic Profiling Techniques, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091128/

Rickinreallife's picture

Actually, I think one of my citations is the same one that Andrew Kniss suggested earlier.