To GM or not to GM? Another look at the data...

A recently circulated paper by Vendomois et al takes an independent look at data from food trials of genetically modified (GM) corn on rats. The data was originally obtained in studies conducted by Monsanto as part of the application for market approval of these GMOs. I'd like to highlight a few points here. But first, some introduction.

The original data stems from a trial where a population of rats was fed different kinds of GM corn over a period of 90 days. The GM crops in question were Monsanto's NK 603, MON 810 and MON 863.

NK 603 is one of the Roundup Ready crops. Roundup Ready crops are genetically engineered to withstand large doses of Monsanto's herbicide Roundup. The idea is that fields can be sprayed with Roundup, the genetically engineered Roundup Ready crops survive, and all the weeds around it die. Let it be mentioned here that this approach has drawbacks all its own, as weeds have started to develop a resistance to Roundup over the years, which led to ever increasing doses of the pesticide being necessary to kill weeds, as documented in another report.

MON 810 and MON 863 are Bt crops, which use a different approach. In these crops, a transgene derived from Bacillus thuringiensis was introduced into the genetic material: These plants were genetically engineered to synthesise the pesticide themselves.

So the suspicion, with all three crops, is that they may contain residual toxins: NK 603 from the exposure to large doses of pesticide, MON 810 and MON 863 because they actually synthesise the pesticide. The original study and analysis by Monsanto concludes that the crops are still suitable as food and feed. And this is what the authors of the independent study dispute.

To summarize, Vendomois et al have two main points of criticism. One is the methodoloy of Monsanto's study. They point out that several important physiological parameters were simply not recorded in the study, that the setup of the study had flaws, that the trial period of 90 days was much too short, and that the statistical power of the recorded data points is not sufficient to conclude that the GM corn is not toxic.

The other point of criticism is derived from a re-analysis of the available data. The authors find signs that point to a possible toxicity where the original Monsanto analysis glossed over certain things, for example claiming that a disturbance in kidney function was nothing to do with the GM corn, but stemmed from a susceptibility to kidney problems of the specific strain of rat used. Vendomois et al point out here that even with such a susceptibility, the rats in the study were too young to spontaneously develop kidney disease, and what's more, the disturbance of kidney function was specific to the MON 863 group - none of the other two GM groups or control groups exhibited this kind of problem.

Generally, Vendomois et al conclude that the study does not support the claim that the GM crops in question are safe. Instead, the data indicates a necessity for further studies and signs of possible toxicity. For a lack of enough data, the authors can only speculate whether the signs of toxicity stem from the residual pesticides in the crops or whether they are due to as yet unknown side effects of the genetic manipulation.

Let me elaborate here: Genetic manipulation is not as neat as one might imagine. It's not a matter of laying out the genomic material on a table, neatly cutting out the features one does not want and inserting others in a suitable place and be done. The way genetic manipulation currently works is messy and known to be mutagenic in ways that are almost impossible to predict. The process is rather disruptive and can cause rearrangements, insertions and deletions in parts of the genome that were never targeted. The mutagenic effects of genome manipulation are explained in more detail in the paper "The Mutagenic Consequences of Plant Transformation" by Latham et al. Consider the following passage from Latham et al:

"One [study] analysed the commercialised Roundup Ready soybean insertion event 40- 3-2. In addition to the intended EPSPS (enoylpyruvate shikimate synthase) transgene described in the original application for commercial approval, the authors found a 254 bp EPSPS gene fragment, a 540 bp segment of unidentified DNA, a segment of plant DNA, another 72 bp fragment of EPSPS, and evidence for additional alterations to flanking plant DNA, (USDA Application # 93-258-01p). These insertion-site mutations were reported only after commercialisation of Roundup Ready soybean insertion event 40-3-2. Interestingly, independent analysis of another commercialised event, Maize YieldGard (event Mon810), also found evidence for previously unreported insertion-site mutations."

So when you introduce new material into a plant's genome, you do not really know in which ways specifically you altered the plant. This is what Vendomois et al are talking about when they wonder whether the toxicity might not be due to some other, unknown change in the corn's genome. What with the ever-dropping prices of genome sequencing, I wonder whether it might not be feasible and insightful to sequence the parent strain of the GM corn, then sequence the GM corn and hunt for unexpected differences that might have arisen during the genetic manipulation.

The paper contains one more interesting point, in the section on Data Collection:

"The raw biochemical data, necessary to allow a statistical re-evaluation, should be made publically available according to European Union Directive CE/2001/18 but unfortunately this is not always the case in practice. On this occasion, the data we re- quired for this analysis were obtained either through court actions (lost by Monsanto) to obtain the MON 863 feeding study material (June 2005), or by courtesy of governments or Greenpeace lawyers. We thank the Swedish Board of Agriculture, May 30, 2006 for making public the NK 603 data upon request from Greenpeace Denmark and lawyers from Greenpeace Germany, November 8, 2006 for MON 810 material."

Well, isn't this just fascinating? Monsanto was obliged to publish the data, but had to be forced to fulfill their obligations through lawyers and court action.

One last word of caution against roundly condemning GM crops: In the case of Roundup Ready crops, we don't know yet whether the signs of toxicity are due to the pesticide residues or due to side effects of the genetic manipulation. If it proves to be the former, then let it be said that genetic engineering would not be the culprit here at all. A similar effect would have been observed had the crops been traditionally bred to withstand high doses of pesticide.

Now go and enjoy your food.