Review of "A Comparison of the Effects of Three GM Corn Varieties on Mammalian Health"

After a brief vacation in the land of poutine, ketchup flavoured chips, Tim Horton's, and my awesome niece and nephews, I'm back in California where it still hasn't rained. The spouse and I have decided to install artificial grass in our yard, but dang!! That stuff is pricey!! Someone should work on implementing some sort of tax break for getting it installed.

This week, I received a request to look over a paper entitled "A Comparison of the Effects of Three GM Corn Varieties on Mammalian Health". The paper was published in 2009, and one of it's authors is Giles-Eric Séralini (you can read about the "Séralini affair" on Wikipedia. My previous posts on his work can be found in the index under "Seralini Study").

The paper (I'll be referring to it as the "de Vendômois paper") is freely available so you should be able to view it. Monsanto wrote a response, but I'm going to go over the paper and my own impressions before reading Monsanto's. I will then provide an overview of those critiques and my conclusion.

When a GMO goes through the regulatory process with the FDA and other agencies, a feeding study is performed where the GMO is fed to rats for 90 days and different parameters are measured. The goal is to determine if there are any health impacts during this time period. Since the rats used in these studies live 2.5-3.5 years, 90 days represents approximately 7-10% of their lifespan.

de Vendômois obtained data from Monsanto's 90 day feeding studies for three strains of corn: one strain was Round-up Ready (NK603) and two strains contained the Bt-toxin (MON810 and MON863 - please see this excellent post from Biofortified on how Bt works). de Vendômois outlines that he had to get court orders to obtain some of the data, and worked with Greenpeace to get these.

The 90-day feeding studies performed by Monsanto consisted of 200 male and 200 female Sprague-Dawley rats for each feeding study. There were two doses of GM-feed, meaning that some rats got more GM corn in their feed than others (11% and 33%).  Of the 400 rats in each study, only 80 were fed the GM diet, while 320 were controls. de Vendômois states that the large number of controls is because there were several types of control feed: some were from the non-GM variety of the GM corn, but other non-related corn were also included as controls. de Vendômois was not pleased with the fact that there were way more control rats than rats being fed the GM stuff.

I understand the use of different types of controls, as well as wanting equal number of treatment and control rats. In having so many controls, I imagine that Monsanto wanted to figure out if any health impact observed was due to the corn itself or due to the transgenic protein. Here's a completely fictional example: if I take a Granny Smith apple and make it glow in the dark, I'd do a feeding study to determine the impact of the glowing gene on rats. As a control, I'd use a regular Granny Smith apple. But I might also want to include a Red Delicious apple as a second control. That way, if I see something odd happening, I'd be able to determine if it was due to the glowing gene or something that's unique to the Granny Smith apple (such as higher acidity). Yet I also understand the perspective of wanting to have a more equivalent number of rats. But doing the logical math, I'd assume that the 80 treatment rats get broken down to 40 per dose, and further broken down to 20 per gender. That's pretty good (I thought that this criticism was pretty ironic, since 20 per gender per treatment is more than what Séralini used in his own study, done a few years later). However, for some reason, apparently only 10 of the 20 rats were chosen each time for the blood and urine collection. Additionally, blood and urine were taken at only 2 time points, and de Vendômois thought that this was far too low for any useful statistical analysis. I'm REALLY curious to see what Monsanto's response is to this! You'll just have to keep reading!

de Vendômois points out that 2 dose levels is not standard and that 3 is the recommendation. I double-checked the OECD guidelines and this statement is accurate (please see point 17 in the link).

The Sprague Dawley Rat
From Wikipedia

Then, the paper starts going downhill. The description of the statistical tests used makes no sense. They run the data-set through a variety of tests, jumping from one to the next, and the only reason I can think of is that they're just fishing for some type of significance, regardless of how. Based on my understanding of stats, you select a statistical method/test for the type of data that you're analyzing and the comparison you're doing, and you stick with it throughout the entire data-set. If you find significance, great! If you don't, then you can't just say "alright, now I'll run it through this separate test to see what I can find," unless there's a very good reason for doing so. No such reason is provided.

Spouse, I can hear your demands for a better explanation about this in my head. This article from Wikipedia gives a great description of why this is important: "When large numbers of tests are performed, some produce false results, hence 5% of randomly chosen hypotheses turn out to be significant at the 5% level, 1% turn out to be significant at the 1% significance level, and so on, by chance alone. When enough hypotheses are tested, it is virtually certain that some falsely appear statistically significant, since almost every data set with any degree of randomness is likely to contain some spurious correlations. If they are not cautious, researchers using data mining techniques can be easily misled by these apparently significant results."

This is a big flaw and basically makes their analysis meaningless. I scanned through the rest of the paper and nothing really jumped out. The measurements where they find significance are not maintained between sexes, and that doesn't make sense for things like liver or kidney function (I double-checked with my brother and sister-in-law, who are MDs, and they agreed that after balancing for weight, a toxic compound should impact males and females equally).

Alrighty... Moving on to Monsanto's response, which is readily available here.

In addition to the issues pointed out before, a solid point that Monsanto makes is that de Vendômois doesn't examine whether or not the "statistically significant" values are within the normal range for the strain of rat. Meaning, is it biologically relevant?

Monsanto also states that their study has enough data for the standard statistical test used for these types of studies. Their point is that if de Vendômois had done his analysis with the "normal" stats methods, there might have been enough data.

Monsanto's response concludes with statements from 3 international regulatory agencies who reviewed the data: the European Food Safety Authority, the Food Standards Australia New Zealand, and the French High Counsel on Biotechnology. All the agencies conclude that the reanalysis of Monsanto's data was performed with crummy statistics and the results don't mean anything.

However, Monsanto does not address the issue of 2 dosages.

Here are my conclusions: regarding the safety of these specific traits, I think there's a LOT to suggest that they're safe. One of the common comments that I've read from those who defend Séralini's work is that his studies indicate that follow-up and longer-term analysis is needed. I completely understand that argument, but the work has already been done. For example, look at this paper which consists of a short-term feeding study of MON810 in pigs (note that I've only read the abstract): its conclusion is that there were a few differences that merited a long-term study. Then, they performed the long term study and found that any differences observed were not biologically relevant. Séralini has been at this for quite some time and he hasn't found anything that is biologically relevant. Feeding studies for NK603 can be found here, here, here, and here (the last link is a study by Monsanto).

The second issue is that of standardization of feeding studies. I've written about this before: I think that there's need for standardized tests as well as their analysis. de Vendômois's paper highlights the point, particularly for the analysis! Imagine how much money and animal lives would be saved if crummy feeding studies weren't performed. If the OECD guidelines are the ones that are supposed to be followed for feeding studies, then everyone should stick to them, whether its Monsanto or Séralini.

I want to be abundantly clear about this: I think that crops should be regulated based on the trait, not on the method used to generate that trait. So standardized tests should be used for conventional crops, too, when necessary. It doesn't make sense to have huge feeding studies on a trait that has already been tested: other experiments and data may be required, but a feeding study to determine the effect of the transgenic (i.e. "added") protein seems redundant. It seems ironic that hybrids such as nectaplums or broccoflowers aren't regulated when so many different genetic events occur during their creation.

Anyhoo, that's it for this paper. The next few posts I have planned are to finish up my series on sequencing papers examining GMOs, and my former work-spouse asked me to write about GMOs and butterflies. If you have any requests, questions, suggestions, or corrections to provide, please comment below!

Learning about GMOs: A reflection on year one

It's been over a year now since I started learning about GMOs and writing this blog. I've learned so much and am humbled every day by how much I have yet to learn. But as I look back and reflect on the knowledge gained, I also see that it's quite a bit, particularly considering all the life-events that have taken place in parallel. I thought that I'd share with you my learnings about GMOs that have surprised me the most.

Some of these were on the level of an M. Night Shyamalan movie-twist for me. Some are not even about GMOs, but just about agriculture and our food in general. Yeah... I kinda feel embarrassed about not knowing a few on the list... Don't judge me!

Corn. But without the syringe in it to depict that it's a GMO,
it's not really scary.
From Wikimedia Commons

1) The vast majority of fruits and vegetables are not transgenics. Before starting this blog, I thought that most of what we ate were transgenic crops, meaning that they had a gene/protein from a different species. I had heard so much about tomatoes with fish genes and strawberries that would never freeze that I just assumed that all that stuff was out on the market. Every time I picked up a fruit in the supermarket that was particularly large, I thought to myself "huh... that's got to be a GMO". You know those grapes that are the size of a tennis ball, and squirt juice everywhere when you bite into them? Every time I ate one, I'd close my eyes and thank the mysterious GMO gods for that sweet delicious nectar. Little did I know that none of these fruits were GMOs. They were genetically modified in the sense that they had been bred and selected to have optimal sweetness and size through cross-breeding. But they weren't transgenic organisms. There are only a handful of transgenic crops such as corn, soy, or cotton. The short list can be found in this database (note that you have to select the type of approval to determine if the GMO has been commercialized or not).

2) Organic food production uses pesticides (EDIT: Not all organic food production and only pesticides that are permitted under the USDA's organic label and approved by the EPA. Which is also true about conventional farming). This one blew my mind. I couldn't believe it! I thought that by definition, organic food production did not use pesticides. Not only that, but some of the pesticides used are more toxic than those applied in conventional farming. The difference is that the pesticides used in organic farming are not synthetic. No idea why that is better... Here's a list of pesticides approved for use in organic farming.

3) Many plant traits are developed using mutagenesis. And can be labeled "Organic". This one melted my brain and the spouse still doesn't get it altogether. Mutagenesis is the use of radioactivity or mutating chemicals to create random mutations in plants, and selecting those with the desired trait (here's my blog post with an overview of various papers, and here's the Wikipedia article on the technique). This article from the New York Times lists wheat, barley and even ruby red grapefruits as crops generated through mutagenesis. Imagine that!! The delicious, organic, grapefruit from my farmers' market was developed using radiation to randomly create mutations, and somehow that's less scary than a GMO. Why the organic food movement isn't fighting for their labeling seems hypocritical, and the fact that they can exist under the umbrella of the organic label is astounding. Again: Mind. Blown.

4) There's lot of peer reviewed research on GMOs, both publically and privately funded. I mean a LOT. I remember the first time I typed in MON810 into PubMed (a database hosted by the NIH), I got over 100 hits. That's 100+ studies that have looked into some aspect, such as identification or safety, on a single seed/trait (MON810 is Monsanto's Bt corn) Since it's a database search, let's assume that some of them are only loosely related to MON810. But even if 50% are discarded, that still leaves us with 50+ studies on a single trait/seed. In a Q&A with the founders of Biofortified.org, they mentioned that the most common misconception about GMOs is that there aren't any studies. Although I didn't think that there were no studies whatsoever, I was blown away by the sheer number/volume of studies, many of which are publicly funded.

Don't get me wrong: just because I haven't read any credible studies suggesting that GMOs pose a health risk does not mean that we should stop studying them, both in terms of technical methods in their generation, as well as safety. Go ahead. Go to pubmed and type in MON810 :)

5) Types of traits used to generate GMOs generally benefit farmers, not shoppers. What I mean is that there aren't many GM crops where the trait introduced was selected because it would make me want to buy it in the grocery store. There are several crops in the pipeline designed for me, such as non-browning apples or soy that has healthy oils (my post about the non-browning apple is here). But at the moment, most crops are designed to benefit farmers, such as Bt crops which help farmers reduce the amount of pesticides sprayed to fight worms, or Glyphosate resistant crops, which help farmers fight weeds using glyphosate (my post about glyphosate is here). I have yet to write on the topic of whether GM crops lead to decreased pesticide use, so I have a lot to learn on this topic. 

It's important not to misinterpret this point: when costs decrease for farmers, the end consumer pays less. But this is an indirect benefit for the shopper. It'll be interesting to see if crops that directly benefit shoppers will impact their perspectives on GMOs.

6) The amount of misinformation surrounding this topic is staggering. And depressing. It ranges from the subtle, where statements are simply taken out of context or the complete findings of a paper are not provided, to outright lies. I expected that there would be misinformation, but I guess I was pretty naïve and didn't think it would be THAT bad. But it's downright awful. For example, the Institute for Responsible Technology's website states "The only published human feeding experiment revealed that the genetic material inserted into GM soy transfers into bacteria living inside our intestines and continues to function." The paper which this statement is based off of actually says "it is highly unlikely that the gene transfer events seen in this study would alter gastrointestinal function or pose a risk to human health" (this topic was reviewed in this post). This is a subtle little white lie, when you contrast it with the downright deceptive (and dangerous) statement that GM insulin poses a health risk (Dr Kevin Folta reviewed this topic here).

I still have a tough time understanding why certain organizations would use such deceptive means to attack a technology. I think Dr Neil DeGrasse Tyson said it best in his recent Facebook post on the topic of GMOs:  "If your objection to GMOs is the morality of selling non-prerennial seed stocks, then focus on that. If your objection to GMOs is the monopolistic conduct of agribusiness, then focus on that. But to paint the entire concept of GMO with these particular issues is to blind yourself to the underlying truth of what humans have been doing -- and will continue to do -- to nature so that it best serves our survival. That's what all organisms do when they can, or would do, if they could. Those that didn't, have gone extinct extinct. In life, be cautious of how broad is the brush with which you paint the views of those you don't agree with."

I was surprised at how many people distrust GMOs because of Monsanto. That's not a good reason for distrusting a technology with broad applications. It's like saying that you don't trust computers because of Microsoft. But conventional food growers buy Monsanto seeds too, and Monsanto doesn't have a monopoly on GM technology. So what do life saving technologies, such as insulin, have to do with Monsanto? What about Golden Rice? What about bananas designed to combat nutritional deficiency in Uganda? I was taken aback at how vehemently these are opposed, just because of the Monsanto-boogie-man.

7) Transgenic seeds are not sterile. I was certain that transgenic seeds could not be replanted, even if a farmer wanted to. I was dead wrong. When farmers buy seeds from a biotech company such as Syngenta, they sign an agreement, and they are not allowed to replant seeds. However, the seed is not sterile or unviable. (The topic of replanting seeds and terminator seeds was covered in my blog post here).

8) Peer review doesn't mean anything these days. Even if you don't factor in the issue of predatory or pay-for-play journals, peer review needs a new paradigm (check out this article for a great expose of predatory journals). In an article that sounds an awful lot like a story about drug trafficking, a "peer-review ring" got recently busted for abusing the academic review process. Although there's a growing number of ways to share concerns or criticisms about a paper, it hasn't led to a change in the review process. There's a whole website dedicated to covering stories about peer reviewed articles getting retracted.

Setting aside the reason behind errors in scientific journals, be they deliberate or not, there needs to be a positive feedback loop.

Personally, I think that scientists in the private sector should be able to provide feedback to the reviewers and editors about one of their products. They provide press-statements anyway once the paper's been published, so wouldn't it make sense to have their feedback and criticism in hand as a non-voting voice in the review process. Do you know who would read every single sentence several times, including the Supporting Materials section, in a paper that suggests that a GM trait is harmful? The scientist who made it and the company who commercialized it. If anyone is going to identify a flaw in a paper, it will be them. I don't think that their statement should carry weight in the decision of whether or not a paper should be published. But I think it will make the reviewer's job easier to have their observations in hand.


For the final point, I interviewed the spouse to find out what had surprised him most from all our discussions:

"9) That the greatest tool in combating misinformation on scientific topics is for scientists to be better communicators and to better educate the public. I was surprised to see that the link between the public's superstition regarding GMOs is directly related to their education or lack thereof. If we had better scientific literacy or better science education, it would cause less freak-outs. As a non-science person, my AHA!-moment came when I finally understood how eating a strawberry-fish smoothie would be same thing as eating a strawberry with a fish gene in it, because we can process and digest proteins from both species. That's such a small-little thing, but it created such a mental barrier."

Well, there you have it. Feel free to comment on the things that have surprised you most on this topic.

Handout for #ABS2014 - Independent Investigation of Truth in Social Media

Hi Peeps,

I'm giving a talk at this year's Association for Baha'i Studies. My talk is about the importance of setting aside biases, prejudices, and preconceived ideas before exploring a topic. This is particularly important for gauging the validity of information about science & tech that is presented in social media where information is not vetted and anyone can post anything. It also explores the idea that targeted marketing and the nature of social media don't expose us to different ideas that force us to consider different perspectives. Rather, we're exposed to more of our own perspective. I'll try to provide overviews of various studies that have analyzed the science of changing minds and the importance of practicing slow, conscious thinking when considering information, so that we do not come to the unconscious conclusions that our biases lead us towards. This will be supported with quotes from Baha'i literature that reinforce the principle of the independent investigation of the truth.

I put together a handout for the participants and here it is. All the information is from other websites, and I've provided the citations in the document:

https://docs.google.com/document/d/10Bi-jntXzxIkuaq6d2mnNKYbqH1A06qNIWRm7FKCNqQ/pub

Remember: before you post it, Snope it!!

If you want a copy of my talk, please email me.