Review of "10 Scientific Studies Proving GMOs Can Be Harmful To Human Health"

As you may know, Mr Chubby-Cheeks is getting potty trained. What I never expected is how exhausting the whole ordeal is. If someone set up a service where you dropped your kid off and
picked him/her up a few days later fully potty-trained, they'd be gazillionaires.

Anti-GMO protest at BIO international conference 2014 in San Diego
Taken by a friend who attended.

Let's get down to business (no pun intended)... A story popped up in my Facebook feed that I have to take the time to address. It is entitled "10 Scientific Studies Proving GMOs Can Be Harmful To Human Health". Really caught my eye. It's actually a pretty good at bringing together the top health concerns that the anti-GMO movement has about the technology. I've reviewed most of them, so there will be a lot of links here to previous reviews and to the studies themselves. I'll go in the exact order as the article.

1) Multiple Toxins From GMOs Detected In Maternal and Fetal Blood.
I first reviewed this paper last year. The authors identified Bt protein Cry1Ab in maternal and fetal blood. This protein is found in some GMOs, but is also commonly used as a pesticide in organic farming. The biggest issue I had with the paper was the "so what" factor. We lack the receptors for the protein, so it has no impact on us. Did you know that chocolate is toxic to dogs? Are you concerned that it might be toxic to you? Probably not (if you are concerned, then you've missed out on the greatest source of joy known to human taste buds...) Some chemical compounds behave differently between species, and both Bt's Cry1Ab and chocolate are examples of this.

Since my original review last year, I've learned that the paper is deeply flawed due to the fact that the researchers' measurements were based on an experiment/assay that was designed to detect Bt in plants, not in humans. This post in Biofortified.org eloquently outlines that the pregnant women in the study would have had to eat several kilos of corn in order to get the Bt measurements that were detected in their blood.

2) DNA From Genetically Modified Crops Can Be Transferred Into Humans Who Eat Them
Ummmm... No. That's not the paper's findings. I reviewed this one fairly recently. The paper found that whole genes from our food can be detected in our plasma. That does not mean that it's been integrated into our DNA: it means that it's been found floating in the space between cells. And that's any food, not just GMOs. I also outlined how the paper's findings are most likely due to contamination, since they did not include a negative control. However, even if the findings are accurate, DNA from GMOs behave no differently than DNA from organic or conventional foods. If you aren't concerned about the DNA from blueberries "transferring" into you, then you should not be concerned about DNA from GMOs either.

3) New Study Links GMOs To Gluten Disorders That Affect 18 Million Americans
The article states that this was a study from the Institute for Responsible Technology (IRT). There is no such study. There's a post on a webpage, but there isn't a peer reviewed article. I wrote about gluten allergies and GMOs last year, and it's a case of association with no causation (i.e the incidence of gluten allergies have increased over the past decade and the amount of GMOs we eat have increased too. But, so have the number of plasma screens manufactured). Additionally, GMO wheat has not been commercialized. The Celiac Disease foundation has spoken out against the IRT's report (Note that the IRT is an NGO which advocates for the elimination of GMOs from our food supply. It's not a university, college, or research institution). Recent studies have shed doubt on the existence of non-Celiac gluten sensitivity. So this "study" is blaming GMOs for something that may not even exist.

4) Study Links Genetically Modified Corn to Rat Tumors
This is the infamous Seralini paper, which was retracted, and recently republished in a different journal. This was the very first paper I reviewed, and frankly, I'm surprised it was ever published (which explains the retraction). The paper identified tumors in rats who were fed GMOs long-term, but the strain of rat used was predisposed to tumors. The paper did not perform statistical analyses and used too few rats, so it was not possible to determine if the tumors were due to the food or were due to the fact that the rats would get tumors regardless of what they were fed. A recent, fantastic re-analysis of their data suggests that their findings are due to chance. Finally, the findings from Seralini's paper are contrary to other long-term feeding studies (you can find a journal review here and a BioChica review here).

5) Glyphosate Induces Human Breast Cancer Cells Growth via Estrogen Receptors
This paper was interesting and here's the breakdown: as this Wikipedia article highlights, approximately 80% of breast cancer cases are hormone sensitive, meaning that they need estrogen in order to proliferate and spread. In this paper, they took 2 breast cancer cell lines: one was estrogen sensitive and one was not, and they examined the impact of increasing amounts of glyphosate on cell growth. They found that glyphosate has similar impact to breast cancer growth as estrogen, although not as strong, and did not have an impact on the proliferation of the non-hormone sensitive breast cancer cell line.

They did a series of experiments which suggest that this growth is mediated through estrogen receptors (suggesting that glyphosate is probably mimicking estrogen). I thought that it was an OK paper. The #1 issue I had with it were the dose-dependent effects. At high concentrations of glyphosate, the cell growth starts to dip back down to the level seen in controls. Here's the issue: often times, there's a saturation point when you're looking at dosage effects of a compound, meaning that at a certain point you won't get an effect no matter how much more of that compound you add. But based on my understanding, you shouldn't really get a decrease in the curve; it should just level out. Like the top two graphs:

From Wikimedia Commons

However, they saw a dip in cellular proliferation at higher concentrations (it was more bell shaped). Their measurements were made based on a comparison to controls, but the data for the controls wasn't provided, so I'm not sure if perhaps the controls were behaving wonky or if there's actually a "protective" effect once glyphosate concentrations reach a certain point. Given the nature of the experiments they were performing, I'm surprised this was omitted. The second issue I have is that their negative controls don't have error bars, despite the fact that they had 3 replicates. My understanding of the statistical test they performed is that the standard error for the negative control is pretty dang important, but it isn't shown in any of their analyses.

In the past, I've highlighted the many issues that surround the use of in vitro assays. The authors of the paper highlight some of these issues, along with the fact that their data doesn't mesh with previous studies that have examined the impact of glyphosate on cell proliferation (this paper that suggests that glyphosate protects against cell proliferation in vitro in 8 different cancer cell lines and even states that it be developed into an anti-cancer drug...). They suggest that it may be due to a) the specific cell-line they used, b) their use of raw glyphosate (i.e. not a formulation, such as Round-Up) and c) the concentrations of glyphosate used.

Monsanto wrote a response to the paper stating that there are many studies that have examined the carcinogenicity of glyphosate and have found that the compound does not cause cancer. Many articles took this study to mean that glyphosate causes cancer when that is not the study's findings: their findings suggest that glyphosate may cause breast cancer to proliferate. Monsanto points out that this finding is contrary to the body of evidence that exists on the topic. As I previously mentioned, the authors admit to this fact and discuss that the next step should be to examine this issue in mice/rats models for breast cancer. I think that that's a great next step. I'd also look at this in a few more breast-cancer cell lines.

So, am I concerned about GMOs based on this paper? I think that this is probably the most compelling research paper that I've read about a potential health risk surrounding glyphosate, but my conclusion is that the study must be reproduced and its issues ironed out. The paper isn't really about GMOs: keep in mind that not all GMOs are glyphosate resistant (i.e. Round-up Ready) and the use of glyphosate is not limited to GMOs (I've said it before and I'll say it again: lumping crops into bins based on the method used to generate them does not make sense). Even a labeling law wouldn't help with that. Additionally, the paper does several experiments with a compound in soybeans that is known to be estrogen-like, and glyphosate's impact is very similar. Meaning that there are "natural" compounds in our food that seem to have the same impact on breast-cancer proliferation that this paper's findings suggest for glyphosate. In learning about this topic, I found quite a few publications that have examined soy food intake in patients with breast cancer (examples here, here, and here) and I couldn't find a study that had found a positive correlation. So more research is needed.

6) Glyphosate Linked To Birth Defects
Ummmmm... No. This is not a peer reviewed, published scientific study which the post claims. This is a publication by Earth Open Source, whose bias I have highlighted here.

7) Study Links Glyphosate To Autism, Parkinson’s and Alzheimer’s
The paper, doesn't constitute research. It's a hypothesis. I tried reading it several times and it didn't make sense. But I felt a lot better when I learned that I wasn't the only one who scratched my head at it: it was reviewed by Keith Kloor over at Discover Magazine who reported an apt comparison between the article and one of Glenn Beck's chalkboard drawings.

So how did it get published? The paper is printed in a pay-for-play journal (also known as predatory journal), meaning that for a fee, you can get nearly anything published. Spouse, I can hear you now... "What do you mean?? Isn't that against research?" Yes. It is. It sucks. There have been several exposés on pay-for-play journals, and many (including myself) believe that it's eroding the quality of science (here's an overview from Nature.com). In this exposé, the journalist cut-and-pasted two articles together: one was a geology paper and the other was a medical paper. For added effect, he added graphs about Mars and the footnotes were about wine chemistry. Yet the paper was accepted in several journals.

Spouse, I know your next question is "then why aren't you submitting tons of articles??". Well, there's the ethics thing, but it costs about $1800 to publish in these crummy journals. Hence the "pay-for-play" label. The important point is that it is often difficult for individuals to determine if the research is any good, unless they're an expert in the field. And, as outlined in the link to Discover Magazine, experts in the field have stated that this particular study is junk.

8) Chronically Ill Humans Have Higher Glyphosate Levels Than Healthy Humans
This paper is published in the Journal of Environmental and Analytical Toxicology, owned by the Omics publishing group. This publisher tops the list of predatory journals, and there's even a Wikipedia entry about the quality of their journals.

Notwithstanding, I read the paper and now my brain hurts from how painful it was to read. They examined glyphosate levels in humans and different animals. There's no indication of what was fed, how much was fed, how the animals were kept, or a million different variables for which there is no information. Any of these should invalidate the study. Their information about humans is even worse. It doesn't say anything about age, sex, weight, height, genetic background, how much food they ate, if they washed their food, how long they had been eating organic/conventional diets and, most mind-blowing of all, there's absolutely no definition for "chronically ill". I really don't know how you can draw any sort of conclusion from this study. Any single issue that I've listed here would be considered a fatal flaw that would exclude the paper from publication in a more prestigious journal, let alone having all of them combined in one hot mess.

9) Studies Link GMO Animal Feed to Severe Stomach Inflammation and Enlarged Uteri in Pigs
I read this study a while ago, but never wrote anything about it. The findings of the paper are pretty much in the title: they gave pigs GMO feed and non-GMO feed and identified differences between the two groups. I never wrote about it because to this day, the paper still isn't in PubMed, which is the NIH's database for scientific publications. It was because of this paper that I learned that PubMed doesn't index journals of low caliber or newly established journals. I felt like the NIH was weeding out the worst of the worst for me.

However, the paper has been thoroughly criticized by many.  Here's a brief list of a few of the issues:

• This post, by Mark Lynas, highlights the degree to which the data is cherry-picked. The difference in "inflammation" between the GM-fed and non-GM-fed pigs is apparent only when you break down the degree of inflammation into subcategories, but there's no difference if you view it as a single category. Overall, there's a high rate of inflammation for both groups, which is not explained in the paper. At the same time, there are several parameters where GM-feed could be argued as having a protective effect (there's 50% fewer heart-abnormalities in pigs fed GM-grain), but this isn't discussed.  
• As explained by Dr Anastasia Bodnar, the authors do not analyze the compositional differences in the feed between the two groups. Previous studies have determined that the environment (i.e., water, soil, geography) of a crop has a greater impact on proteins and metabolites than whether or not the crop is a GMO [my review of the topic is here]. As such, the differences seen in the pigs may not be due pesticides or presence/absence of the transgenic protein, rather, they may be due to differences in composition of the feed.
• The study is a fishing expedition. Meaning that they're looking for something, no matter what it may be. As outlined by Dr David Tribe, if you take 2 groups of things and measure ~20 parameters, one of them is bound to be different. The authors do not perform the proper statistics nor do they examine the relevance of the findings. Does it matter that certain variables are different between the groups? Why are they different?  
• This interview with Val Giddings highlights that the animals had abnormally high rates of pneumonia, which points to the possibility that something wonky was going on.

In conclusion, even if the paper's findings are real, there's no knowing whether it was due to something associated with the transgene or not, because they didn't account for natural variation in the feed.

10) GMO risk assessment is based on very little scientific evidence in the sense that the testing methods recommended are not adequate to ensure safety.
There are three papers associated with this bullet point. The first is a review and I agree with a few of the points it makes. It highlights the need for standardized tests and statistics in animal feeding studies for GMOs, and anyone who followed the Seralini debacle would probably agree. It summarizes papers that have performed feeding studies and their results. The biggest issue I have with the paper is that it doesn't remove flawed papers from their review list and it also doesn't distinguish between feeding studies for GMO crops that have been commercialized vs crops that have never been submitted for regulatory approval. However, the paper does not conclude that "GMO risk assessment is based on very little scientific evidence". The second paper is also a review/opinion, and the first author is affiliated with "Friends of the Earth". Skip! (Spouse, to clarify, the reason I'm skipping is a) it's not novel research, it's a review with an editorial slant and b) it's like reading an editorial by Syngenta advocating for looser regulation on GMOs. Of course that's what they'd advocate for! You don't even need to read it to know what they'll say). The third paper, is not even a review. It's an opinion/commentary published in 2002 in Nature Biotechnology (a high caliber journal). It outlines possible unintended consequences that could happen with a GMO, none of which have ever been documented/identified to the best of my knowledge.

My conclusion: none of these studies prove anything about GMOs. At best, they might suggest something and follow-up is needed. But, many are duds. Actually, to bring this article full-circle, a few are turds. Get it? Because of potty-training? Hilarious, right???

The Seralini saga continues

Well, I'm probably the last person writing about this. Tweets are flying and articles are being furiously typed about the latest in the Seralini scandal. Dear readers, if you've been following this blog since its inception, you'll know that the Seralini article and its retort by Monsanto were the first two items I ever reviewed (links here to the original article review and here to the review of Monsanto's response). This Thursday, the paper was retracted from the journal.

Unfortunately, I don't think this will die down. If anything, it will only make matters worse, because there are already conspiracy theories about how the paper was retracted due to the fact that one of the members of the journal's board is a former Monsanto employee. I've seen petitions and articles about how the biotech industry is attacking Dr Seralini and how we should ask the journal to reconsider their decision to retract the paper.

According to the most popular letter that I've seen circulated on this topic, there are only 3 reasons why an article should get retracted which based on the guidelines of the Committee of Publication Ethics (COPE):

• Clear evidence that the findings are unreliable due to misconduct (eg data fabrication) or

honest error

• Plagiarism or redundant publication

• Unethical research

COPE actually has a whole slew of guidelines and recommendations for unethical conduct and honest error, and I think the paper falls in the category of "honest error" as grounds for its retraction. But in speaking about this whole thing with the spouse, I think that it would have been better if the journal had admitted that the article should not have been published in the first place, and stated that the journal and its reviewers made a mistake. I know that it's wishful thinking. I know that it would never happen. But if the journal came out and stated, in an honest manner, the real reason why the article is being retracted then there would be no doubts and there could not be claims of secrecy or non-transparency, as reported by GM Watch's statement on the matter. The Editor did issue a statement, but fell short on accepting responsibility. I think the Journal's editorial staff should take some of the blame, because they definitely are not innocent by-standers in this matter. Let's face it: if I was able to find fatal flaws in the very first paper related to GMOs that I ever read, then their experienced reviewers should have definitely been able to do the same.

Actually, the real solution to this whole this is to redo the study properly...

The first blog article!! Roundup 'em GMOs!

My first blog article... If you're wondering why I've started this blog, please see the Mission and FAQ section of the page.

So, for my first article, I selected "Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize" published by Seralini, et al, in Food and Chemical Toxicology in 2012. This is one of the few articles I could find in pubmed which referred to health impact of GMO and has been a cornerstone in the anti-GMO movement.

As you can imagine, Monsanto wrote a list of counter-arguments to Seralini's findings. There are a lot of other articles critical of Seralini's paper, and I'll take a look at those later on. At the same time, Seralini recently wrote counter-arguments to Monsanto's counter-arguments, so I'll read that later on, too.

Summary:

• Seralini et al perform a 2 year detailed rat feeding study (if you disapprove of using animals in scientific studies, you'd better stop reading!).
• The rats were fed the Roundup (R) tolerant NK603 strain of corn, developed by Monsanto. The control mice were fed the closest strain of corn that had the absence of the Bt transgene (for more info on Bt, please see http://en.wikipedia.org/wiki/Bacillus_thuringiensis)
• The R-tolerant (i.e. GM) corn was split into two groups: one was treated with Roundup and one was not. Then they made rat-food with different amounts of the GM corn which was grown with or without Roundup: 11, 22, and 33% corn. An additional variable they looked at was the presence of Roundup in drinking water.
• In total, there were 10 groups of rats. 100 male and 100 female rats were split randomly into the groups.
• Plain water, plain corn
• 11% GM corn without R
• 22% GM corn without R
• 33% GM corn without R
• 11% GM corn with R
• 22% GM corn with R
• 33% GM corn with R
• Plain corn, Dilution 1 of R in water
• Plain corn, Dilution 2 of R in water
• Plain corn, Dilution 3 of R in water
• Blood and urine samples were examined from the rats. When an animal was sacrificed, a whole slew of organs were examined.
• Authors present a plethora of findings (I love that word... Plethora... Always reminds me of the Three Amigos). I'm plagiarizing directly from the paper in a few of the sentences listed below. There are plenty of more findings, but these are the ones that stood out to me:
• More rats died in the groups of rats whose diets had the GM maize.
• Females who were drinking the R-treated water had shorter lifespan
• Females had more frequent tumors than males, the majority of them being mammary tumors.
• Up to 14 months in the study, none of the control rats had tumors while 10-30% of the females had tumors with the exception of the 33% GM + R rats
• Authors provide lots of pictures of rats with giant tumors
• In females, androgen/estrogen balance was modified.
• None of the findings were proportional to the dose of treatment
• Authors note that animals fed NK603 without Roundup (R) application also had enhanced tumor incidence and mortality rate. They hypothesize that this may be due to the imbalance of two metabolites (these are molecules that control metabolic pathways), which they had found to be significantly decreased when compared to controls. (If you aren't sure what was done here, it's basically the same thing that your doctor does at a checkup: blood work and urine analysis. The authors of the paper looked a lot of different variables including things like glucose, cholesterol, hemoglobin, etc, and found two factors that were significantly different from controls).
• Death in males was primarily due to messed up liver and kidney function. Again, they attribute this to the imbalance of the two metabolites.
• The authors found that GM maize fed groups with or without R application had decreased mRNA transcription because the DNA was packed more tightly.
• The authors note that the concentration of Roundup used to treat the rats was way below the limit set by the EPA, yet there were "severe hormonal-dependent mammary, hepatic, and kidney disturbances".

You're probably thinking "Yowzers!". But before you dump all your Coca-cola, which is probably made with high fructose corn syrup extracted from GM corn, down the drain, keep reading.


Holy missing statistics, Batman!

Here are my thoughts, but I can summarize this by saying that there's a reason why the paper was published in a journal whose impact factor was 3 (and for all you conspiracy theorists, it wasn't Monsanto paying the publisher to get the article quashed). As a comparison, the New England Journal of Medicine's impact factor is 53.

• Dudes, how could you publish a paper without doing any sort of statistics for your findings?? The only place where statistics were performed were for the biochemical analyses, and I believe that they did stats only because they were fishing for something. They found significance in only two secondary metabolite levels and they blamed all the findings in the paper on these. When reviewing this article, my hubby pointed out that he didn't take stats 101, so I should explain why this is important. Here's my feeble attempt: Statistics basically allow you to determine is something is random or not. God knows how many times I thought that I had discovered something important, but when the numbers were crunched, there was nothing there. For example, I clearly remember a case where I found a DNA mutation in a large number of the patients I was studying, and it was present at a seemingly less frequency in the controls. When a statistical analysis was performed, it was not found to be statistically significant. Meaning that it was random. If I had a completely different group of patients, there was a good likelihood that the mutation would have been present in the same frequency as the controls. That's why stats matter. The control mice DID get tumors. The question that stats have to answer is whether the treated mice got more of them and whether it was sooner.
• Why in the world wouldn't you do more work to explain why there's no link between dose and findings (I hate to call them "findings" since no stats were done)? The authors claim that there's probably a threshold, and that they hit that threshold with the lowest dose. (11% GM) If that's the case, then they should have looked at anything lower than 11% to see if that's true. Also, if your hypothesis is that the tumors are due to imbalances in the metabolites, then you could have even done an in vitro study. They might have even seen the imbalance by feeding the rats just one time, yet they failed to do it. The worst part of the whole thing is that there's no explanation why the most concentrated doses fail to exhibit symptoms. #epicfail
• If their hypothesis is that the imbalance in the metabolites causes tumors in the mice, then they should have looked at the metabolite levels in the rats that developed tumors vs the rats that didn't.
• Ideally, I think they should have more rats. There's only 10 rats of each gender in each group. When the authors make statements like "10-30% of the females had tumors" that means that only 1 rat had a tumor in one of the groups. I think that it's for this reason that the stats weren't presented.
• My final point is just a personal bias: as a geneticist, I would have liked some attempt at explaining why the authors observed different DNA packaging.

My final conclusion is that the authors may have something here. However, until they do the statistics and demonstrate significance (not just an observation), then there is nothing. In my opinion, any anti-GMO article that cites this paper with sentences such as "Monsanto corn causes cancer" should be ignored. There's no evidence of causation or even association.

I'll review Monsanto's rebuttal next week.