A look into Golden Rice

http://commons.wikimedia.org/wiki/File:Golden_Rice.jpg

This week's blog is a look into the numerous claims about the properties of the controversial "Golden Rice".

So, I first learned about Golden Rice a few months ago, when I saw a viral video where a 14-year old girl who stood against GMOs was interviewed on CBC news (I'm going to miss CBC's coverage of the Winter Olympics this year... I don't think I'll be able to get it in CA). When the host asked her about the promise of Golden Rice, she said "Golden rice was scrapped because it didn't work. And in order for the average 11-year-old boy to get enough Vitamin A from rice he would have to eat 27 bowls of rice per day... The reason there is blindness isn't because there is a lack of Vitamin A in the rice, it's because their diets are simply rice."

So, what is "Golden Rice"? It's a grain of rice made by an eccentric food magnate as part of a contest, and if you get one, then you get to visit his biotech company. Hilarious! (I crack myself up sometimes...) Actually, Golden Rice is a genetically modified strain of rice that is not yet commercially available. It has been modified to produce beta-carotene, which is a precursor to vitamin A. Rice plants have beta-carotene in their leaves, but the endosperm (the white stuff that we eat) doesn't have any. Golden Rice has been modified with two genes that help the endosperm make beta-carotene: one gene is from the daffodil and the second is from a soil bacterium (all this information is brought to you courtesy of Wikipedia). The beta-carotene in the rice grain gives it a yellowish hue, which is why it's called "Golden Rice". In 2000, a paper was published in Science describing the grain of rice and mentions that Vitamin A deficiency is a serious health problem in at least 26 countries. WHO's numbers (World Health Organization) are much more staggering: Vitamin A deficiency is a public health issue in half of all nations. It leads to visual impairment and blindness, and significant increased risk for infection. Pregnant mothers are also at high risk during the third trimester when the demand for Vitamin A from the fetus and the mother are highest. As such, Vitamin A deficiency has been labelled by the WHO as the leading cause of preventable blindness in children: 250,000 to 500,000 vitamin A deficient children become blind every year, and half of them die within the first year of becoming blind. The purpose behind Golden Rice is to help improve diets by providing a rich source of beta-carotene for vitamin A biosynthesis, particularly since many regions with high rates of Vitamin A deficiency have rice as their primary staple.

Despite what is mentioned in the quote in the first paragraph, Golden Rice was never scrapped. A new strain of the rice (Golden Rice 2) was introduced in 2005, with 23x more beta-carotene. Golden Rice 2 replaced the daffodil gene with one from corn. So the project is alive and in full progress: the Golden Rice network has partners in numerous countries, and is supported by the International Rice Research Institute (IRRI). The partners work on performing field trials in their respective countries and work with local farmers to transfer knowledge and technology.

Sounds like a delightful project, right? Might even make scientists reconsider their Oaths. Next section focuses on arguments against Golden Rice and their validity.

A September 2013 opinion piece in Huffington Post raised numerous issues, and I'll go through them. But there are three primary concerns regarding the grain's efficacy in combating Vitamin A deficiency (the following section is quoted directly from the article, including the links):

1. "After storing and cooking, will there be sufficient carotenoid levels left in Golden Rice to have an impact?
2. How much remaining carotenoid will actually be "bioavailable" for already malnourished bodies to convert?
3. And are there likely, unintended health and safety risks associated with consuming Golden Rice?
   
   We don’t know the answers to these questions, in large part because the necessary studies have not been completed (two flawed and controversial studies notwithstanding). Or if they have been conducted, they have not been published or released for public and independent scientific scrutiny."

Point #1:

Storage:
I found a paper from 2006, published in a journal of a rice research institute in Vietnam. They found that the amount of beta-carotene decreased between 5-10% after 5 months, and that the beta-carotene was more stable at 4ºC. The paper is pretty basic and I had a few issues with it: first, they dehusked the rice right before using it. I'm pretty sure that in the "real world" that's not what will happen. I think most people worldwide buy their rice dehusked/milled. Second, the significance was fairly weak (but still there) and they should have really looked beyond 5 months. So I definitely agree that more studies are needed about the proper storage of the rice. (In discussing this with my boss, she pointed out that even if the amount of beta-carotene in the rice decreases by 50% in 6 months, isn't it better than nothing?)

Cooking:
There have been a few human trials that have been published where they had to cook the rice in order to eat it (duh). I was able to find two feeding trials, and most recent one was from 2012, where they fed Golden Rice to 68 children from China. The study found that the beta-carotene in Golden Rice was as effective as pure beta-carotene oil, and better than spinach, at providing vitamin A to children. So why does the article from HuffPo call the study "flawed and controversial"? Apparently, the researchers cut corners and didn't fully inform the parents of the children or Chinese regulatory agencies about the fact that the rice was genetically modified. But as sleazy as the researchers may have been, many believe that the conclusions of the paper remain valid. The scientists have since been sacked. So, I'd say that this one has been semi-demonstrated, although not under the best circumstances. Also, the findings indicate that the response given by 14-year-old Rachel Parent to CBC's Kevin O'Leary was highly inaccurate.

So why do I say "semi-demonstrated"? The two feeding trials that I found have both consisted of providing the subjects with cooked meals that had been steamed, frozen until use, and then heated in a microwave. Prior to cooking the rice was stored at -80oC, so it isn't exactly a "real world" scenario, although it was necessary for these particular studies to maintain uniformity amongst all subjects. As such, there's no data on what happens when the rice is fried, or the countless other ways of preparing rice, including rice pudding (yummmmm... BTW, if you've never tried Iranian rice pudding, you definitely should).

It's also important to note that these feeding trials could not be performed on animals since the metabolism of beta-carotene in animals is different. So an animal feeding experiment would not answer questions about vitamin-A conversion in humans, and a whole slew of different animal trials would need to be performed in order to get a vague understanding of the numerous aspects of beta-carotene metabolism.

Point #2:

The reason why this point is raised is that individuals convert beta-carotene into vitamin A at different efficiencies depending on a variety of different factors, including malnutrition and intestinal health (parasites, infections, etc). I imagine that human feeding trials (such as the one performed in China) will help answer these questions. But differences in the conversion of beta-carotene into vitamin A between different individuals would be an issue with any source of beta-carotene, whether it's from a GMO or not, right?

ADDITION SEPT 4, 2014: Note that this is an instance where a human feeding trial is actually needed, because the goal of the crop is to address a human nutritional deficiency. The argument against human feeding trials for current GMOs is that animal trials provide us with the answers we need, which have to do with safety.

Point #3:

According to the Golden Rice project's webpage, they will comply with the regulatory requirements of each nation where the rice will be used. Since it isn't available yet, it makes sense that the tests haven't been done/completed. According to the same webpage, standard allergenic tests have also been done (bioinformatic prediction). They also state that gene expression profiling has been performed, and I think it would go a long way if that data were made available (for more information on this test, please view this previous post). Additionally, the Golden Rice Project webpage notes that the rice has been backcrossed with local varieties of rice from different countries, so that the rice is adapted to each location. I'd speculate that it makes sense to perform these tests using the local variety that will be submitted for approval in each country.  Maybe the authors are waiting to publish a huge paper at the end of their studies, who knows? However, if Point #3 is about GMOs in general, then there really are no grounds for the concern. As outlined previously, there are numerous long-term feeding studies in animals showing that there are no health impacts in eating GMOs (please read every entry in this blog for more details :) ).


Other concerns/complaints:

-This is just another way for Monsanto to make tons of money: the seed is not developed by Monsanto. The private partner in the endeavor is a company named Syngenta, who is making the seeds available for use freely, on humanitarian grounds. There's no Golden Rice-specific fertilizer or pesticide that needs to be used. Additionally, you can save seeds from one season to the next.

-There are better ways to address vitamin A deficiency: I'm sorry, but this is the lamest excuse ever. If the popular belief is that "the reason there is blindness isn't because there is a lack of Vitamin A in the rice, it's because their diets are simply rice" (quoted from the first paragraph), are you seriously going to change the diet of millions of people around the world? My rant on this is below.

My conclusion:

I think that Golden Rice has the potential to be a fantastic product. Potentially. It has the potential to benefit those who suffer from vitamin A deficiency, those who are at risk of developing it, as well as local farmers and traders. I think that there's still a ways to go, but that's understandable. I've always felt that the time and effort that science takes is grossly underestimated. For example, one of the projects I just completed consisted of a one month test to change an identical plastic consumable from one vendor to another. 1 month. For a piece of plastic. Now that I have the initial dataset, I have to start the project all over and go out till 3 months. In the end, the project will have lasted 5 months. For a piece of plastic from a highly reputable vendor. Keep in mind that this is a piece of plastic being used in a research environment where no humans/animals are at risk. So imagine how long it would take if my work were clinical in nature or subject to regulations. This powerpoint presentation by Syngenta (the private partner in the Golden Rice Project) outlines all the delays they've experienced in their research, including 2 years to transfer seeds from the Philippines to Vietnam. So I think it makes sense that they're still working on things. Yet according to numerous articles I've read, many feel that it's time to put Golden Rice aside because it has yet to deliver anything.

I have a few serious issues with the outrage over Golden Rice. A few months ago, anti-GMO activists vandalized a field of Golden Rice in the Philippines, allegedly setting back the study by a few months. Here's my beef: you can't complain that GMOs aren't tested thoroughly enough, and then destroy the progress being made in their testing. You can't state that Golden Rice has failed to deliver anything since its conception and that after many years of research it's "still stuck in the lab", and then hold-up its research or complain about the lack of thorough tests. Yes, there are many socio-economic factors involved in vitamin A deficiency and you can definitely argue that bio-enriching rice is not the best way to address the problem. If that's your argument, then go ahead and work on an alternative solution, but don't try to sabotage the ideas and potential improvements that others are working on. Alternative ideas that I've read about include providing vitamin supplements and teaching farmers how to grow leafy greens. Those sound like fantastic ideas. Go ahead. Start working on them. There's no reason why these efforts can't work in parallel to one another. Providing leafy greens and vitamin supplements would probably help prevent a whole slew of additional vitamin deficiencies. I'd like to believe that if Baby Boy and I were living in poverty and that we both suffered from malnutrition, that people looking into vitamin A deficiency would be trying any means at their disposal to help us out. So now it's my turn to ask: why hasn't it been done already? The alternative measures suggested are items that you could be working on right now or for the last 5 decades. If it's lack of funds and your argument is that Golden Rice is a "flashier" project with strong endorsements from the likes of the Bill and Melinda Gates Foundation, then perhaps there's a reason for that. Perhaps it's because, sadly enough, many realize that private funds are required for such endeavors and Golden Rice is the right fit to garner those funds. But as an individual raised in a developing nation, I can envision the logistical nightmare of getting vitamins into the hands of those who need it most or trying to convince populations to eat spinach when they aren't familiar with it. In general, products are most successful if they can be easily integrated into one's daily life and Golden Rice fits in this category.

According to the HuffPo article, the message we're being fed by the Golden Rice Project is to "swallow our technical fix, despite its failure to deliver on its promises, or you consign millions to misery and death." I don't think those are the two choices being offered. I think that the options are to keep quiet, embrace the Golden Rice Project's work, or to find an alternative solution and to work on it. I think that the message that the Project is also trying to convey is that roadblocks and baseless complaints won't help anyone. At least that's what I think they're trying to convey.

Biochica out.

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...

Death Match: Transgenesis vs Traditional Breeding

For this week's blog, I wanted to learn and read papers about a common claim made by the pro-GMO scientists: that creating a crop by transgenesis is better than traditional methods for creating plants. I'll explain a bit more, but we'll have to start with the very basics: as this paper outlines, there are three broad categories of plant breeding, and for the sake of simplicity, we'll be focusing on only two of these:

• Transgenics: when you take a gene from an organism and stick it into another organism that it traditionally could not breed with. These new species are popularly known as GMOs, and are subject to regulations.
• Traditional breeding: every other method of creating a plant and are not subject to regulations. This includes mutagenesis through chemicals or through radiation, which brings about random mutations creating new traits. Reminds me of X-Men, the first movie, where they zapped the senator and made him a mutant. But that was in the good 'ol X-Men movie days... 

So, the pro-GMO parties state that creating a new strain of a plant through transgenesis can be better than mutagenesis, where you get random mutations, or even cross-breeding, where two genomes with thousands of genes integrate (although I wonder where Napoleon Dynamite would be if he didn't have a hybrid Liger). A few recent news articles have reported that plant breeders are turning more frequently to radiation and mutating chemicals to create new strains because there are fewer regulations, so this topic is all the more relevant.

Before you read on, I feel the need to clarify a few things. I've been working on this blog article for over one week, because the spouse is stuck on one fact: "How can nuking a plant be OK, but a GMO isn't? Do you mean to tell me that if a pomegranate with grape-size seeds appears in Fukushima, that's OK?" Spouse: you'll be reading this again in a few hours when I ask you to review. Don't get stuck on that. Read on. The whole point of this is to find out whether it is OK or not. (Addendum: it's important to note that plants derived through mutagenesis are not excluded from the "Certified-Organic" label. Transgenic crops, however, are excluded).

So this week, it's the battle of the methods thunderdome-style: traditional breeding vs transgenesis. Two methods enter, one method leaves... Or maybe neither one leaves. Or maybe both leave a little
bloody. We'll see. (BTW, I'm pretty proud of my little image here.)

Round 1: Mutagenesis vs Transgenesis

To get started, I reached out to the folks at Biofortified.org. I had tried finding a review on the topic, but I couldn't find a good comprehensive paper that summarized the different methods. Someone should get on that :) Anyway, they sent me a paper from the Proceedings of the National Academy of Sciences (PNAS), which served as a great starting point, because then I could start cross referencing.

This paper, released in 2008, looked at the expression of thousands of genes to find out if there were any unintentional changes in gene expression in transgenic crops (I can hear the spouse now saying "huh?"). Gene expression refers to how much of a gene is turned on or turned off, and is measured by amounts of RNA. If you remember high school biology, DNA is transcribed into RNA which is then translated into protein, and the protein is generally considered to be the final goal. Now, proteins generally do not work independently and often regulate one another. For example, if protein A and protein B work together in the cell and you change the amount of protein A, you might also affect protein B. That consequence is often easier to identify, particularly if you know that protein A and B work together. But sometimes, you see a change in protein C and then you scratch your head and try to think of how protein C could possibly be affected by protein A. So, in this study, they wanted to determine if there were any unintended changes in gene expression when you add a gene in a transgenic plant (i.e. GMO), and compare it to the unintended changes in gene expression when you create a plant by the more "traditional" mutagenesis route, such as by gamma-irradiation. Yes... Gamma-radiation is real and is not confined to creating the Hulk or other super-heroes (BTW, don't scientists in comic books seem incredibly error-prone?)

The study seemed pretty straightforward and included the appropriate controls (although the plants were grown in the lab). The authors compared transgenic rice strains (i.e. GMOs) and strains of rice generated through mutagenesis, to the closest non-modified strain (i.e control). The authors found that in all the strains, there were unintended changes in the expression of genes that are related to plant stress or defense, and the paper spends a lot of time breaking down these genes into various categories. There are also changes in gene expression in certain genes that might be related to the transgene or mutant gene itself (i.e. changes in protein B in my previous explanation). The authors draw several conclusions:

• Although there were unintended consequences in gene expression using both methods, transgenic strains had fewer changes.
• Changing a plant through mutagenesis or transgenesis creates stress in the plant and leads to changes in gene expression, which are carried through several generations.
• The authors recommend that food safety assessments should be carried out on a case-by-case basis and not just limited to foods obtained through genetic engineering.

Round 1 Results: advantage to transgenics


Round 2: Hybrids vs Transgenics

So, at first I was a bit disappointed. I couldn't find a paper that had done a battle between hybrids created by cross-pollination/cross-breeding and GMOs. But then when I thought about it, a head-to-head battle didn't really make sense. What would you use as a control? What would be the GMO equivalent of a broccoflower? As a consolation, there were plenty of papers that had examined genetically modified strains of corn vs their non-GM control strains.

The most comprehensive paper I found was a 2010 paper that had looked at changes in gene expression, as well as proteins and metabolites, in Round-Up Ready corn and Bt corn, compared to the closest unmodified control. They used seeds from the same location over several years, as well as different locations in the same year, to make sure that they had accounted for geographical and year-of-harvest effects. Their conclusions are:

• Year-to-year variation can account for more differences in gene expression, protein levels and metabolites than whether the plant is genetically modified.
• Geographic location can account for more differences in gene expression, protein levels and metabolites than whether the plant is genetically modified.
• The authors also reiterate that food safety assessments should be carried out on a case-case basis, rather than just lumping all genetically modified foods into one category.

There are many other papers that have done assessments on changes in gene expression in plants, and this freely available 2011 review does a really nice job categorizing the studies based on crop. If you quickly scan through it, you will see that it's a topic that has been studied quite a lot. So why is any of this important? Well, "substantial equivalence" is the starting point for food safety assessment. That means that you have to show that the food item is equivalent to conventional food in several different categories including nutrients, toxins, allergens, etc. So examining changes in gene expression is a different way (and I'd argue that it's a more rigorous way) of determining "substantial equivalence". There are a few conclusions from the review that are worth highlighting:

• There doesn't seem to be a single, consistent method for assessing changes in gene expression. Each paper looks at different variables and factors, different number of plants, and with plants grown in different conditions. It would be nice to have some consistency.
• Environmental effects consistently play a bigger role in gene expression than the transgene.
• None of the large scale studies examining thousands of proteins, genes, and metabolites have raised any food safety concerns.
• Since transgenics has less of an impact than other breeding methods, the regulatory standards on transgenics should be lowered (the authors highlight that the more likely scenario is that conventionally bred plants will be regulated).

I agree.  I fail to see how mutagenic technologies are any safer than transgenesis. I agree with the fact that food safety should be regulated and determined based on the trait and not based on the method used to generate that trait.

So, unfortunately, there was no clear victor in today's thunderdome because there haven't been enough head-to-head battles. What is clear is that stringent regulations against all forms of transgenics don't make sense considering their history of safety and substantial equivalence.

The Secret Oath of Scientists

This week's blog is a departure from my usual format. Because I have something to confess. To all my fellow scientists: the jig is up. It's time. I hate to be the first person to say something, but I think that people are on to us and it's better for us to come out with our hands up.

For me, it all started when I was a teen. I wanted to become a scientist because I wanted to increase the rate of cancer in our population. Not only cancer, but I wanted to make something that would cause autism amongst children. You heard me right. At first, this dream was a small flickering of a flame, but during grad school it became a full blown bonfire. The thousands of dollars that I made during my 10 years of education only fanned these flames and pushed me onward towards my goal. Soon I learned that I wasn't the only one with such hidden secrets: while chatting with my professors in 3-star Michelin restaurants, I learned that my fellow grad-students all had similar goals. Some were trying to figure out how to extend the life of the rich and famous in wealthy countries. Others had less lofty goals like figuring out how to cause irritable bowel syndrome in adults. I signed the Oath, which is signed by every scientist throughout the world, where we solemnly swear to maintain the secrecy of our true natures and passions.

We fooled our friends and families into believing that we were working long hours and that our careers were toilsome. But in truth, we made tons of money mostly by reviewing papers. Reviewing papers was a cash-cow. Reviewing a paper that the government or a company didn't want published was a dream come true: not only would you get paid by the journal, but you'd also get paid by the government/company for rejecting the paper!! My professor bought his first Porsche when he rejected a paper that conclusively proved that an herbal supplement cured cancer. My supervising post-doc bought his first apartment in Paris for burning a paper that showed how GMOs cause some weird leaky gut disease. Why on Earth would we want to get that knowledge out!??! Oh, the naïveté of some people is just plain cute.

Once I graduated, I started working for big biotech companies because I thought it would be the best way to accomplish my goals. I have a few friends in big pharma and we all agree that it's been a really interesting experience! We've learned that if we make bad products, no one really cares. In fact, our shareholders just buy more and more stocks and the media never reports on it. Also, all the big pharma and biotech companies don't compete against one another; if one company manages to make a vaccine that causes autism, not only do all the other companies stay quiet about it, but they all share the knowledge with one another. It's all part of the Oath. And an additional dream of mine has finally come true: I have the enormous blessing of never being allowed to quit or to take advantage of the federal whistleblower laws. Even if I disagreed with all the cover-ups that these companies do or disapproved of all these untested drugs that get released, there's nothing I could do about it. It's so great working for companies where every employee shares your vision of world domination and control.

Some day I hope to work for a company that slaughters puppies to fuel our manufacturing systems, where we make drugs to remove arm flab, test it on the homeless in Panama, and have a survival rate of 30%.

So there you have it. It feels real good to get this off my chest. I really want to thank everyone who has recently posted articles about the evils of vaccines and GMOs. It has made me realize that there's now a critical mass of people who are aware of what we scientists do, so we'd better quit while we're ahead.

IRT - GM food supplement caused deadly epidemic

Before I get started, I have a confession to make: I love pomegranates. Love probably isn't a strong enough word. I ate 2-3 a day while I was pregnant, to the point that the hubby planted two trees for me (one of which had it's first fruit this year). But it's a "work food". Like crab legs. Or pumpkin seeds. You have to put in a good amount of effort before you can eat the stuff. Anyway, since it's pomegranate season, I've been eating them all the time and I woke up thinking "someone should make a pomegranate that's easier to clean". And I'm guessing I'm not the only one who wishes for this: Wikipedia has a good section dedicated to suggestions on cleaning out pomegranates (including my preferred method of cracking them open under water). Well, according to this review, a genetically modified pomegranate tree is possible because one has already been made to express GFP (green fluorescent protein). It's probably what Sheldon used to make his goldfish glow in the dark. The authors recommend making pomegranate crops that are stress tolerant or have other horticulturally-beneficial genes, but none have been made (although that hasn't stopped people from marketing GMO-free pomegranate juice). None of the suggestions in the review included recommendations on making the fruit easier to eat...

Now, getting onto juicier topics (no pun intended!)

If you've been following this blog, you'll know that I started reviewing the "Health Risks" section on the Institute for Responsible Technology's webpage several months ago. This was due to the fact that numerous anti-GMO webpages were using it as a resource, so I thought I should look into it. Today, I finish its review by covering a section entitled "GM food supplement caused deadly epidemic". I'll be honest here: I started out upbeat and open minded when I started reviewing the IRT's site, but I haven't come across a single valid statement. Consequently, every time I sit down to read from this webpage, I feel the same way as when I think about Jar Jar Binks. Or just Episode 1 in general. A sense of dread and gloom. Consequently, it's only this bowl of pomegranate that I'm currently eating that will get me through this last section.

The segment would have been more aptly entitled "Dietary supplement produced using recombinant DNA technology was associated with a deadly epidemic". Here's the first section directly from the IRT: "In the 1980s, a contaminated brand of a food supplement called L-tryptophan killed about 100 Americans and caused sickness and disability in another 5,000-10,000 people. The source of contaminants was almost certainly the genetic engineering process used in its production." It goes on to state that it took years to "find" the disease and that an investigation only took place because the symptoms were so dire. The IRT argues that there is no monitoring of GMO-related illnesses - particularly long-term effects - and it may take decades, if ever, to identify the source of a problem. I've already reviewed the topic of long term effects of GMOs, so I'll focus on the first part of their argument.

Unfortunately, there are only two citations. The first is to an article on the IRT's webpage and the second is to a book written by one of the founders of the IRT. So neither one are peer reviewed sources. However, Wikipedia has a pretty good entry about this event, with several citations. The disorder is known as eosinophilia-myalgia syndrome (or EMS) and the outbreak took place in 1989, leading to an eventual ban of tryptophan dietary supplements by the FDA. I started by reading a few abstracts for papers that investigated the cause of the EMS outbreak:

• The abstract for the first paper simply states that they traced the bad lot of L-tryptophan to a single manufacturer from Japan.
• The second abstract says the same thing (a different population was tested) and hypothesizes that a contaminant was introduced in the manufacturing process.
• The third abstract says the same thing, adding the point that the incidence of EMS decreased drastically once the product was recalled.

So far, there's nothing about a mysterious genetic engineering contaminant. There's reference to a contaminant, but no mention of when/where/how it could have been introduced.

If I were to magically design the perfect pomegranate, I think it would peel like a tangerine.

The next item I read was a 2001 report by the FDA (I thought it was odd that the IRT article did not mention the FDA's involvement). The FDA report was written up to clarify their position on tryptophan supplements. The report stated that 37 people died as a result of the bad batch of tryptophan. They state that there were numerous impurities in the batch, several of which were associated with EMS, but no one really knows how. They pointed out that not everyone who took the contaminated supplements got EMS, so there may be a genetic predisposition/factor involved as well. Again, nothing about a contaminant from the genetic engineering process.

I'd also magically make that white fluffy stuff disappear so that the seeds would just drop out. I looked it up and the white fluffy membrane doesn't have a specific name. You'd think it would have an uber-geeky scientific name.

Next, I found a New England Journal of Medicine article that looked into the whole tragedy. The article points out the fact that the manufacturer in Japan had switched to a new bacterial strain for the synthesis of tryptophan in 1988. In 1989, they made another change in their manufacturing process: instead of starting with 20kg of one of the starting materials, they cut it down to 10kg. During that same time period, some of the batches of tryptophan that they were making skipped one of their filtration steps. The authors find statistical significance between the amount of starting material used with EMS. They also find correlation between the bacterial strain used and EMS. However, they highlight numerous times that they cannot disassociate the bacterial strain used from the amount of starting material used, so they cannot tell the impact of the bacterial strain alone. Then they state: "For this reason, it is possible that strain differences were unrelated to the production of the etiologic [disease causing] agent." They also mention that the manufacturer's tests had shown no difference in the biological and physiological properties of the old and new bacterial strains. So the New England Journal of Medicine does not point to a weird by-product of the genetic engineering process. Also, article sheds a lot of light on the timeline: the first cases of EMS were identified in October 1989 and by early November 1989 the link between tryptophan and EMS had been found. It didn't take months or even years for this to be identified.

I only have two pomegranates left in the fruit basket... I'd better add 'pomegranates' to the shopping list. I wish I could write 'peel-able pomegranates'. I'd pay extra for those suckers.

So here's why I think that this is, by far, the most ridiculous "health impact" on the IRT's webpage and the molecular geneticist in me cringes at the thought that this is even considered a GMO, as defined in the GMO debate. In 1922, the first human patient received an injection of insulin isolated from a calf pancreas, and patients had to rely on insulin isolated from animals until the 1980's. To make human insulin, the DNA sequence of insulin is inserted either into bacteria or yeast, which then start making the protein. It is isolated, purified, and sold to millions of patients worldwide who rely on this lifesaving technology. Patients are not exposed to the bacteria or the yeast. These organisms are just used in the manufacturing process of insulin to make it scalable and, often, easier.

Statistically, insulin is a drug that me or someone I love and care for will probably end up taking in our lifetimes. And insulin isn't the only drug produced this way. Countless other drugs and dietary supplements,  including tryptophan, are produced using recombinant DNA technology (this article highlights that malarial drugs are being made this way). So why is the IRT focusing on this story about tryptophan and EMS? I really can't explain it.

In my perspective, the EMS outbreak highlights another issue altogether: the need to have more stringent regulations in the world of dietary supplements. The quick sequence of changes introduced in the manufacturing process of tryptophan and their immediate rollout to the market would have never even been contemplated if it were regulated as strictly as pharmaceuticals. Or if they wanted to make the changes, they would have had to perform rigorous testing to demonstrate that there's no change in the function of the product. Cutting back on starting material by 50%?? Changing the strain of bacteria used once the product is in the market? Utter craziness!! Please do not misconstrue this and think that I'm implying that the pharma/clinical world is perfect. Far from it. I worked on my first project in regulated markets this year and learned first-hand of the craziness that exists. But at least the regulations and trials that they have to go through put a few checks and balances in place.

Whew! With that rant I finish the review of the IRT's health risks. My conclusion: they focus on fear-mongering. Most statements were misleading or misrepresented the studies, and several statements were outright lies.

Till my next post, I'll continue enjoying pomegranate season and keep my fingers crossed that someone out there is working on a peel-able version of the fruit.

PS: After reviewing this, the spouse thought that the pomegranate seeds should be the size of grapes. Pure genius!

GMO DNA and your health

I'm behind on my blog: I've been on vacation. My new job also has a longer commute time, so I've been falling asleep in front of the TV every night, instead of diligently reading papers. Someone

should really start working on that teleporter.

A reoccurring statement that I've read time and time again on anti-GMO webpages is about the dangers of eating GMO DNA. I've always just glossed over these claims, because they seemed a bit too science-fiction-y. But before I proceed, a voice in my head (which sounds like my husband's) is reminding me to give a bit of an intro on why I've glossed over these claims. Here are my top two reasons:

• Nearly every cell-type in the body of every living creature has DNA. Whether that cell is from the organic beef of a cow or a pesticide-infested fruit, they all have DNA. And your digestive system does not know the difference between the two. So if GMO DNA is going to "sneak into your body", so will the DNA of that delicious bacon you ate this morning. As well as the DNA from those pork-chops. And ham. (Those are all from the same animal you say? That's preposterous!)
• Even if DNA from your food got into your body, then what? The DNA would have to hijack your body's cellular processes in order for anything to happen, similar to how a virus operates. 

So that's why I've ignored these statements, which really seemed like fear mongering when I read them. However, I've read a few articles that claim that the DNA doesn't necessarily have to transfer into you. It might just transfer into the healthy-bacteria that lives in your gut. Due to this possibility, I decided to look into matters. In fact, taking a look at the Institute for Responsible Technology's section on "Health Risks", there's a whole section on "Functioning GM genes remain inside you".

The most commonly cited paper tied to these statements is from a  2004 Nature publication entitled "Assessing the survival of transgenic plant DNA in the human gastrointestinal tract". Apparently, the publication of this paper was quite the coup for the anti-GMO field. The paper looks at the survival of GMO DNA in the intestinal tract, because in order for the DNA of a GMO to transfer into bacteria from the gut, then it has to survive the digestive process. The authors looked at DNA from GMO soy and native soy, in ileostomists (basically, individuals who do not have a lower intestine) and individuals with intact digestive systems. Here's the summary:

• GM soy and regular soy were fed to participants. DNA from soy and GM soy was detected in the "digesta" of the ileostomists, but it was not detected in regular individuals. The authors conclude that the DNA can survive in the upper intestine, but not lower intestine.
• GM soy and regular soy DNA were degraded at similar rates.
• The authors identified fragments of GM soy DNA in bacteria from the intestinal flora in ileostomists at very low concentrations (probably existed before the study started). The authors were unable to isolate the bacteria. Additionally, they were unable to reproduce this experiment in individuals with intact digestive systems.

I'd like to take the liberty of copying the conclusion from this paper (my clarifications are in brackets): "In conclusion, we have shown that a small proportion of the transgenes [GM DNA] in GM soya, like the native soya DNA, survives passage through the human upper gastrointestinal tract but is completely degraded in the large intestine. Although we found some evidence of preexisting gene transfer between the GM soya and the human small intestinal microflora, the bacteria containing the transgene represented a very small proportion of the microbial population, and there was no indication that the complete transgene [full gene from the GMO] had been transferred to the prokaryotes [bacteria]. Thus, it is highly unlikely that the gene transfer events seen in this study would alter gastrointestinal function or pose a risk to human health. Nevertheless, the observed survival of transgenic DNA from a GM plant during passage through the small intestine should be considered in future safety assessments of GM foods."

Note the sentence that I highlighted. Contrast this with the health risk from the Institute for Responsible Technology's webpage that refers to this paper: "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. This means that long after we stop eating GM foods, we may still have their GM proteins produced continuously inside us." For the first time in this blog's history, I will use the phrase: 'that is a blatant lie'. First of all, the genetic material wasn't found in bacteria of individuals with intact digestive systems (i.e. the overwhelming majority of people on the planet). Second, the whole gene was never found in bacteria, which makes it impossible for an intact protein to be produced, much less for that protein to "function".  #EpicFail #IRT

The next three statements on the IRT's webpage are:

• "If the antibiotic gene inserted into most GM crops were to transfer, it could create super diseases, resistant to antibiotics.
• If the gene that creates Bt-toxin in GM corn were to transfer, it might turn our intestinal bacteria into living pesticide factories.
• Animal studies show that DNA in food can travel into organs throughout the body, even into the fetus."

Let's start with the first two statements. Note that there's no evidence for them, they're "if" statements. Let me make a few "if" statements:

• If an ocean waterspout were to move onto land, it might transfer sharks thereby creating a sharknado.
• If the rabies virus were to merge with the flu virus, it may cause a zombie apocalypse.

Do I have any evidence? Well, I provided a few links and citations there, didn't I? And they're all to legitimate sources. Note that that is more evidence than the IRT provided for their two hypothetical scenarios.

There's one final statement: "Animal studies show that DNA in food can travel into organs throughout the body, even into the fetus." This is tied to a slew of articles and a quick scan through the titles and abstracts indicates that it's accurate. However, as I pointed out earlier, "then what"? DNA in food can travel into organs throughout the body, even into the fetus, whether that DNA is GMO or not. So DNA from our food has been circulating through our systems ever since we started eating.

If your argument is "Mother Nature never intended for us to eat foreign DNA", then what about when you eat a broccoflower? Or a pluot? In fact, if you eat any fruit or vegetable that is exotic, then Mother Nature never intended for you to ingest the DNA from that plant. For example, if you're Northern European and you eat a banana, or a mango, or a dragon fruit, isn't that DNA foreign to your system?

There's one final argument in my head that puts a nail in the coffin of this whole deal: humans aren't the only species that have bacteria in their gut. Mammals have been eating plants for millions of years. If any sort of absorption of genetic material were to happen between gut bacteria and plants, wouldn't it have happened by now? We've been part of this "human feeding experiment" ever since mammals starting eating plants, and even birds and fish before that (birds also have bacteria in their guts, as do little Nemos). If you consider that the most abundant protein on the planet is thought to be RuBisCO (a plant protein), then throughout the course of evolution, the bacteria in the gut of some animal would have taken up RuBisCO DNA. But that has not been identified (however, my husband wisely points out that this may have been the origin of the Ents in LOTR).

There are dozens of papers that have looked at the absorption of DNA in our food. All of them have the same conclusions: DNA from our food behaves the same, whether its GMO or not. Our digestive system breaks down the vast majority of the DNA (although this paper did find that complete genes may make their way through, but I reiterate: then what?). That DNA can be detected in feces and our organs.

Well, that's all I've got. If you have any questions, please comment below.

GMOs lead to suicide of farmers in India

A few months ago, I remember reading an article which indicated that GMOs were leading farmers in India to commit suicide. The title of the article was a bit odd, so prior to reading it, I thought that GMOs were leading to some sort of chemical imbalance leading to depression. However, when I read the article, I found out that many farmers in India were committing suicide because they had bought Monsanto seeds at sky-high prices, the crops did not perform miracles as it had been promised, and they were in so much debt that they would commit suicide. Just type in "Indian farmer GMO" in Google. Here's a typical article on the topic.

So, I've received 2 requests to review this topic. At first I declined, because I felt that it was a socio-economic phenomenon rather than a health impact. But I'm on vacation this week with limited journal subscription access, so I thought that this might be a good topic to tackle.

The first document I read was entitled "Thirty Minutes: Farmer Suicides, Human Rights, and the Agrarian in India". The document was put together by the Center for Human Rights and Global Justice from the NYU School of Law. The report's goal is to outline the human rights of cotton farmers in India in the hopes that the Indian Government will act. I thought it would be a good place to start since it's a fairly recent document. The numbers are pretty staggering: official numbers indicate that over 250,000 farmers have committed suicide in the past sixteen years (and the actual numbers are probably higher).

Numerous studies have found that the predominant cause for these suicides are indebtedness. The report goes on to explain that in the 90's, the International Monetary Fund and other organizations encouraged the Indian government to open it's markets to international trade and multinationals. This led to the abolition of agricultural subsidies that had helped farmers for decades. Additionally, since the cotton was being traded internationally, prices were much more volatile. These factors alone led many farmers into debt.

To compete on the global market, the farmers turned to "innovative, but expensive, biotechnology" which promised higher yield and greater pest resistance. Often, these didn't deliver what was promised, driving the farmers even deeper into debt. These seeds became available in India only after the economic reforms. The report specifically calls out Monsanto's Bt cotton, where the area of cultivated Bt cotton jumped 260% in just one year (2005-2006). The Bt seeds cost 2x more than "normal" seeds. Many farmers lost their crops due to droughts, which drove them to suicide. According to the report, Bt cotton requires more water than average cotton in order to get high yields. So rain-fed crops often fail and Bt crops generated much lower yields in the years of drought than non-Bt crops. This fact had not been well communicated to the farmers, and although the boxes for the seeds had warnings stating that the fields had to be properly irrigated, many farmers could not read English and remained unaware of this requirement. Apparently, the Bt seeds were being aggressively marketed, and demos were set up in irrigated fields which showed high yields and plenty of crop.  Coupled with additional cultural issues, including huge dowries, the number of suicides among farmers drastically increased.

The rest of the document focuses on other issues that are not really associated with GMOs (although, incredibly important). But items that stood out are:

• Suicide of women farmers are most tragically under-reported, because they are not officially considered farmers since the land they work on is seldom in their name. Likewise, tenant farmers are not counted either.
• Although suicide data is segregated based on profession, there are no records of type of crop planted, where the seeds were obtained, or whether they were GM crops or not.
• The shortage of fields with suitable irrigation systems is likely to become worse as India moves to privatize water supplies and irrigation pathways.
• The suicide of farmers in India consists of a failure of the Indian government to respect, protect and fulfill the right to life. This includes ensuring that third party entities, including businesses, do not interfere with the enjoyment of this right.
• The report included one page of recommendations, both for the Indian government as well as agribusinesses. All the recommendations were incredibly reasonable and make great sense. Recommendations to agribusinesses include "revising their practices to take account of the human rights of Indian farmers".

The next document I read was put together by the International Food Policy Research Institute and is entitled "Bt cotton and farmer suicides in India". Written in 2008, this investigation specifically looks into whether Bt cotton is "the main reason for a resurgence of farmer suicides in India". Here are the highlights of this 51 page document, many of which are the same observations noted in the previous report:

• GM cotton was first introduced to India in 2002, and by 2006 nearly 40% of the cotton crops were Bt cotton.
• There are two official sources that have contradictory data on the number of suicides in India, which have lead to contradictory reports and findings. This report reviews data from what is considered to be the more reliable source, and finds:
• The number of suicides amongst farmers represents a "minor and stable share of total suicides in India".
• The number of suicides amongst farmers is significant and seems to be increasing, but so is the total number of suicides in the general population.
• There were also two peaks in the number of suicides per year: 2002 and 2004.
• There are more suicides amongst farmers in specific states.
• In 2003, the yield average for cotton was far below the global average due to many different factors including the lack of irrigation systems, the reliance on monsoons, and the infestation of pests, particularly the American bollworm.
• The first GM crop approved in India was a strain of Monsanto's Bt cotton (MON531). Data shows a significant increase in cotton production at the point in time when Bt cotton was introduced. This increase is not equivalent across all states/regions. Assuming that the increase is not due to climate or other factors, the authors hypothesize that the increase in yield may be due to the introduction of Bt cotton.
• There was a drop in pesticide consumption, which coincides with the introduction of Bt cotton. However, there's no real proof that it's due to Bt cotton.
• Bt cotton seeds were initially sold at 5x the price of the local variety of seeds. This lead to a black market of sorts for seeds, where you could get Bt seeds at a cheaper price. However, these were generally a blend of Bt/non-Bt seeds which didn't perform well and often led to the loss of crops.
• There was a huge surge in the variety and number of GM seeds available in a very brief time period, with little/no information or education for the farmers. This left the local farmers at the mercy of the ag companies to receive education on how the crops should be planted and what was required.
• Bt crops require less pesticides, particularly against bollworms, but there are pests that these seeds are not resistant against. Additionally, there's an optimum schedule and spectrum of pests that should be sprayed against. The farmers were not aware of these requirements, and followed their own pesticide schedules, leading to bollworm resistance and the return of the pests (this particular issue seems to have been resolved in later years).
• This report also cited studies showing that irrigated Bt cotton fared better than rain-fed crops.
• "On average, a large majority of Indian farmers gained significantly by adopting Bt cotton varieties in most locations and seasons." Some of the regions that had higher suicide rates were those where the impact of Bt cotton was less significant on yields and net income.
• Although indebtedness is not new to Indian households, the nature of the debt is new (i.e. the attitude of "going for broke").
• There is no correlation between the rate of adoption of Bt cotton and farmer suicides. In fact, the rate of suicides decreases after the introduction of Bt cotton. However, the possibility that Bt cotton may have caused a "discrete increase" in the number of suicides in specific regions and in specific years cannot be discarded.

The reports point out that the issue of suicide amongst farmers is far too complex to attribute it to any single factor, but indebtedness in undoubtedly the leading factor (which arises though several different causes). The report aggressively states that "it is not only inaccurate, but simply wrong to blame the use of Bt cotton as the primary cause of farmer suicides in India", particularly since it has been quite successful. There's a sentence in this latter report that I think can summarize the whole issue (or at least my thoughts about it): "the technology, represented by the Bt trait, should not be blamed, instead, the conditions in which it was introduced, sold, and used explain some of the observed losses in specific regions of India."

Here's a thought: if Monsanto had introduced a non-GM seed and marketed it in the same way, the exact same issues surrounding the lack of appropriate information and education may have existed. So I honestly don't think that genetically modified seeds have anything to do with the issue at all, as pointed out in the second report. So then we're back to the question of whether we're blaming Monsanto because we think it's an evil corporation. Although I strongly feel that Monsanto could act more ethically and work with local partners to improve the condition of farmers in India, there are so many factors in this equation that even if they did fix things on their end, I'm not sure that it would solve the problem altogether.

So there you have it. GMOs are not causing the suicide of farmers in India. Before researching this topic, I felt it was a socio-economic problem and I still feel that way.

If anyone has a more cheerful suggestion for next week's blog, I'm all ears :)
 

Link between GMOs and gluten allergies

http://www.flickr.com/photos/bike/3752517045/

So, my former work spouse asked me to write an article on gluten allergies, and I had read a few times that GMOs might cause gluten allergies, so I thought I'd give it a shot. I knew nothing about gluten, other than the fact that I hear more and more about gluten allergies and gluten-free diets (apparently, a third of the US population want to cut back or cut-out gluten from their diets). I relied on Wikipedia more than usual to learn about this (I know... Not always the best source of information...), but looked into a lot of papers as well. Here's a summary of what I've gathered:

According to Wikipedia, gluten is a protein composite (a mixture of glutenin and gliadin) found in wheat and other grains. It helps dough rise and gives it that delicious chewy texture. Are you imagining a freshly baked loaf of bread right now? Is there any scent in the world more apetizing than that of fresh bread?? I'm drooling a-la Homer Simpson right now. Anyway, gluten has been in our diet for over 10,000 years, so I have to assume that we've been digesting it successfully for that period of time.

Individuals who have autoimmune reactions to gluten have Celiac Disease, which is characterized by irritation in the small intestine, which over time, leads to the loss of the lining of the gut. Over time, you may lose the ability to absorb nutrients.  There are both environmental and genetic factors that play a role in susceptibility to the disease.

There are two additional categories to gluten allergies: allergies to wheat, and the newly labelled "gluten sensitivity". The former is a "standard allergy": skin reaction, wheezing, etc. The latter category are cases where there is neither an allergic nor autoimmune reaction. Individuals who experience "distress" when eating wheat and other grains, feel better when switching to a gluten free diet. Basically, these  individuals might have some of the symptoms of celiac disease (such as bloatedness or diarrhea) and feel better when they switch to gluten free. Their small intestine is usually normal. The issue is that it's difficult to diagnose, because there's no real immune response, and it's subject to a placebo effect. In addition, there's a whole slew of symptoms for "gluten sensitivity" (also known as "non-celiac gluten sensitivity"), including eczema, headaches, fatigue, depression, anemia, joint pain, etc. Additionally, there's evidence that patients with irritable bowel syndrome may also have gluten sensitivity.

Now we get to a huge point of contention: are gluten allergies on the rise?

The stats for celiac disease are all over the place. Two decades ago, it was considered to be extremely rare in the United States (1:10000). But more recent studies, with more accurate methods of detection, place the incidence rate as high as 1:33 or 1:57. So, it seems like the increase in incidence may have to do with our methods for diagnosis and definition of the disease (for example, in the first paper, the definition of celiac disease was a patient with diarrhea plus diabetes or short stature. In the latter paper, the definition included a category where the only symptom was abdominal pain). Additionally, and as mentioned above, "gluten sensitivity" is a category that has only recently been added to the medical lingo.

This review points out that our change in diet may also be cause of the increase in gluten-related disorders. The authors point out that the spread of the Mediterranean diet, increase in the amount of gluten used in the production of bread, mechanization of farming and overall increase use of wheat, may all be contributing to "gluten-related pathology". A paper published in 2010 identified that the variety of wheat we use today has more gluten than varieties that were cultivated over 100 years ago. So it sounds like traditional plant breeding may be to blame!

So, the conclusion I'm coming to is that our definition of gluten-allergy/sensitivity has broadened AND we've gotten better at diagnosis PLUS there seem to be changes in how much and the types of wheat we eat. However, there are a LOT of people jumping on gluten-free because it's the latest fad. Gluten sensitivity is very difficult to diagnose, and apparently, the best way to do it is through a "double-blind, placebo-controlled gluten challenge test", which is not easy to do, so it's possibly being over-diagnosed (and in many cases self-diagnosed). In a double-blind test, 68% of patients receiving gluten had clinical symptons, versus 40% of those receiving the placebo (the numbers for placebo effects in wikipedia suggest that 40% is on par with other studies).

So now we get to the key question for this blog: do GMOs have anything to do with the "increase in gluten allergies"?



Midichlorians from http://starwars.wikia.com/wiki/Midi-chlorian

The tubes are exploding with "evidence" on how GMOs are the cause for gluten allergies (there were too many links to provide here). However, a search in pubmed found 0 studies linking the two. Reading through a few of webpages, it's evident that it's another case of association, not causation (similar to how TV sales irradicated polio or my kid's growth has contributed to my shoe purchases). The theory that's currently proposed, is that Bt from corn and other GMOs (Bacillus thuringiensis, please see previous blogs for explanation on Bt) is leading to a "leaky gut". As outlined previously, we lack any receptors for Bt. There is greater evidence for midichlorians than there are for the "leaky gut". After all, George Lucas showed us the midichlorians in their full glory, and even produced a blood test for them.

But in my mind, the greatest evidence that GMOs are not tied to gluten allergies, is that GMO wheat is not yet on the market. It's in development and is being tested, but isn't available. You really can't argue with that. Wikipedia, Monsanto, and several other sites all say the same thing: GMO wheat is not commercialized.

An interesting side tidbit is that if the gluten-free trend continues, there may be financial reasons to produce low-gluten GMO wheat. According to gmoanswers.com (which is set up by a bunch of agro companies to answer questions on GMOs), there are two papers that have been published where they've managed to decrease the amount of gluten produced in wheat (one in 2010 and the second in 2011). Wouldn't it be funny if we had to turn to GMO to address an issue that may have arisen through traditional plant breeding? Hilarious!! OK, maybe only to the geeky people...

Next week's blog may be delayed. I'm switching jobs (no... I won't be working for agribusinesses... Actually, the FAQs about Biochica don't even need to change), so I have to wait to find out if I'll have journal access. Fingers crossed for a smooth job transition and awesome journal subscription services!!

GMOs and Reproductive Problems

This week, I resume the task of reviewing the health impact of GMOs, as outlined on the Institute for Responsible Technology's webpage. As a reminder, I have yet to find a single item that is a true health concern from their page, yet it remains one of the most highly cited anti-GMO pages. So, I must march-on!!

This week, I'm going to tackle the section entitled "GMOs, reproductive problems, and infant mortality". We'll go through these statement by statement.

• More than half the babies of mother rats fed GM soy died within three weeks. This statement is attached to three references. The first is from a talk or abstract at a conference, the second is from a news article in a Russian paper, and the third is a reference to preliminary (i.e unpublished) studies. As outlined in my explanation on types of references, none of these are vetted, peer reviewed sources of information. All three are from the same author, I.V Ermakova, so I decided to check pubmed to see her publications. There are 33 publications by the author and only one was about GMOs. The publication in question was a letter published in Nature Biotechnology (note that it was not a scientific paper). And then I started reading it... Holy GM controversies, Batman!! So here's the TMZ scoop: in 2007, Nature Biotechnology interviewed Dr Ermakova. She had reported that feeding Round-up Ready GM soy beans to rats leads to pups with low survival rates or stunted growth. The report had been widely circulated in the press, leading to calls for independent studies of GM crops. However, two years later (in 2007), Dr Ermakova's study had not been published (and based on my pubmed search, it still isn't published). So Nature Biotechnology (a very high impact journal) decided to do an interview with Dr Ermakova to ask for a detailed account of her work. And then they brought in experts to review the information that she provided, who proceeded to point out all the flaws including:
• The feed that she used didn't exist. Literally. The author claims that she purchased the soybeans from a company in the Netherlands, but that company had never sold the type of materials she used in her study.
• The study didn't meet the standard norms for number of animals
• The author claimed that over one-third of surviving pups born to mothers who were eating GM soy had stunted size and low birth weight. Additionally, she claimed that males have high levels of anxiety and aggression. As if that weren't bad enough, mice who were fed GM soy failed to breed to a second generation. No evidence or data was presented, and Dr Ermakova's description of issues/results do not match with previous reports in the literature which have looked at GM soy beans (last week's blog looked at multi-generational effects of GMOs, if you're interested).
• The author claimed that 50% of pups died by the end of the 3rd week when fed GM soy, versus 8% in the controls (they actually shared the numbers for mortality). The panel of experts point out that 99.5% of the control rats should survive for the strain being used; since only 92% are surviving, probably something wonky was going on and quite possibly, they just weren't taking good care of their mice. Additionally, no post-mortem examination was performed and no cause of death is given. They state that a 50% pup mortality rate defies credibility and such a strong lethal effect would have never escaped researchers or agricultural agencies (I completely agree!! 50% mortality rate???)
• The author claimed that 33% of the pups from rats fed GM soy had smaller sizes and lower weights than the controls. The critics point out that more than 90% of the control rats were more than 20% below normal weight, suggesting that they were malnourished or subject to poor environmental conditions.
• The author concludes that Round-up Ready Soy has a negative influence on the strain of rat used, as well as their offspring, causing high mortality, infertility, decreased weight gain, change in behaviour, and changes in internal organs. The critics conclude that no meaningful conclusions can be drawn because there were so many flaws in the study.
• One of the more intriguing sections of the interview was when Dr Ermakova was asked why she hadn't yet published her findings. She explained that she had presented her data at several conferences, where she had appealed to scientists to repeat her experiment, which drew the attention of a journalist, and things took off from there.  However, she explained that she was in the process of submitting her finding for publication. The critics rightly point out that if "she had questions about her own results, as she says she did, she should not have devoted so much time to publicizing what are demonstrably flawed studies". Ouch.
• You'd think that the saga would have ended there. But... no! Dr Ermakova wrote back to Nature Biotechnology to try to polish the turd. That letter is the one article by Dr Ermakova that I was able to find in pubmed on the topic of GMOs. Dr Ermakova basically blamed Nature Biotechnology for misrepresenting her work, for not giving her the chance to defend her responses prior to publishing, and questions why the journal would not publish her paper yet would publish such a long interview and she suggests that perhaps this is due to the "reluctance of the predominantly industry-funded agbiotech community to condone the publication of studies that detail negative effects of GMOs". The letter also includes corrections by Dr Ermakova (such as details on how the rats were raised, etc).
• The fact remains that 6 years later the study has not been published and has not been reproduced. That says more than a dozen interviews or letters ever could regarding the quality of the study.

There's no doubt that Dr Ermakova felt insulted by what she considered to be mistreatment by the journal. And I can't help but sympethize for her, because some of the comments made by the critics were personal. At one point, the critics actually point out that maybe all the mistakes made were because of the fact that Dr Ermakova didn't have proper training in performing a reproductive toxicological animal study. That's a pretty personal diss. But I don't think that the journal did anything wrong here: the study was making so much ruckus in the news that the editors probably felt compelled to step in to figure out what was going on; yet, at the same time, the study wasn't good enough to publish. So what other options could there have been?

Well, I was going to go through the rest of the reproductive risks, but I think I'll resume next week.

In summary, Dr Ermakova's findings which are plastered all over the interwebs have never been published, most likely due to the quality of the study. Since my legilimency skills are not strong enough to sneak into her mind and see what the study entailed, I must discard references to her "findings".

Long-term health impact of GMOs

From Occupy-Monsanto.com

One of the more common arguments against GMOs is the lack of data or studies performed. As was eloquently stated in this viral interview from the CBC, "we're the guinea pigs" in the GMO experiment, particularly when it comes to the long-term health impact of GMOs.

I've actually been really surprised at the number of papers there are in pubmed when I've look up references and sources. The GENERA project looks at peer-reviewed studies to assess the risk of GMOs and  their database has 600 papers, 1/3 of which are independently funded. A quick pubmed search revealed that there are over 130 papers on MON810 (that's Monsanto's Bt corn); of course, not all of them were about health: a large number of papers were environmental studies, looking at the impact to soil, bugs, etc, and a fair number were methods papers describing ways to identify the GMO based on DNA or protein.

In trying to learn about the long-term health impact of GMOs, I didn't know where to start, so I decided to read a 2012 literature review that examined long-term and multigenerational impact of GMOs to health. If you have access to the paper, I suggest you take a look. The review has a helpful table, where each study is listed together with the source of funding, # of animals in the study, parameters that were examined, conclusions, and criticisms, among many other things. The long term studies, defined as any study greater than 96 days, ranged from 26 weeks to 104 weeks, used various model organisms (including cows) and the authors examined 12 of them. Some studies did not meet international standards (ironically, two of these were reviewed last week where I stated that they were indeed horrible papers). The most common criticism for several of these studies is that they didn't use isogenic lines as controls. An isogenic plant is the genetic equivalent to the GM variety, but without the GM trait. Why is this important? Well, take the corn that popcorn kernels are derived from vs the sweet delicious corn that you eat with butter in the middle of summer. As learned in my "Plants as Human Resources" course in my sophomore year, the two have different amounts of starch and sugar. So if you were to make a GM-variety out of the sweet corn, but use popcorn as your control, then the study will not be accurate. You won't know if your results are a consequence of the GM trait or if it's because of nutritional differences.

Anyway, getting back to the review: papers that met International Standards generally concluded that feeding GMOs to animals was safe and there were no long term effects. After looking at all the long-term studies, the authors conclude "the available long-term studies do not yield new safety concerns and confirm that the studied GM varieties ... are nutritionally equivalent to their non-GM conventional counterparts)."

Moving on to the multigenerational studies, these also used a variety of different model organisms, and the authors again looked at 12 papers. These ranged from 2 to 10 generations, and goal of all the papers was to determine if feeding GM plants to one generation would have an effect on the next. Several papers suffered from the same issues regarding controls. Two papers observed unexplained differences (one saw a difference in lactic dehydrogenase enzyme activity, which may affect metabolism; a second found changes in the immune system). The review concludes "overall, the multigenerational studies on animals fed GM plants do not reveal signs of toxicity or other macroscopic effects on health ... The relevance of the observed differences in some of the parameters is not known and may reflect some natural variations. The authors suggest that additional multigenerational studies should be done in order to study the reproducibility of these results and to try to find the true causes of the detected changes." The authors go on to repeat that several studies had serious flaws so "the data cannot be interpreted in terms of toxicological effects".

The authors' discussion had a few interesting points:

• They point out that there are norms and standards for feeding studies, and that all these studies (which were publicly funded for the most part) just have to stick to the rules in order to be successful.
• They point out that long term studies didn't discover anything new. They suggest that long term studies should be carried out only if there's something odd or alarming in standard 90 days feeding studies (I'm not sure I agree with this, but it's an interesting argument. I think that studies longer than 90 days add value to the debate regarding GMOs and should be conducted at this point in time).
• The authors point out that their critical examination found that studies where changes in some parameter were identified did not follow the required standard protocols.
• That due to "recurrent lack of compliance with international standards of many studies", the private sector is now unwilling to provide plant material for studies (it's no wonder after scenarios like the whole Seralini publication disaster). They highlight that without some level of cooperation, scientists may never be able to get the appropriate controls for their studies.
• The authors suggest that protocols and methods should be harmonized and standardized. They highlight that no two studies in their review were conducted the same way. Each study used a different organism, different duration for the study, different parameters, etc. Having a standard experimental design would help control for variability. I couldn't agree more.

As a side note, I think we can all agree that scientists need to quit making either a) making stupid mistakes or b) being misleading. There's no other explanation as to why you would perform a study that doesn't meet International Standards. And on top of that, journals should stop publishing crummy papers.

But let's get back to the crux of the matter. The review highlights the fact that, other than the poorly designed studies, no paper has found significant differences between GM and non-GM. So... when is the evidence sufficient enough to be conclusive? How long does a study have to be or how many generations need to be examined? That's a great question. There seem to be quite a few papers published where no difference was found between GM and non-GM food. In fact, if I were running my own lab, I'd be pretty unwilling to perform another study because a) animal studies are expensive, particularly large mammals and b) odds are, I wouldn't find anything and the absence of interesting data generally does not lead to high impact/sexy publications. So given the fact that getting grant money is pretty difficult and using private sector funding would label my study as being biased, what options are there? I think collaboration between public and private sectors may be needed, and perhaps oversight is required to ensure that studies remain impartial.

In investigating this topic, I think that the statement "long-term studies have not been performed" or "we're the guinea-pigs for the GMO industry" are false and misleading. However, I do think that norms and standards need to be universally adopted for these studies, and once a well-designed experiment is performed, it's findings need to be accepted. For example, there is a study that examined the impact on milk when feeding Bt corn to cows for 100 weeks. According to this review (note: I haven't read the paper myself), there are no criticisms of the study and it concludes that there are no differences in milk yield and composition when feeding Bt corn to cows. So, do we need another study? Or is it time to start to break out the celebratory chocolate milkshakes made with milk derived from Bt-corn-fed cows? Given the number of 90 day studies that exist examining Bt-corn and the testing standards adopted by the biotech industry, I vote for the latter.