Tuesday, December 22, 2015

GMO DNA in our Blood

Some of you may know that I was recently given notice of my laid off due to a corporate re-org. Luckily, I've had a few good leads and will hopefully start working soon after my last day at my current job. But, needless to say, I find myself with more time on my hands than usual. I've been trying to make the most of it, so you may see an uptick in my number of blog posts and infographics. I also started a Facebook page, which I encourage you to go "Like" and share. I also have a few pieces of brain-candy waiting to be read of the non-science variety. So much to do, so little time!!

This is a cross post from my Facebook page, which I'm broadening here to include links and more information. 

Every few months, anti-GMO websites will publish a meme about the latest paper that has "detected GMO DNA in (insert an organism or fluid that will cause alarm here)". Yes, DNA from GMOs has been detected in goats, humans, blood, organs, colostrum, you name it. But that's not the whole story.

Our DNA is packed away very neatly in the nucleus of our cells and is the "code of life". This cellular DNA is the blueprint for the proteins that are the building blocks of our cells. This is the DNA that gets replicated when our cells divide and is the DNA that gets inherited.

In our blood vessels, there's another type of DNA known as cell-free DNA (cfDNA). It's found in the plasma or the space between cells. It is made up of our DNA from cells that have died, but also foreign DNA including DNA of viruses and bacteria. In pregnant women, there's DNA from cells of the fetus, and this is the material that is used as the basis for non-invasive prenatal screens which allow to test the fetus for Trisomy-21 and other genomic conditions. Finally, there's DNA from the cells of food we've digested. Cell-free DNA is thought to be very short and degraded.

When a GMO feeding test is carried out, it is not uncommon to check to see if the animals fed GMOs have segments of DNA from the food in their blood/tissues. The standard test that is used (PCR) does not distinguish between cellular DNA and cfDNA. This is because the PCR assay requires that you know what to test for, so we can only test whether the transgene is present or not in our sample, whether it's in cellular DNA or cfDNA. To determine if it's integrated into the cell's DNA (i.e horizontal gene transfer), you'd have to know where it's integrated into the genome in the cell's DNA and design the assay with that information in hand. The other option is to look at all the DNA in the cell (i.e. sequence the entire genome) and look to see if DNA from our food has integrated into our genomes.

To date, there's no evidence suggested that DNA from our food gets integrated into cellular DNA. If DNA from our food did integrate into our DNA, then we should see these random DNA snippets in our DNA. However, in the thousands of human genomes that have been sequenced to date, this has never been observed. In the thousands of genomes that we've sequenced, from humans and other species, we have observed that DNA from other species get integrated into cellular DNA (horizontal gene transfer), but it is usually done by a virus or other microorganism. This article outlines how the sweet potato is a "natural GMO" because thousands of years ago, DNA got integrated into its genome using the same method that scientists use today to make GMOs. 

The fact of the matter is that, from a biochemical perspective, DNA from GMOs is identical to DNA from any other organism. It's not toxic, it's not different, it's made up of the same A, T, C, and G, as anything else. Our bodies cannot tell them apart. So DNA from our food has been floating in our plasma since we became a species and ate whatever plants and animals existed back then. I can say with quite a bit of certainty that there is DNA from tangerines currently floating in my bloodstream. I think I've eaten about 5 today.

When the spouse read this post, he commented that "eating Yoda wouldn't increase your midichlorian count and make you a Jedi". I think a more apt analogy is "eating plants and veggies doesn't make you an Ent". 

If you want to learn more about GMO DNA and some of the papers I've reviewed/rebutted on the topic, please see here and here

Tuesday, December 15, 2015

Why aren't GMOs tested on humans?

How much corn is enough corn for a feeding study?
From Wikimedia
A very common question or criticism of GMOs is that they are not properly tested, particularly on humans. The spouse and I had a discussion about this a while back and he asked why GMOs weren't tested like drugs since they're regulated by the FDA. I've read comments such as "I won't believe GMOs are safe until they're tested for 5 years on humans and we examine long-term impact", so I thought we should explore this point.

The regulation of GMOs is based on the principle of "substantial equivalence", meaning that the nutritional content of the GE crop and the non-GE crop that it originated from is the same. In the past, I've reviewed papers that have done comparisons between crops generated by transgenesis (the method used to make GMOs) vs crops generated by traditional cross breeding and mutagenesis. The transgenic crops had far fewer unintended consequences than the crops generated by traditional breeding methods. What remains to be demonstrated is that the protein introduced poses no greater risk to human health than non-GE crops, which is why studies on allergenicity and animal feeding studies are performed.

So "why don't we do clinical trials on GMOs the same way we do for drugs?" Drugs are designed to cause a change in the human body: that's the whole point behind them. Since drugs are altering something in humans, it's important to know the side-effects that they may cause and whether or not they're causing the anticipated effect (i.e. is it better than placebo). In contrast, GMOs are designed to be equivalent to their non-GE counterparts: they aren't drugs or nutritional supplements. GE crops which ARE designed to impact human health, such as vitamin-A enriched rice, should be tested in humans to determine if the desired outcome is achieved (i.e that the rice actually delivers vitamin-A to the body). But such studies are not the same as looking for unknown long-term effects.

Another reason why is that there's no plausible mechanism for harm. In the past, I've explained how nothing can truly ever be proven to be 100% safe, whether it's water, a computer or a car. Researchers examine safety when there's a plausible mechanism whereby harm can occur. For example, a cholesterol lowering drug may act by interfering with cholesterol synthesis in the liver, so it may make sense to see if it impacts other metabolic functions in the liver. But when it comes to the traits that are introduced into GE crops, there isn't really a mechanism of harm: for example, the Arctic Apple is engineered to have a gene turned off, and the gene doesn't even exist in humans, so how could that harm us? This is why most scientists wouldn't want to spend years trying to secure grants for a long term feeding study when the likelihood of having an important discovery or contribution to the field is so low. Safety is relative, and there have been many long-term feeding studies in animals which haven't observed any harm, suggesting that follow-up testing of GE crops in humans is unnecessary.

An additional issue is that the experimental design would be incredibly difficult. Unlike animal feeding studies, you cannot control for other dietary factors or for lifestyle of the humans in the study. In animal feeding studies, all the animals are inbred so there's very little genetic variability. All the animals live in the same type of cage, get the same amount of food, sleep, water, etc, but none of this applies to humans. As a mental exercise, let's imagine that we're going to embark on a study examining the long term effects of GM crops. We'll narrow it down to a single GM crop: Bt-Corn. Since corn derivatives are found in many processed foods, we'd have to eliminate other sources of Bt by making all the participants adhere to an organic diet. Most sweet corn in the US is not of the Bt-variety, but since we want to be able to keep track of how much GE corn our participants are ingesting, we'll have to use this type. Then, we have to figure out the duration of our experiment: how long will these people have to eat Bt-corn to get this unknown effect? 1 year? 2 years? 5? 10? Let's keep it simple and say one year (although I seriously doubt that any die-hard anti-GMO activist would be satisfied with 1 year). Then we have to figure out who we will be feeding: will we focus on individuals of a single genetic background to eliminate other variables? Will we include children? Pregnant women? (I mention these specific categories because there's no end to anti-GMO blog posts about the dangers of GMOs for these individuals). Next, we'd have to grow all the corn in the same place: studies have shown that geographic and seasonal variability changes the nutritional content of crops more than whether the crop is a GMO or not (see here and here). Since we want all the participants to get the same corn for the entire duration of the study, we'd have to grow it all in a single place, process it, and all the participants would need a deep freezer to store their 1 year's worth of sweet corn. Then, we have to decide how much corn they'd need to eat in order to observe this unknown effect. One ear a week? A day? Who would sign up for a study eating an ear of corn a day for a year?? And then who is going to pay for this 1 year study on many people of organic food consumption plus GE-corn? If Monsanto or other seed developers pay for it, will anyone trust the data?

There are FDA guidelines for examining the impact of food additives in humans has several important points including this one: "A food or food additive generally will be considered suitable for clinical testing if the substance is unlikely to produce significant toxic effects at the levels to which the subjects of the clinical study will be exposed. This usually is determined from the results of toxicity studies in animals or by examining existing data on population exposure. However, in cases where the type of toxic response associated with the consumption of a food or food additive by experimental animals is judged to be severe, exposure of subjects in clinical studies to the additive may need to be significantly below the level found to produce no toxic effects in an appropriate species." If the individuals who want to do long-term feeding studies in humans are looking for evidence of harm due to "long term toxic effects", then based on the statement above from the FDA, such studies would never be cleared by an ethics panel. Other important points from the document include the fact that such studies should have different dosages and the language used for long-term studies is weeks/months, not years.

This isn't a cop-out. If we're looking for a harmful effect but don't know what it is because we don't have a reasonable mechanism whereby harm may occur, how can you design the experiment? What variables will you measure? As this document from the FDA outlines, clinical trials for drugs go through very specific phases and can be variable in duration and size. However the thing they all have in common is that they're looking for a very specific effect (improvement of the disease or its symptoms in the patient). Doctors know exactly what to measure, and look for any possible side-effects, which end up getting listed in the package insert for the drug, even if they are not causal.

The final point is this: what is exclusive or unique about GMOs that merits such rigorous testing, yet excludes other crop modification techniques? If your argument is that GMOs are made by scientists in a lab and are consequently riskier, so are seedless watermelons. If your argument is that GMOs have genes from other species and are consequently riskier, so do sweet potatoes which have genes from bacteria naturally introduced thousands of years ago. If your argument is that we've had thousands of years to co-evolve with other crops but not to GMOs, then I ask you how it is that I, an individual of Iranian descent, have a passion fruit vine, which is native to South America, growing in my backyard in California? I'm pretty sure that the passion fruit and I didn't co-evolve and adapt to one another throughout our evolutionary history. The passion fruit, the sweet potato, and the seedless watermelon did not undergo any testing, animal or human, yet many continue arguing that all GMOs regardless of trait should undergo animal and human testing.

Well, I hope you all have a wonderful holiday season. If you don't subscribe to this blog, please consider doing so or you could also follow me on twitter where I post everything I publish from this blog and Biofortified.