Wait, There's How Many Independently Funded Studies on GMOs?

I just came across this list of 126 independently-funded peer-reviewed articles on GMOs this morning, and I'm really surprised I hadn't seen it a long time ago. Clicking through some of the studies, they run the gamut of genomic analysis between conventional and genetically modified crops (particularly on unintended alterations of untargeted genes), the potential for transferring antibiotic resistance, the risk of allergenicity, analysis of tissue and metabolites in rats, amount of pesticide use, and the effect of Bt corn and GM soya on mouse testes. In all but a handful of studies, the investigators found no evidence that GM poses an additional risk over conventional farming. Again, these are the independently-funded studies so many critics of the technology have asked for for years. There's simply no excuse for ignoring it.

I didn't see any studies about cassette tape genes. I'd just steer clear for now. (Source)

I've written before about systematic reviews and meta-analyses, and how if you don't look at the full picture, it's extremely easy to cherry-pick to find the results you're looking for. Without really looking too hard, you'll find some studies that contradict the consensus this list represents, as you would expect in just about any field. For instance, one study may say eating eggs provides nearly the same cardiovascular risks as smoking, while a meta-analysis of all prospective cohort studies, including the previous one, on eggs and cardiovascular health representing data from over 260,000 people, shows no additional risk. Which conclusion do you think holds more weight? I can't stress enough that science isn't a push and pull of individual studies floating in a vacuum, it is a systematic way of looking at an entire pool of evidence. It takes work to train yourself to do this. It's just not how we're wired to think, and even people who have been exposed to it still struggle with it, as I see in my everyday experience in evidence-based medicine. People naturally have their preferences, but if there's a way to minimize this effect it's inconceivable to me not to use it to guide our decisions, from adopting a new technology, abandoning existing ones that don't work as well as we hoped, and in the way we determine our public policies.

In my many, many conversations on GMOs, I've found that confirmation bias isn't the only barrier, there's also a significant amount of conflation going on between what's specific to GMOs and what is just poor agricultural practice. For example, it's quite clear that pesticide resistant weeds (aka superweeds) are popping up on farms around the U.S. Certainly, growing Roundup Ready corn would logically facilitate the overuse of a single pesticide on a single area, but resistance will occur anywhere there's over-reliance on a single pesticide, and it's up to the particular farmer to rotate their crops to avoid this. Just because many have failed to do it doesn't mean that GMOs are the primary problem. On the spectrum of possibilities of genetic modification, in my view pesticide resistance is securely on the bottom, but let me put it this way: if we just simply banned them, totally removed pesticide resistant crops from all farms in the U.S., would we solve the problem of superweeds for all time? Obviously not. For every potential risk you've heard of about GMOs, ask yourself the same question. You'll almost always find that the problem comes down to general issues of large-scale agriculture.

GMOs Part 2: How The Digestive System Works

In my last post, I gave an overview of why there's no scientific basis for claiming that GMOs by definition are harmful for human health, focusing mostly on the molecular biology angle. Now, I'd like to add on to that by describing how food gets digested on a molecular level. If GMOs are going to be harmful, it's going to happen on this scale, and it's going to be unique to the specific GMO in question. Hopefully, both pieces together will help you spot what the real issues are and what is BS in the GMO debate. Not coincidentally, a major concept here is that DNA is DNA, just like in the molecular biology discussion.

Everything we ingest is essentially made up of four basic types of macromolecules: sugars, fats (or lipids), proteins, and nucleic acids. We're only concerned with the latter two, because all life, genetically modified or not uses the same range of sugars and fats. Let's start with how proteins are digested. Remember, the point of a GMO is to get an organism to code for a specific different, or set of different proteins that it wouldn't otherwise produce. Proteins are fascinating molecules, and I would totally have enjoyed an entire course on just them alone. Depending on its sequence of amino acids, a protein can be an enzyme, a hormone, or used for structural purposes, like collagen or the exoskeleton of a crustacean. Our digestive system is full of hundreds of different enzymes that each break down a single macromolecule, including other proteins, and no matter what type of macromolecule it is, they are broken down largely by the same type of reaction, called hydrolysis.

The dehydration synthesis reaction for two amino acids, in this case glycine on the left, and alanine on the right. (Source)

The proteins we ingest are made up of a combination of 20 different amino acids, each with a unique structure giving its own properties, like whether it is able to be in contact with water or not. They also vary widely in size. Both of these properties are very important in determining the structure and function of the protein by determining how it folds up. Each amino acid is bonded to the next by removing a hydrogen ion (H+ or proton) from one, and a hydroxide ion from another (OH-). The H and OH- spontaneously attract each other to form water, thus giving the reaction the name of dehydration synthesis. The reaction is easily reversed by adding a water molecule back into the bond to cut it (root of hydrolysis = water cutting). Hydrolysis is a thermodynamically favorable reaction, meaning it happens fairly efficiently on its own spontaneously, but enzymes are needed to speed it up to meet our body's demand for new building blocks.

Enzymes in our digestive system that do precisely this include pepsin, trypsin, and chymotripsin, and each specialize in breaking the bond at just a few specific amino acids in the stomach and the duodenum. These enzymes are able to reach virtually all peptide bonds due to the low pH in our stomachs unfolding the protein from its complex shape into more of a chain. The end result is that the protein we ate is broken up into individual amino acids for absorption into the bloodstream through the lining of our intestines. When this happens, they have none of the properties of the protein we ingested, and do not have a function on their own. It doesn't matter which protein it is, or where it came from, it almost always ends up as nonfunctional pieces that are recycled to new dehydration reactions elsewhere in the body to create new proteins. There's an exceptionally small chance for a novel GMO protein to survive the digestive system intact and functional, and GMO proteins are not any more likely than any other protein to do so.

Many food allergies, however, are indeed caused by proteins that do resist full digestion in any one or several of these steps for one reason or another. When this happens, our immune systems recognize that it's a foreign protein and attack it, causing the allergy. It's certainly plausible that this could theoretically happen to any GMO protein, but the risk is not deemed serious enough by the FDA to require a clinical trial for new GMOs. I think it's perfectly reasonable for consumers to demand testing for potential food allergies, but I also think the potential risk is quite a bit overhyped. It's certainly worthy of debate. I'd be open for requiring independently operated small scale clinical trials.

Digesting the nucleic acids DNA and RNA follow a very similar process. They too are polymers where each building block is bound in dehydration reactions, and are broken up by hydrolysis by enzymes called nucleases. The nucleic acids can either be reused to build new nucleic acids, or they can be broken down further into a sugar, the base that makes up the genetic code, and a phosphate group.

Hydrolysis of DNA. An arrow on the bottom left shows a water molecule approaching the phosphate (PO4) group that binds the pair of nucleotides, The pentagon is a sugar, called deoxyribose. The molecular structure of the bases are not shown (Source).

Some critics have claimed that the transgenes have been taken up by bacteria in our digestive system intact, but there is no evidence that they've ever survived through the entire digestive tract. This is a hypothetical and exceedingly unlikely event that currently is not supported by the science. Furthermore, a transgene is no more likely than any other gene we digest to be transferred like this. Also, if, say, the gene providing Roundup resistance in Monsanto's corn were to be transferred in full to a bacteria, how exactly would it provide a survival benefit without constant exposure to Roundup in our digestive systems?

When people claim that the corporations are buying and paying for the science on GMOs, they don't realize it, but they're saying that everything we know over decades of research in molecular biology and digestion is suspect. Because so much of what we do know is fundamental, the FDA long ago declared that GMOs are "substantially equivalent" to any other non-GMO, and required no additional testing. They didn't do it specifically to appease powerful interests, they did it because it would have been irrational for them to do otherwise. Their jurisdiction is public health, and in this case they made the choice with much more science behind it. If you listen to vocal critics of GMOs, it seems they're starting to get this message.

When people say "we have the right to know" what's in our food, hopefully now you can get an idea of why a label saying something is genetically modified doesn't really tell you much except what you already know: this organism was grown using industrial agricultural methods.

What To Talk About When You're Talking About GMOs

Oh boy, the first ever genetically modified animal passed the last major regulatory hurdle, and presumably has the green light for FDA approval. AquaBounty Technology's AquAdvantage salmon will soon appear (unlabeled) in supermarkets and restaurants around the United States. Back in April, the FDA finalized its environmental assessment on the salmon, and finally released the results this past week, indicating that they see little risk of negative environmental impact. There's certainly valid reasons to make a personal decision to avoid this salmon, but I do want to try and separate the science from the science fiction to help you make a more informed decision about it. This seems like the perfect time to introduce the concepts and issues around GMOs as someone with personal experience in the lab with them, and, since at this point I think pretty much anyone who reads this knows me, you can vouch that I'm hardly a shill for Big Ag.

At 18 months, the transgenic fish is clearly much larger than the same-age normal fish. But overall growth of the same generation of fish evens out by 36 months. (Image Credit: Aqua Bounty Technologies)

To develop AquAdvantage, AquaBounty isolated the gene in the largest species of salmon, the chinook, that contributes to its size. Then, they inserted it in the genome of a wild Atlantic species to replace their own growth gene, allowing it to grow at twice its normal rate. However, this gene only affects the rate of growth, and does not create a new giant species of Atlantic salmon. Just by looking at the full-grown transgenic fish and a full-grown natural Atlantic salmon, you'd never be able to tell a difference. While I grant it may sound a little bizarre, and I definitely thought so about GMOs in general before I became more familiar with them, the techniques are hardly novel at this point. Every biology major for the last 30 years will likely have performed these techniques dozens of times. The ick factor, I think, comes from a misconception about what genes actually are, and an ethical issue of toying with nature that usually underestimates the prevalence of genes transferring from species to species. There's nothing wrong or shameful about this, really. It's more shameful that this information is so arcane.

Ultimately, the first issue comes down to the fact that DNA is DNA. Think back to your high school biology class, where you learned about its structure. It's the same stuff in every cell in my body, yours, and in the virus I got the other day that's really pissing me off right about now. A gene is basically a stretch of DNA that codes for a specific protein, with molecular switches nearby that turn it on or off. While this stretch of DNA, and the switches that make it up between species may vary in size and the precise code, there's nothing uniquely "chinook" about the chinook's DNA, just as there's nothing uniquely human about ours. Nobody is injecting any crazy new hormones into anything, it's simply replacing the existing hormone with a pretty similar new one using the existing one's own "machinery" to control its expression.

Who wants a tri-colored fish that was injected with some sort of red shit? (Image Source: Yvonnegraphy)

Because of all this, any stretch of DNA is theoretically fungible from species to species. Evolution occurs because the order of base pairs changes over time due to mutations, or perhaps from viruses leaving traces that get inserted into the host's DNA. Roughly 8% of every person's DNA initially came from viruses, just from natural gene transfer. That doesn't mean we're part virus, and it certainly doesn't mean that our ancestors were more natural humans. Nature is constantly changing and adapting to outside stimuli, and the adaptation happens at the DNA level. The concept of genetic modification is to preconceive these types of gene transfers, nothing more, nothing less.

Based on everything we know about molecular biology, chemistry, and toxicology, it just doesn't really make sense for GMOs, by definition and across the board, to present a public health issue, apart from the possibility that the specific novel protein the new gene encodes produces an allergic reaction. This is reflected in a broad consensus (AAAS, WHO, systematic review of 42 peer-reviewed studies, Royal Society of Medicine) of science and health organizations around the world. I understand why many people do not trust this consensus. It's absolutely true that chemicals or pharmaceuticals once deemed completely safe by industry and regulatory agencies were later found out not to be so safe. I'm always very suspicious of industry, but I try not to let my suspicions replace or override evidence. Evidence is the sum of the best of our understanding about a particular topic, and while it can sometimes be incorrect or incomplete, in our case with GMOs the quality of the small amount of contradictory evidence is of very poor quality. I could write an entire post about the problems in a recent article that came out linking GMOs to cancer in rats that ultimately make this experiment of little to no value at all, but the conclusions it claimed to reveal will never fully disappear.

So, getting back to AquAdvantage, how exactly did this salmon pass an environmental assessment? The first question that needs to be answered is whether this new growth gene will escape into natural populations of Atlantic salmon. Now, think back to high school biology again. It's not enough for a gene to get passed on from a parent, the gene must provide a definite selective advantage to survive. It's plausible for quicker growth to be naturally selected for once it hits the ecosystem, but certainly not definite. The risk is real enough, though, that AquaBounty claims they will make, at minimum 95% of the transgenic fish sterile females that cannot possibly pass on the gene in question. Of course, while this does not completely eliminate the theoretical risk, it does reduce the probability of it actually occurring. To further reduce the possibility of a worst-case scenario, the fish will be bred at a facility in Prince Edward Island where, if they do escape, it will be very difficult for them to survive due to the extra cold winter temperatures and high salinity of the Gulf of Lawrence that they would escape to. Ultimately, this was deemed good enough by the FDA. If you have a quibble with the FDA, look at the study and determine how and why you think this is insufficient. They aren't going to listen to assertions and arguments without evidence.

That's the science behind GMOs, and none of what I said is all that controversial within the relevant fields. In the science bubble, these facts speak for themselves. It's a mistake, and a bit arrogant, to act as if that is or should be the case outside of science, in the court of public opinion as they say. Most people make decisions based on much more complicated factors, not the least of which are anecdotes that strike an emotional chord. Sticking only to arguments based in evidence doesn't really take those complicated factors into account. It's important to try and tell a compelling story, one that competes with powerful anecdotes, so my hope is that what follows below is a decent attempt at it.

To someone who uses evidence to guide decisions on science and technology, there is a bit of irony in labeling the political right as "anti-science", because we notice that for many on the left, science is more valid depending on whether or not corporations fight it or hold it up. We on the left are often amazed at the mass delusions the right has accepted as truth, from climate denial, to intelligent design, to conversion therapy to "save" people who "made the choice" to be gay. Unfortunately, we are not as critical of our own misconceptions, from the way we talk about GMOs, to not vaccinating our children. I don't think both sides are totally equivalent here, but they do all stem from a sometimes, but often not justified mistrust. It's a difficult thing to accept, but if you believe in science, you have to accept that this is not an appropriate lens from which to view biotech. I haven't read the full environmental assessment, and I'm certain there are valid criticisms to be made from it; there always are. However, none of them amount to a (albeit probably half-serious) headline saying "The Apocalypse is Here". I think we have the capacity to be a whole lot more rational than the current makeup of the right wing, but this requires examining our own thinking and being secure enough to accept that maybe our gut reactions are leading us to places that aren't totally justified. While it's totally OK to have a visceral reaction to an article saying this fish will destroy humanity, I hope your next reaction is questioning whether those emotions are closing you off to accepting more information that makes things a bit more complex. That is totally not OK, because very little in the world is purely black and white. It wasn't the case when George W. Bush was saying "you're either with us or you're against us", and it's not the case when thinking about organic vs. industrial agriculture.

While Monsanto is certainly is prone to exaggeration, unethical business practices, and are one of the largest contributors to an unsustainable food system, this does not undo the science on their side about GMOs. Technology pretty much always comes with some risk and some benefit, and the question is always whether the benefits outweigh the risks. Often, it seems that the only benefit is in the bottom line of the company that develops the GMO, and AquAdvantage is not really an exception. The benefits do go to AquaBounty, but I think what tends to get overlooked is that fish farmers who can cycle out their enclosures more quickly will also perceive a benefit. There's plenty of family farmers who actively choose to use Roundup Ready corn because they perceive it to be a more reliable means to provide for their families. I may not want to support either one with my own money, because I don't want to support "conventional" agriculture, and I don't approve of fish farming, but I'm an unapologetic pragmatist. The burden is on us to demonstrate a better way accepting that economics matter, and they matter from a self-interest point of view. I don't want to force someone to be more environmentally responsible with no assurance that their ability to finance their huge, expensive equipment is safe, and I don't want to advocate for any sort of policy that is based more in ideology than evidence. Most of these farmers are heavily in debt and make short-term economic decisions because of it, so make your solution more enticing from a short-term economic point of view. Demonstrate the utility of your solution, and do it without expecting much help from government. We really need it.

Right now, scientists are working to develop drought-resistant GMOs that can survive dry spells like we went through in the Midwest this past summer, and also require less irrigation and conserves our aquifers. There's also a group working on crops that use less nitrogen, potentially minimizing the use of synthetic fertilizers made from petroleum, and thus reducing the type of agricultural runoff that has created a giant dead zone in the Gulf of Mexico. Some of these issues could possibly be helped by conventional breeding, but compared to genetic engineering it's less efficient in time and money spent. It's certainly possible that neither GMO ever pans out at all. Sure, the ideal solution is to grow our food in a diverse field, without monocropping and synthetic inputs, but I don't see much value in dismissing something that tries to improve the latter issue without forcing farmers to adopt an entirely new and economically unproven method. We certainly are willing to give electric vehicles time to develop, knowing full well that they are mostly impractical right now, while the electricity is still mostly generated by fossil fuels. They are nowhere near their potential, and even the biggest cheerleaders acknowledge this. Same goes, I think, for GMOs. Monsanto doesn't help by insulting our intelligence and acting as if the potential has arrived, but really, what does that even matter? Nobody really believes that. Why would we want to dismiss GMOs like these out of hand because of the techniques used to create them? Are there really more barriers to competition in biotech than any other industry, where the companies involved now will always control it? Just think about where IT once was. In 20 years, I have little doubt that we'll know full well where biotech stands, and today will be looked back upon like the 1960s are in IT, just replace IBM and Bell with Monsanto and Cargill. They'll lose control, because big corporations are good at using influence and access to maintain their market share, but not through innovation. That's where the proverbial college dropout in his or her garage comes in, and they'll most definitely be coming.

Please don't be afraid to comment on this post if you disagree. I'm happy to engage with people who think I'm crazy.