"I've got allergies out the wazoo, and I'm worried that they'll take genes out of corn and ruin more foods for me." I'm paraphrasing, but this was an interesting point @phoenixwren raised in response to my gloriously titled corn snot post.

I've been fortunate that neither I nor anyone close to me suffers from severe food allergies, so that issue is not something I've really considered. After reading, it looks like a lot of other people out there are interested and there's a lot of good and bad science (and interpretations thereof) flying around.

It was interesting enough that I decided to make this a full article instead of a reply. If you like seeing stuff like engaged comments leading to (hopefully) quality discussion I encourage you all to pick one of @phoenixwren's comments from within the payout period¹ and upvote the heck out of it, ideally letting them know why.

^{That's not actually how it works, but it's photogenic. Even if gene guns are so much cooler. Also, you try finding a public domain GMO image that isn't rabidly pro or con. From Pixabay, under CCO}

Obligatory disclaimer and disclosures

Before I begin, just note that while I have training in molecular biology, I'm neither a dietitian nor a medical professional.

Also, wow, I knew people were concerned about GMOs but I had not fully realized how much vitriol is out there until I started reading up. I assure you that I do not work for Monsanto nor do I intend to. Given that the biggest issues in my household involve answering questions like whether or not we can afford the extra buck this week for the 'good' peanut butter² , it's a safe bet that I'm not getting paid off.

Part of my training as a scientist and engineer is to read and think critically - I have done so to the best of my ability here and do not think I have been 'fooled' by big food nor have allowed my biases to unduly discount arguments from GMO critics. I look forward to all the discussion that any GMO stuff seems to engender, I ask only that people keep it civil.

Basic grounding in proteins, GMOs, and allergies

Before I can write sensibly about this stuff, it's important that we have a few key facts.

Genes encode proteins. When we alter genes, we alter which proteins are made

There's a thing called the central dogma of biology. It states that DNA gets transcribed into RNA then RNA gets translated into proteins. Moreover, the reverse does not happen.

There are lots of cool caveats and exceptions which we should bear in mind but altering DNA to make proteins is the crux of genetic engineering. We may be interested in the protein itself or the product of a reaction it catalyzes.

Point One: Genetic engineering involves deliberate attempts to create specific, predictable proteins.

^{A delightfully simple schematic of the stuff of life. Source, by Squidonius, under public domain.}

What is an allergy, exactly

I found out a lot of really neat things about allergies while reading up for this article. First, although getting an allergy diagnosed and determining its source can be a struggle, the mechanisms of an allergic reaction and what causes it are well defined. If you remember any biology stuff about your immune system, you probably remember the word antibody - they are essentially smart tags which get the attention of various parts of your immune system.

We mammals have a special kind of antibody called IgE. This little molecule is hugely important for fighting off malaria, other parasites, and maybe even cancer. IgE coats special Cells of Doom called mast cells and if it recognizes a foe (be it a parasite or pollen), the mast cells release all sorts of fun chemical weapons like cytokines and histamines.

^{The reason you spend money on Allegra. Also why you're less likely to have worms. Source via Wikipedia, by SariSabban, under CC3.}

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Point Two: Food allergies are a specific response to particular compounds, often proteins. refs: 1,2,3

What does that mean for GMOs and food allergies?

Given those two points, and so long as we aren't deliberately altering the food to produce allergens⁴, it is unlikely that a GMO food will trigger allergies if you are not allergic to its non-GMO counterpart. However, that's a very superficial analysis and there are a few 'yes, buts' that should be considered.

Yes, but... what about producing stuff that's not quite what you planned on

This issue crops up mostly in two cases: post-translational modification and mutations.

Post-translational modification is one of those issues which complicates point one. A protein can change after translation; it may be chopped, spliced, and decorated by the organism. Of particular concern here is that these modifications vary from organism to organism. The big deal here is the protein you want may not be the protein you get.

There's a few safeguards against this leading to allergies, some logic-based and some test-based.

First, people are not putting genes into crops for the fun of it - the proteins they encode have a specific intended purpose. Unforeseen modification will probably lead to the protein not doing what you want, and that product either won't go to market or the modification will be fixed.

Second, as a matter of development and quality control, the proteins themselves are sequenced. It will be come quickly apparent both if an unintended change has occurred and we can use those sequences to see how close the expressed protein is to known allergens.

Third, it appears that most food allergens are very specific proteins from a few classes. It is exceedingly unlikely that modifications to an unrelated protein will make it suddenly become an allergen.

Finally, there are a whole battery of tests (which you can read about, thanks to open access!) which GMO foods are subjected to specifically to test for allergic reactions.

Briefly, these tests are of three classes:

• testing in the blood serum of people with existing allergies and checking for a reaction
• checking the structure of proteins against known allergens, like we discussed above
• checking to see if the protein resists digestion, which is a hallmark of many food allergies

Mutation is the other complication leading to 'weird' proteins. This may be either natural mutation or part of efforts to evolve better proteins (site directed mutagenesis and directed-evolution). In all of these cases, the same safeguards still apply.

It also bears mentioning that the mutations seen in GMOs, particularly when intentional, are much, much more predictable than those which are produced by exposing seeds to chemicals and/or radiation in mutation breeding, which has produced over 1000 varieties of food crops.

^{I could not find a good unencumbered image of mutant breeding, so here's one of mutton breading. Source via pxhere under CCO.}

Yes, but... what about proteins we don't know cause allergens

This arises both because there's almost certainly food proteins out there we don't know are allergens and because we're inserting genes from organisms we don't normally grow as crops.

It's difficult to predict beforehand if a protein will be an allergen, but the tests I've mentioned before can catch them before they get to market. To my knowledge, there is no confirmed example of this happening.

Yes, but... inadequate tests

Here, I have to agree that the tests can always be improved.

A major example of testing is the Brazil nut case - soy beans were modified with some Brazil nut genes and before they made it to market were tested and shown to cause severe food allergies. First point, the title of the article is horribly misleading, and shame on the author and editor. Second, I find myself agreeing with Dr. Pauli's statement from the above article:

"The study shows that caution is needed, but that we are on course as far as regulations go," [...] "Industry is following our guidance and essentially has been notifying us about what it is doing, regardless of whether it is required or not."

My issue is that I don't trust industry to self-regulate and we should always be improving our test methods.

I would also argue, however, that there is no such thing as a perfect test. GMO crops are subjected to stronger tests than novel non-GMO foodstuffs (Kiwi), and that holes in testing appear to be filled as weaknesses are discovered. It comes down to potential risk, which I'll get to later.

Yes, but... non-protein allergens

Proteins, proteins, proteins. There are non-protein molecules which can cause allergic and pseudo-allergy reactions, like codeine, nickel, and penicillin. The issue here is that it's a lot harder both to predict their production and likelihood as allergens. It is however, fairly easy to determine if they cause an allergic response and the nature of the testing done for protein allergies should catch those as well.

Yes, but... correlation of allergies to GMOs

Food allergies are probably increasing, but it may also be an artifact of increased testing and reporting. If the prevalance is increasing, the reasoning goes that is may be due to a correlated increase in GMOs. However, this is only a correlation, and a casual, almost anectdotal one at that. I have seen no rational evidence of a causal link. In fact, no one is quite sure why allergies may be increasing, but the rise in other, non-food related allergies points to something else.

I am aware that 'no causal link' was also one of the first defenses of both tobacco companies and climate change deniers. The difference, so far as I can tell, is that in those cases, there is a preponderance of supporting evidence and definite theory-supported mechanisms. In the case of food allergies I am not aware of a sufficiently strong set of evidence upon which to infer causation.

The link between food allergens and GMOs is less outwardly spurious than the link, pictured below, of "why encouraging people to buy mozarella will help me finish my dissertation". I could be wrong, but I would not bet on it.

^{This is truly a correlation, one of many found by Tyler Vigen and graciously released under CC4.}

So, there's a ZERO percent chance?

Heck no. I would be a terrible scientist if I thought much of anything was 100% likely or unlikely⁵. However, my personal stance is that the probability that you're going to have an allergic reaction to a GMO food is much, much lower than that chances of having a reaction due to contamination somewhere during food production, transport, storage, and processing. In fact, the only direct link between GMOs and allergies I could find was research on using genetic editing to eliminate allergens in peanuts - which means that some of you may also be able to enjoy the Good Peanut Butter soon!

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Footnotes

<sup>1. The originating comment is beyond payout, since I'm a slow-ass writer.
2. Peter Pan Honey Roast Crunchy, for the curious. I have no affiliation with them,other than that an embarrassingly high amount of the carbon of which I am currently composed was probably made by them. I half-seriously considered adding a wishlist link but decided it was déclassé. I do encourage you to buy some and donate it to your local food bank and make someone's day.
3. Well, I won't die from an allergic response, but I do have an unhealthy love of PB sandwiches as a midnight snack. Damn the 'good' peanut butter and caloric surpluses.
4. We actually have a really great database of known food allergens which we can check.
5. Well, I might be a good Sith scientist.</sup>

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side note: Here's a direct quote from @phoenixwren, "Like honestly, that's my biggest GMO question, and I can't find diddly squat about it when I've looked." Consider that an intelligent, motivated member of the public can't find information they need, even though the relevant research was probably supported by their tax dollars and they were stymied even when taking pains beyond what a normal citizen would to use legal methods to circumvent journal paywalls. Make of that what you may.