I was on a bit of a hiatus on blogging last month, but a lot of good things happened. I had a manuscript accepted for publication at Cell, I got my box checked (which means I have permission to start writing my dissertation, which means I should be graduating this year), and my fiancée and I finally picked a date for our wedding (November of this year!).

But I also received an e-mail from a farmer interested in the question of genetically modified organisms and allergies. She contacted me because of my post last year for the guest blog, and since I spent some time in e-mail correspondence with her, I thought her question and my response would be a good way to revisit the topic (and to get me back in the habit of blogging). Her question (quoted with permission) arose during a discussion with an opponent of the use of genetic engineering (GE) in food who was

...insistent that we separate "Bt" from the GE foods & allergenicity question because "the allergenic response might be different from other GM technologies."

She then said (I redacted some info to maintain her anonymity)

This makes little sense to me and so my response is if we are going to separate out Bt GE foods, then we also need to look at allergenicity of all foods sprayed with Bt because the protein is essentially the same. The use of GE "technology" did not structurally change the Bt protein or make it a "novel" protein and therefore we wouldn't be seeing a different response whether it was sprayed on a crop or inserted into a crop. Is that a fair statement to make?

I use Bt to control for [a specific pest]. The [crops] are neither organic or biotech, I'm just using the best insecticide at my disposal to control a susceptible pest. While the Bt 'strain' may be different, is it not the same protein structure? Or is the Bt used in GE somehow "different" from what I use as an insecticide?

Before I get to my response, a little background:

Peanut plants fed to lesser cornstalk borer larvae. The bottom plant was genetically engineered to express Bt Cry proteins. Source: Wikimedia commons

"Bt" refers to the bacterium Bacillus thuringiensis, which is a soil-dwelling bacterium that can produce a variety of crystal-shaped proteins that are toxic to specific strains of insects. The insecticidal nature of these bacteria has been known for over 100 years, and spraying cultures of Bt spores has been (and still is) an effective strategy for controlling insect pests. It's also incredibly safe - Bt Cry proteins are non toxic to mammals even in extremely high doses, and Bt is used in organic agriculture.

But as I explained in my previous post, since these Cry toxins are proteins, we can insert the gene for Cry into plants so that they produce the proteins in their leaves, no spraying required. So to the letter writer's question: with respect to allergenicity, is there any difference between spraying the bacteria that produce the toxin and engineering the plants to produce the toxin themselves? And is this particular example any different from other GM technologies?

In the coming month, I'm going to write a series of posts about the immunology of allergies, but for now, here's the response I wrote (lightly edited):

First, the notion that you should separate out Bt from other GM because "the allergenic response might be different from other GM technologies" is non-sensical because the allergenic response will almost certainly be different from other GM varieties. But then, glyphosate resistance will also be different from other GM varieties, so will the modifications in golden rice. Every single gene product will have different potential to cause allergy, and that's true for the products currently on the market and those that will be introduced in the future. They should certainly be evaluated and monitored, but there's no reason a priori to treat a new GM variety any different from a new fruit that hasn't been on American shelves before (no one freaked out about allergenicity when quinoa started to make it big for instance), and there's certainly no reason that technologies classically labeled as "GE" are any different than things like mutation breeding that don't fall under GMO opponents' radar.

That said, I think that the person the e-mailer was discussing this with might be referring to some papers suggesting that Bt might be an adjuvant (that is, something that stimulates the innate immune system). Someone in the comment thread of a blog linked them to me at some point. I read them and did not find them particularly convincing - stimulation of the innate immune system is precisely what I'm getting my PhD in, and the papers were missing a lot of critical details. Besides that, they showed adjuvant activity when they were injected directly into the body cavity of mice, not upon ingestion, which is not super relevant to the food question.

But this leads to her other point - is Bt you spray on your crops any different than the Bt engineered into plants? Yes, there are differences, but probably not ones that matter. First, there are a lot of different strains of Bt that make Cry proteins with different specificities. They kill different types of insects, and some even kill roundworms and not insects. The strains of Bt used in different types of GE plants might be different than the variety she sprays on your crops. There also could be differences in terms of where on the plant the proteins end up. For instance, I've seen studies showing that the expression pattern in Bt corn shows that very little is actually found in the corn kernels (it's fairly trivial to design promoters to restrict protein expression to certain parts of the plant). I haven't seen complimentary studies showing where sprayed Bt ends up, but there could be differences. Frankly, it seems like this would probably be a mark in GE's favor since it would be easier to control, but I haven't seen the data. In any case, I'm not aware of any studies for any strain of Bt that shows any negative impact when fed to a mammal, even at extremely high doses.

To answer the question that I think she was really asking though: assuming you have the same strain of Bt Cry protein, and assuming they are present in the same dose in the food, is there any reason to suspect that Cry protein delivered in the context of a plant cell will be different than when given in the context of a bacterium that's sprayed on the plant. No. In fact, the presence of the bacterium would seem to be more allergenic, since the immune system is designed to recognize bacteria (though truthfully, Bt probably doesn't have any way of surviving mammal ingestion, and there's certainly bacteria present on ANY uncooked food, so this point is a bit disingenuous). I think opponents of GE would say that you can wash the bacteria off, so the dose will be lower, but until someone compares the levels of Bt found on an ear of corn in the supermarket when grown with the inserted gene vs that sprayed with Bt, I don't think this assertion holds water.

Finally, is there any reason that GE technology itself is different from other types of agriculture. Again, maybe, but probably not. In order to make transgenes, you have to insert other genetic elements in order to get proper insertion and expression of the genes of interest in the right place. I don't think there's any evidence that these things have any immunogenic potential, and if fact many of these technologies are used with great success in studying other aspects of the immune system, precisely because they are basically silent by themselves. It's always worth doing more research, but I think that the people holding on the the precautionary principal are on tenuous ground, especially considering the great things that could potentially be done with GE.