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Another Year, Another Post on GMOs and Allergies

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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.

The structure of the Cry5b protein, solved using a technique called "X-ray crystalography" (proteins are too small to be seen even using the most powerful microscopes). Source.

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.

Kevin Bonham About the Author: Kevin Bonham is a Curriculum Fellow in the Microbiology and Immunobiology department at Harvard Medical school. He received his PhD from Harvard, where he studied how the cells of the immune system detect the presence of infectious microbes. Find him on Google+, Reddit. Follow on Twitter @Kevbonham.

The views expressed are those of the author and are not necessarily those of Scientific American.

Comments 10 Comments

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  1. 1. Rhino3000 12:02 pm 01/3/2014
    BT toxins sprayed on plants break down quickly when exposed to UV light. BT toxins produced in the plant are protected from UV light.

    It would appear there are effects to soil biology
    Reaped crop residues, comparable to post-harvest maize straw (a common practice in current agriculture), rapidly influence the soil bacterial cells at a functional level. Overall, these data support the existence of short Bt-induced ecological shifts in the microbial communities of croplands’ soils.

    Could the bacteria in human gut also be affected?

    Link to this
  2. 2. Annie0123 1:27 pm 01/3/2014

    I really appreciated the authors discussion of the real risks of GMO. I feel like often times we become so concerned with new technologies we forget we have been doing GMO experiments since the 1700s and corn is inherently GMO. GMO technologies do have a lot of promise with proper studies and safety protocols there is the potential for major positive changes environmental and social food policies.

    Link to this
  3. 3. Kevin Bonham in reply to Kevin Bonham 2:56 pm 01/3/2014

    The fact that sprayed cry proteins are inactivated by UV light means that repeated spraying is required to get the same activity, and the light would not make it disappear. I’d love to see a study that looks at the amount of Cry protein present on or in food made with Bt-sprayed crops vs transgenic crops (I don’t know if it’s been done, but I haven’t seen that study).

    That PLoS study you linked to seems to note differences in conventional vs Bt corn, but does not compare to corn sprayed with Bt spores (or corn that controlled pests with some other method). I suspect that crops sprayed with copper or sulfur (common organic pesticides) would have far greater effects on microbial ecosystems in the soil. Microbial ecosystems are pretty resilient though, and what exists is not necessarily what’s best (or there might be a lot of different “bests”).

    I’m a bit surprised that a single protein seemed to cause measurable differences in the microbial ecosystem, but the study also didn’t address whether the difference was beneficial, harmful or neutral. In any case, the shift didn’t seem particularly long lasting.

    Based on my understanding, just about everything we ingest can affect the gut microbial ecosystem, from fiber to vitamins to medications etc. Causing a change is not necessarily bad, and there are lot of different ways to have a healthy microbial ecosystem, though we don’t know a huge amount about what a healthy gut microbiome is nor how to support it (though we’re learning more all the time).

    Link to this
  4. 4. Rhino3000 3:25 pm 01/3/2014

    Bt spray is more degradable, “Bt is susceptible to degradation by sunlight. Most formulations persist on foliage less than a week following application.”
    Cry proteins expressed by Bt crops degrades much slower, ”Cry1Ab proteins persist in maize leaves and can be measured in the water column even 6 mo after harvest.”
    Studies suggest Cry proteins can persist in maize leaves for even 11 months and that Bt corn can produce 1500-2000 times more Cry1A toxin than Bt spray.
    With Cry proteins taking longer to degrade this can impact soil life.

    Here we have tested for the very first time Cry1Ab and Cry1Ac Bt toxins (10 ppb to 100 ppm) on the human embryonic kidney cell line 293 Cry1Ab caused cell death. In these results, we argue that modified Bt toxins are not inert on nontarget human cells”

    It appears likely glyphosate and Bt engineered crops are having a negative consequence on the soils.

    Link to this
  5. 5. jimbobobie 3:47 pm 01/3/2014

    I am not necessarily opposed to all gmo’s but I would remind anyone wondering about them to remember: margarine’s supposed health benefits; the one-time miracle of thalidomide; the non-gmo hybridizing of African and native honeybees; and leaded gasoline. These are all things we were once told were entirely safe; no reason to fear. I side with the anti-gmo people because I do not believe we know enough about them yet despite the many, mighty protestations of scientists.

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  6. 6. Marc Lévesque 6:15 pm 01/3/2014


    “we forget we have been doing GMO experiments since the 1700s and corn is inherently GMO”

    GMOs have been around since the 1970s, so I’m not sure what you mean when you say “we have been doing GMO experiments since the 1700s”.

    “GMO technologies do have a lot of promise with proper studies and safety protocols”

    GMO technology do have a lot of potential, and well designed long term studies are definitely needed.

    “Health risks of genetically modified foods”

    “A literature review on the safety assessment of genetically modified plants”

    Link to this
  7. 7. jrstark 2:17 am 01/4/2014

    Nobody freaked out about quinoa because they knew what it was. It was labeled. GE foods aren’t. People who are allergic to certain ingredients can avoid them if they are labeled. That is the difference, knowing what to avoid. Just because something has a low allergenic response doesn’t mean it is safe for everyone. People die from allergies, and those who are strongly allergic react to more things than those who aren’t.

    Link to this
  8. 8. Kevbonham 9:57 am 01/6/2014

    @ Jimbobobie – It’s always easy to point to counter examples, but remember also the supposed fears of microwave ovens, cell phone radiation etc. Further scrutiny is always warranted, but there comes a point when the obvious potential risks have been evaluated, many of the less obvious potential risks have been scrutinized, and there are benefits to be had with letting the technology flourish.

    @ jrstark – Really? You know all the proteins expressed in quinoa? You knew before you ate it whether you were allergic or not? What if there are different strains of quinoa, and you’re only allergic to some of them? As I said in a previous post – maybe we should put the entire genetic sequence of all the crops in our food on the label – surely that information might help someone avoid something that they don’t want to eat.

    Link to this
  9. 9. scilo 10:29 am 01/8/2014

    I don’t know what benefits GE has that is worthy of distrupring the entire evolutionary machanism over. Or the ill effects on the environment, such as super weeds and super bugs. It’s about more than just eating. RoundUp Herbicide Toxicity – Nature’s Country Store‎What‘s Wrong With Roundup?‎
    Report: Roundup and birth defects – is the public being kept in the …–-public-being-kept-d.

    Just to show a few of the many reports that are showing how toxic Glyphosate Products really are. It is even found in the blood of city folk. But the science claims that it is non toxic, and nonresidual. Now, we move onto birth defects. I don’t trust this technology one bit. I think it has more to do with exploiting the food industry rather than to be a benefit for the Earth of it’s peoples.
    The political history on monsanto is glaringly evil enough to put me off. Starving out 3rd world farmers with higher and higher seed prices, to the point they commit suicide, is not the sign of a beneficient entity.
    Science will never replace nature. Because nature is all inclusive, science is not even all aware.
    Farming is not about maximun crop yield, it is about sustaining the land for future generations. The same for science. It should be a shared effort in sustaining nature in it’s natural balance, for the sake of the future generations. It should be about understanding our place in nature, not treating it as an enemy.
    When it comes to GE, my spirit says “NO”! I wouldn’t expect a scientist to understand that. In fact, I hope it never does. It requires quite a different type of intelligence. One that is all inclusive. One that comes from nature. If science understood spirit, it would soon be extracted, exploited and destroyed. No thanks guys.
    I write this in hopes that some scientists will stand against the prevailing accepted trends. And see it clearly for what it is.
    To be a scientist so easily manipulated by industrial propaganda is a bad fate. But, it boils down to who is paying for you’re sevices?

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  10. 10. hkraznodar 5:46 pm 01/8/2014

    I certainly don’t know what Quinoa is. I don’t seem to have much in the way of food allergies or intolerances except a mild intolerance of corn and certain “health food” grains that actually come from weeds that cause my throat to swell closed. I’m allergic to inhaled pollens from trees, grasses, weeds, bushes and vines as well as almost all animal dander.

    If we are to warn people of everything that may cause an allergic reaction then get your signs made because ragweed pollen can travel up to 400 miles from the plant. Be sure to slap a sign on your forehead if you have been in pollen range of any plant that has airborne pollen.

    I’m a lot less concerned about GMOs than I am about pesticides and herbicides in my drinking water or chemical components in plastic breaking down and turning children transgender. I’m more worries about coal slag and fly ash and how radio active and toxic it is.

    Link to this

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