GMOs used as pesticides in a brand new way!

I just returned from Reno, Nevada attending the Entomological Society of America’s annual meeting. I went to a bunch of really neat talks, saw some old friends and met some new friends. It turned out to be a great networking opportunity, and I met some folks doing amazing research I would really like to work with in the future. Unfortunately, I wasn’t presenting data because I missed the submission deadline but I was still fortunate enough to be on the debate team.

The topic of the debate was “can organic agriculture solve food scarcity problems?”. The subjects were randomly chosen and don’t necessarily support the views of those engaged in the debate, so I will not speak for anybody but myself. I was on the con team, and we were charged with arguing that organic agriculture is an inferior method of food production. We were up against a very good team and all day folks were coming up to us and telling us how much they enjoyed our debate. Ultimately, we won the best overall debate team and took home an engraved trophy and left the meeting $125 richer after splitting a $500 prize between the four of us.

My role on the team was to look into the pesticides used in organic agriculture and their treatment regimes. To my surprise, I found that organic operations actually increase the amount of inputs put into the environment by requiring higher concentrations and more frequent applications of pesticides. The insecticides used in organic ag are often less effective, less selective, and can have greater non-target effects than synthetic insecticides. Some organic pesticides, like the biopesticide Beauveria bassiana, are assumed to have a very low environmental impact quotient (EIQ), but haven’t been tested for potential ecological side effects. My position (and position on the debate team) is that GMOs like Bt corn are better for the environment because they decrease the amount of pesticides that we must put on crops and that organic pesticides are worse for the environment because they must be constantly reapplied in very high concentrations.

This, however, wasn’t the idea that earned me my stripes during the debate. During the Q&A session, somebody asked us to clarify why we thought organic ag was able to innovate to a lesser extent than sustainable or conventional agriculture. My response was that we can modify pesticides to become less toxic, more easily degradeable and more difficult for insects to detoxify by producing insecticides synthetically and making it more or less difficult for the insecticides to degrade. While organic ag could certainly benefit from new chemistries, they reject them as soon as modifications such as these take place because the new pesticide is synthetic. In short, organic producers are unable to take advantage of novel chemistries. I used the example of adding carbon atoms or benzene rings in a specific place to keep beta-lactam antibiotics medically relevant during the debate, but there was a much better example I could have used but unfortunately neglected to discuss. But, hey… that’s what the blogosphere’s for isn’t it?

Very recently, the lab of Reddy Palli has figured out a way to genetically modify an organism to become a spray-on pesticide. To fully understand and appreciate what’s going on, there are a lot of things I need to explain. Fortunately, I’ve got about 12 hours of travel time ahead of me. Awesome, right?

A Colorado potato beetle. USDA photograph by Scott Bauer via Wikipedia.

First, let’s talk about the animal discussed in the paper. The Colorado Potato Beetle is what’s referred to as a ‘superpest’. It’s highly prolific, and essentially bulletproof. This insect specializes on solanaceous crops like potatoes and tomatoes, the crops most closely related to nightshade plants. These plants are famous for defending themselves by producing deadly secondary metabolites. By specializing on these plants, the Colorado Potato Beetle has evolved with some incredible detoxification mechanisms which shields it from our pesticides. As an unfortunate (for us) side effect, it manages to become resistant to every pesticide we throw at it very quickly. It can defoliate entire potato fields, and we can’t stop it very easily. We’re desperate for new chemistry to counteract this pest.

Next, let’s talk about a very basic part of insect physiology. Insects, like humans, are made from proteins encoded by DNA. When a protein needs to be made, an RNA polymerase translates DNA to RNA, and a ribosome transcribes the RNA molecule to protein. This is pretty constant throughout the kingdom of life plants, humans and insects all use a similar system and there is RNA in everything you consume. It can get a bit more complicated than this (see below), but there’s one thing I need to point out – mRNA is always single stranded in eukaryotic organisms. Some viruses use a double-stranded RNA (dsRNA) molecule. This is kind of like DNA, but it’s made out of slightly different stuff. Insect immune systems are good at picking up stuff that looks like it shouldn’t be there and dsRNA sticks out like a sore thumb.

The beetle has an immune system just like us. Ever get sick? Did you get better? That’s your immune system working. Beetles are exposed to pathogens just like we are every day. A good example of this is a cypovirus, which is kind of like an insect rotavirus. When the beetle gets a cypovirus, a series of enzymes pick the dsRNA it makes from the crowd of mRNA and selectively degrades it by using that dsRNA as a template to scan all the RNA in the insect and then degrade it. This is called RNA interference, or RNAi.

How can we use this to our advantage?

A special shoutout to Jafsica and Bug G Membracid, to whom I nerded out about this at ESA

The experimental setup Palli's team used. Everything's labeled pretty well, and very self explanatory. The larvae eat the leaf, eat the dsRNA which causes their own body to shut down vital systems.

Unlike our antibody production system the RNAi system is kind of stupid and won’t distinguish self from nonself mRNA. The reason for this is that RNAi is also used to make sure the beetle doesn’t produce too much of a particular protein. If it wants to shut down certain specific proteins, it can make small interfering RNA (siRNA) and allow the RNAi system to destroy the RNA. It’s physiologically important for the beetle to be able to do this, but there’s no doublecheck system. The beetle can’t tell if it produced the RNA or if the dsRNA came from another source.

Reddy Palli’s lab did something ingenious with bacteria. They inserted several sequences into a bacterium that made double stranded RNA to a variety of important proteins. These included the muscle protein actin, sec23 which is a protein involved in the transport of newly produced proteins, and a couple ATPases which are responsible for producing the ATP energy currency of the cell. After killing the bacteria but preserving the RNA, they sprayed the bacteria onto potato plants which contained Colorado Potato Beetles. They also did this with just straight dsRNA. The beetles eat the plants, they eat the bacteria and a whole load of dsRNA.

What happened?

Here’s the cool part: it actually worked. To me this is mind blowing because RNA is incredibly unstable, thanks to an oxygen attached in a rather unfortunate place which allows it to break the backbone of the molecule. There are also nucleases which degrade RNA so the bacteria had to be modified so they wouldn’t produce these enzymes. Keeping the molecule double stranded helps by making it more difficult for either of these reactions to occur, so dsRNA is more stable than regular mRNA. But it’s still an incredible thing to me that this even worked.

If you want to show this works, you need to first show that the mRNA levels drop in response to the treatment. Turns out that they do for all the genes involved. Actin is the muscle protein, the ATPases produce energy and sec23 and CopB are involved in protein transport. The control was something which has relatively constant transcription that wasn't target by RNAi.

The beetles ate the killed bacteria, digested the outer wall and released the dsRNA. The cells take up the RNA, and the RNAi process occurs just as described above. The RNA coding for actin gets degraded, so that the beetles don’t make new actin or repair their existing actin polymers. In short, their muscles fall apart, their cells don’t divide. Even their sperm wouldn’t move…all these processes are dependent on actin.  As a direct result, the beetles stop eating, stop moving and die. Similar things happened with the other genes. When sec23 and COPB are silenced, their proteins don’t properly get transported and modified, resulting in a buildup of nonfunctional machinery. When the ATPases are silenced, ATP is no longer produced and the beetle can’t produce enough energy to maintain vital life functions. From this research, it would appear there are a great diversity of genes we could target which opens up a lot more avenues of attack when making pesticides.

Now, there are some neat implications to this research. This was a ‘proof of concept’ paper, which means that this works on a particular organism with a particular set of proteins under ideal lab conditions but doesn’t directly deal with the economics, field conditions or range of pests that could be targeted. It’s exciting and this technique has a lot of potential, but a lot more research needs to be done before we could use this in the field. That doesn’t mean there aren’t good reasons to be excited to see this further developed, though. Even though this may be a somewhat limited technique (see below), I could still see this being used to create very highly specific insecticides that quickly degrade in the environment.

In general, this would be the ideal pesticide for an environmentalist because RNA is all around you, as are nucleases. The Colorado Potato Beetle produces RNA and siRNA. We produce RNA and siRNA. Bacteria produce RNA, but I’m not sure if they produce siRNA. This is essentially all-natural, with the only difference being that we’re telling the beetle to degrade proteins at the wrong time and at a much higher rate than it normally would. RNA degrades by itself pretty easily and RNA degrading nucleases can be found almost anywhere you look. The bacteria can degrade in the environment and have no components which aren’t found in soil bacteria except foreign RNA sequences. There’s no reason to think there would be any issues with the bacteria staying around in the soil for an extended period such as we’d see with DDT.

Despite my enthusiasm for this clever technique, I also don’t want to give anybody the impression this is a ‘magic bullet’ for pest control. Some critters take up RNA better than others. RNAi was discovered in nematodes using this technique, so we could potentially use this on nematodes as well as beetles. Honeybees are able to ingest RNA and acheive silencing, so we might even be able to target sawflies. We could not use this on moth pests because lepidopterans are notoriously difficult to perform RNAi in, which has led to caterpillars being more of a biochemistry rather than genetic model organism. Since a lot of pests like aphids pierce the plant and suck the juices out, this would be useless against them because they’re not actually ingesting anything on the outside of the plant. There also may be better ways to introduce the dsRNA and for all we know using viral machinery may be a better way to introduce and replicate the dsRNA. There’s a lot more basic research which needs to be done on this before I’d be willing to say ‘we could use this’. With this paper, there are good reasons to think this would work.

The results from the experiment. This is a survival curve, with the percentage of the larvae surviving plotted on the Y axis and the time of survival plotted on the X axis. As you can see, the survival curves dropped far below the controls. A is the bacteria encapsulated dsRNA, while B is the dsRNA without bacteria. Both work, despite the limitations I explained earlier.

In addition to needing to pay attention to the pests this could work on, we need to pay attention to the kinds of beneficial insects and other animals this would potentially harm just as we would any other pesticide. Actin tends to be pretty similar in all organisms. The other genes are really important, and are probably very conserved in genetic sequence. I would think this could have some potential nontarget effects on other beetles, flies or wasps that I’d be pretty concerned about the potential for syrphid flies to eat aphids coated in dsRNA filled bacteria, for example. I think it’s unlikely that RNAi would be able to be done for humans in this manner because we’re coated in nucleases and to perform RNAi we must actually envelope dsRNA viral components in artificial cell walls to prevent degredation in the bloodstream if we inject RNA into the body as we would with medication used to treat ebola. I’ll go into more detail about this in the next paragraph but even if we found that we could potentially perform RNAi in humans by doing this I wouldn’t expect any big nontarget effects because we could choose the systems interfered with in the insects and avoid using systems humans and insects have in common. We aren’t able to do this with conventional insecticides as well as we could with dsRNA because they often target systems humans and insects have in common like sodium channels and acetylcholinesterase. We do OK by making pesticides less toxic to humans (synthetic pyrethroids have LD50s 10x less than natural pyrethrum for a quick example), but we could always do better.

I’m not sure how big of a problem resistance would be, but I can kind of sort of speculate on this. RNA is difficult for some organisms to take up, so I don’t think it’s impossible for the organism to change its ability to uptake RNA. As far as easily imaginable forms of resistance go, I think this would be the most problematic form of resistance. Increased nuclease activity in the digestive tract would be an issue from a resistance management standpoint, as well. The beauty of this technique is that we can put any sequence of RNA into the bacteria to perform this technique. If we were to target insect specific insulin-like peptides, we could kill the beetles by causing growth deformities or by putting the insect in a diabetic coma. If we found that we could silence some of the metabolic machinery in a species specific manner we could target this. We could target single genes, or groups of genes and thus custom-tailor our pesticides to the pest itself. If the sequence of the RNA changed in response to the management, we could just determine if a different RNA sequence would work. It’s very exciting stuff, and it uses chemistry that’s already existing all around (and even inside) you.

It’s a good example of how technology can be applied in novel ways. In this particular example, we are doing something very simple-genetically modifying bacteria-to accomplish the relatively simple goal of killing crop pests. If we were to develop this further and get it ready for field use, organic agriculture proponents would be sadly unable to take advantage of this technique because they ban both synthetic insecticides and genetically modified organisms. Organic agriculture rejects many tools which could help them further goals which are certainly admirable. Unfortunately organic agriculture proponents attempt to maintain a false dichotomy between synthetic insecticides, genetically modified organisms and environmental issues. A lot of this stems from simple chemophobia, the idea that synthetic things are inherently bad. This causes the field to reject many good tools like this based on little more than fear and misunderstanding. Unfortunately, as a result of this I reject organic agriculture and refuse to buy anything organically produced despite the fact I agree with their goals wholeheartedly. I sincerely hope the field moves in a direction which places an emphasis on environmentally friendly solutions rather than perceived naturalness of interventions. Unfortunately, from what I’ve seen I don’t expect that to happen anytime soon.

ResearchBlogging.orgZhu, F., Xu, J., Palli, R., Ferguson, J., & Palli, S. (2011). Ingested RNA interference for managing the populations of the Colorado potato beetle, Leptinotarsa decemlineata Pest Management Science, 67 (2), 175-182 DOI: 10.1002/ps.2048
Zehnder, G., Gurr, G., Kühne, S., Wade, M., Wratten, S., & Wyss, E. (2007). Arthropod Pest Management in Organic Crops Annual Review of Entomology, 52 (1), 57-80 DOI: 10.1146/annurev.ento.52.110405.091337

Bahlai, C., Xue, Y., McCreary, C., Schaafsma, A., & Hallett, R. (2010). Choosing Organic Pesticides over Synthetic Pesticides May Not Effectively Mitigate Environmental Risk in Soybeans PLoS ONE, 5 (6) DOI: 10.1371/journal.pone.0011250

Kovach, J., Petzoldt, C., Degni, J., & Tette, J. (1992). A Method to Measure the Environmental Impact of Pesticides New York’s Food and Life Sciences Bulletin

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Joe Ballenger is an entomologist working on biocontrol somewhere in the Southern US. He spends most of his spare time breeding tarantulas, and he has a thing for parasitoid wasps as well. He's an excellent cook, and knows how to make an excellent Old-Fashioned. One day far in the future, Joe hopes to be able to study insect physiology and figure out how to make safer and better pesticides.


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35 comments to GMOs used as pesticides in a brand new way!

  • Jason

    Interesting article.

    Terms like natural and synthetic are pretty hard to pin down. I am wondering if the methods you outline here are absolutely forbidden in organic agriculture or you are assuming they probably would be based on current interpretations of such terms?

  • Jason, any legalese is open to interpretation so I’m going to post my interpretation, the parts of the text I feel are relevant and the hyperlink for the USDA regulations so you can critique either if you so choose. I think this is a really good question to ask, because there’s always the possibility I’ve misinterpreted something. The only reason I didn’t include this was because the post was already pretty big, so thanks for asking.

    I’m not a lawyer, but from the text below it seems to me that using this hypothetical pesticide would fall under ‘excluded methods’ as per USDA regulations for organic labeling because these organisms are both transgenic (introduced gene for RNA of choice) and have been modified by artificially deleting inconvenient genes and both of these are expressly forbidden under the section.

    The relevant text of the law:

    Excluded methods. A variety of methods used to genetically modify organisms or influence their growth and development by means that are not possible under natural conditions or processes and are not considered compatible with organic production. Such methods include cell fusion, microencapsulation and macroencapsulation, and recombinant DNA technology (including gene deletion, gene doubling, introducing a foreign gene, and changing the positions of genes when achieved by recombinant DNA technology). Such methods do not include the use of traditional breeding, conjugation, fermentation, hybridization, in vitro fertilization, or tissue culture.

    Section e is of particular interest here:

    § 205.105 Allowed and prohibited substances, methods, and ingredients in organic production and handling.

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    To be sold or labeled as “100 percent organic,” “organic,” or “made with organic (specified ingredients or food group(s)),” the product must be produced and handled without the use of:

    (a) Synthetic substances and ingredients, except as provided in §205.601 or §205.603;

    (b) Nonsynthetic substances prohibited in §205.602 or §205.604;

    (c) Nonagricultural substances used in or on processed products, except as otherwise provided in §205.605;

    (d) Nonorganic agricultural substances used in or on processed products, except as otherwise provided in §205.606;

    (e) Excluded methods, except for vaccines: Provided, That, the vaccines are approved in accordance with §205.600(a);

    (f) Ionizing radiation, as described in Food and Drug Administration regulation, 21 CFR 179.26; and

    (g) Sewage sludge.

    Full text of the law:

    http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=ac1d493c3010c08853e7811162f41458&rgn=div5&view=text&node=7:3.1.1.9.32&idno=7#7:3.1.1.9.32.7.354.1

    • Jason

      Thanks Joe, that helps. It seems like the beef is with certain processes of breeding, not necessarily the resulting “pesticide” itself. Looking ahead I am not sure how rigid the organic regulations will be.

      Organic farming in a quasi “pure” sense would set up systems of rotation and habitat for beneficial species that reduce the need for insecticides, and these tend to work when done right, but are not perfect. I do think that many methods developed by organic farmers will become more widespread, based on purely economic pressures. This is a good example:
      https://www.agronomy.org/files/publications/crops-and-soils/sod-based-rotations.pdf

      • There are definitely things about organic agriculture that I like, and preserving refuge areas for beneficial insects is one of these. As you say, though…biocontrol isn’t perfect and pesticides are required occasionally.

        I completely agree that an emphasis should be placed on cultural and ecological control methods with pesticides used as a last ditch effort with certain caveats. I’ve never seen how this is incompatible with conventional/sustainable agriculture.

    • Thanks, Jason, for your question, and thanks, Joe, for your thoughtful response. I agree with your interpretation of the regs (although I have no training in law so take that with a grain of salt).

  • OrchidGrowinMan

    Hmmm… Could this be used to render mosquitoes’ metabolism inhospitable to Plasmodium?

    • Remember that this is a proof of concept paper. We know a lot about the things which make mosquitoes hospitable to Plasmodium, and we know that mosquitoes possess RNAi machinery. The problem, however is that this isn’t the best method by which to perform RNAi. The dsRNA just doesn’t get introduced efficiently this way in most organisms, and this is a huge hurdle to development.

      If we could figure out better tools to introduce RNA, then maybe. Personally, I’d like to see how viral vectors would fare in comparison to bacterial vectors. But a lot more research needs to be done before we can say ‘oh, this will totally work in .

      It could be exciting, or it could fizzle out in a few years. There’s no way to know without doing the proper science.

      I wish I had a more exciting answer, but I’d rather undersell something than be surprised when it doesn’t pan out.

      • Kurt

        I totally agree with you Joe. From what I hear from my R&D colleagues delivery is the bottle neck for now as well. Although they are working on human applications primarily, however same issue (although maybe even more complexed :-)).

        Totally with you on under promising as well, RNAi has been blown up in the past and not being able to deliver on the promise, which has had quite significant impacts. It is only now that we’re seeing the first promising results coming, e.g. Alnylam’s results published earlier this month, which showed success in delivery.

        • Kurt, do you think you could post a reference to this paper? My project involves possibly doing RNAi in either caterpillars or caterpillar cells and I’ve been looking into how it’s done in mammals.

          Enveloping the dsRNA in micelles seems to work well in some cases, but if there’s another way I’d be really interested in looking at that.

  • Kurt

    Hello Joe,

    I truly enjoyed your blog post. As a marketeer working for a company who makes and sells RNAi products, I always enjoy these real life applications. As I am personally not a big fan of chemical pesticides, I’m looking forward to the progress that is going to be made in this field.
    I hope your 12 hours trip went smooth, from this post I can surely tell it was highly productive.

    Kurt

    • Remember that all pesticides are chemical pesticides, including this which has an active ingredient containing ribonucleic acid.

      The trip was fine, with the exception of a few truly bizarre events which happened during the travels.

      I also may have accidentally set off a security scare in Denver by absentmindedly leaving a bag behind that was later confiscated by HLS.

      But other than that…everything went fine. Got this post done as well as a homework assignment finished. Fun times.

  • MikeB

    Very interesting. It furthers my distance from the “organics” movement even more than it was about fifteen minutes ago. I’m a simple lay reader and micro-farmer, a former employee at an organic farm, so I don’t get the details, but the gist of your article is stunning.

    You say:

    “If we were to develop this further and get it ready for field use, organic agriculture proponents would be sadly unable to take advantage of this technique because they ban both synthetic insecticides and genetically modified organisms. Organic agriculture rejects many tools which could help them further goals which are certainly admirable.”

    If only the organic movement was that coherent in its philosophy: It isn’t. There is a whole list of “allowed synthetics” which makes mincemeat of any “admirable” qualities one might perceive.

    Included in “allowed synthetics” is copper sulfate, which is chemically inorganic, persistent in soils, and potentially harmful if ingested.

    The “goals” of organics include stopping genetic modification technologies and conventional farming in their tracks. What’s “admirable” about that?

    This applies to the movement, not the farmers, by the way, most of whom, I suspect, have not looked into the details of the movement to the extent that I have. Most of them are simply looking for the best ways to farm on a small scale. If only they knew how ideologically bankrupt organics really is, they might relent and use some of the better tools available to them.

    • I hope you didn’t get the impression I was anti-GMO from this post. I tried to make it very apparent that I was sympathetic towards the environmental issues many followers of organic agriculture are passionate about.

      • MikeB

        Not in the least. If that’s how my comment came off it was my fault for not being clearer, perhaps.

        My point is that organic advocates are never going to accept GM technologies, and that doesn’t make them “admirable.” One doesn’t need organic certification to be concerned about environmental issues.

    • Eric Baumholder

      Mike,

      The organic industry opposes GMOs because that is another way to distinguish their products on the market as being different.

      And they’re very consistent on that approach.

  • Nicely done, Joe! You forgot to post a photo of your big thingie, though.
    (I mean the trophy, of course :)

  • Steven Hoffman

    Good argument, but light on any data to back your claim that organic farmers use more pesticides than conventional farmers. Plus, you can bet that Colorado Potato Beetle will find a way to build resistance, as it has with every toxic synthetic pesticide thrown at it- pesticides that are incredibly persistent in the environment. Also, are there any long-term studies done about releasing a new engineered bacteria into the environment to determine its impact on the eco-system? The one issue I have with technology is that in agriculture and medicine, there is little holistic thought. So for every synthetic fertilizer solution, there’s runoff and a dead zone created that kills our fisheries. For every pesticide solution, children raised near fields of application have a 6-fold increase in the risk of autism. For you to reject organic completely is a political decision, not a scientific one. With the USDA’s own testing, a conventional apple, even after it’s washed, contains up to a dozen pesticide residues. So these days, “It’s the organic apple a day that keeps the doctor away.” With the conventional one, you are exposed to that many more carcinogens in your diet. We could go on with this debate. I am not anti-technology. I am however, totally against the way biotech companies have foisted GMOs, based on very little long-term science, on our food systems, to the point where they are in 80-90% of our consumer food products. You want a level playing field–then why is the biotech industry so afraid of labeling of GMO ingredients in food, like is required in Europe and Japan? I am a consumer and I have a right to know so I can make an informed choice. You can choose GMO if you want to, but I can’t not choose GMOs, unless I choose organic, and then, due to genetic drift, I can only minimize my dietary exposure to GMOs. This stuff is getting loose in the environment and we don’t even know the long-term consequences. And I can show you a growing body of science showing that GMOs are not the same as regular foods. In fact, the BT toxin engineered into GMO crops is now showing up in the blood of pregnant women and fetuses, according to a study published by researchers at a Canadian hospital in May. Thank you for listening! Steven Hoffman, M.S. in Entomology and Agriculture, Penn State University

    • MikeB

      >>With the USDA’s own testing, a conventional apple, even after it’s washed, contains up to a dozen pesticide residues. So these days, “It’s the organic apple a day that keeps the doctor away.”<<

      Your post reads like the usual litany of calumnies against non-organic farmers issued by the organics ideologues. I will only address this one:

      You mention "science" earlier in the your, as if this were something you value. Yet the item quoted above is unscientific in the extreme: it ignores the central issue of toxicology, dose, or exposure. It sounds like you're quoting the execrable Environmental Working Group. They're anti-everything-except-organic zealots.

  • Actually, Steven…I cited two sources at the bottom of the article which dealt with this. The point of this article was to summarize my debate experience and discuss how this new technology worked, not discuss organic pesticides in general. Because this wasn’t my intention, I decided not to go too deep into the data as my post was already long enough. I refer you to Kovachs 1992 and Bahlai et. al 2010 the EIQ data which supports my claims.

    There are, of course, no long term studies on releasing these bacteria into the environment because this is still something that only exists within the confines of a laboratory. Had you actually read my post, you’d have read this no less than three times in three different ways. The bacteria used in the study were heat killed, so they’d degrade harmlessly in the environment. The only difference between this and BT toxin (in terms of stability) is that the active ingredient of this is much less stable than the BT protein and wouldn’t persist as long. Again…I mentioned that the bacteria in this post were dead and that this was nowhere near field use. Multiple times.

    Manure used in organic agriculture has runoff issues, as well. The only reason this isn’t a bigger issue is because organically grown food has such a small share of land. Any time you have a nutrient rich solution that runs into water, eutrophication occurrs. The only difference between synthethic fertilizer and manure is that manure introduces pathogenic bacteria into the equation, and E. coli in manure can live far longer than the treatments required. This is off topic, and wasn’t discussed in the post.

    As for your pesticide/autism claim, this is again off topic because I didn’t mention anything like this. If you want my response, however, correlation doesn’t equal causation. Folks have pointed to vaccines, pesticides and nondescript toxins in the environment. Because I was diagnosed with autism when I was young, I keep up on this literature and the current literature points to ASDs being developmental disorders which arise before birth but little is known other than that. Besides a few desperate correlation/causation claims as you’ve made here, I am aware of no evidence that there has been anything specifically linked to autism. Taking correlation/causation claims as seriously as you’ve done here impedes research by clouding the issue.

    Pesticide residues have been discussed elsewhere on the site by Anastasia, so I’m not going to go through that again.

    http://www.biofortified.org/2010/08/produce-pesticide-rankings/

    Biotech companies aren’t necessarily evil, but they’re going to find a way to take advantage of any way they can profit. Even if you’re going to the anticorporate argument, this angle doesn’t really make sense either if you want to claim that organic agriculture is an economically viable option.

    I reject organic agriculture because many of its proponents religiously believe the perceived naturalness of interventions has anything to do with how these interventions benefit the environment. I stand by this statement, and since you didn’t read my post before commenting I feel I’ve said all I need to say.

  • Steven Hoffman

    Thanks, Joe. Your stance against organic is no less adamant and not based on science. Please visit the Institute for Responsible Technology (www.responsibletechnology.org). GMOs, designed in a laboratory, or laboratory-mutated bacteria or bugs, where you are manipulating and changing the DNA/RNA, are a very high risk to humans, animals and the environment, when loosed upon the ecosystem with little long-term studies. Guess what? That becomes the experiment now! There is very little research being promoted about the long-term input of genetic engineering in our food and agriculture system–it is all about what pesticides can I incorporate into the genetics. That is now appearing in the blood of fetuses–something the biotech industry said would never happen. They are driven by greed and thus, actually, do demonstrate evil, in my respectful opinion. I am not going to debate further. You either see the risks or you don’t. As I said, as you are a believer in the “miracle” of GMOs, I’m not going to convince you at all. But please don’t tell me the science is balanced. Your beliefs are just that–beliefs based on limited science that you choose to believe. However, I do support the precautionary rule, something the GMO companies have completely denied. Thank you and happy thanksgiving. Enjoy your GMO meal!

    • Eric Baumholder

      Steven,

      When it comes to organic vs. GMO, the rule of ‘know your enemy’ applies. Organic people have for over a decade refused to embrace coexistence, a level of prejudice not seen since the collapse of Apartheid in South Africa. They discriminate against all but their counterparts, and are willing to libel and slander against other farming methods at any excuse. All organic advocates should be considered guilty until proven innocent.

      But I can play nice. Steven, are you guilty?

  • OrchidGrowinMan

    Steven,

    GMOs, designed in a laboratory, or laboratory-mutated bacteria or bugs, where you are manipulating and changing the DNA/RNA, are a very high risk to humans, animals and the environment, when loosed upon the ecosystem with little long-term studies.

    Citation?

    it is all about what pesticides can I incorporate into the genetics

    Eh? herbicide resistance, nutrient enhancement, virus resistance, salt/drought/heat-tolerance, nutrient-use efficiency, wide-crosses/ploidy manipulation, and several others appear to be exceptions.

    now appearing in the blood of fetuses

    Something like that has been discussed extensively here. Unless you can cite a more credible study than the one I think you mean, it’s a non-issue. It’s even a non-issue if true: What do you THINK happens to the chemical constituents of the food you eat? I remember reading an alarmist report that HIV was still detectable after samples went through a sterilization protocol. I reply that you can undoubtedly identify a cat after it has gone through an autoclave, but it’s not going to chase mice anymore.

    As far as the “safety” of OG: let me just mention in passing that E. coli infections are “organic.” If manure is kept far from our food, that danger is reduced.

    As far as the “Precautionary Principle,” let me recommend you read-up:

    MENDEL IN THE KITCHEN: A Scientist’s View of Genetically Modified Foods
    Nina Fedoroff and Nancy Marie Brown.
    Joseph Henry, (352p) ISBN 0-309-09505-1

    Starved for Science: How Biotechnology Is Being Kept Out of Africa (Harvard University Press, March 2008), Robert Paarlberg

    It would be easy to make a case that OG, or at least the publicity and effects of the advocacy, the catastrophization, has generated a “Body Count.” I have not seen anything like that specifically applicable to genetically-engineered crops and foods other than as mediated by things like denying food aid, withholding crops that are disease-resistant, more nutritious, more productive, or that won’t receive as toxic or as much pest control, all out of overblown fears of “GMO.” That is sufficient reason to me for me to avoid “organic” labeled products.

  • Fascinating stuff. I recently wrote a post on my blog about Bt sweet corn and how we could benefit from that technology by applying a great deal less pesticide on sweet corn acres. One comment I recieved was concerned that we may be using less chemicals, but that the Bt toxin in a GMO plant cannot be washed off like an organic pesticide could be. Can you speak to that at all? I’m sure at some level Bt toxin could affect the human body (and maybe it would have to be very concentrated, I don’t know), but the argument you hear all the time is how Bt affects the insect gut implying that’s what happens to humans when in fact our biology is so different that is not the case.

    • OrchidGrowinMan

      Brian,

      I have written a comment on this before, but let me recap: there are LOTS of proteins in every organism, tens, hundreds of thousands, and many different ones in each organism, performing all sorts of functions, most of which we just don’t know what they are doing. Some have to do with making plant epidermis, some are hormones or metabolic regulators, some are structural, some are just for storage (as in seeds, fruits), some are enzymes that make all sorts of things, including toxins, and some ARE toxins. Many, as I point-out above, are unfamiliar to our bodies. But, with vanishingly few (but important!) exceptions, our bodies just don’t care what they do, our bodies just digest them: we are MADE to do that. There is no reason to suppose that a protein that, for example, controls sexual maturity in an insect or one that does something similar in a plant is anything but a digestible food substance to us. Likewise the exquisitely precisely targeted CRY proteins from Bt: they are keys that lock into particular receptors in the guts of specific insects, but to us, there is no reason, theoretical or experimental, to think of them as anything (continuing the metaphor) but a bit of brass to be melted-down. And even so, they are present in very very small concentration. Yes, experiments have been done, and Bt “toxins” have repeatedly been shown to be safe to us, and various other non-target organisms. Now, if someone were to incorporate a protein that DOES target/affect us or something related to us, something like botox or ricin, there would be reason to worry.

      “TOXIN” is often used as a scare-word. But “toxic” is not defined unless there is a “target.” CRY1 is “toxic” because of the effect it has on lepidoptera. Oxygen is toxic because of its effect on Clostridium. The acid in our stomachs is toxic because of its effect on a wide variety of organisms, including some that might otherwise harm us if we didn’t have an acidic digestive system (insects have an alkaline system). Menthol, Thymol, Cinnamaldehyde and others are toxic because of their effects on fungi etc., but we seek them out to flavour our food. Undoubtedly, there are many proteins that function as toxins in plants, bacteria, insects, etc., but we don’t know about them yet (at least _I_ don’t).

      I think that it would be interesting (and very expensive) to try feeding studies where a mammal is fed a diet with a grossly large concentration of CRY protein (and the rest of the diet balanced for amino-acid composition). I predict that it would be less pleasant than a normal diet, but that the protein would have minimal specific effects, and certainly not any effect related to that it has in target insects. To be fair, the results of this experiment would have to be compared to those of similar experiments done with other specific proteins, say bacterial vs. gymnosperm EPSPS (illuminating “Roundup Ready” potential toxicity), bacterial vs. plant rubisco (can Spirulina really be treated as a vegetable?), etc.

      • Brian

        Thanks for the recap! I’m aware of all that, but I don’t think the average consumer would know as much. I guess that’s why I’m out here blogging, tweeting, etc about issues such as this.

    • the bug guy

      The acute oral rat LD50 of the various B.t. forms (insect control products are made from several different Bacillus thuringiensis serovars) is in the >15,000 to 30,000 mg/kg body weight range. Meaning, you have a difficult time stuffing enough material into lab rats to kill half of them.

  • As a proof of concept, using RNAi on something like the genes for actin or the ATPase in mitochondria might be ok (under sufficient containment and using only killed bacteria), but all eukaryotes use actin and mitochondria for ATP production.

    I don’t know enough about the immune systems of all eukaryotes to appreciate how safe this is (or is not), but research on something that would appear to be effective at killing all organisms with actin and mitochondria gives me the heebie jeebies.

  • Daedalus,

    I kind of explained this in the post, but I really don’t think this will be an issue for a couple reasons.

    First and foremost, we would really like to be able to perform RNAi in mammals but we can’t. If it were easy, there would be more and better treatments for serious illnesses like flu and AIDS. The only way that I know of where anyone has ever successfully performed RNAi in a whole mammal is in a post-exposure filovirus (thimk ebola) vaccine. To do this, researchers had to wrap the dsRNA in a lipid bilayer and inject it directly into the test animals.

    More details here:
    http://scienceblogs.com/erv/2010/07/post-exposure_filovirus_vaccin.php

    Secondly, a lot of other pesticides we use already target systems both insects and humans have in common. Sodium channels, chloride channels, acetylcholinesterase, even the oxidative phosphorylation machinery…both insects and humans have these systems in common and there are pesticides on the market right now which target all these systems.

    Third, this was just a proof of concept paper and this means little more than ‘Hey guys…look at this! It *works*!’. The potential targets are nearly limitless, and insects have many systems that are not present in humans. Anything involved in ecdysis would make an excellent target, for example.
    http://en.wikipedia.org/wiki/Ecdysis

    It’s all very new, but not nearly as scary as it initially sounds.

    • Ewan R

      It’s all very new, but not nearly as scary as it initially sounds.

      I just worry that it isn’t as cool and useful as it initially sounds. Hopefully the utility of the technology hits at least 10% of the coolness factor of the technology.

  • This UN-OECD doument discusses the safetu of Plants expressing Bt proteins.

    CONSENSUS DOCUMENT ON SAFETY INFORMATION ON TRANSGENIC PLANTS EXPRESSING
    BACILLUS THURINGIENSIS – DERIVED INSECT CONTROL PROTEINS
    ENV/JM/MONO(2007)14
    ENVIRONMENT DIRECTORATE
    JOINT MEETING OF THE CHEMICALS COMMITTEE AND
    THE WORKING PARTY ON CHEMICALS, PESTICIDES AND BIOTECHNOLOGY

    Pg 33:
    3. Human Exposure
    64. The primary significant human exposure to δ-endotoxin in plants is by the oral route for food
    crops. Exposure to the aerosols produced during the processing of material (e.g. seed) of Bt plants is an
    additional, although small, route of human exposure. Many countries require pesticide residue studies to
    determine the maximum levels of chemical pesticides in or on raw agricultural commodities. Due to the
    lack of mammalian toxicity for the δ-endotoxins tested at very high doses, these traditional pesticide
    residue studies are not necessary. Microbial B. thuringiensis pesticides that are registered in countries that
    require tolerances (a.k.a Maximum Residue Levels) have been given an exemption from the requirement
    for setting a numerical tolerance (MRL). However, an analysis of δ-endotoxin expression levels in various
    parts of the plant is useful for analysis of non-target organism effects as well as issues related to insect
    resistance management. These data show that the transgenic plant pesticides in current commercial use
    have relatively low levels of δ-endotoxins in edible plant parts.
    4. Human Risk Assessment
    65. The acute oral toxicity data on Cry1Ab, Cry1Ac, Cry9C, Cry3A, Cry1F, Cry2Ab2, Cry3Bb1,
    Cry34Ab1, and Cry35Ab1 supports the prediction that the Cry proteins would be non-toxic to humans.
    When proteins are toxic, they are known to act via acute mechanisms and at very low dose level (Sjoblad
    et al., 1992). Therefore, since no effects were seen in the acute tests, even at relatively high dose levels,
    these δ-endotoxin proteins are not considered toxic to humans. Both the long history of safe use of B.
    thuringiensis and the acute oral toxicity data allow for a conclusion that these and other δ-endotoxins pose
    negligible toxicity risk to humans. The one aspect of human health concern identified in their assessments
    was the potential for the Cry9C protein to be a food allergen. Cry9C was conditionally registered in the
    U.S. for animal feed uses only, with restrictions on cultivation to provide containment. However some
    unintentional mixing occurred probably either in the field through pollination or after harvest at grain
    handling facilities and resulted in low levels of the toxin appearing in a few processed maize products. The
    registration was subsequently withdrawn at the company‘s request. Studies by the U.S. Food and Drug
    Administration and the Centers for Disease Control and Prevention did not reveal any cases of human
    allergenicity attributable to exposure to Cry9C. One individual who showed possible allergenicity to the
    Cry9C protein by self-administered oral doses and one skin test volunteered for a fully controlled, doubleblind,
    test in a medical centre which proved that he was not allergic to Cry9C protein (Sutton et al., 2003).
    The overall safety record for Bt has been established in laboratory and field studies, which have looked at
    both formulated Bt sprays and specific Bt genes in planta (Betz et al., 2000; Siegel, 2001; Federici, 2002).

  • I specialize in Biochemistry and Molecular Biology labs and i can tell this forum the use of siRNA is huge and expanding in applied research areas around the world.

    Stay tuned for some really amazing stuff in the near future.

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