GMO bacteria vs malaria

Posted by ERV on July 18, 2012
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WARBLEGARBLE!!!

Fighting malaria with engineered symbiotic bacteria from vector mosquitoes.

Malaria kills 1.24 million people a year.  Mostly babies under 5 years old.

Malaria is becoming resistant to our drugs.

We cant figure out how to make an anti-malarial vaccine.

We can make GMO mosquitoes that are resistant to carrying malaria, but we dont know how to implement them in nature.

NEW IDEA: Make GMO bacteria that make mosquitoes resistant to malaria colonization.  ‘Bait’ wild mosquitoes with sugar water filled with GMO bacteria.  See a potential 84% decrease in mosquitoes carrying malaria, with a 98% reduction in malaria replication in the colonized mosquitoes, which will hopefully drastically reduce malaria infections in humans.

This could totally work.  Mosquitoes have a symbiotic relationship with their bacteria the same way we do– they need their ‘good’ bacteria to get all the nutrients they need to survive.  This group took a regular ol bacteria that mosquitoes have in their guts, and gave them a few bells and whistles– several different proteins that make the mosquitoes gut unattractive for malaria colonization.  Doesnt hurt the bacteria.  Doesnt hurt the mosquitoes.  Only affects the malaria (which the mosquitoes dont ‘want’ anyway).

BONUS: Since all mosquitoes need these ‘good’ bacteria, these GMO bacteria will work in any of the ~100 species of mosquitoes that can carry malaria.

BONUS: The bacteria naturally replicate more after a blood-meal.  Which means there will be more anti-malaria proteins around right when malaria is trying to find a new mosquito home!

And it would be relatively simple to implement this plan– set out sugar-water ‘bait’ loaded up with these GMO bacteria.  Cheap, easy, sugar water (its easy to forget that mosquitoes dont always need blood.  its only the females when they are producing eggs).

Combine this strategy with anti-mosquito strategies (insecticides, nets)… we might have a really damn good solution to malaria on our hands here.

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  1. #1 Charles Midgett
    July 18, 2012

    You should check out the story in Nature about using GMO mosquitoes to fight dengue fever in Florida and the opposition that has sprung up.

  2. #2 Dave
    July 18, 2012

    But, But . . . MONSANTO! And FRANKENFISH! GMOs BAD!

  3. #3 JC Haven
    July 18, 2012

    Why Freddie Mercury?

  4. #4 Anne
    United States
    July 18, 2012

    :P , Dave.

    I’m not a super hippie, but I don’t want to eat tons of GMO food before there’s real longitudinal testing on what other effects it might have. There are some short term, preliminary studies that show marked differences in the nutritional content of some GMO’s.

    As far as I know, no humans are using mosquitoes as a food source, but it might be worthwhile to study the bacteria before we go wholesale with this idea, namely, to see if there’s any discernible difference in the output of their excreta or other biological products, and if there are, if those changes would impact their involvement in the food chain.

    That said, I’m not against genetic modification, and this sounds wonderful. I hope it gets research, funding, and implementation!

  5. #5 qetzal
    July 18, 2012

    This is a great idea, but I have a question about one line in your post. You say,

    Mosquitoes have a symbiotic relationship with their bacteria the same way we do– they need their ‘good’ bacteria to get all the nutrients they need to survive.

    I see this claim periodically – that we “need” certain gut bacteria to survive – but I’ve never seen the evidence for it. Is it really true? Do you know of evidence for it?

    Obviously this is off topic, so no hard feelings if you ignore it or delete it. I’ve just been curious for a while now to understand the actual basis for this sort of claim, and I haven’t much luck on PubMed.

  6. #6 Bryan
    July 18, 2012

    I see this claim periodically – that we “need” certain gut bacteria to survive – but I’ve never seen the evidence for it. Is it really true? Do you know of evidence for it?
    Its been well established for a long period of time, although it is somewhat over stated.

    Gut bacteria do a number of things – out-compete potentially harmful bacteria, help digest stuff, release vitamins we cannot otherwise get, even release chemicals that modulate gut structure and gut immunity.

    The idea that we need them or we die is based partially on animal studies, and partially on unfortunate events in human medicine. If you sterally birth mice, and keep them in sterile environments, their guts do not form properly and eventually they die of malnutrition. The human stuff though, is where the claim comes from. High-dose antibiotics or whole-body irradiation (for bone marrow transplant) depletes the gut of most bacteria. These patients, historically, would often suffer (and frequently die) as they were re-colonized by pathogens rather than by normal flora. The solution today is often to give them a shit “milkshake”. They literally (via a feedingtube) re-introduce the right bacteria; either from a pre-collected stool sample form the patient, or from the stool of a close family member.

    Hows that for a pre-dinner thought?

  7. #7 Bryan
    July 18, 2012

    OT, as a former research malaria guy, I wish them the best. But malaria is amazingly quick to evolve, and I have my doubts about how well this will work.

  8. #8 qetzal
    July 18, 2012

    Thanks, Bryan,

    Do you have any citations for any of that? I know that germ-free (gnotobiotic) mice exist. I haven’t seen direct evidence that they die if they’re not colonized.

    I’ve also heard about fecal transplants. I accept that the absence of ‘good’ flora can at deleterious by leaving room for pathogens. I’m also aware of data showing that the immune system develops abnormally without gut flora. To me, those justify claiming that we need them or we’re at risk, but not that we need them or we’ll die. If there really is evidence for the latter, even in non-human mammals, I’d love to see it.

    PS – I’m not trying to pick on ERV here. I’ve seen others claim that gut flora are absolutely essential for digestion. It seems to be one of those things that many people ‘know’ but so far no one’s been able to point me to adequate evidence.

  9. #9 Optimus Primate
    July 18, 2012

    JC Haven

    1:36 pm
    Why Freddie Mercury?

    Why NOT Freddie Mercury?

  10. #10 Thanny
    July 18, 2012

    First, that Freddie Mercury icon has become a meme to indicate celebration of success in some endeavor or another, or simply great satisfaction with some turn of events.

    Second, while I can’t say with certainty that humans would die without gut flora, the evidence makes it unreasonable to doubt that outcome. I can say with complete certainty that many/most herbivores are entirely dependent upon bacteria to digest their food. Basically, anything that survives on grass and other cellulosic plant material relies absolutely on bacteria to break the cellulose down.

  11. #11 makeinu
    July 18, 2012

    I’m not a super hippie, but I don’t want to eat tons of GMO food before there’s real longitudinal testing on what other effects it might have.

    Then you might want to stop eating entirely, because we’ve been genetically modifying our food supply for tens of thousands of years ;)

  12. #12 Charl
    July 19, 2012

    qetzal – there’s an assumption that many of the people who don’t carry known lactase persistence mutations, but CAN digest lactose, probably have lactose-digesting bacteria in their guts. I know anecdotally of several people who have lost their ability to digest milk products after surgery that involves a lot of antibiotics/painkillers/steroids, and again, I assume they’re individuals who had friendly milk-digesting bacteria they’ve now lost. Bacteria in your gut = useful for life [I CBA to Pubmed this, but I'm sure you could].

  13. #13 Bryan
    July 19, 2012

    If there really is evidence for the latter, even in non-human mammals, I’d love to see it.
    As I said, the best evidence is from individuals who dies as a result of infections that their gut flora would normally prevent. There are a huge number of case studies and reviews of this in the literature; C. difficile being the more common (although one of the less deadly) pathogens that take advantage of lost gut flora.

    As for “perfect” data, in humans there is none. Even SCID (bubble) babies were colonized, despite having life-long exposure to antibiotics and living in a near-sterile environment.

    Gnotobiotic doen’t mean ‘germ free’, btw (it means they are colonized only with known microorganisms). Germ-free animals suffer a number of health issues, including circulation problems, which leads to a lot of non-specific mortality (i.e. they die, we don’t know why*). I cannot think of a reference; I’ve worked on-and-off with germ-free mice for ~15 years, so its more of an experience/widely known fact thing.

    *most deaths happen in young animals; I’ve read studies showing that the survivors often outlive conventional mice of the same strain.

  14. #14 harold
    United States
    July 19, 2012

    I see this claim periodically – that we “need” certain gut bacteria to survive – but I’ve never seen the evidence for it.

    Do you have any citations for any of that?

    Decent question, but you may have wrongly assumed that since you were unaware of the literature on this topic, that there is no literature.

    You could have answered your own question with Wikipedia or Google, as well, but sometimes asking is more efficient.

    However, by adopting what appears to be an exaggeratedly defiant tone toward extremely well-known facts, you risk making yourself look mildly foolish.

    Links will bury my comment in moderation land, but use Wikipedia articles for basic coverage, and then go to the citations for more information, if you wish. You may also wish to do a pubmed search for the topic “commensal bacteria”.

    1) Gut bacteria produce a form of vitamin K. Humans can also absorb vitamin K in other ways; nevertheless, prolonged treatment with broad spectrum antibiotics is a major risk factor for vitamin K deficiency, which leads to a serious coagulopathy.

    2) As was mentioned above, normal gut flora compete against pathogens, and loss of normal gut flora is a major risk factor for Clostridium difficile colitis.

    3) Gut flora are even more important for ruminants.

    As I noted, I avoided links because they trigger moderation at ScienceBlogs. Use Wikipedia, Google, and PubMed to do searches on the topics I mentioned. PubMed is by far the most rigorous but likely to provide too much information for the interested lay person. Wikipedia is a good starting point on these particular topics. Google could lead to anything but is always of value when used with caution.

  15. #15 H.C.
    Belgium
    July 19, 2012

    Abbie, thanks for blogging. You’re good.

  16. #16 qetzal
    July 19, 2012

    Harold

    Thanks for the tone trolling. I was not assuming there was no literature. I tried hard to make it clear that I wasn’t denying the claim, I just wanted to see the evidence it was based on. Sorry my efforts didn’t come through clearly.

    I’ve tried searching PubMed, unsuccessfully. Admittedly I didn’t try as hard as I would if I were researching the literature on a topic relevant to my own work. But I did look, and I hoped maybe someone who’s more familiar with the area could point me in a better direction.

    And FWIW, I’m not exactly a stranger to the scientific literature. I’m a PhD mol biologist who’s been working in biotech for 25 years now. So feel free not to assume everyone who asks a question is some lazy pinhead.

  17. #17 qetzal
    July 19, 2012

    PS – another search of Pubmed reveals the same kinds of things I saw in the past. Lots of data showing gut flora can affect host health invarious ways, including preventing colonization by pathogens and promoting proper immune system development. I acknowledged those effects previously (see my July 18th post at 3:35 PM.)

    What I haven’t yet seen is evidence that gut flora are essential in most mammals. In ruminants? Sure. But we aren’t ruminants. And FWIW, it’s apparently quite possible to breed completely germ-free mice for at least two successive generations. See PMID 21278760.

  18. #18 Bob Powers
    July 19, 2012

    Interesting.

    GMO essentially short-changes the normal, slow evolutionary process (as I understand things) such that scientists can create specific traits within the GMO.

    As such, the odds that malaria can quickly recover by mutation is pretty low; it might be possible to effectively wipe the disease out. Obviously, it would be difficult (if not impossible) to eliminate all reservoirs of this pathogen worldwide.

    But I could see commercialization of the process– shipping small containers of GMO bacteria that the user would simply open to activate, perhaps needing only to add water to re-energize the bacterial colonies within.

  19. #19 H
    July 20, 2012

    Oh, hell yes. This looks great.

    Of course, we would have saved uncountable numbers of lives if we’d just use DDT.

  20. #20 harold
    July 20, 2012

    qetzal –

    What I haven’t yet seen is evidence that gut flora are essential in most mammals.

    You are technically correct that modern technology can allow some mammals to exist in almost completely sterile environments, including several strains of very commonly used severely immunodeficient mice. This is

    With antibiotics and vitamin K supplements, humans can live after severe depletion of gut flora.

    I’m fairly sure that many lineages of mammals have not been studied with regard to their gut flora. I would be very surprised if there were mammals that did not have useful commensal gut flora in the wild, but can’t say for certain.

    This is just playing games with the word “essential”. Mammals evolved for millions of years with bacteria. For humans, gut flora are very important, and loss of the normal gut flora has health consequences which are potentially fatal, except with, and sometimes even with, modern medical treatment.

    I’ve seen others claim that gut flora are absolutely essential for digestion

    I haven’t. That”s why I initially thought you were asking about the beneficial role of gut flora. To me this looks like a straw man version of explanations that normal gut flora are very important for health.

    Can you give a citation of someone saying exactly this?

    What I see above is –

    Mosquitoes have a symbiotic relationship with their bacteria the same way we do– they need their ‘good’ bacteria to get all the nutrients they need to survive.

    I’m not an entomologist and don’t know off the top if my head if mosquitoes can absorb all their required nutrients without gut flora. Humans normally rely on gut flora for vitamin K. Humans without normal gut flora are at high risk to become vitamin K deficient. Vitamin K deficient humans can be treated with vitamin K supplementation, even in the absence of most normal gut flora. I guess it’s a semantic argument whether we “need” them.

  21. #21 J
    NYC
    July 20, 2012

    the original paper states “The increase in midgut-specific Akt signaling also led to an 18–20% reduction in the average mosquito lifespan”
    Just to clarify that this DOES have an impact on the mosquito and potentially the ecosystems.

  22. #22 qetzal
    July 20, 2012

    harold,

    Here’s an example from PZ Myers on Panda’s Thumb:

    Let’s begin with the most widely known factor: we’re mostly bacterial in cell numbers, with about ten times as many bacterial cells as human cells. Most of these are nestled deep in our guts, where they are indispensible. [emphasis added]

    I asked the same question there, but got no reply. BTW, is that you commenting in that very thread, starting 10 comments after mine?

  23. #23 harold
    July 20, 2012

    qetzal –

    I don’t comment on Pharyngula.

    I think it is perfectly okay to say that gut commensal bacterial are “indispensible” for humans, “required” for normal human life, and so on.

    They are not absolutely essential for life in the way that oxygen and water are absolutely essential, in the sense that, with modern technology, we can sometimes overcome the immediate term problems that their absence creates (although plenty of people do die of C. difficile colitis and it undoubtedly took many deaths to get the vitamin K thing figured out). For that matter we could probably kill off the commensal bacteria of a cow, and keep it alive for some decent period of time using modern technology.

    None of my comments made the claim that commensal bacteria are required for human life in the same way that, say, oxygen is. I don’t think P.Z. Myers or Abbie Smith is making that claim. I did not understand that you perceived others to be making such a claim. If they did make such a claim, you are correct that they would technically be wrong, but I think you may be misinterpreting claims that merely emphasize the importance of commensal bacteria in well-studied organisms.

    Because of the highly specific and semantically precise nature of your issue, I did, in fact, initially think that you were asking about the importance of commensal bacteria and the relative risks associated with disturbance of the gut flora ecology.

  24. #24 qetzal
    July 20, 2012

    harold,

    FWIW, it was on Panda’s Thumb, not Pharyngula.

    I don’t think I’m being overly precise or excessively semantic at all. Indispensible and essential have very clear and specific meanings. If the loss of something doesn’t automatically lead to your death, but merely puts you at risk, it’s not essential or indispensible.

    I can certainly accept that people don’t really mean indispensible. But like I said, I’ve seen it stated that way more than once or twice, so I assumed it was meant it as written, and became curious to know how that was (supposedly) known.

  25. #25 harold
    July 21, 2012

    qetzal –

    Those are my comments on PT, and obviously, I did raise the issue that immunodeficient mouse models live in effectively sterile conditions in that thread.

    I’m a fan of precision in language, so we don’t have much dispute.

    I suppose I’m conditioned to assume that the fact that bacteria are important for normal human health at all is surprising, therefore I took your original comment as a question of that principle, when you were really asking a much more precise question.

  26. #26 daedalus2u
    http://daedalus2u.blogspot.com/
    July 23, 2012

    In zebra fish, exposure to bacteria is essential. If you try to raise zebra fish bacteria-free you get 100% mortality by ~24 days post fertilization.

    You can’t do those experiments with humans.

    Asking if commensal bacteria are “essential”, is like asking if food is “essential”. Food is not “essential”. People can derive calories from fluids infused intravenously, so food is not essential. Similarly breathing air is not essential because people can be connected to a heart-lung machine and get oxygenated blood from the machine.

    Depending on your definitions, a living brain is not essential either. People can have a beating heart even when they are brain dead.

    I think this degree of specificity and pedanticness is not terribly useful in general discussions of commensal bacteria. It is the idea that all bacteria are harmful that is wrong, and if you have been conditioned to think that way you should change your thinking.

  27. #27 pyst
    July 24, 2012

    it should not be automatically assumed that this technology is a good thing. All living organisms experience constraints on growth with carrying capacity being the operative metric.
    Malthus was right and a major human population crash will occur, pick your date and guess the number of survivors. Pity them as the planet will be severely by then.

  28. #28 Malaria and the Inner Armies – Page 3.14
    July 30, 2012

    [...] the liver and goes on to parasitize red blood cells. Now, a little genetic engineering could put a stop to this scourge. Smith says “Mosquitoes have a symbiotic relationship with their bacteria the same way we [...]

  29. #29 JKR
    August 29, 2012

    quetzal,

    I found an interesting article regarding gut flora and survival. It turns out that killing/inhibiting gut flora with antibiotics as quickly as possible is absolutely required for survival when an animal is exposed to lethal dose of radiation.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137691/

    Rosoff CB, The Role of Intestinal Bacteria in The Recovery from Whole Body Radiation. J Exp Med. 1963 Dec 1;118:935-43.

    Make what you will out of it.

  30. #30 IW
    September 13, 2012

    @Anne:
    You’re already eating GMO food, or did you think those huge corn cobs are natural? Did you think apples really grow that big and juicy in the wild? Did you think that grapes really have no seeds? Did you think that animals are naturally muscle-bound? Do you think that plants, in the wild, don’t routinely pick up genes from each other? Did you think that animals don’t commonly garner extra genes from bacteria and viruses?