What if Bt saved human lives?

When I was in grad school, there was a lab in our department that studied intestinal parasitic roundworms.  Although this wasn’t related to what I was doing in any way—everyone who has been to grad school will know that you attend the department seminars for the donuts and/or pizza no matter what the topic is.  I have to say, though, that the seminars from this lab made the donuts and pizza a little less appealing.
T. Anderson and thesis defense projectOne of the students of the lab defended his thesis work during this time frame.  He was a terrific speaker who made us understand the medical and economic burdens of these parasites on the impoverished communities he studied.  Somehow he managed to make the story of sample collection amusing…. And the details of the discovery of his own infection (after a very hot curry meal) made that defense one of the most memorable during my career in science (Figure 1, right. Speaker and his infectious agent).  But I still remember the scientific point: these infections have real impacts on the humans and the agricultural animals that live in close proximity to them in the developing world.  And that there appear to have been separate and distinct infections in humans and in pigs in the studies they performed.
Until recently I hadn’t thought much about the roundworms.  But this week when this paper came across my desk, I was glad to see that there was a potential breakthrough in the treatments for roundworms that could improve the health of millions of children.  And how might this be accomplished?  Using the Bt protein.
For some people, a great deal of the conflama around genetically-engineered (GE) crops has to do with the presence of a pesticide in the plant material—mainly the Bacillus thuringiensis or Bt protein—rather than coating the surface of the plant as organic Bt sprays or chemical-style pesticides would.  No matter how many times I explain that there are benefits to this strategy (such as reduced impact on non-target species and on improvements in farm family health among others), it doesn’t seem to help. No matter how many times I explain that pesticides aren’t the only modification to plants (as we see at Biofortified regularly), it doesn’t matter to critics of GE.  The fact that plants make their own pesticides? Not interested.  And no matter how many times I explain how the Bt proteins work only on species that have the specific receptor for that interaction—and therefore does not affect humans as it would the corn borer pest—it doesn’t seem to have any impact.  The misplaced fear continues to be used by the critics.ResearchBlogging.org
So when I saw this paper that suggested the Bt protein may be a powerful strategy for improving the lives of impoverished children around the world, all I could do was wonder if that might finally register with those who make unsupported claims of the effects of Bt on humans.
A team from UCSD studies the biology of infectious diseases (Aroian Lab), with the hope of harnessing biological strategies to combat the scourge of the roundworm parasitic infections.  As they describe, millions of people are affected by this:

These parasites infect the gastrointestinal (GI) tracts of 1 in 3 people in the world and may cause as much morbidity as malaria. STH infections in children result in growth and cognitive stunting and severely impact learning, school attendance, and future income potential. The World Health Assembly (WHA) in 2001 has urged the deworming of 75% at-risk school-aged children (nearly 400 million children). Over 44 million hookworm-infected pregnant women are at increased risk for premature delivery, low birth weight, maternal ill-health, and maternal death.

There have been chemical drugs used to treat the affected individuals.  However, these chemicals are losing their effectiveness as resistance builds in the parasites.  The UCSD team has sought a natural solution to this problem, and they are making progress toward that goal.
Earlier work established that the Bt protein may have effectiveness on certain nematodes (Wei and Hale et al, 2003).  Further work looked specifically at the effectiveness of Bt protein on an intestinal parasite species that can infect humans (Capello et al, 2006).   This new work examines the effectiveness of a Bt protein on a mouse model that more closely mimics a naturally-occurring infection situation in humans.
The experimental details are quite straightforward.  Mice were infected with a parasite (under the guidelines for animal use).  A Bt protein (Cry5B) was prepared and examined for bioactivity, with appropriate controls.  Bt protein solutions or control solutions were given to infected mice in a single dose.  The egg levels and worm burdens were determined among the experimental animals.  And the data were very clear.
When the researchers counted the levels of nematode eggs in the feces of the infected mice, there was a remarkable reduction in the counts of mice treated with the Bt protein solution—greater than 95% of eggs were reduced on the first day, and even greater over the next sample days.  The adult worm count drop wasn’t quite as dramatic (only 67% reduced).  The authors suggest that this means the worms that did remain in the intestine were probably severely compromised, and therefore not effective at reproduction.
The effectiveness of the Bt treatment was compared to a current anti-roundworm chemical treatment (tribendimidine).   It appeared that the Bt protein treatment was potentially more effective than this compound.  And these experiments used Bt protein in solution—which is highly degraded by stomach acids, as they demonstrate.  The authors suggest that wrapping by the Bt in a coating to bypass the stomach to get to the intestinal environment—commonly done for medications, it may be that Bt could be even more effective and use quite a low dosage.
This was a small scale pilot experiment in mice, and the work would certainly need to progress to humans to be sure of the efficacy.  And like all treatments that we have in the infectious disease arms races, awareness and monitoring of resistance would certainly be an issue.  But I suspect it will be harder for the anti-GE factions to use the fear of Bt if it can be shown that Bt has dramatic and remarkable benefits for humans in the developing world.  Like the impending launch of many nutritionally-improved GE products, as more people understand the benefits of these strategies for human health, hopefully the fear can recede and the facts can enter the discussion.
You may also want to hear from the research team themselves on this—they have created a Quicktime movie to tell you more about their work:
To download: http://aroianlab.ucsd.edu/Wormfreeworld1.mp4
You can “virtually” meet the researchers who performed this work, and hear more about the historical and current understanding of the effects of the roundworm infections on humans.  I would just like to add that the researchers performed this work with funding from the NIAID (National Institute for Allergy and Infectious Diseases), and had no corporate funding in their declaration statement on their paper. I have no relationship with this lab or any relationship to the work performed.  I just read the paper and thought it was nifty.
Hu, Y., Georghiou, S., Kelleher, A., & Aroian, R. (2010). Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice PLoS Neglected Tropical Diseases, 4 (3) DOI: 10.1371/journal.pntd.0000614
Photo provided by T. Anderson, personal communication. Used with permission.
MaryM is Mary Mangan, co-founder of OpenHelix, a company that provides training on open-source software in bioinformatics/genomics. PhD in molecular/cell biology, with training in plant + animal systems, she’s the kind of independent scientist people claim they want to hear from, until they dislike the conclusions.  She also enjoys hot curry dishes regularly, and not just for their curative properties.

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  1. Great post, Mary. I hope that this treatment works; it is an interesting idea to use an existing bio-pesticide specific for those parasites.
    I also wonder if this becomes an actual approved medicine what effect that might have on the people who seem convinced that Bt is causing allergies and other health problems. What is interesting about this is that they are trying to get the Bt to survive digestion, when in GE crops it is expected to be destroyed during digestion. If even after surviving digestion it doesn’t cause any reactions it will be a further nail in the coffin of the anti-Bt claims.

  2. Oh noes! Bt kills more than insects! Ban it!
    On a more serious note, this would be massively beneficial, but likely wouldn’t put a nail in the coffin of anti-Bt claims as the anti camp would suddenly ‘get’ science and fall back on the perfectly sound reasoning that just because this Bt toxin (Cry5b) has no adverse effects despite not being digested this doesnt mean that other Bt toxins dont (or the old chesnut that you havent done a n generational study in humans, which is for those who refuse to accept any science) – hopefully what it would do is switch the animosity on GM away from the technology itself, and exclusively onto the big corporations who are used to it, don’t need public funding, and have their own rather large PR budgets and lobbying budgets to deal with it – tools not readily available to academic research.

  3. What an excellent first post Mary!
    I don’t know what the cost of tribendimidine is per treatment, but it seems quite possible that a treatment based on the cry protein would end up being a lot cheaper (in addition to being as or more effective than current treatments) given how easily it can be produced.

  4. Hi guys–thanks for the comments. I’m about to grab a flight so I can’t chat long.
    I know it won’t be the final word on this topic. But maybe it’s another handy data point to use.
    @James: wouldn’t it be ironic if they extracted the Bt and created the pills from that….Probably easier to generate it in bacteria like insulin, though.

  5. It would make me laugh if the product that finally made “pharming” a reality was the cry protein, something that’s been expressed in plants since the beginning of genetically engineered crops.

  6. Keep in mind though it isn’t the Cry protein that has been expressed in plants since the beginning of genetically engineered plants – it’s in the same class of proteins but if I’m not mistaken (and I may be…..) the commercially used Cry proteins are generally Cry1/3/9
    Has a tree showing where 5b sits compared to 1A

  7. A fair distinction. Obviously the same cry proteins that target lepidoptera would not also be effective against nematodes. Thanks Ewan.

  8. Yeah, they’ll have to determine which Bt is appropriate for the specific human-affecting worms, of course. And that may vary by location. There could be a different nematodes in South American populations and in sub-Saharan African populations.
    And they’d have to determine the best production method. Could be bacteria, could be yeast cultures, could be plant cell cultures, field plants, depends on the best way to standardize the materials. Might also depend on the local capability. It would be very cool to have people trained in the local biotechnology to develop and produce the right stuff.
    But all of them would come with safety and efficacy studies. There will be data on liver effects, and on allergic reactions, etc.

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