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Making the Enemy of your Enemy

What? Another science paper post? Yup, I’m trying to get ahead of my paper-a-month deadlines by posting February’s while actually still in February!

This month’s paper comes from Science and is a topic which is extremely relevant to global health. As you probably know, malaria kills close to 1 million people a year, with most of these deaths in areas lacking in the financial resources and public infrastructure needed to tackle the disease. In addition to the socioeconomic factors, the biology of the disease itself is extremely challenging to deal with because the malaria parasite Plasmodium falciparum not only rapidly shifts its surface proteins (so the immune system can’t get a good “fix” on it) it also has a very complex multi-stage life cycle (diagram below), where it goes from being carried around by a mosquito as a sporozoite, to infecting and effectively “hiding inside” human liver cells, to becoming merozoites which then infect and hide inside human red blood cells, and then producing gametocytes which are picked up by mosquito’s which combine to once again form sporozoites. Each stage is not only difficult to target (because the parasites spend a lot of their time “hiding”), but the sheer complexity of the lifecycle means the immune system and drugs humans come up with are always a step behind.

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So, what to do? While there is active work being done to build vaccines and drugs to fight malaria, the “low-hanging fruit” is getting the upper-hand on the mosquito transmission phase. Unfortunately, controlling mosquitos has become almost as bad a nightmare as dealing with the Plasmodium parasite. The same socioeconomic factors which limit medical treatment for the disease also make it difficult to do things like exterminate mosquitos. Furthermore, pesticides not only have adverse environmental impacts (i.e., DDT) but will ultimately have limited lifetimes as the mosquito population will eventually develop resistance to them.

imageWell, enter the enterprising scientist. I can’t say for sure, but I have to believe that the scientists here must have read comic books like Spiderman or Captain America as a kid because the approach they chose feels like it came straight out of the comic book world. But, instead of building a monstrosity like the Scorpion (pictured to the right), the researchers built a super-fungus super-soldier to control malarial transmission.

Instead of giving the powers of a scorpion to smalltime thief Mac Gargan (who then named himself, appropriately, The Scorpion), the researchers engineered a fungus which naturally infects mosquitos called Metarhizium anisopliae to:

  • kill the infected mosquito more slowly (as to not push mosquitos to become resistant to the fungus)
  • coat the infected mosquito’s salivary glands with a protein fragment called SM1 to block the malaria parasites from getting there
  • produce a chemical derived from scorpions called scorpine which is extremely effective at killing malaria parasites and bacteria

Pretty cool idea, right? But does it work? Figure 3 of the chart below shows the results of their experiments:

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Mosquitos were fed on malaria-infected blood 11 days before they were dosed with our super-fungus. Typically sporozoites take about 2 weeks to build in any reasonable number in a mosquito’s salivary glands, so 14-17 days after exposure to malaria, the researchers checked the salivary glands of uninfected mosquitos (the control [C] group), mosquitos infected with non-super-fungus (the wild-type [WT] group), and mosquitos infected with the super-fungus (transgenic [TS] group). As you can see in the chart above, the TS parasite count was not only significantly smaller than both the control and wild type groups, but the control and wild type groups behaved exactly as you would expect them to (the parasite counts went up over time).

So, have we discovered a super-soldier we can count on to stop mosquito-borne illnesses? I would hold off on that for a number of reasons. First, on an experimental level, the researchers only looked at 14-17 days post-infection. To be confident, I’d like to see what this looks like with different doses of fungus and over longer periods of time and a wider range of mosquitos (as nearly 70 species of mosquito transmit malaria and I don’t even know what the numbers look like for other diseases). Secondly, its not clear to me what the most effective way to dose large populations of mosquitos are. The researchers maintain that you can spray this like a pesticide and the fungus will adhere to surfaces and stay effective for long periods of time – but that needs to be validated and plans need to be drawn up to not only pay for this (I have no idea how expense this is) but also to deploy it.

Lastly, and this is something that almost any naturalist or economist will tell you: human actions always have unintended consequences. At a first glance, it looks like the researchers covered their bases. They build what looks like a strategy which avoids mosquito resistance (and, because it uses at least two ways of controlling the parasite, is probably less vulnerable to Plasmodium resistance than drugs/vaccines). But, more research needs to be done to ascertain if there are other environmental or economic impacts of using something like this.

All in all, however, this looks like a promising start for what could be an interesting and inspired way to help control malaria.

(Image credit – Malaria lifecycle) (Image credit – the Scorpion) (Figure 3 from paper)

Paper: Fang et al., “Development of Transgenic Fungi that Kill Human Malaria Parasite in Mosquitos.” Science 331: 1074-1077 (Feb 2011) – doi:10.1126/science.1199115

Published in Blog

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