GM fungi to kill malaria mosquitoes

Hundreds of millions of people pick up malaria every year; and faced with rising resistance to the chemicals used to control the infection, the World Health Organisation have been looking for new ways to stamp out the parasite itself, or the mosquitoes that spread it. Well, step forward two scientists from the University of Maryland, Raymond St Leger and Brian Lovett, who've taken a strain of fungus that naturally infects mosquitoes, and weaponised it by inserting a gene used by spiders to make the venom that kills their insect prey. Working in a special facility in Burkina Faso, they smear the fungus spores on a dark sheet, and, when the mosquitoes land, the fungus invades, activates its spider venom gene and quickly despatches the insect. Chris Smith spoke with both Raymond and Brian...

Raymond - We used to be able to treat mosquitoes with insecticide-treated bed nets, but recently mosquitoes have become increasingly resistant to chemical insecticides. And so we developed this biocontrol as it's called. We’re using a natural enemy of the mosquito, a fungus called metarhizium, which just targets the mosquito. But the fungus is very slow to kill, so we've engineered the fungus with a spider toxin specific to insects.

Chris - And Brian tell us a bit about the fungus. What is it and how does it get into a mosquito? How does it spread, how does it kill, normally?

Brian - Metarhizium is a genus of fungi, and these fungi act as contact insecticides. So if they land anywhere on the outside of the insect, then they can burrow through the cuticle into the blood of the insect, and from there the fungus changes form and starts growing as a yeast. And when it changes form, it also expresses genes that are only expressed in the blood of the insect, so we can take advantage of this biology to produce strains of metarhizium which can deliver new proteins only into the inside of the mosquito.

Chris - And Raymond, you've sort of weaponised that process with a spider toxin so that when it gets in, you’re absolutely certain to kill?

Raymond - That's right. Now the fungus would kill the mosquito anyway eventually, but it takes its time about it. But we need the fungus to kill the mosquito quickly, so the mosquito can't spread disease. So what we've done is we've engineered the fungus with this what we call a transgene, that's a gene from another source, in this case a spider, we put that gene into the fungus so it's only turned on in the insect blood.

Only mosquito blood gets the fungus to make this spider toxin. Basically, we've converted the fungus into a hypodermic. The fungus is going to penetrate into the blood and then respond to the blood by producing this toxin.

Chris - And Brian, have you got to the stage where you've actually been able to test this?

Brian - We have tested this in the lab. This engineered fungus kills the mosquitoes quicker, it kills more mosquitoes, but what you find in the lab doesn't always translate into field conditions. So a major driver of the study was to answer the simple question “is this technology as effective in field conditions?”

Now because this was a transgenic technology, we needed to test it in containment. So in order to do this, we built a really large facility, called a mosquito sphere, which allows environmental conditions in, but prevents our experiments from getting out. So what this facility is is essentially a really large greenhouse, but instead of having glass it has a double wall of mosquito netting, and this allows us to test whether or not this is effective at controlling mosquito populations.

Chris - And is it?

Raymond - One of the things we really wanted to do was to produce a product which would be easy for the local community to exploit. Now mosquitoes, after they feed they're attracted to dark surfaces so we bought black cloth, easily available. We bought sesame oil, easily available. We put the fungus in the sesame oil, and then just smeared that on the black sheets and then we just hung those black sheets up in these experimental huts.

As a food source for our mosquitoes, we introduced little male cows (bullocks) into each of these huts and our transgenic fungi killed the mosquitoes very quickly. And basically, it meant that after a couple of generations the mosquito populations had collapsed.

Chris - But Brian, is there not a chance though in the same way, as Raymond was saying, bed nets are no longer effective because mosquitoes are not killed by them, is there not a chance that the mosquitoes are just going to sidestep it, they're going to evolve to become resistant to it?

Brian - I certainly wouldn't be comfortable telling you that resistance could never occur. But we have studied this fungus for a very long time and people have tried to force insects to become resistant to these kinds of fungi in the lab and have found that it's very difficult.

And one of the reasons why is because a major difference between chemical insecticides and this fungus is that this fungus wants to kill these insects and has been co-evolving with insects to kill them. So when you look at the evolution, there's an arms race going on where insects may develop a way to try to prevent these fungi from infecting, and these fungi will come up with a work around.

Regarding our toxin, it is also unlikely that the insects would develop resistance to that toxin because the toxin targets two different channels on insect neurons, the calcium and the potassium channel, and insects would need to evolve resistance to both of those channels simultaneously to be resistant to the toxin that we’re delivering to their blood.

Chris - Does this mean that you could, potentially, go to the field with this?

Brian - No. And the reason why is because the evidence that we reported in this paper is primarily scientific evidence. When you're talking about developing a new technology, particularly one that you want to introduce into people's homes, you need to have more than just scientific results to back up taking that next step.

So other factors that we would have to consider are regulatory approval and also community engagement. Even the very best technology, the most effective technology, if it doesn't have acceptance from the local community, is not going to be successfully implemented. So in order to take this out into the field we're it going to have to have a long period of dialogue with the community and local stakeholders to make sure that they understand what we are offering to them, and also address any concerns they might have before we start testing this in the open field.