What Could Possibly Go Wrong? What Could Go Right?

For Charlie Sanders – who’s suffering

Monash University has billboards around town promoting things they are doing with the tag line “We think that’s brilliant”. One of them has a huge image of the relevant insect with something along the lines of “Monash researchers are infecting mosquitoes to defeat malaria.” It’s true, and I do indeed think it’s brilliant, but they left out the fact that Monash is just one part of a collaboration working on this idea, which includes hated rival Melbourne, and comes out of work done at much maligned La Trobe.

The story starts with Wolbachia, a genus of bacteria that infects lots of different arthropods, including mosquitoes. In some cases the Wolbachia species is a parasite, even a deadly one, on the host, but in other cases they form a symbiotic relationship where it actually confers advantage.  Back in the 80s Professor Ary Hoffmann, then at La Trobe and now at Melbourne discovered a species of Wolbachia bacteria that kills mosquitoes.

That’s interesting, but what was really exciting was that it only kills them when they are quite old, or at least well into middle age in human terms. The reason this matters is that mosquitoes are really, really good at developing resistance to things that kill them. You can find an insecticide that kills 99% of a mosquito population and in a few years the 1% will have bred their way back to leave you where you started.

This is why all the talk about environmentalists having killed millions by banning DDT is rubbish. Not only was DDT never banned for public health purposes (as opposed to agricultural uses) but in most of the places it was abandoned it was because it no longer worked – the resistant mosquitoes had taken over. In other places people could see this coming and stopped first.

But a bacterium that only kills old mosquitoes? Resistance would be really slow to appear for something like that. On the other hand, for humans this is really useful. Mosquitoes are not born carrying a disease like malaria or dengue. In order to catch it they have to reach sexual maturity, mate (only pregnant females bite mammals) and bit a human who has been infected with the disease. The parasite or virus then has to develop inside the mosquito for a couple of weeks before it is ready to be transmitted through the saliva when the carrier bites someone else.

In other words only old mosquitoes can give you an infectious disease. Mosquitoes old enough to have been killed by Hoffman’s Wolbachia. So this is where Monash comes in. Together with the University of Queensland they’ve been working on a trial of infecting dengue mosquitoes with the appropriate strain of Wolbachia and releasing them in patches of far north Queensland.

The Intellectually Tricky Bit

The problem is how to spread the Wolbachia to the population as a whole. It doesn’t spread sideways from mosquito to mosquito, but rather from mother to child as the bacterium gets into the eggs carried by an infected mother.

However, it turns out that Wolbachia carries a special bonus in this regard. In some insects, including all mosquitoes we have studied, Wolbachia carries cytoplasmic incompatability. This means that if an infected male mates with an uninfected female the embryos die. All of them.

According to Hoffman 100% that we have observed. We don’t understand how, but that is the deal. So if an infected female mates, whether with an infected male or not, the offspring carry Wolbachia. If an infected male mates with an uninfected female the offspring die. So the only uninfected offspring come from the mating of two uninfected parents.

If you can push the infected population above a certain point the chances of two uninfected individuals meeting is low enough that the population becomes overwhelmingly infected and stayed that way. This is the case both in models and in the north Queensland experiments. Brilliant.

So all we have to do is infect so many mosquitoes with Wolbachia in the lab that we can release them to become the dominant population in an area and we will get rid of dengue and malaria forever. Perhaps you see a problem. It’s one thing to produce enough infected mozzies to take over a few square kilometres outback of Townsville. Quite another to change the balance in the jungles of the Congo.

Hoffmann however, has not been resting on his laurels (nor spending all his time studying the impact of climate change on biodiversity – his other major project). He’s found another strain of Wolbachia in fruitflies that doesn’t kill mosquitoes. In fact it seems to give them a slight advantage, assisting with the spread through the community. On the other hand, it appears to block the transmission of dengue, although he can’t get it to infect Anopheles mosquitoes, the ones that carry malaria.

This might eventually enable us to wipe out dengue if the population carrying this strain can slowly take over, but we are talking decades or centuries. We still need something else, something to give the Wolbachia carrying mosquitoes a wing up.

The Ethically Tricky Bit

Hoffmann’s solution is to genetically engineer Wolbachia carrying mosquitoes to be resistant to insecticides. Then you spray the area in which they are released, killing off most of the non-infected mosquitoes so that the wolbachia carriers are the majority and away you go.

Sounds great right? except the bit about genetically engineering mosquitoes to be resistant to the thing we use to control them. Ok a couple of things. First up, we now have a lot of different sorts of insecticide. We wouldn’t make them resistant to all sorts, just one kind that has not been used in the area for a time so resistance would not be widespread in the local population. If we ever need to come back and fight the Wolbachia carriers we would still have all the other insecticides at our disposal.

Second, Hoffmann would be engineering in a resistance that has already appeared naturally in some other part of the world where that insecticide is widely used. If you really want he could probably go and get some resistant mosquitoes from somewhere else, infect them with Wolbachia and release them, skipping the genetic engineering part entirely.

Still not happy? No, neither am I. The phrase “what could possibly go wrong?” sounds appropriate. Here is our most deadly animal enemy, and we are encouraging it to become resistant to one of the few weapons we have, while possibly also infecting it with a bacterium that somehow makes it stronger. You could write a horror movie along those lines. They probably already have. (Maybe Hoffmann should sell the rights to Hollywood to make up for reductions in ARC funding).

But there is another side to this. Dengue kills people. And even when it doesn’t it is a truly horrific disease. They don’t call it breakbone fever for nothing – in a bad case it feels like someone very efficient is torturing you. For weeks. Without stopping. There is no cure, nor treatment beyond keeping you hydrated. If you recover and are infected with a different strain it can easily be fatal. Recovery may not be complete. My friend Charlie Sanders got it three years ago (in a part of Timor that was supposed to be free) and she said to me today,

“Having Dengue was really, really unpleasant.’
And my immune system has never recovered.
Here is a specimen of some chest phlegm as evidence.”

Then she gave me a list of symptoms I will not repeat here because you may be eating. Or hoping to sleep tonight. Sure, not all of them are constant, but her immune system is so shot she’s prey to every virus or bacteria that happens passed. At least she has access to western medicine. How much worse would life be with this condition in a developing country, where most people get it?

Half a million people are hospitalised with dengue every year and 25,000 die. Estimates of the number of infections range as high as 400 million. And of course all this is tiny compared to malaria, which is locked in a battle with AIDS to see which can take the crown of the most devastating infectious disease since we knocked of smallpox. While some of us are hanging out for Krystal Evans to create a vaccine against plasmodium and win Union Street, Brunswick, a Nobel Prize, it would be nice to have a back-up, just in case. Infection of  Anopheles could do that.

I believe in the precautionary principle. I accept that “first do no harm” is a good starting point for health professionals. But people are dying. More are suffering. If genetically engineering super mosquitoes could stop that should we run the risk? I don’t think that is an easy question to answer.

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About Stephen Luntz

I am a science journalist, specialising in Australian and New Zealand research across all fields of science. My book, Forensics, Fossils and Fruitbats: A Field Guide to Australian Scientists is out now through CSIRO Publishing. I am also a professional returning officer for non-government organisations. I'm very politically active, but generally try to restrict this blog to scientific matters.
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