From Wellcome Trust Blog

We’re publishing the shortlisted entries to the 2012 Wellcome Trust Science Writing Prize. Here, Michael Conway writes about efforts to stop the spread of dengue fever by using genetically modified mosquitoes.

It is 6am in the cool of the tropical morning, and early risers in the village of Itaberaba, Brazil, are waking to a strange yet increasingly familiar ritual.

As the early morning sun begins to warm the low-slung houses with hints of the brutal heat it will inflict as the day progresses, a small white truck bumps along the unpaved road between them. In the back sit two men, surrounded by what appears to be a collection of small ice-cream tubs. As the truck makes its way slowly along the street, its passengers set to work: with a calm deliberation, the ice-cream tubs are picked up one by one, opened, shaken. Then, looking almost like participants in a bizarre parade, the two men confetti the community with what many of its slumbering residents might consider their worst nightmare – small black clouds of mosquitoes.

Watching it unfold, an uninformed bystander might be forgiven for taking the whole exercise to be a particularly well-planned and malicious prank. But these are no ordinary insects, and Itaberaba’s streets are, in fact, host to a ground-breaking experiment that has opened a new front in humanity’s battle against a dangerous and highly resilient pest: the Aedes aegypti mosquito. Tiny, voracious, extremely bothersome, it can also be a killer, and so far it’s been winning the war hands down. But in Itaberaba, a new weapon has been unleashed.

Mosquitoes have always been an annoyance and a menace to people, but the real flash point for this interspecies conflict is disease. Dengue fever, spread by Aedes aegypti, infects between 50 and 100 million people each year, and the numbers are growing; up to a quarter of the world’s population is now thought to be at risk. The flu-like fever and joint pain it causes can be so crippling that it has become known to its unfortunate victims as ‘break-bone’ fever. For at least 25,000 people a year, the infection is fatal.

The rapid spread of this dangerous virus is due to the wanderlust of the Aedes aegypti mosquito, which during the last century has hitchhiked upon international trade and travel networks to establish itself in more than 100 countries. Where the mosquitoes go, dengue fever can follow, and thus far our best efforts at removing these unwelcome immigrants have proved woefully inadequate.

But new technology developed by an Oxford University spin-out company may change that. For the past 10 years, Oxitec Ltd has been applying advanced genetics to the problem of mosquito control. Led by Dr Luke Alphey, its scientists have genetically modified Aedes aegypti mosquitoes so that they pass on to their offspring a fatal inheritance: a gene which, when activated, results in an untimely death for the unfortunate insect.

Now, in the streets of a small Brazilian town remote in every sense from the sandstone and greenery of Oxford, genetically modified insects are being released, distributing this genetic timebomb.

The principle is simple: release male mosquitoes (the males don’t bite, so there is no additional risk to the human population) carrying the lethal gene into the environment and they will seek out and mate with wild females. Any female which mates with a modified male will have offspring that inherit the lethal gene and die before reaching adulthood – reducing the wild population. Keep releasing the modified males and eventually the wild mosquito population in an area will be dramatically reduced or eliminated altogether. The approach is pesticide-free and completely specific to the target species.

It’s a simple theory but Oxitec scientists had to overcome another problem – how is it possible to rear insects that harbour a lethal gene? The solution developed by Dr Alphey and Oxitec was to engineer a ‘back-door’ to their genetic system. The gene works by enhancing its own activity – in effect, switching itself permanently on. In doing so, it greedily cannibalises cells’ genetic machinery, sacrificing more and more essential regulatory proteins to its drive for self-propagation – with catastrophic results for the cells. But an antibiotic, tetracycline, binds to the protein produced by the lethal gene and stops it from activating this terminal cycle.

This crucial molecular switch allows Oxitec to rear millions of healthy GM mosquitoes in the lab by adding tetracycline to their diet – ready for them to be released into the wild unaware of the deadly bequest they will pass on to their offspring.

Oxitec’s approach has already been demonstrated in the Cayman Islands, where releases of its modified mosquitoes reduced the Aedes aegypti population of the treatment area by 80 per cent.

Now, the company’s novel form of pest control is being tested in one of the most dengue-infested areas in the world. If it works, it will be an important step towards a completely new way of combating a dangerous and debilitating disease. And in the power of genetic technology, Aedes aegypti may finally have met its match.

Michael Conway

This is an edited version of Michael’s original entry in the general (non-scientists) category. Views expressed are the author’s own. Michael is a PhD student at the University of Oxford conducting research in collaboration with Oxitec, whose vector control project to combat dengue is part-funded by the Wellcome Trust.

Find out more about the Wellcome Trust Science Writing Prize in association with the Guardian and the Observer and read our ‘How I write about science‘ series of tips for aspiring science writers.

For more on this story go to:

http://wellcometrust.wordpress.com/2012/11/15/family-planning-for-mosquitoes-genetically-modified-insects-to-fight-dengue-fever/