'Disease-Proof Mosquito' Could Spread Like Wildfire

Suppose you're one of the many scientists racing to design mosquitoes unable to transmit malaria or another major scourge—and you succeed. Now what? You can release the critters in the real world, but if they don't have some unique advantage, they will be vastly outnumbered by the billions of natural mosquitoes already out there.

Now, scientists have developed a new genetic trick that could help those disease-resistant mosquitoes spread like wildfire. The system, a so-called gene drive mechanism, is published online today in Nature.

The new study is part of an explosion in mosquito genetics research that aims to stop mosquitoes from transmitting malaria—which killed an estimated 800,000 people in 2009—and several other diseases. Already, scientists have identified several mosquito genes that, when tinkered with, decrease the mosquitoes' ability to transmit a virus or a parasite; they have also given the insects new genes that do the same.

But a question clouding the field's future has been how to “replace” natural populations with these new and improved mosquitoes. For that, scientists need a system that will help the lab-bred mosquitoes take over wild populations, to ensure that genes conferring resistance become ubiquitous. Scientists are working on several strategies; many involve so-called selfish genes, strange stretches of naturally occurring DNA that have ways of spreading through populations in almost parasitic fashion. The idea is that these genes could be hitched to others that mess with the parasite's life cycle and make those spread as well. But although researchers have had some success in fruit flies, nobody has been able to get a gene drive system going in mosquitoes.

The new study, led by molecular biologists Andrea Crisanti and Austin Burt of Imperial College London, was done in Anopheles gambiae, the mosquito species that is by far the most important carrier of malaria. The scientists used a so-called homing-endonuclease gene (HEG), a selfish gene found in fungi, plants, and bacteria that has the ability to create a second copy of itself in individuals that have only one. This ensures that all offspring have the gene as well, and it's one of the fastest ways genes can spread in nature, says insect geneticist Jason Rasgon of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who was not involved in the new study.

To show that they can harness that power, the researchers bred a population of Anopheles mosquitoes that glowed in the dark, thanks to a green fluorescent protein. Then they released into their cages small numbers of mosquitoes with a HEG designed specifically to break up the fluorescent protein gene in sperm cells and insert itself into that same place on the chromosome, thus ensuring its propagation into the next generation. This way, the team could simply monitor the spread of the HEG by counting how many mosquitoes in each generation was glowing green.

As the scientists' models predicted, the cages quickly grew darker over time. If, for example, just 1% of the mosquitoes had HEG at the start of the experiment, approximately 60% did 12 generations later. That means the gene has the ability to transform even large populations in a short amount of time, Crisanti says.

The next step, he says, is to make HEG break up not the fluorescent protein gene but one that is crucial for malaria transmission. It could be an odor-recognition gene that helps the mosquito finds its host, for instance, or one that the malaria parasite needs to enter the mosquito's salivary glands; the team already has 10 to 15 candidates.

Rasgon hails the study as the first to prove that a gene drive mechanism is possible in mosquitoes, which has long been a crucial challenge in the field. "They still have a long way to go," Rasgon says. "But as a proof of principle, this is pretty impressive."