The Answer to Zika May Be More Mosquitos
Insects that have been implanted with a virus-blocking bacterium will finally be tested at large scales, over two cities in Brazil and Colombia.
The mosquito Aedes aegypti is infamous for carrying Zika and dengue fever. The quest to kill it has consumed enormous amounts of money, time, and effort. So it seems counterintuitive that a team of scientists and health workers have just received $18 million to release these mosquitoes over densely populated parts of Brazil and Colombia.
Their insects are no ordinary mosquitoes, though. They’ve been implanted with a bacterium called Wolbachia, which stops them from spreading the viruses behind Zika, dengue, yellow fever, chikungunya, and other diseases. It's not totally clear how it does this, but it may be by competing with the viruses for nutrients or boosting the insects' immune system. With this microbe inside them, the mosquitoes are no longer carriers of sickness. They are dead-ends.
Better still, Wolbachia also excels at spreading through a population, manipulating its hosts to maximize its chances of entering the next generation. If you release small numbers of Wolbachia-infected mosquitoes over a region, within a few months, almost all the local insects should carry the microbe and thus be unable to spread several human diseases.
I wrote about the history of this approach, and the science behind it in my recent book, excerpted in The Atlantic back in August. It’s the brainchild of Scott O’Neill from Monash University, who has been working on it since the 1980s, despite a vexing succession of problems. “It’s probably a personality disorder on my part, not being able to let go,” he says. For example, it took several decades for his team just to introduce Wolbachia into mosquito eggs—a process that’s like slipping a needle into a balloon and then pulling it out without popping anything.
After finally succeeding in 2006, they started testing their insects in the field. In January and February of 2011, they released 300,000 infected Aedes aegypti over two suburbs of Cairns, Australia. By May, Wolbachia had spread to the vast majority of the local mosquitoes. The approach worked, and the team have since gone broader and bigger. Under the banner of Eliminate Dengue—the non-profit organization that O’Neill and his colleagues founded—they established teams and pilot studies in Indonesia, Brazil, Colombia, and Vietnam.
The organization’s focus was initially trained on dengue. But after Zika took the world by surprise earlier this year, Eliminate Dengue researchers quickly showed that Wolbachia also curtails the spread of that disease—and perhaps even more potently than it does for dengue. With successes mounting, the team has just received $18 million in funding from the Bill and Melinda Gates Foundation, the Wellcome Trust, and the governments of the U.S., U.K., Brazil and Colombia. The money is a boon but also a challenge: Show that this works at scale.
There are already promising hints. The team hasn’t seen any signs of dengue transmission in places where they’ve released Wolbachia-carrying mosquitoes, even when outbreaks occurred in surrounding areas. And in the island of Nha Trang, Vietnam—the site of one of the pilot projects—there were just a couple of cases of dengue last year, compared to the dozens the island used to see annually.
That’s encouraging, but also anecdotal. To get better evidence, Eliminate Dengue is now running a randomized controlled trial in Yogyakarta, Indonesia, releasing their mosquitoes over some areas and not others to see if dengue cases fall in the former. “That will provide the gold-standard evidence that epidemiologists would like to see,” O’Neill says.
It will take a few years for the results to come in. But dengue and Zika aren’t waiting around; they are current problems that demand current solutions. That’s why the team is now going big. They’ve already been doing small projects in suburbs of Rio de Janeiro, Brazil, and Antioquia, Colombia, home to tens of thousands of residents. They’re now going to expand into bigger stretches of those cities, covering 2.5 million people in each.
Cities like these are the dominion of Aedes aegypti. “It is a very house-adapted mosquito; they say it lives in every puddle of water, every flower pot,” says Trevor Mundel, the president of the global health division at the Bill & Melinda Gates Foundation. Short of carpet-bombing an area with insecticide, there are few good ways of getting rid of urban Aedes. Even intensive house-to-house eradication campaigns often fail to root out the insect enough to make a dent on numbers.
But where other campaigns have failed, Wolbachia might succeed. Once the infected mosquitoes are released, you’re simply banking on their ability to spread the bacterium by mating with their own kind—and there’s nothing better at finding mosquitoes than other mosquitoes. (And Aedes only mate with Aedes, so this approach won't spread Wolbachia to other species.)“Unlike insecticides, you’re not getting the collateral damage of knocking out other species in the environment,” says Mundel.
And unlike insecticides, Wolbachia-bearing mosquitoes don’t need to be constantly resprayed. They are self-sustaining, so a single release ought to do the trick. O’Neill thinks that this should make it considerably easier to scale up the approach from suburb-level to city-level. “We don’t need to deploy simultaneously,” he says. “We can have a number of teams stepping through the urban landscape, deploying behind them. It’s quite achievable.”
Scaling up does have challenges, though. The team needs to find ways of breeding enough mosquitoes and distributing them. But for O’Neill, the biggest hurdle is engaging with communities that are thousands of times bigger than what they’ve been used to. That’s always been vital for Eliminate Dengue, which uses a quarter of its budget to knock on doors, hold public meetings, and respond to queries. In Australia, they were doing that for years before they had even successfully infected their first mosquito. In Colombia, they’ve developed a Wolbachia Warrior program, where schoolchildren aged 8 to 11 can raise their own mosquitoes and do their own releases.
Consequently, the team have gained strong support everywhere they’ve worked. “It’s not that we sold people on it—it’s that we listened,” O’Neill emphasizes. For example, they did experiments specifically to address public concerns that Wolbachia might pass to fish or birds that eat mosquitoes. “Keeping that in line with the scale of deployment will be critical,” he adds. So will reducing costs. Currently, the technique costs between three and six dollars per person; O’Neill wants to get it down to under one.
“They have a tech that’s so close to being able to come to the market,” says Wendy Taylor, Director of the USAID Center for Accelerating Innovation and Impact, one of the team’s funders. “I think it’s a revolutionary approach.”
If Wolbachia behaves as the team thinks it will, they should know pretty quickly. By simulating the spread of the microbe, Neil Ferguson at Imperial College London has calculated that it should lead to a complete collapse of disease transmission in the sites of release six months after the infected mosquitoes first take flight. (They only fly for hundreds of meters, which is why so many of them must be released to cover a city.) So the team will be keeping a close eye on the rates of Zika, dengue, and chikungunya over the next few years. “Really, within three to six months, we should have a very good sense of whether this works or whether it’s questionable,” says Mundel.
After O’Neill’s decades of frustration, things are now moving very fast—especially compared to other fancy mosquito control methods. There’s been a lot of chatter, for example, about using gene-editing tools like CRISPR to drive mosquitoes extinct. But these “gene drives” are still in an early stage of development, and haven’t even been tested in a lab. By contrast, the Eliminate Dengue team have five years of data showing how their Wolbachia mosquitoes behave in real field conditions.
That they are so ready is a triumph of basic science—research for knowledge’s sake that isn't geared towards any practical application. Wolbachia was discovered in 1924 by scientists who were peering into the cells of another species of mosquito. They had no idea what they discovered. Other entomologists later showed that the microbe was found in some 40 percent of insect species; they knew it was incredibly common and biologically fascinating, but, again, they had no applications in mind. Even when O’Neill began his work, he couldn’t have known where it would lead.
“History shows us that investments in basic research are the primary engine with which humanity has advanced,” said Sue Desmond-Hellmann, the CEO of the Bill and Melinda Gates Foundation, when introducing the Wolbachia story at a recent meeting. “You don’t always know how or when or in what way human problems will surface, but with basic science, you know the fundamental way in which things work. And that will speed up your response.”
It wasn’t just research into Wolbachia either. “A lot of other labs did science that was fundamental to understanding the ecology of the mosquitoes, the biology of the viruses, and the how societies and their cultures work,” says Jeremy Farrar, the director of the Wellcome Trust. “Without that, you couldn’t make these advances work.”
“It’s a testament to the power of making those big bets early on,” adds Taylor. “Unless we make those incremental investments, we won’t get these massive shifts.”