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Can GMO mosquitoes really help us stop Zika? A closer look.

We could use some more ideas here.
We could use some more ideas here.
(Shutterstock)

It sounds utterly bizarre at first. But the idea of using genetically modified mosquitoes as weapons to kill off wild mosquitoes is rapidly gaining traction.

On Tuesday, the World Health Organization said that GM mosquitoes could prove necessary to eradicate the Aedes aegypti mosquito that is spreading the Zika virus all around the Western Hemisphere. The WHO had earlier declared a public health emergency over the possibility that Zika was causing microcephaly, a birth defect associated with infants being born with shrunken heads.

"Given the magnitude of the Zika crisis," the agency said, "WHO encourages affected countries and their partners to boost the use of both old and new approaches to mosquito control as the most immediate line of defence."

The logic here is simple: It'll be tough to stop the outbreak Zika without limiting the spread of Aedes aegypti, which can breed in all sorts of small nooks and crannies in our cities. But our best methods of mosquito control are faltering. So maybe we should consider futuristic techniques like Oxitec's GM mosquitoes, which interbreed with wild mosquitoes to produce unviable offspring — causing populations to crash.

I asked a number of mosquito control experts whether this would actually work. They thought Oxitec's technology was safe and looked very promising. But there were still serious questions about its effectiveness in halting disease — or whether it could scale up at a reasonable cost. Most thought it would eventually be just one tool among many in halting mosquito-borne viruses.

Why consider GM mosquitoes? Because other control methods are faltering.

Aedes aegypti is the chief villain in the Zika outbreak. This mosquito has a particular taste for human blood, and it's capable of carrying viruses like dengue, yellow fever, chikungunya, and Zika — diseases that immiserate millions. If one of these winged syringes bites an infected human and then bites a non-infected human, the disease spreads.

The crucial thing to know about A. aegypti is that it's really, really hard to kill off. The species is native to Africa, hitched a ride over during the slave trade, and rapidly infested Latin America. During the 1950s, many countries launched massive control programs, using DDT to eradicate the pest. But these campaigns were costly, tough to sustain, and eventually subsided. The mosquitoes that were left began breeding — and quickly overran the Americas again, spreading dengue, yellow fever, and other assorted miseries:

Aedes aegypti was eradicated in parts of the Americas in the mid-20th century but has since made a major comeback. (<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317603/">Gubler, 2011</a>)

Aedes aegypti was eradicated in parts of the Americas in the mid-20th century but has since made a major comeback. (Gubler, 2011)

Today, things are worse than ever. The Aedes mosquito has become especially well-suited to modern cities because, unlike other species, it doesn't need large bodies of open water to breed. It can lay eggs in virtually any nook or cranny it finds: buckets, tires, cups, plastic bags — anything that will later fill up with rain, allowing the larvae to hatch.

"The diversity of breeding sites means it's tough to find them all, which makes them harder to kill with larvicide," explains Catherine Hill, an entomology professor at Purdue. It doesn't help that heavy rainfall driven by El Niño seems to be boosting Aedes populations throughout South America this year.

Right now our best strategies involve trying to avoid contact by telling people to use repellent, wear long sleeves, and use window screens. (The Aedes is hard to avoid because, unlike many mosquito species, it bites during the day rather than evening.) Local officials sometimes attempt costly campaigns to remove potential breeding sites and spray larvicide. But these campaigns only wipe out a fraction of the insects, and it doesn't help that Aedes mosquitoes are becoming resistant to pyrethroids and other favored pesticides. We're losing the battle.

How GM mosquitoes could help us fight wild mosquitoes

This explains why everyone's so jazzed about using genetic engineering to kill off mosquitoes. The most realistic idea to date is being tested by a British firm called Oxitec, which ramped up testing after a dengue fever outbreak in 2014 infected 1.5 million people in Brazil.

What Oxitec's scientists have done is modify A. aegypti mosquitoes so that they contain a self-destructive gene — these mosquitoes will eventually die unless they receive antibiotics in a lab. The company then releases genetically modified males into the wild. The GM males mate with wild females and pass on the self-destructive gene to (some of) their offspring. The offspring, in turn, die before reaching adulthood. Boom, population crash.

Field tests have been encouraging so far. In 2015, Brazil's government gave Oxitec the go-ahead to release hundreds of thousands of GM mosquitoes in the southeastern city of Piracicaba. Early results suggest this technique killed off 80 percent of mosquitoes in places it was tried — way more than conventional treatments. And, encouragingly, the number of dengue cases went down:

(Oxitec)

Hence the excitement. Oxitec's "weaponized" mosquitoes kill way more insects than pesticides do, without the environmental downsides.

By the way, this isn't the only idea for unleashing sterile mosquitoes that can't breed. Some groups are using radiation to create infertile males that breed with females, which then lay eggs that don't hatch. Alternatively, male mosquitoes infected with Wolbachia bacteria can be released to breed with females, which, again, lay eggs that don't hatch. Oxitec's solution is unique in using genetic modification, but the concept is similar.

There's some controversy around testing Oxitec's mosquitoes in places like Florida, since people tend to get icked out by anything GMO-related. But experts agree that these methods seem to be quite safe. Scientists have been using sterilization to control insect pests for decades. And the Oxitec mosquitoes are unlikely to get very far because they are, essentially, programmed to die off. The real question is whether this will work on a large scale.

It's not yet clear, though, whether GM mosquitoes are the solution to Zika

You're not going to get rid of me that easily.
(Shutterstock)

I was surprised to find that several mosquito experts I contacted urged caution about getting too excited here. Thomas Scott is a professor of entomology at the University of California Davis who has collaborated with Oxitec in testing (other) modified Aedes mosquitoes. He said the technology is very promising, but also pointed out a few key practical hurdles.

For one, we still need rigorous tests to see how well Oxitec's mosquito rampage can actually reduce diseases like dengue or Zika — which is, after all, our ultimate goal here. It's possible that Oxitec could kill 80 percent of A. aegypti mosquitoes but the remaining 20 percent would still be enough to sustain an outbreak. Or it's possible that another mosquito species, like the closely related Aedes albopictus, could move in and start transmitting the disease instead. We need to find out.

"If you had an 80 percent reduction in mosquitoes, you'd expect to see an effect on transmission," Scott says. "But you have to demonstrate that." Doing so requires large-scale randomized control trials that are complex and slow. But those epidemiological tests are critical. Deploying GM mosquitoes will cost money, and poor countries with finite health budgets need to be sure they'll see results.

The WHO agrees on this point, and is recommending "further field trials and risk assessment to evaluate the impact of this new tool on disease transmission." (The same goes for other sterilization techniques, like the Wolbachia method.)

A related question is whether Oxitec can scale up its GM mosquito strategy at a reasonable cost. Because the modified males quickly die in the wild, the company will need to keep manufacturing and releasing thousands and thousands of modified mosquitoes over and over to suppress populations. (The minute you stop, Scott notes, the mosquitoes come back with a vengeance.) Is that cost-effective? Is it feasible in major cities with millions of people? No one has any idea yet.

Bottom line: Oxitec's GM technology is very cool. But the need for more testing means it may not be much immediate help in the Zika crisis. And even in the future, it may just end up being one (valuable) tool among many in fighting mosquito-borne disease. No expert I talked to thought it would be the answer.

"Vector control needs to be an integrated effort — repellent, source reduction, vector control," Heidi Brown, an expert on mosquito-borne diseases at the University of Arizona, told me by an email. "I worry if we all think it’s solved because Oxitec has developed GM Aedes aegypti."

In the meantime, here are our best ideas for fighting Zika

(Javier Zarracina/Vox)

That brings us back to the current Zika crisis. On this, the experts I spoke to were mostly in agreement on what should be done.

First, public education. People need to be aware of A. aegypti and its awful ways and know how to combat it. Wear protective clothing, use insect repellents, and put up screens on windows and doors. Get rid of anything that might create a pool of standing water outside, whether a bucket or Styrofoam cup or whatever else.

The next step would be for governments to launch mosquito control campaigns in earnest. That means treating certain bodies of water with larvicide, and organizing cleanup crews to get rid of trash, old tires, and other places where water can pool. (See more details here.)

"You have to go back to past successes," says Peter Hotez, dean of the National School of Tropical Medicine at the Baylor College of Medicine. "In the 1950s we eradicated Aedes through brute force — insecticides, drainage control. The problem is that these campaigns are labor-intensive, they're not cheap, and they're difficult to sustain." Once an outbreak fades, governments lose the political will, and the mosquitoes return.

Thomas Scott of UC Davis cautions, however, that it may be difficult to replicate past eradication campaigns precisely. The man who led that early mosquito war, Fred Soper, worked closely with authoritarian governments in South America to force inspectors into every home and inspect for breeding sites. That heavy-handedness is harder to pull off in democratic countries. "Plus, Soper didn't have to deal with massive cities of 8 to 10 million people, or all the plastic trash we have now," Scott notes. "So we're dealing with things he didn't have to deal with."

Oh, hell no. These tires have to go.
(SCHNEYDER MENDOZA/AFP/Getty Images)

Another difference: In the 1950s and 1960s, countries used ample amounts of DDT, a low-cost insecticide that stays on surfaces for months, making it especially effective at killing mosquitoes. Unfortunately, DDT also had adverse effects on wildlife — which is why it was eventually banned in many countries. Hotez says that countries may want to consider bringing it back for more selective indoor use, where the drawbacks are smaller. (That said, DDT resistance is a real problem too, and Hill notes that R&D for newer, better pesticides is lagging.)

Ultimately, beating back Zika is going to be incredibly difficult. "People are reluctant to accept that there is no magic bullet," concludes Uriel Kitron of Emory University. "It's a tedious process, it involves a lot of commitment; it involves community participation."

That's not as fun to write about as GM mosquitoes. But for now, it's the best we've got.

Read more: 9 questions about the Zika virus you were too embarrassed to ask

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