Original post by Brad Plumer on 

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Zika Virus GP General Paper Tuition Singapore We’re coming for you, buddy. (This is Aedes aegypti, the mosquito spreading Zika.) MARVIN RECINOS/AFP/Getty Images

Ever since health officials hit the panic button on Zika — the mosquito-borne virus that may be causing terrible birth defects in Latin America — we’ve seen story after breathless story about how we’ll soon be able to use genetic engineering to crush the mosquito menace and halt this disease.

There’s so much excitement around this possibility, in fact, that some outlets have already moved on to debating whether we should use our newfound powers to squelch every last buzzing mosquito on the planet. See this piece by Daniel Engber in Slate (he says kill ’em all) or this rejoinder by Melissa Cronin at Vice (she says maybe not).

It’s a fun debate. Put me down for eradication. But after talking with a half-dozen mosquito experts about this, I’ve also become convinced this discussion is awfully premature. The hype around genetically modified mosquitoes, in particular, has gotten a bit out of hand.

The sad truth is that we’re not yet close to declaring victory against mosquitoes or the deadly diseases they carry. It’s true, genetic engineering has fantastic potential to save lives — someday. But the obstacles are daunting and could take years to surmount. With Zika, we can’t wait that long. The virus has already infected more than 1 million people and is poised to conquer much of the Western Hemisphere this year. If we want to stop this outbreak, we’ll have to rely on some old-fashioned tricks.

Why the Zika mosquitoes are so damn hard to kill

Public Enemy No. 1 in the Zika outbreak is a pesky little critter called Aedes aegypti. This mosquito has a particular affinity for human blood. It’s also capable of carrying viruses like dengue, yellow fever, chikungunya, and Zika. So if one of these winged syringes jabs a human infected with one of these viruses and then goes to jab a non-infected human, the disease spreads.

The main thing to know about A. aegypti is that it’s really, really hard to kill off. The mosquito was originally 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 and tough to sustain, and eventually subsided. The remaining mosquitoes began breeding — and quickly overran the Americas again:

(Centers for Disease Control and Prevention) Distribution of Aedes aegypti in the Americas.

Today, things are worse than ever. The Aedes mosquito has become particularly 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 all sorts of moist nooks and crannies: buckets, old tires, plastic bags, anything. “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.

Right now, our best strategy involves 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 occasionally try costly campaigns to eliminate standing water and spray insecticides. But these attacks are imperfect, and it doesn’t help that mosquitoes are becoming resistant to many of our best chemicals. We’re losing the battle.

Despite all the hype, we still don’t know if GM mosquitoes are a solution

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, Oxitec. The catch, however, is that we still don’t know if this is an effective solution.

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 releases genetically modified males (which don’t bite) into the wild. The GM males mate with wild females and pass on the self-destructive gene to many of their offspring. The offspring, in turn, die before reaching adulthood. Boom, population crash.

Field tests have been very 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. Results suggest this technique killed off 80 percent of mosquitoes in places it was tried — way more effective than conventional treatments:


These results have attracted lots of attention. Oxitec’s “weaponized” mosquitoes kill way more insects than pesticides do. They’re safe. They don’t have environmental downsides. And they’re just plain cool.

So 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 thinks the technology is extremely promising, but also pointed out a few important practical hurdles.

For starters, we still don’t know if Oxitec’s mosquito rampage will actually lead to a reduction in diseases like dengue or Zika — which is, after all, our ultimate goal here. It’s possible that Oxitec could kill 80 percent of Aedes mosquitoes in an area but that the remaining 20 percent would be just as capable of sustaining an outbreak.

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

A related question is whether Oxitec can scale up its GM mosquito strategy at reasonable cost. Because the modified males soon 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 second you stop, Scott notes, the mosquitoes come back with a vengeance.) Is that cost-effective? Will it work in major cities with millions of people? We still don’t know.

Bottom line: Oxitec’s GM technology is very cool. But the need for further testing means it probably won’t be much help against the current Zika crisis. And even in the future, it may just end up being one (valuable) tool among many in fighting mosquitoes. No one I talked to thought it would be the answer.

Advanced genetic editing might one day wipe out mosquitoes for good — but we’re not there yet

Oxitec’s scientists aren’t the only ones working on this problem, meanwhile. The really thrilling technology that could someday revolutionize mosquito control involves something called “gene drives.”

The basic idea goes like this. Using advanced genetic, editing scientists have been able to modify fruit flies so that they contain a desired gene — but also are more likely to pass that gene on to their offspring. In other words, rather than a 50-50 chance that a fly will pass on its modified genes to the next generation, scientists can increase the odds to nearly 100 percent.

(Oye et al 2014) How gene drives can spread altered genes (in blue) through populations.

The possibilities here are astounding. Imagine if you modified some mosquitoes to be resistant to malaria and released them into the wild. With gene drive, in theory, all of their offspring would soon be incapable of spreading malaria. And all of their offspring’s offspring.

More radically still, you could program mosquitoes to, say, only produce male offspring. If this gene modification eventually propagated throughout the entire population, mosquitoes would go extinct. Gone. Forever.

I called Zach Adelman, a molecular geneticist at Virginia Polytechnic Institute and State University in Blacksburg, to walk me through the possibilities. He started with a cautionary note: “You need to be careful about the timeline here.”

In other words, gene drives could one day prove enormously powerful — but we’re not there quite yet. And we’re certainly not going to figure this out in time to stop the current Zika crisis.

So far, gene drive systems have only been described for fruit flies. It will take a lot more research to develop a system for Aedes mosquitoes, our hated bloodsucker. Scientists would then need to demonstrate in a lab that they could, say, program mosquitoes to only produce male offspring and get that gene to propagate for many generations, through an entire population. (Adelman is doing research in this area.) They would also likely need to develop “failsafe” mechanisms to stop the process if something goes wrong — there are some ideas being kicked around, but nothing concrete yet.

Once the lab tests are done, there’s another bar to clear. You need field tests to see how many mosquitoes it would take to push the modified genes out to the entire population. Do you just need to release five mosquitoes? A hundred? Thousands? In one place? Many? After all, if you just wipe out mosquitoes in one area, others will rush in to fill the gap. Then, of course, regulatory agencies like the Environmental Protection Agency will want to scrutinize the technology to make sure they don’t cause unforeseen problems.

The most optimistic estimates predict that this is all at least three to five years away. So this isn’t the answer to our current Zika woes.

(Shutterstock) Total extinction? Man, I need a drink.

Now, granted, Zika won’t be the last outbreak. Even if this crisis subsides, we’ll still have dengue and yellow fever and malaria, and god knows what else is coming. Mosquito-borne diseases kill nearly a million people each year and cause untold suffering. So it’d be nice to have a sweeping solution someday.

That’s where we get into the interesting ethical debates. Would it be worth it to wipe out mosquitoes once and for all? Possibly! The benefits would be considerable. Though, of course, we’d want to consider unintended consequences, such as what might happen to all the birds and fish that feed on mosquitoes each year. (Ecologists seem to be divided on whether it would all turn out fine or not.)

(Also, for those squeamish about TOTAL EXTERMINATION, there’s always the less radical possibility that we could use gene drive systems to make mosquitoes resistant to malaria or dengue or Zika. But Adelman points out that this is actually harder from a research perspective — we don’t know enough about mosquito immune systems yet. And, of course, there’s the risk that pathogens might evolve in response.)

So where does that leave us? Gene drive systems could one day prove incredibly powerful for fighting diseases. But we’re not there yet. It’s going to be some time before we need to have a serious ethical debate about wiping out mosquitoes for good.

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

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. And it’s not very futuristic.

First, public education. People need to be aware of A. aegypti and its horrible 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 and 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 stronger than ever.

Thomas Scott of UC Davis cautions, however, that it may be tricky to replicate past eradication campaigns. The man who led those earlier mosquito wars, Fred Soper, worked closely with authoritarian governments in Latin America to force inspectors into every home and inspect for breeding sites. That heavy-handedness is harder to pull off in today’s democracies. “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.”

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

Another key difference: In the 1950s and ’60s, countries were spraying lots of DDT, a cheap insecticide that lingered on surfaces for months, making it particularly effective at killing insects. But in the years since, many Aedes mosquitoes have developed resistance to DDT, making the pesticide a less suitable option today. (DDT can also kill birds and other wildlife, which is why the US banned it in 1972.)

Ultimately, beating back Zika is going to be incredibly arduous. “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.”

Sadly, that stuff isn’t nearly as fun to write about as GM mosquitoes or futuristic gene drives. But for now, it’s the best we’ve got.

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