Mighty Mutants

Genetically modified mosquitoes could wipe out the world’s most deadly viruses. If we let them.

Elena Scotti/FUSION

The Aedes aegypti mosquito is a beautiful, brilliant killer.

Dark with white spots and a wingspan of only a few millimeters, it is smaller and stealthier than the mosquitoes that might keep you up at night, buzzing in your ear. There are thousands of species of mosquitoes, but only a few hundred are interested in humans. The Aedes aegypti is among the deadliest of them all.

The Aedes lives and breeds in places where people are, laying its eggs in a few droplets of stagnant water at the bottom of a forgotten beer can and then spending its short life hiding under beds and in closets. Its hardy eggs can survive months without water, waiting until conditions are just right to hatch. It bites legs and ankles, feeding quickly before it gets swatted away. It prefers small meals from many people, spreading disease with incredible efficiency as it goes.

Native to Africa, globalization has aided the Aedes‘ travels to nearly every continent, and with it, the proliferation of disease. It is the primary carrier of yellow fever, dengue fever, Zika virus and chikangunya. With the exception of yellow fever, these diseases do not have vaccines or cures. The Aedes assists in the killing of tens of thousands of people each year and infects many, many more. As its footprint has widened, our methods of fighting it have weakened. Insecticides are still our best form of defense, but Aedes aegypti have begun to develop resistance.

At long last, though, mankind may be on the verge of a mosquito-busting panacea. In August, faced with the Zika crisis, the Food and Drug Administration gave the green light to Oxitec, a British biotech company that aspires to release millions of genetically modified mosquitoes into the wilds of the Florida Keys. Oxitec has engineered male mosquitoes to turn the species against itself, giving them a lethal gene that kills off any offspring they might have with a wild female. The idea is to flood the local mosquito population with genetic mutants, until the wild population eventually dies out. In Key West, Oxitec hopes to assess how well the Frankenskeeters fare in the realm of Mother Nature.

Such innovations offer a dream of a world free from many of the ailments that plague it.

But the Keys is not Oxitec’s first test site. It has similar projects underway in Brazil, Panama, India and the Cayman Islands. And others are also testing their own visions for disease-smiting killer mosquitoes. The Bill and Melinda Gates Foundation has invested $75 million in a plan to use a technology called gene drive to quash troublesome mosquito populations. Another company, MosquitoMate, has developed a mosquito that relies on a type of bacteria called Wolbachia to render them sterile. MosquitoMate has already begun trials in California. It recently received regulatory approval to expand them to Key West.

Such innovations offer a dream of a world free from many of the ailments that plague it. It could mean the end of malaria and dengue fever. It could mean crops free from pests and pesticides. It could offer a way to combat ecological damage wrought by insects showing up in places they do not belong.

What crushes that dream may be us. While at one point in history, genetic modification was a beacon for the future’s glittering possibility, today you can scarcely utter the words “genetic” and “modified” without causing a fuss.

Oxitec has faced opposition in all corners of the globe. In the Cayman Islands, the rollout of its mosquitoes was briefly delayed after anti-GMO activists took their fight to court. But nowhere has the resistance been stronger or more hostile than in the Florida Keys where local activism threatens to upend the whole thing.

As the pioneering synthetic biologist Jack Newman put it to me, “What stands between us and addressing one of the biggest public health issues in the world is not science. It’s how we talk about science.”

Absent a vaccine, Oxitec’s technology could be our most effective tool in fighting Zika. Genetically engineered mosquitoes could go a long way towards fighting some of the world’s deadliest viruses. The bigger question is whether we will let them.

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Lightning flashed over a dark sea as a hurricane made its way north towards the Keys’ western coast. The air was heavy and damp. It smelled of salt water. And bug spray.

“People here really love this place and they will protect the things they love,” Barry Wray, an aging Keys entrepreneur, told me over dinner. “We love the ecosystem here.”

I had come to the Keys to better understand the opposition that threatens Oxitec’s proposal. Wray, a short, stubbled man who favors the local uniform of pastel colors and shorts, is the executive director of the Florida Keys Environmental Coalition and one of the residents leading the charge against Oxitec’s mosquitoes. The Keys, he explained, are a fiercely autonomous community that has always been hostile to outsiders trying to make changes.

“You’ve just walked into a very independent subset of America called the Conch Republic,” Wray told me.

Key West once even talked of seceding from the U.S.

Florida Keys resident Barry Wray is leading the charge against genetically engineered mosquitoes.Kristen V. Brown/FUSION

Florida Keys resident Barry Wray is leading the charge against genetically engineered mosquitoes.

Key West was chosen as the trial site for Oxitec because of the isle’s geographic isolation and historical propensity for attracting disease-carrying bugs. But that isolation has become a hurdle, politically. Key West is separated by a few hundred miles and a whole lot of water from the Florida mainland’s Zika problems. It has yet to have its own locally transmitted case.

Mainland Florida, though, is in the midst of a full-on Zika panic. It is the only state in the US to have local transmission of the disease, with now more than 70 cases on the mainland. Tests for the disease are backlogged, as hundreds of pregnant women have rushed to take them. We don’t know the full impact that mosquito-borne Zika can have on people, but we do know that when the virus is present in a pregnant woman, it can lead to miscarriage, severe birth defects and other threats to a baby’s health.

The situation in Florida is grim and as Zika spreads it seems clear fighting it with chemicals alone is not enough. This month, a bipartisan coalition of Florida politicians petitioned the federal government to grant an emergency use of Oxitec’s technology areas affected by Zika. Delaying its use, they wrote, poses “an unnecessary health risk” to the people of Florida.

But without an emergency intervention, whether Florida uses genetically engineered mosquitoes to beat back Zika is up to the people of the Florida Keys.

The Keys trial has FDA approval. Now it requires the go-ahead from the local mosquito control district, which is waiting to decide until after the public casts a vote on the proposal in November. The result of the public vote isn’t binding, but three of the five commissioners on the mosquito control board have promised to decide in line with voters’ wishes. Come November, a community of 80,000 people living just off Florida’s southern tip will have a hand in deciding the fate of a technology that could prevent major public health crises.

“People here really love this place and they will protect the things they love.”

Wray’s opposition movement is small, but effective. A letter signed by local physicians raising questions about the mosquitoes’ potential for creating antibiotic resistant “superbugs” went viral locally, racking up more than 200 Facebook likes. A Change.org petition started four years ago has garnered nearly 170,000 signatures. Members of Wray’s group have traveled to Washington D.C. to petition Congress. And they have tapped into wider online communities of anti-GMO activists and conspiracy theorists for support, circulating rumors of Zika cover-up scandals, underhanded corporate controversy, and general government mistrust. One particularly sticky rumor, which seems to have begun on Reddit, suggested that Oxitec’s mosquitoes were actually Zika’s source. Another said the bite of its mosquitoes could make children sterile. Their outrage has made the pages of The Guardian and The New York Times.

Back in 2013, 59% of residents in Key Haven, the neighborhood where the trial is planned, supported Oxitec’s project, with only 9% opposed. Now, 58% are in opposition.

img_9412Kristen V. Brown/FUSION

Campaign signs for the Florida Keys Mosquito control board abound on every intersection of Key West.

Oxitec has actually been pressing for this trial since long before Zika arrived on Florida’s shores. The company first came to Key West when it was fending off an epidemic of dengue. In 2009 and 2010, Key West had more than 100 confirmed cases, spread locally by infected mosquitoes.

This was despite the fact that the Keys have one of the most advanced mosquito control efforts in the nation, if not the world. Its annual operating budget for mosquito control is more than $15 million, with four helicopters, two airplanes and more than 30 inspectors, their efforts spent mainly on spraying insecticide and hunting for standing water where mosquitoes might breed. By contrast, prior to Zika, the budget for fighting mosquitoes in Miami-Dade County, which is 20 times larger and has 30 times as many people, was just $1.5 million.

In 2010, desperate for an alternative to seemingly ineffective chemicals, the mosquito control district reached out to Oxitec’s founder and CEO. In 2012, they attended a town meeting to explain the science of eradicating disease-carrying mosquitoes from the Keys with genetic engineering. But by then, the town had managed to quell its dengue outbreak, so interest had waned.

However, within hours of the meeting agenda going public, the opposition mobilized, plastering flyers all around the city. Since then, it has only grown.

“We solved our last dengue outbreak with boots on the ground,” said Kathryn Watkins, a social media consultant running for the mosquito control board on an anti-GMO platform. “Why do we need a different solution now?”

Friends have taken to calling her “Spill-the-Water Watkins” because she pesters them to make sure their homes have no empty flower pots or coffee mugs with standing water where clever Aedes might breed. Education about such tactics, Watkins believes, is the best solution. When I visited her, she had just come back from patrolling her neighbor’s house. But Key West is the tropics. On average, it rains 100 days a year. The giant empty lot across from Watkins’ house is filled with stagnant puddles .

“If Zika comes here, we’ll all be asking for this. We don’t have a problem, so the risk is not worth it.”

Those opposed to genetically modified mosquitoes have many concerns. While the Aedes aegypti is not native to the Keys, and makes up a small percentage of the area’s 46 mosquito species, opponents still wonder how removing it might impact the environment. And they worry about the effect of adding a mosquito that contains DNA cobbled together from E.coli, coral, a vinegar fly and a cabbage looper moth. While Oxitec aims to only release male mosquitoes, an estimated one in 500 will be female, and female mosquitoes are the ones that bite. What happens if someone gets bit by a genetic mutant? The mayor of Key West told me that even if those fears are remote possibilities, they could still be bad for Key West by discouraging tourists from visiting.

img_9427Kristen V. Brown

Kathryn Watkins is running for the Keys' mosquito control board on an anti-GMO platform.

Drive through Key Haven and every third lawn bears a placard reading “No Consent to Release of Genetically Modified Mosquitoes” in aggressive red-and-white. I went door to door asking for citizens’ thoughts on the project. Some were in favor and a few hadn’t heard of it, but most were not fans of the idea at all. “We’ve never had a mosquito problem here. Why would I want genetically altered mosquitoes?,” explained 80-year-old Mary Murray, who moved to the Keys 20 years ago.

When I visited the mosquito control board, an hour’s drive north of Key West in Marathon, a dozen or so protesters campaigned outside with signs such as “We are not your experiment.” One of the protesters followed me inside. She sat down next to me as the mosquito board chairman talked on camera with the local news. For every fact he offered the camera, she hissed in my ear that it was “hearsay” or “lies.”

Inside, Oxitec scientist Derric Nimmo, who runs the Keys project, told me that he spends his time more often on public relations now than science. Oxitec rents two small labs from the mosquito control district, with which it would partner in releasing the mosquitoes if the trial is approved in November. Oxitec would ship engineered eggs from the U.K. and rear them in Florida. For now the stainless steel shelves that one day may hold thousands of mosquitoes lay empty and bare.

Derric Nimmo, the head of Oxitec's Florida Keys project.Kristen V. Brown

Derric Nimmo, the head of Oxitec's Florida Keys project.

“As a scientist you deal with data and facts and you have to say a lot to prove something quite small. But with the public you have to be able to boil that down. When you do that you lose certain information,” Nimmo told me. “You can say we release males and people say, ‘You’re lying,’ because a very small number of our mosquitoes wind up being female. We’ve learned by trial and error.”

Oxitec maintains that it has always been forthright with the community about its intentions, but some even within the scientific community say it could be more transparent. There was the perception, in both the Keys and Grand Cayman, for example, that public meetings were not advertised quite vigorously enough.

Protestors outside of the Florida Keys Mosquito Control District.Kristen V. Brown/FUSION

Protestors outside of the Florida Keys Mosquito Control District.

Wray and his comrades parse with unforgiving exactness every “fact” Oxitec puts forward. Why, for instance, does Oxitec claim to reduce the local mosquito population, when their technique includes releasing many more?

“We called the insects sterile in the beginning and people said, ‘You’re lying,’ because they do produce eggs,'” Nimmo told me. “So we’ve gone more towards ‘self-limiting’ now in terms of description.”

It certainly didn’t help stem corporate conspiracy claims that Oxitec—a small upstart born of an Oxford zoology department—was acquired by a major international conglomerate in 2015. Or that when Oxitec first came to the Keys, the technology was so novel the federal government had no idea how to regulate it.

Nimmo fights fears and fiction by going door-to-door in Key West to explain Oxitec’s science. Recently, the company placed an ad for canvassers to help with the spread. But some dissenters, like Wray, Nimmo said, will never be swayed by science or fact.

“If people don’t want to listen,” he told me, “There’s nothing I can do.”

Oxitec’s supporters fear the danger of waiting. If Zika comes to the Keys, it will threaten both locals and the tourism industry on which the economy relies. With all the chemicals in the world, the Florida Keys have only been able to suppress about half the Aedes population.

“This is a tool we have to fight disease that we could be using today if we weren’t trying to get the public on board,” Phil Goodman, the chairman of the mosquito control board, told me. “We are in the business of public health, not public opinion.”

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Though this feels like the future, the truth is that there’s little about Oxitec’s technology that is truly “new.” As one scientist put it to me, “this technology is rooted in what we’ve been doing since the 50s. It’s just a slightly more clever way to do it.”

Oxitec’s technology is riff on what’s known as the sterile insect technique, an approach to insect management first proposed in the 1930s by a U.S. Department of Agriculture scientist named Edward Knipling. Knipling suggested using radiation to “sterilize” male screwworms, pests that were terrorizing the American cattle industry by laying flesh-eating larvae in the open wounds of cows. By blasting the flies with gamma rays in the lab, scientists could mutate the flies, rendering them unlikely to produce viable offspring. The wild females that mated with them would then go on to produce eggs with little chance of survival. Eventually, the population would die out, no nasty chemicals necessary.

By the end of the 1950s, after field trials on Florida islands and in the Caribbean, the screwworm was all but eradicated from the American Southeast. By 1982, it was gone from the US.

In “Silent Spring,” the 1962 best-seller that sounded the alarm on DDT and spawned modern environmentalism, citizen-scientist Rachel Carson suggested the sterile insect technique as the antidote to pesticides. Solving crises by creating altered insects was the environmentally friendly approach—hard as that might be to believe today when anti-GMO rhetoric has become part of most environmentalist platforms.

A house in Key Haven with an anti-GMO mosquito sign.Kristen V. Brown/FUSION

A house in Key Haven with an anti-GMO mosquito sign.

The problem with the radiation technique was that it didn’t work on every insect, including the mosquito. Radiation made it too weak to compete with its non-irradiated brethren for a female mate.

In 1994, Oxitec founder Luke Alphey was working on editing the genome of a fruit fly when a friend told him about the sterile insect technique. The work he was doing, he realized, might be used to improve it, but the mosquito genome hadn’t yet been edited.

“To do this kind of thing in [fruit flies] was not that big a deal,” said Alphey, who left Oxitec in 2014 to return to academia. “But the ability to put any kind of foreign DNA into any pest was a big deal.”

When a scientist later successfully edited the mosquito genome, Alphey decided to give his idea a shot. He inserted two new genes into mosquito eggs—one that made the mosquito over-produced a protein that interferes with gene regulation, stymying development, and another that gave the mosquitoes a red glow under the microscope, so that scientists could track the spread of their lab-created population. Because mosquito female pupae are significantly larger than males, scientists could use size to sort the mosquitoes with near-perfect accuracy and release only males.

Oxitec’s original target market was agriculture, but it turned to mosquito-borne disease after it realized agriculture was already too crowded with other takes on the sterile insect approach. The company hopes to court consumers one day, in addition to governments. Oxitec CEO Haydn Parry told me that the company imagines selling its genetically modified mosquitoes at the garden store, competing with citronella candles as a way to prevent bites in your yard.

“I can send you eggs and you can protect your own biosphere,” he told me.

Part of the reason the scientific community has embraced Oxitec’s proposal so vigorously is that it hinges on a method scientists have long thought of as an ideal way to kill pests. One scientist told me Oxitec’s approach actually feels safer than older sterile insect techniques, since genetic engineering allows scientists to render a mosquito sterile with just one known mutation, rather that rely on radiation to create many unknown ones randomly. Oxitec has already released millions of genetically engineered pink bollworms, a cotton pest, in the US.

“I can send you eggs and you can protect your own biosphere.”

The biggest concern the scientific community has about Oxitec’s technology is whether it will work on a scale large enough to solve the world’s urgent Aedes Aegypti problem.

“At this point, I know that this is safe,” Matthew DeGennaro, a mosquito geneticist at Florida International University, told me. “What we don’t know is how effective it will be at scale, or how effectively reducing the mosquito population will also reduce disease.”

Signs protesting Oxitec's proposal in front of the Florida Keys Mosquito Control District headquarters.Kristen V. Brown/FUSION

Signs protesting Oxitec's proposal in front of the Florida Keys Mosquito Control District headquarters.

So far, test results have been encouraging. Oxitec’s biggest effort is in Brazil, where in 2015 it began releasing mosquitoes in two small neighborhoods with a combined 5,000 residents in the city of Piracicaba. By the end of the year preliminary results showed wild mosquito larvae were reduced by 82%. Three prior trials had shown even higher suppression rates. According to the city, dengue cases dropped from 112 cases per year to 13 in the neighborhoods where the mosquitoes were released.

The city’s mayor was so pleased that he lobbied for state financing to expand the program. Oxitec is now building a new mosquito production facility in Piracicaba, which will have the capacity to produce 60 million mosquitoes a week to help protect over 300,000 people and is slated to open by the end of this year.

“I don’t see it as a silver bullet.”

In July, Oxitec began a similar program in the Cayman Islands, where it’s in the midst of releasing millions of mosquitoes in a 300-acre area over nine months.

“We have already begun to see evidence of males mating with wild females,” Bill Petrie, the head of Grand Cayman’s mosquito program, told me. “It’s too early to see reduction in the population, but it is encouraging.”

Petrie said that it will likely take five years to do the whole island. He’s optimistic that the technology will help get Grand Cayman’s mosquito population under control. But he cautioned against viewing it as an emergency solution to an epidemic or a cure-all. “I don’t see it as a silver bullet,” he told me.

Oxitec’s technology has a good shot at working well in a relatively confined area, such as a small island or a specific neighborhood, said Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases at the NIH. He’s more skeptical, though, that it will work as well in larger areas such as mainland Florida or all of Brazil.

“Mosquitoes do not fly more than 500 feet and so you would have to release multiple iterations of modified mosquitoes over a vast geographic area to get ‘scale,'” Fauci said.

The need to release mosquitoes frequently over long periods of time could wind up making it financially taxing. Malaysia, where Oxitec conducted trials, decided to not go ahead with the project after trials, citing cost. Negotiations are under way in Panama to release more mosquitoes, but cost is a factor there as well. In Brazil, the pilot project cost about $50,000, which the city of Piracicaba split with Oxitec. Piracicaba anticipates paying about $2.7 million a year when it scales up the number of mosquitoes released.

In the Keys, Oxitec has said it will pay for the trial. But it is still unclear how much it will cost once the trial is over if indeed the FDA grants Oxitec’s mosquitoes a commercial license.

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For some, the phrase “genetically engineered” alone inspires an immediate resistance to Oxitec’s mosquitoes.

A recent Pew survey found 60% of Americans fear genetic engineering. According to another Pew survey last year, 88% of scientists believe it’s safe to eat genetically modified foods, but only 37% of the public does. That gulf is even wider than the one between the public and scientists on the subject of climate change.

“The public perception of danger is unwarranted and largely based on poor understanding and perceptions of risk,” Paul Eggleston, a molecular entomologist at Keele University, told me.

Mosquito Mate’s sterile mosquitoes, which rely on the addition of bacteria instead of altered DNA, were released earlier this year in California with hardly any public comment and skated through the regulatory process.

In testimony before Congress in May, Oxitec CEO Parry pleaded for legislators to consider the implications of the technology itself, rather than getting hung up on the fact that it’s “genetically modified.”

“We want to make this technology available in the coming months rather than the coming years,” he said. “We need to be able to distinguish products by what their risk profile is, rather than assign a label.”

Encouragingly, though, the Pew survey found that people were more willing to embrace a technology if they had more knowledge of it. As the threat of Zika virus raises awareness of both the disease and the technologies that could stop it, society might warm up to the potential benefits of genetic engineering. A recent national survey by Purdue University found both high levels of awareness of Zika virus and “overwhelming” support (78%) of using genetically altered mosquitoes to stop it. The fear isn’t of science; it’s of the unknown.

Bill Irwin, a one-time protestor of Oxitec that has become a supporter.Kristen V. Brown/Fusion

Bill Irwin, a one-time protestor of Oxitec that has become a supporter.

Before I left Key West, I met Bill Irwin, a Florida Keys Community College biology professor who helped found the local environmental group that birthed the mosquito resistance movement. Irwin has since defected to become one of Oxitec’s most vocal supporters. I wanted to know what changed his mind.

He told me that when Oxitec’s proposal first came up, he was dubious. Genetically altered mosquitoes inherently just sound like an awful idea.

“When I teach environmental biology, generally I am teaching the evils of genetically modified things,” he told me. “There are some good GMOs, like insulin of course, but generally I am not a fan.”

Then, Irwin said, he spent hours digging into the science. For every query the opposition brought up, he would immerse himself in the literature to understand exactly how Oxitec’s mosquitoes work and what kind of impact they might have on the environment.

“And as I analyzed it,” he told me, “I said, ‘Wow, this is exactly what we need.'”

Like Rachel Carson before him, Irwin felt that using altered insects was more environmentally friendly than pesticides. He feared what increased spraying to guard against Zika would do to the treasured habitat he wanted to protect. His fear was prescient: The next week, after heavy insecticide spraying in South Carolina, millions of bees wound up dead.

Not every Key West resident has a Ph.D. in biology. It’s the complicated job of scientists to explain science in an era where more and more of it interfaces with the public’s world. In this time of great fear, maybe we will finally listen.

Fusion reporter Manuel Rueda contributed reporting from Brazil.