How a tiny Florida community could influence the way we fight Zika around the world.Graphics by Ella KoezePhotography by Erika LarsenIllustrations by Tom McCartenDevelopment by Justin McCraw

The first thing Billy Ryan does after he arrives at work most mornings is drive to a yacht club or construction company lot, crawl into a mangrove, and stand for 60 seconds to count the mosquitoes that land on him. If there are five or more, he’ll request that a crew come spray the area the next day.1

From there, the 56-year-old inspector with the Florida Keys Mosquito Control District will visit commercial and residential properties, hunting for standing water and the mosquito larvae and pupae that are frequently found within it. On a Thursday morning in late August, he made his way to a commercial lot nestled between a boatyard and an auto-body shop. Sliding past the property’s chain-link fence, armed with a turkey baster and a plastic cup on a stick,2 Ryan spent the next three and a half hours climbing into boats and turning over plastic buckets, pipes and other bits of debris. “You think a spray truck is gonna get in here?” he muttered. “No way, you have to do this by hand.”

There are 48 breeds of mosquitoes in the Florida Keys, the string of islands that sweep off the southern tip of Florida and toward the Gulf of Mexico like a flyaway hair. Several of the mosquito types are an extreme nuisance, swarming and biting with fervor. The one Ryan was looking for, however, stands out for its stealth, affection for residential areas and ability to carry viruses that infect humans: the Aedes aegypti. It was the cause of a 2009–11 outbreak of dengue fever, a virus that can cause flu-like symptoms and debilitating pain, in Key West. And it’s the same mosquito that’s wreaking havoc in southern Florida, where the Zika virus is hitching rides between humans in tourist-filled Miami Beach and other nearby neighborhoods. Ryan found 10 breeding sites on this single property.

The species is also at the center of an intense debate about genetically modified mosquitoes. In November, a small group of Florida voters will wade into the center of that debate and make a decision that could have lasting effects in the U.S. and around the world.

Aedes aegypti is very difficult to control. Although insecticides can drastically reduce the numbers of salt marsh mosquitoes, which are merely a nuisance to humans, the same techniques have been less successful in addressing populations of the far more dangerous Aedes aegypti. These mosquitoes live in residential areas (they love closets, for example) and can lay eggs in dry places, where they will sit dormant until rain comes. They can breed in a space the size of a bottle cap. “With salt marsh mosquitoes, you can kill 95 percent on a good night,” said Michael Doyle, who was director of the district from 2011 until he resigned on Sept. 1.3 “With Aedes aegypti, you’re lucky if it’s 50 percent.” To date, the only programs that have been successful in combating Aedes aegypti have been essentially militaristic: door-to-door campaigns that punished people for not getting rid of standing water.

Arduous labor, like Ryan’s daily routine, is currently the best technique we have for keeping the mosquito in check. But these methods are expensive and require enormous human resources: 35 full-time inspectors must cover the entire Keys, which stretch 110 miles from end to end, and although Aedes aegypti account for less than 1 percent of the mosquitoes in the Keys, the district says it spends about $1 million of its$10 million budget battling the species each year.

This is why Doyle and his colleagues have been searching for new tools to beat back the Aedes aegypti on the islands — and why they’re now involved in a messy public battle over genetically modified organisms. The mosquito control district has been in talks for years with Oxitec, a British company that engineered a strain of mosquitoes with a gene that causes the insect’s offspring to die before reaching maturity, and in August, the company finally made its way through the maze of the federal government’s approval process for field testing. Oxitec is now cleared to conduct a trial of its mosquitoes in the United States. But earlier this year, amid growing concern from some residents about the use of genetically modified mosquitoes, the Mosquito Control District Board of Commissioners — five elected officials who oversee mosquito-control efforts for the whole of the Keys — made what one commissioner described as a relatively rash decision: The board would let the public choose whether to go forward with the research.

And so when Florida Keys residents go to vote in the presidential election this November, they will also vote on whether to release Oxitec’s mosquitoes in Key Haven, a small community off of Key West. Although the vote is nonbinding, three of the five members of the Mosquito Control Board have said they will abide by the public’s decision. But the board members haven’t made clear who that public is, which turns out to be an important point, because there will actually be two votes: one for residents of Key Haven and another for all residents of the Keys. The latter asks whether voters are in favor of conducting the trial anywhere in Monroe County, which includes all of the Keys and a section of the mainland that’s mostly occupied by Everglades National Park.

The pending vote has raised important and difficult questions that are rippling out to shores far beyond the Florida Keys: How do you judge unknown risk against known risk? How much is enough evidence to say it’s safe to deploy a new technology? And when it comes to public health, who should decide what’s in the public interest?

## The Science

East of mile marker 5 on the Overseas Highway, which runs from Miami to Key West, a wide, flat road just barely above sea level juts off toward Key Haven, a residential neighborhood with about 450 homes. To an extraterrestrial, the island might look like it had been terraformed to support boat life: Canals cut through nearly every backyard, effectively dividing the island into thirds. This unusual landscape is what makes Key Haven an ideal place to conduct the Oxitec trial; the company needs a research area that can be split into three defined but contiguous sections: a test zone where the mosquitoes would be released, a buffer zone, and a control zone that would be free of modified mosquitoes. The island already has plenty of Aedes aegypti, according to the Mosquito Control District. Zika is also on its mainland doorstep; 155 people were known to have been infected with the virus locally as of Oct. 13.4

Concerns about Zika are growing alongside evidence that the virus can cause a variety of health problems. When pregnant women get the virus, their babies can be born with microcephaly, a condition in which an infant’s head is much smaller than average and which is associated with a number of neurological defects. There’s also growing scientific consensus that the virus can cause Guillain-Barré Syndrome, a disorder where the body’s immune system attacks the nervous system, which can lead to full-body paralysis, though most patients regain much of their mobility as they recover. Lab research has found evidence that Zika could be causing eye infections such as conjunctivitis, and recent studies in mice suggest that the virus could attack the adult brain as well.

Although the Keys have had only one serious outbreak of a disease carried by Aedes aegypti in recent memory, officials say they can’t rely on their current mosquito-control approach forever. Not only do current methods require enormous investments of time and money, but the Keys are also now seeing more insecticide-resistant mosquitoes. The problem is ballooning globally and has rendered several insecticides useless in places such as Puerto Rico, where thousands of cases of mosquito-borne diseases, including Zika, chikungunya and dengue fever, have been registered this year.

Oxitec officially began seeking approval for its research in Key West in 2010. At first, regulatory questions got in the way, the biggest one being: Which federal agency regulates a genetically modified organism that interacts with humans, not agricultural products, with the intention of decreasing a pest population to, in turn, reduce human disease? There’s no legislation laying out which government agencies have oversight of genetically modified organisms. Oxitec submitted plans to the U.S. Department of Agriculture and was told about 18 months later that the USDA had no jurisdiction; the company was referred to the Food and Drug Administration instead. At the FDA, this testing is considered a new animal drug trial (in Brazil, the mosquitoes are essentially classified as a novel medical technology). In August, the FDA issued a finding of “no significant impact,” meaning the agency believes the field trial is not likely to affect the local environment.

Although the study’s goal is ostensibly to determine whether the company’s genetically engineered male mosquitoes will mate with the wild female Aedes aegypti in the area, Derric Nimmo says that the modified mosquitoes’ mating viability has already been proven in studies in Brazil, Panama and the Cayman Islands. Nimmo is a principal scientist for Oxitec; he has been with the company for 11 years, and he led research efforts in both the Cayman Islands and Brazil. “The trial is to show it works in the U.S., not to show that it works. I’ve already shown that it works,” Nimmo said. A U.S. trial is required before Oxitec could gain FDA approval and be allowed to enter the U.S. market. Nimmo readily acknowledges that leaping this bureaucratic hurdle is about more than just access to the U.S. market; it may also open doors to numerous countries in the Americas that largely rely on the U.S. regulatory process to decide whether new products and technologies are safe.

When I met Nimmo, he was coming off of 48 hours of giving speeches about Oxitec’s mosquitoes: to journalists at the Miami Herald, to a slew of TV crews from around South Florida and to citizen groups in the Keys. He expressed none of the exhaustion or frustration that I imagine would go with repeating the same information over and over. He says his job is to help the public learn about the science. At least, that was his job until April of this year, when the Keys’ mosquito board decided to let the public vote on whether to release the Oxitec mosquitoes. Since then, his job has been to lobby likely voters.

## The People

So what are the voters thinking? It’s a bit unclear. Back in 2012, the Mosquito Control District wasn’t sure how the community felt about the Oxitec trial, ex-director Doyle said. So the district solicited the help of Michael Cobb, a political scientist from North Carolina State University who had previously completed a national survey on genetically modified mosquitoes. Cobb studies public perceptions of novel technologies and had attended some of the community meetings in the Keys, so the district hired him to poll residents in 2013. He found what he saw as clear support for the trial: 61 percent were in favor. Since Zika took hold in the U.S. this year, several more surveys have been conducted, which show that a majority of Floridians support deploying modified mosquitoes in areas where Aedes aegypti is found, as do a majority of all Americans.

Cobb became interested in public perceptions of genetically modified mosquitoes because he was troubled by Oxitec’s approach in other countries. After the company conducted its tests in the Cayman Islands beginning in 2009, other researchers criticized the secretive nature of the trials. At the time, Anthony James, a pioneer in mosquito research who was leading a giant international effort to develop and test genetically modified mosquitoes, expressed prescient concern that by going ahead with the study — the world’s first known release of genetically modified mosquitoes — without the full consent of residents, Oxitec might make the public more mistrustful of all research into genetically modified organisms, even if the trials were successful.

The trials were also found to be lacking in transparency and scientifically deficient in a 2012 review by four scientists from the Max Planck Institute for Evolutionary Biology in Germany and an independent researcher. Like other scientists, Cobb didn’t like the way the company glossed over the details of the research. “You do release some females by accident, and they do bite, and you don’t know what could happen if some survive,” he said, citing concerns the community has raised.

But Cobb is also frustrated by what he says is false balance from the media, which often gives equal weight to his scientifically conducted surveys, which show a majority of locals support the trial, and to unsupported claims from residents who oppose the research and say the community doesn’t want it. “Press behavior is the worst sometimes. When you don’t know what to trust, you just give balance. I’m not a supporter of the damn thing, but I don’t like how it’s being covered because it’s just not accurate,” he said. “The surveys all point in one direction: If people are forced to choose, they would say OK.”

That polling was conducted in 2013, however, and it’s hard to say whether sentiments have changed. A handful of residents have been lobbying hard to get the community to vote “no” on the referendum. This spring, the UPMC Center for Health Security published the results of a survey mailed to all Key Haven residents in 2015 (before the Zika outbreak reached the U.S.) that found that 58 percent were opposed to the use of genetically modified mosquitoes; just 9 percent said they were opposed in a 2013 door-to-door survey conducted by the Mosquito Control Board.5 The sample for the mailed survey was small, however, and may not be representative of the whole community.6

It was largely the controversy over the polls that led the Mosquito Control District board to hold a community vote.

Board Chairman Phil Goodman doesn’t think there should be a vote. He worries that it will establish a precedent of letting the public vote on mosquito-control techniques. He’s also worried that politics are getting in the way of public health (three of the five board seats are up for election in November, the same seats held by the three commissioners who voted to hold the referendum and agreed to be bound by its results, though one incumbent isn’t running for re-election). “Our job is public health, not public opinion,” Goodman said. “I feel like I’m very well informed of this, I think our board is very well informed. It’s unfortunate that this got political. We don’t have one of the best mosquito controls in the world because we have to ask the opinion of everyone for everything we do.”

Mila de Mier, a real estate agent who made herself the face of the opposition when she started a petition on Change.org that has garnered signatures from about 170,000 people (the majority of whom aren’t from the Keys),7 is worried that the trial will establish a precedent about the use of genetically modified organisms. “No matter what, when we’re talking about biotech, this is about setting the standard between the government, local government, the community and the company. For good or for bad, our little community is in the front line of setting the standard of this relationship.”

When I drove around Key Haven in late August, about a third of the homes there featured yard signs that read “No Consent,” the rallying cry of those opposed to the Oxitec trial. I showed up a few minutes early for a meeting with de Mier and other opponents, which was being held at Gilda Niles’s home on the north side of Key Haven, in the area slated for the release of Oxitec mosquitoes. When I pulled up, de Mier was outside placing signs on the corner in preparation for the arrival of a TV crew. One of the signs read, “We Are Not Your Experiment.”

Niles emigrated with her family from Cuba in 1967. She says the United States she came to wouldn’t force an experiment on someone who doesn’t want it, which is the point the “No Consent” lawn signs are echoing. She and other residents feel that this research should not be allowed to proceed unless the people who might interact with the Oxitec mosquitoes give their informed consent, which is a requirement of human drug trials. To participate in a drug trial, people must first have the research explained to them and be told about their role in the work and the possibility of unforeseen risks. But the mosquitoes are classified as an animal drug, not a human one, which means that Oxitec is not legally required to obtain informed consent from people who live in the testing area.

The people opposed to the trial are also frustrated because the genetically modified mosquitoes won’t be able to halt or mitigate current Zika outbreaks. That’s partly because approval for commercial use of the mosquitoes likely won’t come in time to help, even if all goes well with the trial, but also because the insects aren’t suited for stopping the spread of an outbreak. “The thing to think about is that if you’re in the middle of a disease outbreak, you have to kill infected mosquitoes now. And a technique like that is not going to do that,” said Stanton Cope, president of the American Mosquito Control Association, a nonprofit group that works on science and education relating to mosquito control. What Oxitec’s mosquitoes could do is help suppress Aedes aegypti populations so that viruses are less likely to spread in the future.

Other opponents of the testing worry about the small percentage of genetically modified females that will be released into the environment and what could happen if those insects bit a human. Only female mosquitoes bite, so Oxitec’s goal is to release only males, but the company’s sex-sorting method isn’t 100 percent accurate; about 1 in 10,000 of the mosquitoes released would be female, according to Oxitec,8 but the company says its research has shown that the engineered genes don’t show up in the mosquito saliva that’s transferred to mammals during a bite. De Mier says she wants peer-reviewed studies from independent researchers showing that the technology is safe, but Oxitec counters by saying that numerous researchers have worked with its mosquitoes. An Oxitec employee has been a co-author on most relevant peer-reviewed studies, which critics worry could bias the data, but Oxitec says that because its technology is proprietary, it’s difficult for scientists to research its techniques without assistance from someone at the company.

“What bothers me most is that they say we are stupid or unscientific,” Niles said during the meeting of the “No Consent” crowd, which took place on Niles’s artfully landscaped patio overlooking a canal. Then, indicating the verdant backyard with a Vanna White sweep of her hand, she added, “Or they say we are rich.” She resents the implication that they are entitled; she’s read the literature, and she’s not convinced the mosquitoes are safe.

Niles and her companions explained that they’re more worried about the potential risks of the Oxitec mosquitoes than they are about Zika or dengue; during the 2009 outbreak of dengue fever, only three cases were reported from Key Haven, and all three were residents of a single home. (Many members of the group also think there are very few Aedes aegypti mosquitoes in their area, though the Mosquito Control District says otherwise.) Their bigger concern is whether either a company with a financial interest in the trial’s success9 or a federal agency they see as too friendly toward industry can be trusted to properly assess the risks of this new technology.

Not everyone is suspicious of the research, however. Several people around Key West told me that they weren’t against the trial, which in effect made them in favor of it, even if they were somewhat apathetic. Others explained that they didn’t want to go public with their support because they were afraid of being harassed by the opposition. Quincy Perkins is one of the few Keys residents who has spoken publicly in favor of the research. He said the debate has gotten vicious; his support of the trial has mostly resulted in petty insults hurled on Facebook, but he says a recent online threat directed at his wife and daughter prompted him to call the police.

On a recent stormy afternoon, sitting on a patio pressed up against the ocean, Perkins explained that four years of working in the Galapagos Islands showed him the role that genetically modified organisms can play in conservation and human health. Though he’s now an independent filmmaker, at the time he worked for the Charles Darwin Foundation, a nonprofit group that promotes conservation on the islands. Perkins says he met numerous scientists on the island who were working on genetically engineered organisms meant to combat invasive species or to help fortify struggling indigenous wildlife populations. He also saw the toll dengue fever can take — there have been hundreds of cases on the islands since the virus first appeared there in 2002.

“We would go to these hospitals and kids would be screaming for 72 hours straight,” Perkins said. “These were real things in front of me.”

He’s frustrated by what he thinks is misinformed rhetoric about genetically modified organisms and perplexed by what he sees as an anti-science stance from people who are otherwise science-minded. “These are people who believe in climate change,” he said. He is also deeply concerned about the amount of insecticide currently being sprayed on the island and hopes Oxitec mosquitoes could help reduce that. “The big thing for me is that I’m sick of pesticides. It’s mindblowing to me that there’s not more outrage about them.”

Every year, the district sprays thousands of pounds of six kinds of insecticides, which have varying degrees of toxicity. Some insecticides kill more than just mosquitoes; South Carolina recently started spraying for adult Aedes aegypti, and residents there said the spraying was followed by an apocalyptic die-off of other insects. That spray, naled, is just about the only insecticide available for killing adult mosquitoes, but it’s banned in Europe because of concerns over its safety; its recent use in Miami has been hotly contested (though the CDC says it was successful in stopping the spread of Zika), and a proposal to use it in Puerto Rico led to large protests earlier this year. That same insecticide has been sprayed 19 times this year in the Keys as of Oct. 7. “This is my community; this is where I hope to raise my child,” Perkins said. He paused. “You’ve heard that same thing from Mila [de Mier], haven’t you?”

The answer to the question of how much evidence is enough to go forward with these trials is different depending on who you ask. De Mier and Niles say they’d like independent, peer-reviewed studies and a much longer follow-up period on the earlier trials in Brazil, the Cayman Islands and elsewhere. Nimmo points to numerous published studies and a decade of evidence that was convincing to the FDA. Mosquito Control Board employees and commissioners are charged with preventing infectious diseases spread by Aedes aegypti, which affect millions of people around the world every year and are both deadly and expensive to keep at bay — they want new tools in the pipeline, and this is the only one available to deploy now, though others may not be far behind.

Another method of sterilizing mosquitoes, which involves infecting them with bacteria, whizzed through the regulatory process after being classified as a pesticide, which placed it under the jurisdiction of the Environmental Protection Agency rather than the FDA. Another genetic-modification technique related to Oxitec’s, called a gene drive, recently received millions of dollars of financial support from the Bill and Melinda Gates Foundation, practically assuring that it will be field tested in the near future, though the International Union for Conservation of Nature recently decided to refrain from supporting the technique until more research has been conducted. Technology is developing so fast that scientists and the public have little time to debate the ethics of each new technique or device before it gets put into use.

The scientists I spoke to agree that the available evidence suggests that the Oxitec mosquitoes would pose little risk to the environment and the humans who inhabit it. But others point out that with new and poorly understood technology, the community should be consulted before such research takes place. Taking chances is a part of any scientific endeavor, especially with the creation of a new technology, but keeping people safe is an ethical obligation. On the other hand, declining to use new technologies is also a choice, one that carries consequences of its own.

Which is to say, it’s not entirely clear how a democratic society should deal with new technology and risk. Is voting the best way forward? Should we be striving to do no new harm, or should we weigh all the risks and proceed with caution? Come November, the voters of the Florida Keys will be forced to wrestle with these questions. Their decision will have implications that reach far beyond this sliver of land off the Florida coast.

## Footnotes

1. Generally, inspectors call for a truck to spray the area with insecticide after five or more mosquitoes appear during a count. They request an aerial spray when the mosquito count is three times the area’s baseline average of the last 10 years.
2. Inspectors use the turkey basters and dippers to gather and examine standing water, both so they can look for mosquito larvae and so they can carry samples back to the lab. Ryan was collecting samples to see if they included Aedes albopictus, a mosquito that isn’t yet widespread on the island but whose larval form looks similar to that of the much more common Aedes aegypti. Both types of mosquitoes can carry a number of viruses that are dangerous to humans, but it is Aedes aegypti that is believed to be primarily responsible for spreading Zika, in addition to yellow fever and other diseases.
3. Doyle started a new position in September with the North Carolina Department of Health and Human Services as a public health entomologist.
4. The Centers for Disease Control and Prevention maintains a frequently updated tally of the number of U.S. cases. Most of the more than 3,800 cases of Zika reported in the U.S. as of Oct. 12 resulted from travel to other countries. To date, Florida is the only state where people are known to have acquired Zika from mosquitoes in the U.S.
5. Some opponents of the Oxitec trial distrust the results of both this study and Cobb’s because the Mosquito Control Board was closely involved in both.
6. Only 22 percent of residents responded to the survey, and, in general, people who have the strongest feelings about their position are more likely to respond to surveys. From my interviews with residents, it seems, at least anecdotally, that those opposed to the testing are more likely to feel strongly than those who support it.
7. Fewer than 80,000 people live in the Keys, so at least 90,000 signatories must live elsewhere.
8. Earlier reports stated that about 1 in 500 of the mosquitoes selected for release were female, but Nimmo said the company has since improved its sorting method.
9. Oxitec is now owned by Intrexon, a corporation that works with synthetic biology technology.

Anna Maria Barry-Jester reports on public health, food and culture for FiveThirtyEight.

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