Genetically Modified Bugs Glow Red and Self-Destruct, but Can They Keep Away Disease?
It's a pristine spring morning on the remote tip of Big Pine Key, 30 miles north of Key West. The lone paved road is surrounded by dense brush and wetlands that give way to the Gulf of Mexico. On this particular Tuesday, though, the usually silent landscape is dominated by the pulsing whoosh of a brown and tan helicopter that just touched down. Half a dozen workers in neon safety vests, surgical masks, and sunglasses emerge from the roadside and hustle toward the aircraft. Under the whirling two-blade rotor, they form an assembly line and dump bags of a yellowish substance called larvicide into cone-shaped containers on the sides of the chopper.
This is the modern frontline of the war on mosquitoes, an epic, centurieslong struggle between mankind and nature that has left an indelible mark on the Sunshine State. Minutes after landing, the helicopter is back in the air, buzzing treetops. The pilot banks a tight U-turn, cuts down to an altitude of 60 feet or so, and delivers the payload. As the helicopter bolts out of sight, a barely visible granular trail flutters toward the ground. "Don't look up," says one of the workers on the ground.
The commander in chief of this latest skirmish that's unfolding in the Keys is entomologist (insect expert) Michael Doyle, a slight, mild-mannered Midwesterner with a fastidiously trimmed salt-and-pepper mustache and rimless eyeglasses. Executive director of the Florida Keys Mosquito Control District, Doyle says that about $45,000 will be spent by the end of the day just to counter the onslaught of mosquitoes hatched in the three to four inches of rain that fell over the weekend.
Back at the agency's headquarters in Marathon, Doyle explains that the larvicide unleashed by the helicopter consists of ground-up corncobs slathered in naturally occurring bacteria that is toxic to mosquito larvae. (It would take a pickup truck-and-a-half of such larvicide to kill a human.) When the pellets land in puddles and nearby water, larvae gobble them up and die before they can morph into the flying, blood-sucking pests we so loathe.
But this method is expensive, labor-intensive, and ineffective against one of the most troublesome mosquito species, Aedes aegypti. Of the 44 species in the Keys, Aedes aegypti is the one that keeps Doyle up at night. It's the stealth bomber of mosquitoes: silent, capable of biting 20 people in a day, breeding in the shallow puddles around densely populated residential areas. Most alarming: It's the only species in the region capable of spreading dengue fever — a nasty and sometimes fatal disease that popped up in the Keys in recent years and could scare away the tourists who drive the local economy.
When Doyle left behind his days at the Centers for Disease Control and Prevention in Colorado, where he studied mosquito saliva, to take charge of the Keys in July 2011, board members who oversee the mosquito program gave him a more than $10 million annual budget, staffers with PhD's, and a fleet that includes four helicopters and two airplanes. They also gave him two orders: Cut the budget while killing more mosquitoes, and ensure that no cases of dengue fever grab headlines like they did in 2009 and 2010.
"The dengue cases were a big deal," Doyle says. "It was the first time [the disease] had been back in more than 60 years. The concern is that the Keys could be a way for dengue to get a new foothold, or a refoothold, in the United States."
Doyle's solution? To move ahead with a controversial experiment that has been in the works since before he arrived: importing and releasing millions of Aedes aegypti mosquitoes that have been genetically modified in the labs of a British biotech firm called Oxitec. These minute marvels of science are tweaked to pass down a gene that causes their progeny to self-destruct soon after hatching. Only males would be released; theoretically, they would breed with normal females and spawn offspring that keel over and die just before adulthood. The dengue-spreading population would collapse generation by generation.
If Doyle's plan goes forward, Key West will be only the fourth site ever in which these genetically modified insects have been let loose, behind Malaysia, northern Brazil, and the Cayman Islands. But not everyone is eager to tinker with Mother Nature's genetics, perhaps put off by the idea of getting bitten by a mutant mosquito. This is, after all, the Conch Republic — full of sinners, sailors, developers, and assorted rebellious characters who, in 1982, famously declared they were seceding from the United States. Here, the environment teems with beauty and biodiversity, which in turn draw legions of money-spending tourists. Local residents will fight like hell to protect their unique way of life.
Doyle understands the complexity of the situation. "We are in a weird spot, because we want to get rid of dengue and not make headlines...," he says, then adds, laughing, "Then come GM mosquitoes."
As dusk settles over the hordes of sun-soaked tourists lumbering down Key West's boozy Duval Street, an eclectic gaggle of locals, without a formal group name but united in their concern about modified mosquitoes, gathers around a table in a cavernous real estate office. A delectable aroma from a platter of gourmet goodies hangs over the table as ice-cold bottles of Corona are passed around.
Kicked back in a chair is Joel Biddle, a mellow, slow-talking, Bermuda-born man who operates at a cosmic tempo that matches the pace of life near the southernmost point of the continental United States. His thick, bushy white hair, lazily parted to the side, flops around as he gestures with his meaty hands. Biddle's smooth skin and striped pants belie his 68 years.
Three years ago, Biddle sat on the edge of his bed in tremendous pain staring at his feet. His bones ached. His head had the woozy, second-behind sensation that accompanies a fever. "I was completely out of my mind," he recalls. "I had been sick for two weeks and thought I finally had the strength to go to the clinic. I put a sock on my foot, which was hard to do, and just sat there for three hours. Then I just went back to bed."
An Aedes aegypti mosquito had pierced Biddle's skin and infected him with the virus that causes dengue fever, an ailment that's earned the ominous nickname of "break bone fever." Each year, upward of 100 million people are infected around the world, and about 25,000 — mostly in Latin American and Asian countries — die from the most severe form. The World Health Organization calls dengue a "fast emerging pandemic prone viral disease" whose rates have "increased 30-fold over the last 50 years." There's no approved vaccine and no treatment. Thankfully, though, dengue is exceedingly rare in the U.S.
"It's debilitating," Biddle concedes. "It's a tough disease, and I can see why [public health officials] are afraid of it."
No one at the table underestimates the severity of dengue or the potential threat it poses to tourism — an industry they all rely on directly or indirectly. And the more mosquitoes and the more tourists, the bigger the threat.
There are, according to some estimates, 40,000 mosquitoes for every person in the United States. In most of the U.S., mosquito season lasts four months. In South Florida, it's ten months, sometimes 12, depending on rainfall. Because most Florida counties have had mosquito control programs in place since the 1950s or '60s, modern-day Floridians take their relatively mosquito-free lifestyles for granted. It can be tough to appreciate the extent of mayhem once stirred by "our species most deleterious pest," as environmental historian Gordon Patterson puts it in his book The Mosquito Wars: A History of Mosquito Control in Florida.
In the late 19th Century, when Florida was referred to as "the Devil's property," swarms were so dense in some areas that it was impossible to breathe without inhaling mouthfuls of mosquitoes. Union soldiers struggled with the pests during the Civil War, bundling up in overcoats despite the sweltering heat to stave off bites. In August 1864, Acting Master Mate Van Ness of the USS Chambers — a Union ship patrolling the coast of what's now Brevard County — committed suicide by jumping overboard to escape being eaten alive. A "mystery disease" broke out among the remaining crew and killed five. Patterson quips, "Confederate sympathizing mosquitoes were victorious."
Livestock also suffered. In September 1932, in Cape Sable, near the southern tip of the state, 80 cows, 67 hogs, 20 chickens, three horses, two dogs, and one mule were killed in a single night by a blitz of mosquitoes. As noted by Patterson, the animals died either from sheer blood loss, nervous exhaustion, or a toxin. Though mosquito attacks were excruciating and craze-inducing, the diseases they spread have always been more dangerous. Over the course of mankind's history, mosquito-borne diseases, especially malaria and yellow fever, have combined to kill billions of people.
Dengue, though less lethal than malaria and yellow fever, has soared in the Caribbean in recent years. In 2011, the CDC issued a travel advisory for the Bahamas after 1,000 suspected cases were recorded in a one-month span. In Puerto Rico, more than 21,000 cases — representing a financial burden of $40 million — were reported in 2010, the most in the history of the island. But the last major outbreak of dengue in Florida occurred back in 1934, when nearly 1,500 of the 2,000 cases were concentrated in Broward and Miami-Dade. Noxious chemicals like DDT that were brewed in the "Better Living Through Chemistry" era played a vital role in suppressing the disease.
Only a few cases emerged in Florida over the following decades, mostly in people who had picked up the virus while abroad. But in 2009, a woman from New York who had traveled to Key West was diagnosed with it. This set off national alarms; the fact that she hadn't left the country meant the disease was acquired in the continental U.S. The CDC sent investigators to the Keys who worked with local health agencies and confirmed at least 27 locally acquired cases in 2009 and an additional 66 in 2010.
Dengue can't spread from person to person. For the disease to show up the way it did meant that someone already infected must have traveled to Key West and was bitten by an Aedes aegypti, which in turn became infected and traveled around biting other people. Those people now had the virus and spread it to other mosquitoes, which spread it to more people, including Biddle.
This outbreak sent mosquito control into hyperdrive, and the local Department of Health launched massive education campaigns that urged residents to dump any standing water and use bug spray liberally. These efforts appeared successful: There hasn't been a confirmed case of dengue in the Keys since November 2010.
This dearth of recent infections is a rallying point for the concerned Conchs at the table. "There haven't been any reported cases in almost two years, but they're trying to use [dengue fever] as the reason they need to release Oxitec's mosquitoes," says Kelly Young, a blond, soccer-mom-looking lady. "There's no validity to that argument."
An elderly woman with a refined British accent who didn't want to reveal her name worries that decimating the population of one mosquito species could damage the local food chain and ecosystem. "Everything has a purpose," she says.
Mila de Mier, a real estate agent who organized this get-together and started a petition against the experiment, rattles off a litany of concerns at a machine-gun pace in her thick Spanish accent. "They're going to spend our money for us to become guinea pigs," she says. "We want this place to remain natural, to be the way it is. We don't need their mosquitoes... Mr. Doyle wants to be a pioneer. He wants to be the first in the U.S. to do this type of experiment."
Biddle raises his soft voice to tamp down this dizzying powder keg of a roundtable. "Mosquito Control is not an enemy; they're good people," he says, a sentiment that everyone, including de Mier, nods in agreement with. "I'm not against this technology. What I am against is corporations like Monsanto and now this Oxitec company cutting corners and not listening to the scientific community."
Although the mosquito control department had been kicking around the idea of releasing modified skeeters for two years, it wasn't until a newspaper article published this past winter that these Conchs became aware of it. Once Biddle, de Mier, and other critics began to complain, Oxitec and Doyle held a town meeting to discuss the issue and assure residents that the plan is safe. The crew at the table says the event was little more than a sales pitch. So they began doing their own research.
That's when they learned about some troubling controversies ignited by Oxitec's experiments.
Today, the mosquito control industry is an arms race.
After World War II, when developers forged into the swamplands, control efforts were concentrated on DDT, a powerful and notorious pesticide first tested in Florida. By the 1950s, however, scientists discovered that some mosquitoes had become resistant to it. Chemists pushed on and created potent alternatives, a few of which decimated anything and everything in their paths. But the birth of the environmental movement in the 1960s and Rachel Carson's Silent Spring left mosquito control efforts in a quagmire. How could they kill the mosquitoes without destroying entire ecosystems or making humans ill?
"Everything is becoming more smart-bombish. It's like the military in a lot of ways," Doyle says. "In the '50s, it wasn't that complicated. You got into a truck, and off you went. Now the industry is much more specialized. There are computer-aided drift models [to predict how pesticides will disperse in the wind], and you use a laser to calibrate your droplet size [for the sprays]. It's an intricate science."
Despite access to these sophisticated-sounding technologies, Doyle is in a lurch. Although there are effective chemicals for killing pests, he can't use many of them because of tighter regulations and greater public awareness, especially in an area as environmentally sound as the Keys.
The larvicide dropped by the helicopter is good for killing only mosquito larvae, not mature, flying mosquitoes. Doyle estimates that for larviciding to be effective to the point he desires, the mosquito control program would need to add 40 staff members. Efforts to kill adult mosquitoes, a tactic known as adulticiding, rely on chemicals dispersed by planes and trucks. For adulticides — some of which are derived from chrysanthemum flowers — to kill mosquitoes, a droplet actually has to hit a flying mosquito. Achieving this level of precision is pricey, and many of these chemicals are too potent to regularly dump over the Keys.
"There are some really toxic chemicals I could use but won't," Doyle says. "There are some that have a really big impact on marine life, but we're a marine sanctuary, so I'm not going to use those."
Anyway, Doyle explains, Aedes aegypti mosquitoes, the dengue-spreading species, live in and around homes, not out in wetlands and other open areas that are easy to blanket in a fog of killer chemicals and bacteria. "They're highly adaptive to human beings," he says. "They're almost like a parasite." Current efforts against this single species are focused on sending 18 full-time inspectors to thousands of properties throughout the Keys to make sure there's no standing water. If an inspector finds a few Aedes aegypti, he or she can use a handheld fogger to kill them. But to wage a successful war against Aedes aegypti that will get shock-and-awe-like results requires a game changer.
So, Oxitec's genetically modified mosquitoes are an ostensibly elegant solution to Doyle's conundrum. "I've looked at all other options for Aedes aegypti control, but they're too expensive or environmentally damaging. This sounds like the best option we have going."
Over in Oxitec's mosquito factory on the outskirts of Oxford, England, scientists use razor-sharp glass needles to inject small amounts of DNA into tens of thousands of mosquito eggs. Most of the eggs will die, but the ones that survive will incorporate the extra DNA into their genome and go on to develop two genetic modifications that can be passed down. The first causes the mosquitoes to glow fluorescent red when placed under a high-powered microscope. Though this may sound like something from a Michael Crichton novel, it's a relatively old trick that's used to track all types of research animals. The second modification, the insertion of an autocidal gene, is what causes the mosquitoes to self-destruct.
In the lab, the modified mosquitoes are fed tetracycline. This common antibiotic essentially turns the death gene off. This allows the insects to stay alive, breed, and produce eggs that now contain the gene.
"All the fancy genetic stuff is done over [in England]," Doyle explains. "I call Oxitec, they send a boxful of eggs, we grow the eggs in cake pans, give them food and water, and sort them in a lab we'll set up in a trailer."
By sorting, Doyle means weeding out any females by looking at the size of the larvae — males are smaller than females. It's the most crucial step in the process because only female mosquitoes bite humans, and releasing hordes of modified mosquitoes capable of sucking our blood would be counterproductive at best. Doyle acknowledges, however, that this sorting method isn't foolproof; about one female gets through and is released for every 1,500 male mosquitoes, he says.
"The chance of getting bit by a female genetically modified mosquito is pretty small, but it's not impossible. It's going to happen." The effects of such a bite are unclear, but the idea of getting bitten by a mutant mosquito could freak people out. Environmental groups and organizations opposed to genetic modifications of any sort have been vocal over the lack of information on this aspect. Oxitec maintains that the proteins composing the genetic modification aren't present in mosquito saliva and thus won't be transmitted during a bite. It's a sentiment that scientists who are critical of the company tend to agree with.
Doyle and his team are now busy looking for two similar six-block-by-six-block areas in Key West where they can conduct their experiment. In phase one, they intend to release a few thousand Oxitec mosquitoes and set traps. From the mosquitoes that get caught, they can determine the ratio of Oxitec mosquitoes to normal ones. Then, they'll do a second phase, releasing ten Oxitec mosquitoes for every wild one. Doyle says that over six months, 2 million to 6 million genetically modified mosquitoes will be released. Saturating the test site with the modified mosquitoes should increase their odds for successfully mating with normal females.
A potential pitfall is that the street-smart, wild males will simply outgun the lab-pampered mosquitoes. But if all goes as planned and Oxitec mosquitoes get to the females first, the offspring will hatch and live for a few days before the genetic modification kicks into effect and shuts down the cellular machinery needed for the pupae to become functioning adults. Hordes of tiny mosquito corpses will flow through the shallow breeding grounds.
Doyle is well-aware of the experimental nature of a release and says he needs to be a "cautious buyer." At the same time, he's eager to get the test under way because the threat of dengue looms as millions of tourists flock to the Keys each year.
When Joel Biddle, Mila de Mier, and their Conch friends began looking into Oxitec's history, they found a few worrisome things about the decade-old, privately funded company. Oxitec, which employs about 40 people, has consistently come under fire from environmental organizations, anti-GM groups, and academics for its lack of transparency when carrying out experiments. So far, the company has released mosquitoes in Brazil in 2011, Malaysia in 2010, and the Cayman Islands — where more than 3 million genetically modified mosquitoes have been dispatched since 2008.
Few peer-reviewed scientific journal articles have been published demonstrating the effectiveness and safety of genetically modified mosquitoes when released in the wild. Those that have been published include an Oxitec staffer among the authors, and there are no independent, third-party studies under way.
Opponents, including the Conchs at the real estate office, hone in on the Cayman experiment because it's the furthest along. About four years ago, Oxitec and the Cayman mosquito control authority collaborated on an experiment without providing much information to the scientific community or local residents about the release. In November 2010, Oxitec took the stage at a medical conference in Atlanta and delivered findings from what was the first field trial ever of genetically modified mosquitoes. Some researchers in the crowd were surprised that, all of a sudden, a British biotech company was announcing that it had released its mutant mosquitoes in the wild without consulting the larger research community.
In response, the prestigious journal Science published a news article that took a biting tone as it questioned whether the company had rushed to release its mosquitoes in the Cayman Islands and suggested that the hastiness and off-the-radar style of the experiment had strained Oxitec's ties with funders, including the Bill & Melinda Gates Foundation. This past January, researchers at Germany's Max Planck Institute published a paper in the journal PLoS Neglected Tropical Diseases implying that Oxitec exploited a weak regulatory environment in the Cayman Islands to do the experiment with minimal oversight and little effort to inform the locals that millions of genetically modified organisms were being let loose in their backyard.
Environmental group Friends of the Earth, one of Oxitech's harsher critics, says the company has not "been open and honest with the local communities about the possible risks its technology pose." Helen Wallace of GeneWatch UK took that sentiment a step further when she said in a statement that Oxitec's Cayman experiment shows that the "British scientific establishment is acting like the last bastion of colonialism, using an overseas territory as a private lab."
In addition to these transparency complaints, opponents fret over a few lab-based studies showing that 3 percent of the Oxitec mosquitoes survived into adulthood despite possessing the self-destruct gene. Oxitec CEO Hadyn Parry tells New Times that this hasn't happened when they're released in the wild, nor is it likely that such mosquitoes can live long enough to transmit diseases. As for Oxitec's opaqueness, Parry says the company never denies an interview and welcomes reporters into its laboratories and has even shared confidential data with activist groups to quell further uproar.
According to Parry, the Cayman experiment worked well. He says the wild Aedes aegypti population plummeted by 80 percent after the Oxitec mosquitoes were released. Final data from the experiment have not been published in a journal. Parry says they are undergoing the peer review process for potential publication in Nature Biotechnology later this year.
Parry insists that the company doesn't have any special interest in doing a release in the Florida Keys; it's Keys Mosquito Control that is pushing for the experiment. "From our point of view, we're working in a number of different places," he says. "We don't have a hit list saying that we'd like to work in this place or that place. If someone is interested and says, 'Hey, can you help us?' we say, 'Yes, of course we can.' "
The Keys is the only area in the U.S. in talks with Oxitec about the use of modified mosquitoes. Even though the Keys are the sole site of locally acquired cases of dengue, some veteran mosquito experts in Florida are surprised that Doyle is picking up his predecessor's plan.
"Given that [Doyle is] brand new to the job, not even a year on, and is looking to take this step... yeah, we were surprised," says Phil Lounibos of the Florida Medical Entomology Laboratory, a Vero Beach-based facility that's part of the University of Florida's Institute of Food and Agricultural Sciences. "It's surprising because there is not supporting background evidence that we've seen showing that this will solve the dengue problem."
Still, if the Cayman experiment did reduce Aedes aegypti populations by 80 percent, as Oxitec says, that might not be a great enough reduction to control the spread of dengue. Lounibos points to Singapore, where mosquito control efforts are extensive yet dengue persists. "Many people don't doubt that the Oxitec method can reduce abundance of the mosquito that carries dengue," he says. "But it doesn't necessarily mean that it will control dengue."
Lastly, Lounibos says, Oxitec's mosquitoes are not a "self-sustaining technology," meaning that the Keys may end up making hefty payments to Oxitec to keep a steady stream of modified mosquitoes breeding with whatever population of wild females remains. "They're going to have to keep releasing these things," he says. "They're considering investing in this without knowing if the technology will get the end results."
Doyle has set aside $125,000 to cover the initial overhead of an experiment — converting a trailer into a lab, setting and monitoring traps, and paying for similar expenses. Doyle expects to spend half a million on Oxitec eggs the first full year, with the price dropping by half the second year. For the experiment, Oxitec has agreed to provide him with its mosquitoes for free during the first six months, and with good reason.
A successful test could provide a new customer for the fledgling company. More important, pulling off a release in the Keys would go a long way in removing the stereotype that genetically modified mosquitoes are a creepy, sci-fi solution. A release in the United States is a proverbial golden seal of approval, a mark of acceptance from one of the most stringent, red-taped regulatory bureaucracies in the world. Genetically modified mosquitoes could be pitched as a designer solution to dengue that doesn't need to be dropped from helicopters or dispersed from handheld foggers by uniformed men.
There's just one holdup. Genetically modified mosquitoes are so technologically advanced that no federal agency has claimed to have the jurisdiction to give Oxitec final approval for a release. Doyle likens them to a hover car: If Ford were to suddenly make a flying car available to consumers, would the Federal Aviation Administration, which regulates aircraft, have oversight, or would the Department of Transportation, which regulates roadways? Oxitec's proposal to release its creation has bounced through the USDA, the EPA, and the CDC, all of whom have claimed not to have jurisdiction, Doyle says. Now the FDA is reviewing Oxitec's application for what's called an "investigational new animal drug." Doyle says the FDA's decision could come in a few months or drag on for two years. If the agency ultimately denies the application, Doyle could theoretically release Oxitec mosquitoes anyway because there's no law against it — but he says he wouldn't.
As for the concerned Conchs, they have little or no power to stop the plan if it's approved. Even if they fill a petition with signatures and persuade the City Council to pass a law against mutant mosquitoes, the public health authority granted to the Keys Mosquito Control District trumps the power of the city. Biddle, the former dengue patient, doesn't necessarily want to stop the plan from going forward; he just wants independent, peer-reviewed assurance that Oxitec mosquitoes are safe.
"[Oxitec] should have to do a five- or six-year study in the Cayman Islands and see what really happens," Biddle says. "What are the effects on people? What are the effects on tourism? What are the effects on the disease? And what are the effects on the ecosystem? That's what we should be studying. And still, without these findings, we're going to put something in the Florida Keys that's genetically modified, and we don't know what's going to happen."
Doyle is afraid that it will take another outbreak of dengue fever for people to see the wisdom in his plan. "I'm optimistic that it will happen someday," he says. "But I think nothing will happen until there's some external push to make something happen, like if we see dengue again."
While he and Oxitec wait for a federal yea or nay, Doyle does his best to assuage the concerns of people like Biddle and local lawmakers who remain opposed to the idea. A recent survey among Keys' residents found that 30 percent supported it, 30 percent were against it, 8 percent were unaware, and the remainder were undecided. If those numbers shift and the majority turns against the project, Doyle hints that he will still push ahead.
"My job is to protect them," he says, "even if sometimes they don't want to be protected."
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