“This is the big problem right now,” he said as we approached a dilapidated fence. “There are a lot of foreclosures. And once a house goes into foreclosure, the bank shuts down the pool service and the landscaping and whatever else they have going on, and things just go bad.” A trashed-out yard was ideal for breeding Aedes, and Florida vied with other Sunbelt states—Nevada, Arizona, California, Georgia—for the highest foreclosure rate nationwide. Even wealthy Key West had its share. Meanwhile, homeowners’ insurance rates, higher than in any state but Katrina-walloped Louisiana, were only rising as insurers pulled back from the coastline or exited the state entirely. You could not buy a home without additional windstorm and FEMA flood insurance, which often cost more than the main policy. You could not buy windstorm insurance except through the much-reviled, state-backed Citizens Property Insurance Corporation, the onetime insurer of last resort that was now Florida’s largest as it absorbed policies from private firms that had fled the state. The Caribbean is expanding only slightly less rapidly than other seas, and Key West—which has the longest sea-level record in the Western Hemisphere—was overdue for another 1846-style hurricane.
Snell placed his hands atop a locked gate and jumped over in one easy motion. On the other side were a wooden deck, a palm tree, a small swimming pool, and a Jacuzzi. The heat was suddenly stifling. “There could be a twenty-knot wind, and it’s completely still in these yards,” he said. He had appropriated the Jacuzzi to raise fish for his fight against dengue: small, larvae-eating gambusia, which he would release in water cisterns and bird feeders as he traipsed through the backyards of paradise. Keys residents had historically kept cisterns—ideal Aedes breeding sites—under their homes, and more than 350 of them remained, along with nearly 250 wells. Scientists had determined that if less than 2 percent of homes contained Aedes, that was good enough: There could be no dengue transmission. But that summer, two Key West neighborhoods had indexes approaching 50 percent. Snell looked around the yard for signs of mosquitoes, and finding none, we jumped back over the fence. In the street, lined with pastel homes with their shades drawn, their owners gone for the summer, we saw not a soul.
It was extremely difficult to model dengue’s spread, Snell’s boss at the Mosquito Control District, Michael Doyle, told me. There were too many factors. This was especially true when gauging the effects of climate change. Big storms could lead to breeding sites in the rain-soaked debris—witness the Aedes aegypti explosion in the Cayman Islands after 2004’s Hurricane Ivan—but droughts could be equally dangerous if people began storing extra water in open containers. “It’s not the simple connection that if it gets warmer, this mosquito will be everywhere, that it will just move north,” he said. “It’s also how weather affects humans, you know? If it’s really hot, people may spend more time inside, where there’s more air-conditioning going on, so there’s less contact with mosquitoes.” Doyle and his extended family had just moved here from Colorado, where he had battled West Nile virus, another mosquito-borne disease linked to climate change. Already his mother-in-law was complaining about the mosquitoes at their Keys rental house, so his new employees were preparing a special strike team to stamp out the problem.
Until federal regulators decided the dengue threat was severe enough to let in Oxitec’s Aedes aegypti OX513A, the Mosquito Control District would have to back up inspectors like Snell with another kind of air support: a sprayer-equipped Bell 206 helicopter that hovered fifty to sixty feet above Old Town twice a month, raining insecticide onto rooftops and tourists’ rental cars. The insecticide, VectoBac, was based on a strain of the natural bacteria Bacillus thuringiensis (Bt) and, explained Doyle, killed mosquito larvae but little else. On a newly waxed car, its droplets looked like dried milk.
I had timed my visit to watch the helicopter spray. Doyle and I met at dawn the next day to follow twin contrails of insecticide through Old Town. The helicopter had to cover an area of 950 acres, and its hundred-gallon tank could do just 200 before a refill. The pilot rushed through five sorties as quickly as possible, lest his work be ruined if the wind picked up or the humidity dropped, lest the district be billed more helicopter time than it could already barely afford. Our SUV drove slowly through the backstreets, catching glimpses of contrails partly obscured by telephone poles, roofs, and wires. Only when we steered to an open patch of scrub alongside a busy road, across from a Lutheran church, did we have a clear view of it racing to and fro. We stepped out into the sun, and Doyle began telling war stories, like the one about the suppression campaign in Colorado when they’d carried their insecticide in backpacks and hand sprayed an entire forest. “Thirteen guys with thirteen backpacks,” he said. “All scratched up, all dirty. And we did 56 acres!” The helicopter made a beautiful, wide-arced turn above the church and barreled back toward us. We retreated into the SUV. On the street, a homeless man walked by pushing a bicycle. He peered into the sky, covered his mouth and nose with an old T-shirt, and kept walking.
Dengue had hit Key West just as the conservative Florida legislature had limited local governments’ taxing authority. The Mosquito Control District would spend almost $12 million in the 2011–2012 fiscal year but take in less than $10 million. It was burning through its cash reserves. And as aerial combat went, helicopters were much more expensive than transgenic mosquitoes—another reason the district really wanted them to be approved. Oxitec really wanted approval, too: It had already paid $130,000 in lobbying fees to the Washington, D.C.–based McKenna Long & Aldridge—Monsanto’s sometime law firm—but had yet to see results. How the public would react seemed scarcely considered. When I arrived in Florida, outreach about the impending cloud of OX513As had so far consisted of a single presentation to the local gay business alliance. (Soon, after attacks by Friends of the Earth and other anti-GM campaigners, the news was splashed across the front page of the Mosquito Control District Web site: “Special Notice. Genetically Modified Male Release Trials.”) In her presentation, the district’s representative had explained that hundreds of thousands of “sterile” Oxitec mosquitoes would be released every week for six months. Only female mosquitoes bite; these would be males. A cocktail of inspections, insecticides, and OX513As would reduce the native Aedes aegypti population “to zero or near zero.” Sustained, low-level releases would keep it down thereafter for a fee of $200,000 to $400,000 a year. Of course district staff would remain out in force, but to truly beat dengue, they would have to harness nature itself, at least a kind of nature. As she awkwardly explained to the gay business owners, male mosquitoes “are more effective than humans at finding females.”
• • •
“THE KEY ISSUE,” said Oxitec’s founder, Luke Alphey, “is that we need to get enough wild females to mate with them. It’s a question of quantity and quality. This is the quality test: Are the males sexy? Are they fit? Are they healthy? Are they happy?” In mosquitoes, he said, there were indirect proxies for determining this. Longevity was easily measured, and unfit Aedes aegypti died young. Size mattered: Small mosquitoes have smaller energy reserves. Maybe there was something to symmetry. Attractive humans were symmetrical. “Kylie Minogue has a symmetrical face,” he told me when I visited him in England. But the only way to really know if females would accept a genetically modified male instead of the natural variety was to do field tests, and that was why dengue’s expansion to GM-friendly places like Key West was so important to Oxitec.
Neither Alphey nor his company oversold the disease’s complex link to climate change, but Oxitec’s Web site sent visitors to a report by the Natural Resources Defense Council singling out global warming as a major factor in dengue’s global expansion, and its own pages also highlighted warming’s impact. “With the progression of climate change and the globalisation of travel and trade,” read a section marked “Epidemiology,” “it is predicted that dengue fever may spread further outside the current tropical zones.” Climate change was, at the very least, yet another reason that the world
might want to buy Oxitec’s products.
Alphey’s office was on the second floor of a brick building covered in wild grapevines, surrounded by a well-kept lawn and a copse of trees at the edge of an industrial park a dozen miles from Oxford University. The office itself was modest, mostly undecorated but for a scattering of papers, and Alphey, forty-seven, was tall and fit looking. He had a moderately symmetrical face. While activists have attacked Oxitec for its perceived secrecy, with me the former Oxford professor was an eager teacher, happy to spend the morning explaining the science behind his crowning invention.
He called it RIDL: “release of insects carrying a dominant lethal.” Protected by U.S. Patent application 11,733,737 (“the invention relates to a non-human multicellular organism carrying a dominant lethal genetic system”), it was, in Alphey’s explanation, a new way to carry out what was an old method of bug suppression. In the 1950s, entomologists had pioneered the Sterile Insect Technique (SIT): irradiating lab-raised fruit flies or tsetse flies, then releasing them. They mated with wild females but could produce no offspring. Unfortunately, mosquitoes were too fragile for SIT; the radiation killed them. So Alphey had sought a way to bake auto-elimination into their genes. He found it in a synthetic DNA known as tTA—a fusion of DNA segments from the bacteria E. coli and the herpes simplex virus—which he soon began inserting into Aedes aegypti. One difference between Alphey’s technique and traditional SIT was that the mosquitoes it created were not technically sterile. They could mate and produce offspring, but these would not grow past the larval stage without the presence of an antidote, the common antibiotic tetracycline. In Oxitec’s mosquito nursery, there was ample tetracycline. In nature, in theory, there was not.
In one study to test RIDL, Alphey had placed OX513As in one set of cages, unmodified males in another, and thrown in some “wild type” females. The OX513As were clumsy: They inseminated just over half as many partners, possibly because they ran out of sperm, and, unlike their rivals, seemed unable to distinguish between virgin and sullied wild-type females. But over a short time frame, three days, the modified and unmodified lines performed equally well. For investors, this might have looked like a silver lining: Not only would Oxitec have to produce and release swarms big enough to compete with the native population; it would have to do so quite often. A good rule of thumb, Alphey said, was twenty modded mosquitoes per week per human. “For a city of 5 million people,” he wrote in a paper, perhaps imagining Miami or Madrid or Ahmedabad or Belo Horizonte or any number of second cities in the third world, “this would correspond to releasing 100 million males per week.”
To those wary of genetic modification, intentionally releasing a transgenic organism into the wild might seem far scarier than optimizing an already domesticated crop. This is what the agricultural behemoth Monsanto, the world’s biggest seed company and first name in gene engineering, does over the howls of activists. But products like Monsanto’s—supercotton, supercorn—were designed to outcompete traditional varieties, Alphey pointed out. They were built to live. Oxitec’s products, on the other hand, were built to die. “Self-limiting is much better politically,” he told me. “You can say to regulators: If I stop releasing it, it all goes away.”
Yet Oxitec’s first Aedes aegypti field test, in the Cayman Islands 360 miles south of Florida, had been hugely controversial. The precursor to trials in Malaysia and Brazil and planned trials in Panama, India, Singapore, Thailand, and Vietnam, in addition to Key West, it began with local scientists manually separating male and female larvae by size—the females are bigger—using what one called “a sieve-like method.” They achieved 99.55 percent accuracy, and three million OX513As were released in a forty-acre area. Another way to say that is that one-half of 1 percent of those released, nearly fifteen thousand mosquitoes, were genetically modified females capable of biting local islanders who had little knowledge about the experiment. But the results, published in late 2011, were impressive: After six months, the number of wild Aedes aegypti was reduced by 80 percent—“a complete success,” proclaimed Alphey at a meeting of the American Society of Tropical Medicine and Hygiene, where he first announced the tests to a surprised world. (A later test, in Brazil’s Bahia state, would reduce the wild population by 96 percent.)
In the limited public outreach by Cayman Islands authorities before the trials—leaflets, a five-minute promotional spot on local television—there was no mention of genetic modification. The mosquitoes were repeatedly described as “sterile males,” language Alphey himself used until criticized for it. “If a female mates with a sterile male,” read a 2010 joint press release from Oxitec and Caymans scientists, “she will have no offspring, thus reducing the next generation’s population.” Researchers at the U.S. Department of Agriculture and Germany’s Max Planck Institute soon studied Oxitec’s papers and regulatory filings and pointed out an issue that was more than semantic: In the lab, nearly 3.5 percent of the larvae born to a modded male and wild female somehow survived, even without tetracycline. Nearly 3.5 percent of 100 million mosquitoes is a big number. “There is the plausible concern,” they wrote, “that females could inject tTA—the fusion of E. coli and herpes DNA—“into humans.”
Alphey readily conceded one worry expressed by critics: If Aedes aegypti is wiped out, might not Aedes albopictus, the Asian tiger mosquito, come fill its ecological niche? “In places where you’ve got both,” he said, “you’ve got to assume that by eliminating this one, you expand the other one a little bit. But albopictus is just a much less effective dengue vector.” In some cases, he suggested, Oxitec’s campaign against aegypti could happily morph into a campaign against albopictus—a kind of entomological Forever War. Oxitec’s first RIDL prototype, OX3688, had in fact been a strain of albopictus developed as that mosquito expanded across the U.S. market. It was now in the “product optimisation” phase.
• • •
ONE PROMINENT SUPPORTER of GM mosquitoes is the $33.5 billion Gates Foundation, the world’s largest charitable organization, which shares its founder’s focus on techno-fixes. In his 2012 annual letter, Bill Gates declared that “innovation is the key” but noted a structural problem: If profit is the motive, third world problems rarely receive first world solutions. “The private market does a great job of innovating in many areas,” he wrote, “particularly for people who have money. The focus of Melinda’s and my foundation is to encourage innovation in the areas where there is less profit opportunity but where the impact for those in need is very high.”
The Gates Foundation is so big that it can seem to single-handedly dictate global aid priorities, and two of its favorite causes are mosquito-borne illnesses and agriculture. In 2005, it gave a $19.7 million grant to a mosquito-modding consortium that included Oxitec and a number of public universities. (The money went toward open-source mosquito varieties, not OX513A.) The foundation also gave $13 million to a group in Asia and Australia trying to infect Aedes with a dengue-zapping bacteria, $62 million to the long-stalled international Dengue Vaccine Initiative, and half a billion dollars and counting to a partnership with GlaxoSmithKline (GSK) to hasten a long-awaited malaria vaccine that had been neglected—like many candidates for a dengue vaccine—because there had been little profit in a disease of the tropical poor. Like dengue, malaria was on a global expansion. “I think it’s fair to say that all of us in the global health community are aware of the potential impact of global warming,” says Dr. Rip Ballou of the Gates Foundation and formerly GSK and the vaccine’s champion for thirty years, “especially so when it comes to diseases transmitted by vectors.”
In agriculture, the equivalent of the GSK partnership was the Gates Foundation’s collaboration with Monsanto—the emerging leader in the race for climate-ready crops and, like GSK, a publicly traded company that couldn’t otherwise justify products meant for people who couldn’t afford them. Monsanto has revenues of $11 billion a year, and its stock is held by everyone from Deutsche Bank’s climate
funds to the Gates Foundation itself. It was a subcontractor for the Gates-funded African Agricultural Technology Foundation, which had received $40 million to develop drought-tolerant corn for five sub-Saharan countries. In 2009, the continent’s first varieties were tested under the South African sun. Just after Christmas two years later, Monsanto’s MON 87460—also a genetically modified, drought-resistant variety of maize—was quietly deregulated for use in Iowa, Indiana, and Nebraska. It came with a catch: The USDA had found it scarcely more drought tolerant than existing breeds. “Equally comparable varieties produced through conventional breeding techniques are readily available,” read the environmental assessment.
Since 2008, anti-GM activists have tracked preparations for global warming by Monsanto and what they call the five other “Gene Giants”: BASF, DuPont, Bayer, Dow, and Syngenta, the latter the alma mater of numerous senior Oxitec employees. The activists have identified at least 2,195 patent filings related to “abiotic stress tolerance”—resistance to extreme temperatures, resistance to droughts, resistance to anything in the environment that is not living but not friendly.
Dominating the climate-patent race were Monsanto and BASF, partners since 2007 in “the biggest joint biotech R&D program on record”—an eventually $2.5 billion effort to develop stress-tolerant corn, soybeans, wheat, cotton, and canola. Monsanto long ago shed its business as a manufacturer of chemicals—Phos-Chek for fires, Agent Orange for forests, DDT for insects—in the decades following a breakthrough: In 1982, its scientists were the first in the world to genetically modify a plant cell. But the patents upon which an empire was built—for the weed killer Roundup and for crops resistant to it—were beginning to expire. Monsanto needed another breakthrough. It was trying to reinvent itself. “How can we squeeze more food from a raindrop?” asked the Monsanto ad that appeared prominently in The New Yorker, The Atlantic, and National Geographic. When Monsanto and BASF identified a useful gene sequence in one plant, they often filed for a patent on it that applied to multiple plants. One issued to BASF in late 2009 is representative. “We claim . . . a transgenic plant cell transformed with an isolated polynucleotide,” begins U.S. patent 7,619,137. The plant cell was found in any of the following: “maize, wheat, rye, oat, triticale, rice, barley, soybean, peanut, cotton, rapeseed, canola, manihot, pepper, sunflower, tagetes, potato, tobacco, eggplant, tomato, Vicia species, pea, alfalfa, coffee, cacao, tea, Salix species, oil palm, coconut, perennial grasses, and a forage crop plant.”
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