Itchy

For more than 100 years, a swat team of brilliant scientists, pest-control shock troops, and eggheads with bizarre schemes (chicken-scented bug spray, anyone?) have been waging a global war against a foe no bigger than your fingernail. So why are we still getting murdered by mosquitoes?

    Photo: Photo by Corel

NO ONE really knows when the mosquito first evolved, but it's a safe bet that it predated the arrival of people by at least 100 million years. Back then, when the planet was a sweltering hothouse patrolled by giant lizards, the survival prospects for a dainty winged insect must have looked rather dim. Over the eons, though, evolution managed to match a taste for blood with a talent for extracting it, and the mosquito proved hardier than early handicappers might have expected. When entomologists examined the body of a hundred-million-year-old mosquito preserved in a chunk of amber, they found appendages on it tough enough to pierce dinosaur hide.

It's hard to advocate for the annihilation of a species, but if one were to pick a candidate, the mosquito—which has been bedeviling creatures ever since—would have to top the list. Whiny and dogged, they're Mary Poppins crossed with Typhoid Mary: an annoying, pestilential traveler that we can't quite manage to get rid of. Their diseases are grim. Every year, as many as 500 million people become infected with malaria, and close to two million of them die. Thousands more contract dengue, yellow fever, and West Nile virus. After a century of human-versus-bug combat, we're still barely denting this toll.

Even in their nonfatal form, mosquitoes possess a unique capacity to enrage. There are reports of mosquitoes hounding animals until they die of exhaustion, and driving explorers to madness. Whether or not this is strictly true, it's a sympathetic claim. Anyone who has passed a night plagued by a marauding hatch knows something about the limits of sanity.

Spend any time outdoors and this vulnerability becomes painfully clear. A few years ago, when I was 29, I spent a mosquitoey week in western Thailand. I suffered a total of about 20 bites, then returned to Bangkok to catch a flight home. By the time we landed, 14 hours later, I was incapacitated by fever, and my body was covered in tiny red bruises. The virus was dengue, a strain that's considered unpleasant but not earth-shaking. Even so, it took me a month to recover to the point where I could walk around the block without stopping for breath, and I lost half my hair. All because of a mosquito.

After that, I took to following the insect wars like an armchair general. What I learned was this: If we are turning a corner in this fight, it's a strange one. In the past six months, I spoke with one American biologist who was trying to create mosquitoes that didn't salivate at the smell of people and another who wanted to infect the bugs with a fungus that would addle their brains. I learned about one particularly obsessed Canadian scientist who built a set of six steel robots outfitted with heaters, which he dressed in human clothes and left in the woods—part of a complicated effort to prove that mosquitoes could sense body heat. Across the ocean, in Austria, an entomologist working for the International Atomic Energy Agency informed me, soberly, that he was in the planning stages for a factory capable of breeding a million sterile male mosquitoes a day for release in northern Sudan. (The idea being that the sterile bugs would outnumber fertile ones, causing the population to plummet.) All in all, I discovered, the task of concocting new strategies to eliminate mosquitoes now consumes the full-time careers of hundreds of brilliant scientists: a massive, multi-million-dollar effort to combat an insect so fragile that it can be killed by a brief gust of wind.

Expecting that any of these schemes will eventually pan out takes some effort. But I wanted to believe there was hope. We're smarter than mosquitoes, after all, and you have to root for the home team. Besides, we're still the underdogs: a species with skin like a baby zucchini, pitted against perfect killing machines, tiny airborne disease carriers equipped with a hypodermic snout and sensory equipment capable of detecting a person 50 yards away. Assessing our chances from an armchair, though, wasn't the same as touring the battlefield, and in the end I set off to find the front lines. The search led me from Baltimore high-rises to North African marshes, but it started, simply enough, in the swamp. The place where it all began.

WITH ITS ALGAL LAGOONS and moss-dripping trees, Florida is the buckle of the southern mosquito belt. Like much of the South, the state circa 1900 was a wasteland: a bog whose main export was yellow fever. That Miami is now a retirement capital rather than a death zone can be credited to turn-of-the-century scientists who finally made the mosquito–disease connection—and to the nationwide eradication campaigns that followed. Anti-mosquito brigades drained swamps and bulldozed wetlands. Canisters of DDT were handed out like hard candy. By 1950, the lower 48 states were mostly habitable. And there, as far as most of us know, the matter ended.

Except it didn't. The current pleasant state of things, it turns out, is about as

low-maintenance as the gardens of Versailles. And the prevailing, comparatively blithe attitude toward mosquitoes in America—as barbecue spoilers and canoe-trip pests—relies heavily on the work of an infantry of government employees who spend their days enforcing a kind of entomological Homeland Security: preemptively killing off billions of the bugs before they have a chance to become a threat.

In Boston, researchers hoist caged chickens into the trees as bait for mosquitoes that could be carrying West Nile virus, a scourge that arrived in New York seven years ago and quickly moved across the country. In Texas, roving patrols tip the standing water out of discarded tires. And in the Florida Keys, Andrea Leal and John Snell kill mosquitoes by hand.

"You know it's a bad day when you come back with blood spots all over your clothing," Leal remarks as she winches a government-issue low-draft motorboat into the shallows north of Key West. As the field crew for Florida Keys Mosquito Control District, Leal and Snell spend their days bushwhacking through dozens of unpopulated offshore islands, setting traps and killing larvae to keep infestations from spreading to the mainland. They also conduct counts, a process that consists of pushing up both sleeves and recording how many bugs land on your arms in a minute.

The job is much worse than it sounds. Despite their celebrity reputation, the majority of Florida's Keys are lousy real estate: small, mangrove-knitted islets infested with overgrown spiders and collared by sulfurous mud. Their capacity to produce mosquitoes is legendary. In previous years, crews could expect to get 200 bites a day despite wearing net suits, canvas gloves, and thigh-high rubber waders.

Annett Key, where we land, is no different. On the day I go out with Leal and Snell, the tide is at mid-ebb, forcing Snell to push the boat over sandbars with one leg, like a huge skateboard. On shore, the pair wade through the mud and force a path through the matted jungle of branches, seeking out pools of standing water. When they find one containing mosquito larvae, they open a Ziploc bag of gray pellets—corncob bits impregnated with the insecticide Bti (Bacillus thuringiensis israelensis)—and dribble a few in the water. Then they move on.

Because the salt-marsh mosquitoes here don't carry disease, the fieldwork is not especially dangerous. Still, the heat is oppressive and the footing slick, exacerbated by mangrove roots that grow upward out of the ground like pale, rubbery fingers. By the time we reach the middle of the island, I'm speckled with mosquito bites and sweating through my hat. And this, I'm repeatedly assured, is a good day.

Before Bti treatment began, six years ago, the islands were truly horrendous. Leal's predecessor, Josh Vlach, recalls hanging a trap—a plastic cylinder one foot wide and six inches high—overnight on Little Pine Key and returning the next morning to find it had attracted 464,000 mosquitoes. "When you pulled up in the boat, you would literally hear the island humming," he tells me by phone from his new job in Oregon. "I truly believe they could have killed you."

This is not an exaggeration. Mosquitoes have been known to kill cattle in southern Florida by sheer numbers, packing the cows' noses and mouths so densely that they suffocate. "They completely cover your face," Vlach says. "You really can't help but panic." He describes an instance when an assistant failed to bring his head net and, overwhelmed by the resulting swarm, fled blindly through the brush, smacked into a low-hanging tree branch, and knocked himself senseless.

To amuse himself, Vlach once calculated the number of bites a person would have to get before dying from blood loss. It is 424,242—a number close to what an unclothed, unprotected person might have experienced on a midsummer night on Little Pine six years ago.

ALTHOUGH YOU WOULDN'T know it from a day on Little Pine, human beings are an acquired taste for mosquitoes. Of 2,500-plus species, only the females of a few dozen varieties feed on people. And even that is a recent development. Five thousand years ago, when humans were still scattered, mosquitoes fed primarily on deer and cattle. Over the millennia, however, people multiplied and migrated. We made jugs to store water and canals to carry it. Mosquitoes, which need still water to lay eggs, naturally followed.

A handful of lethal pathogens, meanwhile, learned to hitchhike, infiltrating the mosquito's salivary glands and multiplying in its gut. It was a brilliant move. Furnished with door-to-door transport between bloodstreams, diseases traveled far and wide, crossing species and taking hold wherever man's footprint gave them access. West Nile, a bird affliction first discovered in 1937, in an area of Uganda near the Nile Valley, soon colonized people—picked up and passed on in two bites of a mosquito. In Africa, dam building helped spread malaria and Rift Valley fever, while rainforest logging in South America brought species that once bred only in sunny canopies down to the forest floor, to bite people's ankles.

The effects have been staggering, particularly where malaria is concerned. The species that carries the parasite, Anopheles gambiae, is a prolific breeder, capable of laying hundreds of eggs in places as hard to target= as the muddy water filling a hoofprint or the ounce of rainfall left cupped in a plant. As a result, they also adapt quickly to new threats. Even DDT has begun to lose its punch. Malaria parasites, meanwhile, have become drug-resistant in areas throughout Africa, Asia, and South America, rendering chloroquine and other preventives less effective. Faced with these facts, the mosquito wars recently underwent a profound ideological shift: Instead of trying to eradicate the insects, researchers began trying to cure them.

This strategy is driven by a strange paradox of mosquito-borne illnesses: that for all their virulence, diseases like malaria and dengue fever rely on a system of transmission so improbable and Rube Goldbergian, it's amazing they exist at all. Of the millions of anopheles exposed to malaria, for instance, the vast majority successfully fight off the parasite, the same way a person might shrug off the flu. "If you go to a place with a high malaria rate, the number of infected mosquitoes is surprisingly low—a few percent," says Marcelo Jacobs-Lorena, a geneticist who studies malaria at the new Johns Hopkins Malaria Research Institute, in Baltimore. Those insects—the tiny percentage whose immune systems aren't up to snuff—are the ones that spread the disease.

And even that transmission is a crapshoot. The malaria parasite needs a full ten days to reproduce inside a mosquito's stomach—a time frame that falls uncomfortably close to the anopheles's life span. The vast majority of mosquitoes, moreover, die well before then: eaten, drowned, swatted, or crushed by spiders, fish, carnivorous plants, and people. Overall, just three or four infected mosquitoes out of a hundred live long enough to bite a new victim.

Given these odds, Jacobs-Lorena theorized that even a small tweak might be enough to interrupt the infectious cycle. "You have to realize that thousands of different parasites have probably tried to evolve to be carried by mosquitoes," he notes. "Most failed. Finally, after millions of tries, malaria and a few others managed it."

A courtly and patient researcher, Jacobs-Lorena has spent 17 years studying mosquito diseases, 14 of them in relative obscurity at Case Western Reserve University, in Cleveland. Then, in 2003, he rather suddenly found himself being wooed by Johns Hopkins, which had just received a large, anonymous donation earmarked for malaria research. (Prospects in this line of work have also been enormously brightened by another donor, the Bill and Melinda Gates Foundation, which has given hundreds of millions of dollars to malaria research over the past seven years.)

For Jacobs-Lorena, meanwhile, the work at Johns Hopkins intensified. He'd already identified the peptide that protects mosquitoes against malaria, and also synthesized the gene that produces the peptide. But then things turned complicated. While it's easy to endow mosquitoes with a protective peptide gene in the lab, it's far harder to do in the wild. "How do you spread the gene in nature?" Jacobs-Lorena asks.

The problem proved intractable enough for him to switch tacks. Rather than trying to cure mosquitoes with gene therapy, he's experimenting with something like antimalarial medicine for them: an innocuous transgenic bacteria that they can feed on in the wild.

Whether or not it works, interrupting a complex system like malaria with genetics is a bit like damming a river with pebbles. There are a lot of points where something can slip through and perhaps make things even worse. According to David Smith, a mathematical epidemiologist with the National Institutes of Health, reducing the number of infected mosquitoes, while good in the short term, can actually be dangerous, because it causes people to lose the immunity they develop from constant exposure. "As long as the reduction holds, death rates will go down," Smith says. "But if malarial mosquitoes rebound, the number of people dying from malaria could skyrocket."

The upshot, Smith believes, is that "once we start to intervene, we may have to be truly committed. Forever."

GENETICS MAY BE THE BUG WARS' big-ticket strategy—a kind of high-tech entomological bunker buster—but battles can also be won from unexpected corners. While Jacobs-Lorena was breeding mosquitoes in Baltimore, doctors working in malaria-plagued rural villages made an interesting discovery of their own: Some houses attract hundreds of mosquitoes, while others attract almost none. In part, this is a matter of location—the closer the bogs, the thicker the bugs. But it also seems to depend on who lives there. According to recent studies, it now looks like about 20 percent of the people attract 80 percent of the bites. (If you've always felt like the most bitten person in the group, in other words, you might be right.)

What makes a person a pied piper of the mosquito world is a subject of great interest to epidemiologists,

and understanding "the 20-80 problem," as it's known, has become one of the oddest fronts in the mosquito war. In public-health circles, pied pipers are known as "superspreaders," because they are more likely both to get malaria and to pass it along, by infecting the many mosquitoes that bite them. Identifying superspreaders would be a boon to prevention, since they're responsible for the vast majority of new infections: Cure them and you help break the cycle.

The difference between an average person and a superspreader is subtle, although there are clues. Old Africa hands have long noticed that people who drink heavily tend to attract more mosquitoes, as do people who rarely bathe. Ten years ago, Austrian researcher Bart Knols decided to do some tests. He released four species of mosquito into a tall, screened box, then stripped to his underwear and took notes on where they bit.

Tastes varied, he found. The European anopheles, for instance, gravitated to his face, while the African anopheles hung around his feet. Knols then analyzed the bacteria from his feet and experimented by offering the insects a wedge of Limburger cheese, which is cultured with the same odor-producing bacteria. The African bugs swarmed it. But when Knols reported his findings in a journal article, the scientific community was doubtful. "Unfortunately, the article happened to be published in the April 1 issue," Knols says. "Everyone thought it was a joke, attracting mosquitoes with a dairy product."

Nonetheless, the idea—that subtle variations in smell contribute to appeal—was tantalizing. Solve the odor mystery and we could find the superspreaders or create irresistibly scented traps and lure millions of bugs to their deaths. So far, though, the details have proved hard to pin down. The problem is that mammals, crudely speaking, tend to smell the same. Two chemicals that humans exude copiously—lactic acid and carbon dioxide—are so abundant they tend to drown out fainter scents. "It's tough enough to figure out what distinguishes a person from a cow," says Laurence Zwiebel, a professor of biological sciences at Vanderbilt University. "Figuring out what distinguishes one person from another—bearing in mind that people's odors change daily, based on things like stress level and diet—that's really tricky."

Knols eventually left to pursue other projects; he's now overseeing the construction of the sterile-male-mosquito-breeding facility for Sudan. Replacing him on the odor front is Ulrich Bernier, a slight man who smells faintly of sport deodorant. A chemist with the USDA's Mosquito and Fly Research Unit, in Gainesville, Florida, Bernier became interested in smell as a grad student and has spent the past ten years attempting to compile a comprehensive catalog of human odors and their effects on mosquitoes. One recent sample population included a lab technician, a departmental secretary, and Bernier's immediate superior, each of whom spent half an hour with their arms and feet inside bags full of nitrogen gas. When Bernier piped the three mixtures through a gas chromatograph—a machine that identifies the presence and abundance of chemicals—the resulting graph revealed 350 compounds. Bernier combined the 30 most dominant compounds into a batch he felt sure mosquitoes would flock to. Such a concoction could be used to bait a trap—hang one in the yard!—and could provide clues when it came to creating a truly effective repellent. "We thought, This is going to be great!" Bernier recalls.

Bernier and his colleague Dan Kline put a capful of the solution in an olfactometer, an apparatus that consists of two traps and a Plexiglas box full of mosquitoes. Based on the number of mosquitoes that fly into the traps, one can measure a scent's attractant power. Ten minutes passed, then twenty. "It was like Silent Spring," Kline says, grimly. "We didn't get a single mosquito."

Shortly after I meet Kline, he takes me on a tour of the USDA insectary, where different mosquito species are bred. It's a humid space lined with finely woven mesh cages, one of which has a live chicken lashed on top. Typically, Kline explains, larvae are fed yeast and liver powder, while adults get a sugar cube and, once a week, a tube of fresh beef blood suspended in a natural-membrane condom. Some species, however, are such picky eaters that they will feed only on a living animal. Kline shows me his right forearm, which is dotted with lurid red welts—products of an Australian colony's morning meal. "Technically, you're not supposed to feed them off yourself," he says, shrugging. "But sometimes it's the only way they'll eat."

Such finickiness indicates that it may be even harder to fool mosquitoes than anybody expected. Bernier has used his tests to develop more successful compounds, several of which he is in the process of patenting. Even with his best mix, however, 95 percent of mosquitoes will still choose a person over the artificial attractant. "The fact is, we're hard to beat," says Bernier. "We have all the chemicals, in just the right ratio. Mosquitoes can tell that." And while he has yet to discover the blend of chemicals that mark a person as particularly enticing, he did recently come close to identifying several that appear to be off-putting, produced by the departmental secretary (who revealed that she rarely gets bitten).

Bernier thinks that altering our smell even a little could muddle a mosquito's radar, effectively rendering a person invisible—or at least undesirable. This, in turn, could spare us from more toxic chemicals like deet, which is strong enough to eat away at plastic in high concentrations, and permethrin, a neurotoxin that shouldn't be applied directly to the skin. Bernier recently began testing an extract made from chicken feathers that he hopes will confuse mosquitoes by making a person smell like a large, unusually malodorous bird. He admits that a chicken-scented repellent is unlikely to catch on in a place as deodorant-obsessed as the U.S., but he holds out hope that it could flourish somewhere. "It might work for a species like the anopheles, that bites only people," he says. "You wouldn't want to wear it around mosquitoes that feed on birds, of course."

IN THE PROCESS OF combating mosquitoes, we have become strangely intimate with them. We've spent thousands of hours noting their habits; we know what makes them sick and well, the details of their copulation, and the molecular biology of their digestion. But when I ask Bernier whether he ever gets a version of Stockholm syndrome and starts sympathizing with the bugs, he looks at me as if I've lost my mind. "No," he says finally. "I pretty much just hate them."

The grudge is not unprovoked, considering what mosquitoes have wrought—even in places close to home. In the summer of 1999, New York hospitals started reporting mysterious fatalities from encephalitis, with symptoms including fever, coma, and partial paralysis. By September, the Centers for Disease Control had identified the pathogen as West Nile. It seemed the virus had somehow made its way to the U.S.

To this day, the source of the American West Nile epidemic—Insect Zero—remains a puzzle. "A tropical disease originating in New York—it was weird," says Colonel Mike Bunning, a mosquito specialist who at the time was working with the CDC's Division of Vector-Borne Infectious Diseases, in Fort Collins, Colorado. One theory proposed that a diseased mosquito from Africa had arrived accidentally packaged in a shipping container.

Bunning himself is of the mind that West Nile arrived inside an imported alligator, shipped from somewhere in Africa to the Bronx Zoo, and that it invaded local Culex pipiens when they fed. Shortly before the virus was first spotted in people, alligators at six Florida gator farms sickened and died. Bunning tested his hypothesis by infecting several alligators with West Nile and cooling them to 55 degrees for 90 days, to simulate shipping conditions. When the reptiles were warmed up again, Bunning let several dozen culex take blood meals from them. A week later, Bunning says, all the mosquitoes that had fed on the alligators developed West Nile.

Casualty-wise, West Nile has not turned out to be terribly lethal. Between 1999 and this spring, it has killed 785 people in the U.S. But its arrival was an unsettling moment on the seemingly secure home front. And among scientists in the field, the possibility of what mosquito disease might arrive next is a regular topic of discussion.

"The talk of the town these days is Rift Valley fever," says Bernier. A mosquito-borne viral disease found almost exclusively in Africa, Rift Valley fever is not usually fatal, but it can cause serious health problems, and in recent years it's made forays into Saudi Arabia and Yemen. "As far as we know, there's nothing to stop it from spreading to the U.S.," Bernier says. "It's probably just luck that it hasn't."

And not all countries are so lucky. "We're not making a lot of progress in the developing world," allows Paul Reiter, a former CDC scientist now based in Europe. "But I guess I'm still an optimist."

As scientists go, Reiter has the kind of reputation suited to Clive Cussler novels. At the CDC, he was known for frequenting Memphis cemeteries to capture mosquitoes and harvest larvae from graveside flower vases. Over his 30-year career, he has crawled through sewers to flush out filth-dwelling culex, dropped into Kenya when it was plagued by yellow fever, and walked from village to village in southern Sudan, collecting data on a lethal hemorrhagic virus.

These days, Reiter works for the Pasteur Institute, in Paris, and heads a project known as Emerging Diseases in a Changing European Environment. The idea is to learn how viruses like West Nile are carried over long distances, by testing the blood of migrating birds and tracking which ones might be carrying disease. The project will have several outposts: five in Europe and one in Djoudj, a bird refuge on the border between Senegal and Mauritania.

The goal of the Senegal station is to monitor birds migrating from West Africa to various parts of Europe. (Romania recently experienced one of the worst West Nile outbreaks on the continent.) At first, Reiter is reluctant to let me accompany him on a trip there. Djoudj will be a busy place, he says, and workdays will be long. He agrees to my presence on the condition that I shadow him silently.

Given Reiter's warnings, I plan to stay out of his hair when I join him and his colleagues—three local scientists from Dakar—in the town of Saint-Louis, an hour's drive from the refuge, which is on Senegal's northwest coast. But I needn't have worried. As it turns out, the research station we've come to visit hasn't even been built yet. The only thing on view as we pull up to the refuge's center is a horde of French tourists, recently returned from birdwatching and clutching dinner-plate-size lily flowers.

Reiter is apologetic—he wonders aloud about where the project's money is going—but decides to make the best of it. We pile into the long wooden motorboat vacated by the birdwatchers and putter slowly past tamarisk-covered islands and canals choked by lilies.

Although the refuge seems like a place mosquitoes would like, in the heat of the day the insects prove elusive. We spend two hours puttering around the flat brown bays that smell like damp tea leaves without seeing a single one. Reiter snaps some photos and admires a line of pelicans wavering across the sky like a Chinese dragon. Then we head back to the hotel.

The next time Reiter and I talk, it's a rather strange conversation by phone. Although he insists that he remains upbeat about the prospects for a Senegal research station, his observations about the mosquito wars veer, in long stretches, toward something more closely resembling despair. The mosquito, he remarks at one point, is so adaptable that it's hard to imagine any scientific fix working for long.

"That always worries me," he says. He recalls a conference where a researcher working on a malaria vaccine banged on the table and denounced fieldwork like Reiter's as a waste of time. "That was 15 years ago," Reiter says, noting that there still is no vaccine. Then he pauses. "Of course, those of us doing fieldwork haven't really succeeded, either."

It's a melancholy assessment, and it reminds me of a moment—one of the few in Senegal–when I actually saw a mosquito. It was sitting on Reiter's neck. The encounter was opportunistic, of course: The mosquito couldn't know that it was biting its archenemy. At the same time, I felt like a voyeur, glimpsing an illicit kiss. Reiter, who was busy talking, hadn't noticed the contact, and it took a moment for me to react. Belatedly, I raised my hand, but even as I did, the mosquito rose up and vanished.

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