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The Worst Animal in the World
For about a week this past September, I adopted a wellness routine that—at the time—felt like neurotic overkill. I didn’t bother with masks or hand sanitizer; back then, the virus we now know as SARS-CoV-2 was still presumably nestled in the warm body of an unknown animal. Instead, each morning, I spritzed my arms and legs with picaridin, a chemical repellent meant to ward off parasitic bugs. Then I covered myself with one of several increasingly crusty sets of khaki pants and long-sleeved shirts that I had infused with the insecticide permethrin. Only then, force field up, would I venture outside.
I had come to Dakar, Senegal, to get close—but not too close—to Aedes aegypti, a globally invasive mosquito that is arguably the worst animal in the world. The species carries yellow fever and dengue, both of which can cause more severe disease in young adults than SARS-CoV-2; Zika virus, which can lead to birth defects; and chikungunya virus, which can leave victims with debilitating joint pain.
Unlike viruses that travel person-to-person, most of these pathogens can spread only in places where mosquitoes live. Then again, aegypti’s range is immense. All told, her bites—and only females bite—cause an estimated 400 million infections each year, which means that several dozen people have been infected in the time it took you to read this sentence. In 2019, when the World Health Organization compiled a list of threats to global health, dengue got a whole slot to itself. Zika showed up in another slot, sharing billing with Ebola, SARS, and “disease X,” the prospect of some then-unknown pathogen with epidemic potential.
In Senegal, my own illusion of invulnerability lasted until I met Mawlouth Diallo, a medical entomologist from the Pasteur Institute in Dakar. Wearing a matching blue kaftan set, he sat with me in my hotel lobby for more than an hour, earnestly explaining his team’s mosquito research in smooth, French-accented English. Finally, I had to ask a nagging, basic question.
“Sitting here, right here,” I said, gesturing to the air-conditioned lobby, “where is the nearest Aedes aegypti?”
Diallo seemed confused at the question. “Where?”
“Like, could we go find some of them outside right now?”
“No, it is inside,” he said, then laughed out loud at the expression on my face. “For sure, aegypti is inside the hotel.” When dengue broke out in Dakar in 2009, the city’s Lebanese population was hit the hardest. One reason, Diallo said, was that mosquitoes and wealthy foreigners are both drawn to luxury indoor environments. In this lobby, he said, the best place to find Aedes aegypti would be the flowerpots.
I laughed with him, albeit less easily. Of the 3,000-plus mosquito species alive, most are fairly harmless. Only a handful are a concern for public-health officials. But Aedes aegypti is different. Whether in Rio de Janeiro, New Delhi, or Miami-Dade County, it will breed in clean water supplies, it will come indoors, it will make a beeline toward human odor, and it will bite when the sun is up, circumventing bed nets that protect at night. Masks to prevent the spread of COVID-19 won’t make a difference. Neither will staying at home, unless you live in a closed, air-conditioned house. No other mosquito is so perfectly suited to live with, and on, human beings.
The problem will get worse. Beyond the tropics and subtropics, the species has strongholds in Florida, Texas, California, and Arizona, and at least one population has managed to survive multiple winters in Washington, D.C. One recent study projected that by 2050, thanks to the climate crisis, the North American range of Aedes aegypti will extend to Chicago; in China, its range will go as far north as Shanghai.
In response, the world is readying an arsenal of shiny new biological tools. But as scientists and policy makers plan to subvert the species’ evolutionary future, it’s especially important to grapple with its origins, the kind of processes that begin long before once-obscure pathogens emerge from clear-cut rainforests or animal markets. In tropical Africa, especially Senegal, researchers are uncovering the shared history of aegypti and its favorite host, learning how environmental change, slavery, and colonialism turned a local mosquito into a global menace.
After chatting in the hotel lobby, Diallo agreed to find me some mosquitoes. Outdoors, we walked half a block and poked around a construction site, looking for standing water in buckets and concrete blocks before fending off a nervous manager. Then Diallo saw a tire leaning against a wall. Reaching inside with a discarded coffee cup, he scooped out a little water—in which he pointed out at least a dozen larvae.
Cup in hand, Diallo hailed us a cab and negotiated a fare to the Pasteur Institute. In his lab, he led me into a room full of mesh cages of aegypti from all over the country. The mosquitoes looked, in my paranoid imagination, very eager to get out.
That afternoon, when I returned to my hotel, I walked over to the pool. I waited until nobody was watching, then bent to look into the wet, shaded basin under one of the large flowerpots. The shadows wriggled, and I recoiled. The next morning, despite all my defenses, I noticed the first bites on my arm.
Aedes aegypti, whatever else you want to say about it, is a good-looking animal. Entomologists have described it to me as “elegant,” “quite attractive,” and even “beautiful.” Photographs often show it perched delicately on pink skin, displaying long limbs with black-and-white jailbird stripes. That pretty pattern belies an ugly disposition; the name of its scientific genus is derived from the Greek for “unpleasant.”
Fair enough. But aegypti wasn’t always unpleasant. Within the past few thousand years, somewhere in Senegal or farther down the continent in modern-day Angola, biologists suspect that aegypti took its first step toward world domination.
Early hints of this story surfaced in the 1960s, when medical entomologists in the Rabai region of Kenya saw the species breeding in earthenware pots of water and feasting on their human hosts. “Every house they’d go into would just be teeming with these mosquitoes,” says the Princeton evolutionary biologist Lindy McBride, who has revisited the same sites.
No surprise so far. This was the familiar, human-obsessed aegypti. But outside the Rabai houses, researchers spotted another form of aegypti. This variant laid its eggs in holes in the trunks of trees, not pots of water; it preferred to bite animals, not people. Yet it wasn’t a new species. It was a trace of the ancestral aegypti, a relic of a more innocent time.
Scientists have since found undomesticated populations of the species across tropical Africa. They hope to understand not just how the domesticated form picked up its particularly nightmarish set of skills, but how other species might be bending the same way under the same forces. “If we can understand where [aegypti] comes from and how it works, the hope is, we can figure out how to stop it,” says Noah Rose, a postdoc in McBride’s lab at Princeton.
Senegal, especially, might be the key. Starting in 2017, Rose went on a series of road trips across sub-Saharan African countries. In Senegal, Rose teamed up with the ecologist Massamba Sylla, who had already discovered something unique about the country’s mosquitoes.
After an hour-and-a-half-long cab ride inland from Dakar, during which I watched the scenery change from very dusty to extremely dusty, I met Sylla in a café in the city of Thiès. Over croissants and café au lait, we flipped through photos from his expeditions on his laptop as he described his lifelong, wife-vexing passion for field entomology. “Once it catches you, you put all your time into doing it,” he said.
During his travels, Sylla discovered a pattern. Senegal’s climate ranges from desert in the northwest to tropical rainforest in the southeast; as these habitats blend into one another, so do the parasites. In dry cities on the coast such as Saint Louis and Dakar, Sylla and collaborators found only domesticated mosquitoes. But in towns in the far southeast, they collected almost exclusively undomesticated mosquitoes, breeding in tree holes or in the husks of fallen fruit. Between the two extremes, Sylla found a continuum of domesticated and undomesticated aegypti.
When Rose came to the country in August of 2018, he and Sylla drove along the same gradient, from dry Dakar in the south to where the countryside flushes green and rivers block the roads. The trip was not without risk: A decade earlier, another American researcher working in the southeast with Sylla flew back home before developing flu-like symptoms—Zika, it turned out, which he then transmitted to his wife through sex.
This time, though, no one got sick, and the collection process they followed was alarmingly easy. They collected the eggs in oviposition traps lined with filter paper, upon which the eggs can survive dormant for months. Once back in New Jersey, Rose submerged the eggs in water; most hatched overnight. “You’ve suddenly just transferred a whole population of mosquitoes between continents,” he told me, “with almost no effort expended.”
Rose tested mosquitoes from across the Senegal transect and other countries, imprisoning them in plexiglass cages and presenting them with two olfactory options. They could fly down a tube that led to his own arm, or down another that led to a hapless guinea pig. Screens shielded both Rose and the guinea pig from actual bites.
These tests, recently summarized in the study, show that places in northern Senegal near Dakar — with severe dry seasons but crawling with people, who come with their own water supply — host the most human-craving mosquitoes Rose harvested anywhere in Africa. But the country also contains the widest range of aegypti behaviors, from almost exclusive animal-biting in the southeast to exclusive human-biting in the northwest. This diversity suggests that Senegal could be where the transformation happened.
Scientists still don’t know the specific reasons for the change. But here’s one plausible scenario of aegypti evolution, described to me by the biologist Jeffrey Powell at Yale University. Imagine a city near or encroaching on the forest. The climate slides into a drought, and animals are scarce. But human communities still offer warm-blooded bodies to drink from and cisterns of clean water to lay eggs in, enough to support aegypti until the rains return. Now imagine aegypti, over several generations, adapting to this new, more reliable lifestyle.
Some 500 years ago, after our domesticated aegypti had evolved in dry coastal cities in Senegal, Angola, and elsewhere on the African continent, European ships arrived on the Atlantic coast and began to carry away human beings. As the global tragedy of slavery unfolded, aegypti unleashed itself on the wider world.
Dakar, a French- and Wolof-speaking city clogged with determined street vendors, honking cabs, and clomping horse-drawn carts, was once the administrative center of French West Africa. Now it’s Senegal’s capital. The larger metropolitan area, home to some 3 million people, is still trying to cram itself onto the Cape Verde peninsula, which curls out into the Atlantic from the westernmost point of Africa like an arm bent at the elbow.
When the Portuguese sailed into the peninsula’s enclosed harbor in 1444, the city of Dakar did not exist. For societies living between the Senegal and Gambia Rivers, the Atlantic was a dead end. Trade came instead from the Muslim world to the east. But after Europeans arrived, the slave-trading outposts they built along the African coast began to exert their own gravity.
To meet the European demand for enslaved people, some societies launched massive manhunts against neighbors. Normal economies collapsed. Famines struck, leaving victims so hungry that they offered themselves up to enslavers. “This predatory business, which reduced the producer to an export commodity, pushed Senegambian societies into a state of regression,” writes the West African historian Boubacar Barry. “Violence became the dominant motive force of their history.”
At staging grounds such as Goree Island, enslavers conducted invasive physical examinations to screen out unhealthy people. After loading their captives on boats, though, they locked many inside the hold in rank, appalling conditions rather than risk having them revolt or jump overboard. Disease and death were rampant. For the crew and a profitable percentage of the captives to survive the two-to-four-month journey across the ocean, the ships also needed to carry dozens of water barrels. The concentrated humanity combined with the abundant standing water offered domesticated aegypti everything it needed to stow along.
Meanwhile, the same bottomless avarice that brought enslaved people and aegypti to the Caribbean had terraformed their destination. After uprooting indigenous populations, enslavers cleared large areas for sugarcane, then razed even more forest for the fuel they needed to reduce cane juice to crystals. Clearing the dense, moist stands, they assumed, would also eliminate the noxious miasmas that they believed to be the ultimate source of disease.
They were wrong. With forests gone, invasive species replaced insect-eating birds. Erosion caused flash floods. Loose sediments collected into marshland, creating new breeding grounds for mosquitoes. Native Anopheles mosquitoes ingested the malaria parasite from the blood of incoming West Africans and spread malaria throughout the islands. As for the arriving aegypti, it found the Caribbean’s ports and sugar plantations teeming with human victims, standing water, and pure cane juice—which the species will also drink in a pinch. By the 1640s, aegypti had made itself at home in the islands, and was quietly setting the stage for something worse.
Around this time, the yellow-fever virus must have also made the trip over from Africa, likely volleying between mosquitoes and infected enslaved people or sailors during the long voyage. Yellow fever wreaks special havoc on adult immune systems that have never encountered it before. First victims get flu-like fever and aches for a few days, then appear to recover. Typically this recovery sticks. Otherwise, they get sick again, this time with jaundice—hence the “yellow”—and start vomiting up blood, hence the disease’s Spanish name, vomito negro.
An early outbreak hit Barbados in 1647, leaving 6,000 people dead before rippling through the rest of the Caribbean. Yellow fever then sloshed from port to port for centuries, borne on silent wings. Ships, ports, and cities formed an invisible circulatory system. In summertime, the yellow-fever virus could materialize far outside its normal range—as in 1793, when one of America’s foundational disease outbreaks killed one in 10 Philadelphians and abated only once fall brought frost.
Here aegypti, itself shaped by history, began to shape history back. Once established in the Americas, as the historian J. R. McNeill argues in his 2010 book, Mosquito Empires, endemic malaria and especially yellow fever gave local populations an advantage against foreign powers, whose soldiers would show up to fight with less seasoned immune systems. All locals had to do was survive outright confrontation—and wait. Yellow fever helped Spain defend its holdings against European competitors; malaria weakened British forces during the American Revolution. When Toussaint L’Ouverture fought to liberate Haiti, yellow fever may have been his staunchest ally.
The domesticated aegypti had established itself quickly across the Atlantic, altering the history of the Americas in the process. In 2018, Powell at Yale published a landmark study showing that mosquito genomes and epidemiological records reflected the historical timeline. “The histories of the slave trade, the mosquito populations, and the disease outbreaks are all telling the same story,” he said.
And then aegypti kept going. After ships crossed from Africa to the Americas, they headed back to Europe laden with goods such as sugar. Soon, a few mosquitoes likely hitched a ride on this leg of the trip too. In 1801, Spain’s queen consort, Maria Luisa de Parma, suffered from a disease she called dengue. Around then, aegypti was making itself comfortable in the Mediterranean, and would go on to cause outbreaks of yellow fever and dengue there for decades. When the Suez Canal opened in 1869, it offered the species a back way out of the Mediterranean into the Pacific. Before that century’s end, the first clear outbreaks of chikungunya and dengue had appeared in Asia.
Meanwhile, yellow fever kept burning through the tropics. Nobody even knew what carried it until the 1880s, when a Cuban doctor named Carlos Finlay made a then-preposterous proposal: Maybe mosquitoes caused these outbreaks. The U.S. Army pathologist Walter Reed proved Finlay’s theory in 1900, finally giving humans a chance to slow the spread of the disease by putting up screens and getting rid of standing water. Between then and now, though, the sun still hasn’t set on aegypti’s empire.
Yellow fever itself has been mostly brought to heel. The breakthrough came in 1928, when competing American, French, and English research teams across Africa convened in Dakar to discuss the tragic case of one Adrian Stokes.
After France had abolished slavery in Senegal, in 1848, the colonial government conquered inland states and set up peanut farms, devising new systems to profit from African labor that soon expanded into other colonies. “Senegal was a laboratory for the European powers,” says Mor Ndao, a historian of tropical medicine at Dakar’s Cheikh Anta Diop University.
Disease stood in their way. Yellow fever “was an obstacle for the exploitation of the African continent,” Ndao told me. Senegal’s coastal cities had long been gripped by their own yellow-fever outbreaks, which public officials and even scientists invoked to justify race- and class-based “sanitary” segregation long after the mosquito hypothesis had proved what really carried the disease. But the death of Stokes, an Irish pathologist, offered a new way forward.
The year before, in 1927, Stokes had contracted yellow fever while helping isolate the virus from the blood of a Ghanaian man named Asibi. The pathologist demanded that his colleagues draw his blood and let mosquitoes bite him. Injections of that blood and bites from those mosquitoes both caused fatal yellow-fever cases in monkeys, proving that the team really had captured the infectious substance itself. Stokes died four days after contracting the virus, and was buried in Lagos. He was the first author on the pivotal scientific paper.
Upon hearing of this success, the French team at the Pasteur Institute isolated their own strain from a local patient named Francois Mayali. After sharing their findings in the Dakar meeting, multiple groups of scientists started working on vaccines. Mass vaccination campaigns began in the following decades, pushing yellow fever and its bloodsucking vector out of mind and making the tropics less scary for Ndao’s would-be exploiters. Today, virtually every yellow-fever vaccine, including the one I got before visiting Dakar, bears a hint of these colonial beginnings: They still use a watered-down version of the strain taken from Asibi.
With the world’s attention diverted, this win soured. During the past century, similar viruses emerged from forests in Africa and Asia. Reaching urban areas, they all found aegypti ready to ferry them from person to person. First came dengue, which leaked out into a bigger global problem as southeast Asia urbanized after World War II. Then in 2006, more than a million people in India may have caught chikungunya. This past decade, Zika emerged on a similar scale in the Americas. Even yellow fever—still the only aegypti-carried disease with a safe, publicly available vaccine—has staged a comeback: two African outbreaks in 2016.
All this, remember, wrought by what were once inoffensive forest insects.
Rose’s study projects that Africa’s milder, wilder populations of aegypti may crank up their own appetite for humans by 2050, as dense cities spring up across the continent. In response to that alarming forecast, a new collaboration of scientists from across the Sahel, the semiarid region south of the Sahara, is collecting more local eggs—but that research has gotten off to a slow start thanks to COVID-19 and extremist groups in the region, Rose says.
Perhaps a deeper worry is that thousands of other mosquito species out there have their own capacity to change. During the Second World War, when Londoners hid in the city’s Underground tunnels to escape bombing during the Blitz, they were swarmed by a form of the mosquito Culex pipiens that had already adapted to the world’s oldest subway system. That same pest now haunts subterranean Manhattan. And just in the past four decades, Aedes albopictus, an aegypti cousin from Southeast Asia that carries many of the same diseases, has exploded its range through Europe, Africa, and the Americas.
Not to mention unknown others. “We could be missing the tip of the iceberg here,” says Scott Weaver, who directs the Institute for Human Infections and Immunity at the University of Texas. “I think understanding aegypti, as a first step, will be very important.”
As we approached the island, a crumbling stone fort with grass growing on top came into view, then a few buildings painted in fading pastels. Then a dock next to a small beach. The ferry engine kicked into reverse, sending a deep rumble through the deck.
This is Goree Island. Within sight of Dakar, it’s the kind of place where aegypti likely hitched a ride across the Atlantic. A UNESCO World Heritage Site, the island is already steeped in the global memory of slavery. First established as a coastal base by the Portuguese, Goree was controlled by the Dutch, the British, and the French until Senegal achieved independence in 1960.
After disembarking and buying admission to Goree, I headed southeast, passing a massive baobab tree and a few lounging stray kittens on my way to a museum called the House of Slaves. Since the 1990s, historians have argued that Goree was a relatively minor location in the overall slave trade—that perhaps “only” 33,000 captive human beings came through the island—and that the role of this specific house might have been mostly symbolic.
But memory, once established, doesn’t work that way. The three U.S. presidents before the current one came here, and when Nelson Mandela visited, the story is that he sat by himself for five minutes in a cramped chamber marked for “recalcitrant” captives—and then came out shaken, his eyes red.
After the entrance, visitors pass through a pink courtyard. The ground floor under the house is divided by stone walls into various dim holding chambers, each room labeled by the museum with a sign in French: “women,” “children,” “the sick.” Running your hand along the wall, you can feel the occasional seashell embedded in the stone.
Behind the house, visitors paused for selfies in the Door of No Return, an empty frame backlit by the sky and ocean. I waited my own turn. The conceit here is that anyone kept under this house and then led through that door never came back. Their world was forever altered. The wider world was also altered, both by the tragedy of slavery and by its still-unfolding consequences, among them 400 million annual infections.
For this insect problem, at least, fixes are in the works. By asking questions about where aegypti came from, scientists such as Diallo and Sylla in Senegal and their overseas colleagues hope to save lives too. Understanding aegypti’s evolution on its home turf might also help us anticipate and counter copycat trends in other mosquitoes or disease-vector species. And unraveling why aegypti and its viruses are so good at parasitizing us could also help us fight them.
For example, if McBride can pinpoint the genes and neurological systems that control the domesticated aegypti’s fixation on people, hijacking that system to find new chemical repellents could be easier. So would crafting new kinds of bait, which would manipulate aegypti to avoid populated areas and head elsewhere. “We might be able to design a super-stimulus that would be more attractive than humans, that would pull them into traps,” she says.
But the limiting factors in 2020 are focus and funding, especially with another virus falling on the world like an anvil. “I’m optimistic that people are finally understanding we can’t continue this boom-and-bust funding cycle,” Weaver says, “where a new outbreak occurs and we put a lot of resources into that virus—whether it be chikungunya, or Zika, now SARS-CoV-2—and we do that by taking away resources from other diseases.”
For now, though, public-health systems across the Global South have also been diverted to coronavirus work, scientists say, leaving papers unpublished and mosquitoes uncollected. And whereas vaccines for Zika and chikungunya have been in development for many years, the fact that the outbreaks of those diseases are unpredictable and their victims clustered in poorer countries—unlike those of the more widespread COVID-19—means that the vaccines are difficult to test and less lucrative for the pharmaceutical industry, and thus still haven’t made it to market.
As for engineering options to target the mosquitoes themselves, new technologies are already out in the world, aiming to reshape this little critter at the nexus of so much suffering.
One option is a bacterium called Wolbachia, bred into laboratory aegypti and then into wild populations. A greedy pathogen itself, the bacteria competes with the viruses that want to piggyback on the mosquito’s life cycle. Tested in Indonesia, Malaysia, and even in Fresno, California, it reduces the mosquito’s ability to spread disease.
An even more formidable option might be the gene drive, a type of genetic modification that would spread altered genes from a few sterile or disease-free mosquitoes throughout entire wild populations. The method is undergoing preliminary testing in Burkina Faso and elsewhere, and aegypti is high on the list of potential targets.
Meanwhile, less fancy kinds of genetically altered aegypti are already out in the wild. From 2013 to 2015, for example, one mosquito-control program released millions of modified male mosquitoes designed by a British company called Oxitec in the city of Jacobina, Brazil. The idea was that when they mated with wild females, the resulting offspring would die in infancy, causing populations to plummet—which they did.
Apparently, though, not all those doomed offspring actually died. Some found a way to live and breed, passing on little bits of themselves. As Powell and other researchers pointed out in an eyebrow-raising study this past September, the wild aegypti population near Jacobina now contains a sprinkling of mosquito genes from Mexico and Cuba, where the Oxitec mosquitoes’ ancestors were harvested.
This crossbreeding might have actually strengthened the Jacobina aegypti, the study suggested—sparking a media firestorm, a fierce response from Oxitec, and concern from several of Powell’s Brazilian co-authors. “I thought I was pretty conservative,” Powell said, “but it seems like that got blown out of hand.” This summer, both the U.S. Environmental Protection Agency and the state of Florida granted Oxitec permits to begin releasing a version of the same technology in the Florida Keys, although there are still regulatory hurdles to clear.
As we continue to influence its evolution, aegypti, as it always does, is beginning to respond. Standing on Goree Island, though, I didn’t think much about the wizardry of all these fixes in the works, or the engineering required, or the consideration of known and unknown consequences. Instead, I took a moment to dwell on what has already happened.
And maybe with this past in mind, or maybe because of a simpler superstition, I didn’t walk through the threshold of the Door of No Return when I got to it. I just stood there, blinking in the light, looking out at the turquoise waves.
Posting of this article is courtesy of The Atlantic. The article originally appeared in Life Up Close, a project of The Atlantic supported by the HHMI Department of Science Education.
(c) 2017 The Atlantic Monthly Group LLC (This article was originally published on the website www.TheAtlantic.com and is republished here with The Atlantic's permission.)
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