Bugged Read online

  “When a disease first happens, people get really excited about it,” he explains. “West Nile virus back in late 1999 peaked across the country in 2003. There was not a day that there wasn’t an article in virtually every single paper in the country on West Nile.” Flip on the news, and you might get a clear depiction of how adults view insects. Chances are you’ll see one of those superimposed nightly news teasers tucked in your TV screen’s corner—something like an outline of Florida overtaken by an insect of Godzilla-like proportions. Some may feel the imagery is warranted, given that, according to the World Health Organization, yellow fever alone—protocol requires international quarantine at the sign of an outbreak—continues to kill 30,000 people annually.

  Turell has traveled from Thailand to Uzbekistan netting mosquitoes and investigating potential viruses. He knows the impact an insect epidemic can have in war. “The Russians never beat Napoleon! Typhus beat Napoleon,” he emphasizes. One author during World War I wrote that “many officers fear lice more than they fear bullets.” Even as recently as the Vietnam War, says Turell, more soldiers lost duty time to malaria or dengue than to the Vietcong.

  Nature wins most battles. Sometimes the outcomes are simply strange. “Some epidemic diseases,” writes Hans Zinsser, author of Rats, Lice and History, “converted [the world] from uncontrolled savagery into states of relatively mild domestication.” The Old English word onflyge, or “the on-flying things,” describes these sorts of epidemic diseases. It comes from an age when a theory existed that demons caused plagues. “With the increasing concentration of the human population in agricultural communities and cities, the way was open for epidemics,” write entomologists Cornelius Philip and Lloyd Rozeboom. “With no knowledge of the etiology of these diseases, it was inevitable that such catastrophes would be attributed to the machinations of malicious devils or a vindictive god.” If you were to read the firsthand accounts of past epidemics, you might’ve believed it too.

  * * *

  Though its cause remains a mystery, ancient Greek historian and philosopher Thucydides’ descriptive telling of the Plague of Athens back in 430 BCE was accurate enough for today’s scientists to at least theorize as to what killed one-fourth (approximately 100,000) of the city’s residents over a three-year period. The symptoms and consequences, which often meant amputation of fingers and toes, were noted as such:

  People in good health were all of a sudden attacked by violent heats in the head, and redness and inflammation in the eyes, the … throat or tongue [became] bloody and [emitted] an unnatural and fetid breath … When [the symptoms] fixed in the stomach, it upset it; and discharges of bile of every kind named by physicians ensued … In most cases also an ineffectual retching followed, producing violent spasms … If they passed this stage, and the disease descended further into the bowels, inducing a violent ulceration there accompanied by severe diarrhea, this brought on weakness which was generally fatal.

  The Peloponnesian War began a year prior to the outbreak. Iron-willed Spartans had laid siege to Athens. So Thucydides, who’d survived the disease himself, wanted to entrust his observations to others if the disease “should ever break out again.” Yet the damage to the Golden Age of Greece was done, as not only Pericles, a virtuous statesman, was killed by the plague, but as family fortunes were squandered in haste as the world ended around them. “Soldiers have rarely won wars,” writes Hans Zinsser. “They more often mop up after the barrage of epidemics.”

  A popular belief is that the Plague of Athens can be contributed to flea-borne typhus. By then, fleas had evolved from attaching their cocoons along the hairs of our very naked primate ancestors to the fibers of our clothes, Zinsser writes, “thereby gaining a degree of protection from direct attack and a greater motility.” In 2000, a research team found evidence of the typhoid fever bacterium in dental fossils from a mass burial pit in the Kerameikos cemetery, which dates to 430 BCE. (Although other scientists argue the discovered DNA fragments resemble Salmonella species.) The orthodontist responsible for the initial find of the typhus relative continues to conduct DNA tests on a larger variety of teeth samples to affirm his theory. If typhus was not the mystery cause of the Plague of Athens, researchers point to other arboviral diseases and bubonic plague as potential sources. Such arboviral diseases had made their woeful rounds for some time.

  Officials in ancient Persia, according to History of Entomology, noticed the deadly “stranger’s disease” at the inns travelers would frequent. While the Bible does tell the story of Moses raining down some awesome locusts, there’s also a historical account of Assyrian king Sennacherib in the text. While trying to invade Jerusalem in 701 BCE, his army was smitten by a disease carried by fleas. It’s possible mosquitoes even played an earlier role in shaping human civilization. As far back as 500 BCE, Herodotus witnessed fishermen using mosquito nets at night. The famous Greek scientist also believed he could avoid mosquito bites by sleeping in tall towers.1 One contending theory for Alexander the Great’s demise in 323 BCE, courtesy of an especially observant epidemiologist, was that the West Nile virus (transmitted by mosquitoes) was at play, as evidenced by the “omen” when potentially infected ravens fell at the conqueror’s feet. Insects during that time directed fates like army generals, especially flea-infested rats. During the Roman civil war of 88 BCE, epidemic disease killed 17,000 of Octavius’s soldiers. A plague likewise stopped the Huns’ assault on a very vulnerable Constantinople in 425 CE.

  The Plague of Justinian—the first record of the bubonic infection Yersinia pestis—gave the “coup de grâce” to the Roman Empire, writes Zinsser, killing 50 million people in a 200-year period. It began at a Mediterranean port in Alexandria in 542 CE. No one paid any mind to the black rats on the docks, but soon more sailors reported symptoms. Travel continued and the bubonic plague followed despite the “magical amulets and rings” used to ward it off, writes William Rosen, author of Justinian’s Flea. Death set in 17 days after infection. People began carrying name tags should they collapse and die in the street. “Constantinople,” Rosen says, “was a window onto Hell.”

  And the Renaissance? Thank the same fleas that transmitted Yersinia pestis, causing the Black Death pandemic of 1346–1353. As a result, one-third of Europe’s population died, which in turn propagated a number of cultural and socioeconomic changes, and wealthy patrons who supported the arts, which led to a cultural rebirth and the creative geniuses that sprang from it. Two centuries later, in 1530, when Charles V of Spain was prepared to surrender Italy to the French, a typhus plague struck 25,000 French soldiers down, handing Charles V the crown to the Roman Empire. During France’s Saint-Domingue expedition to conquer what is now Haiti, Napoleon Bonaparte lost 23,000 men to yellow fever by 1803. This resulted in the Louisiana Purchase. Napoleon’s luck didn’t end there. From June to September 1812, his army was reduced from 500,000 to 100,000 men due to typhus as they marched to invade Moscow. Only 40,000 soldiers remained by the time they made it back to the Polish border. One-fourth of the deaths during the US Civil War (approximately 155,000) were caused by flies spreading “Camp Fever,” otherwise known as typhus. And before the Civil War began, the Third Pandemic took hold of China in 1855, killing an estimated 12 million. The bubonic plague officially ended in 1959, but not before hitting India in the late nineteenth century, taking another 6 million with it.

  By the end of the nineteenth century, scientists were determined to finally crack the insect epidemic code. France sent thousands of workers and engineers to build the Panama Canal. But over an eight-year period during the 1880s, over 30,000 of them died from malaria and yellow fever. The tropics became known as the “white man’s grave.” Panic from the preceding years of US outbreaks had peaked. ALL MAIL FUMIGATED WITH FORMALDEHYDE had been printed on the majority of letters coming from the South. The last straw came in 1898, when 3,000 US soldiers succumbed to typhoid and yellow fever during the Spanish-American War. Papers at the time mocked the idea of mosquitoes transmitting disease, so the
US Army surgeon general assembled a team to find out how yellow fever spread.

  In the past, doctors had tried their hand at self-infection to understand the virus, even to the point of ingesting pills made of the black vomit from infected patients.2 Others thought that yellow fever may be transmitted to telegraph operators via wires and “air-electricity,” as suggested in the 1881 paper entitled “The Electro-Galvanic Theory of Yellow Fever—Disturbed Electricity the Exciting Cause.” Enough said. Coincidentally, that same volume of the New Orleans Medical and Surgical Journal contains a paper by Carlos Finlay that outlines the exact agent of the transmission. “It seems natural,” Finlay writes, “that this agent could be found in that class of insects which, by penetrating into the interior of the blood vessels, could suck up the blood together with any infecting particles contained therein, and carry the same from the diseased to the healthy.”

  Finlay spoke rapidly and stuttered. It made him appear all the more kooky. “He was dubbed ‘Mosquito Man’ by the US press,” writes Molly Caldwell Crosby in her incredibly researched book The American Plague. “[He] became known as a ‘crank’ and a ‘crazy old man’ in Havana.” Public acceptance would take time. Finding the proof of that connection would take a curious physician at the dawn of the twentieth century whose lab methods verged on human sacrifice. His nemesis was what might be considered the principal buggy villain of the past two centuries: the mosquito.

  You have to appreciate the ethical dilemmas of US Army physician Walter Reed in Cuba during the Yellow Fever Commission of 1900. At first, Reed believed a bacteria was at play. However, a young bacteriologist by the name of Jesse Lazear, who had also been assigned to the commission, was keen on Carlos Finlay’s initially dismissed mosquito hypothesis. Two years before the yellow fever experiments in Cuba, scientists discovered that the bubonic plague–causing bacillus was carried by fleas and that mosquitoes transferred malarial parasites to birds. So Lazear bred mosquitoes for dissection in jars filled with bananas. But Reed saw that although the lab work would yield conclusive evidence, it wouldn’t be enough to prove mosquitoes are vectors of yellow fever. A direct correlation was necessary. So the commission members enlisted a few brave men and women.

  If you were asked to dip your hand in a jar full of yellow-fever-infected mosquitoes, I would hope you’d say no. But, fortunately for science, one group of human volunteers said yes. In the first experiment with informed consent of death, the subjects agreed to be repeatedly bitten by mosquitoes, specifically the female Aedes aegypti—they’re the bloodsuckers.

  The expected symptoms include searing headaches, sensitivity to light, and yellow-tinged skin. During the fall of 1900, patients at Havana’s Las Animas hospital were already in the throes of the disease. Here, Jesse Lazear let Finlay’s mosquitoes feed on the sick and then healthy volunteers, which included all of the scientists on the commission. Of those who were bitten, two men became sick but later recovered. Jesse Lazear, expecting his second child, continued experimenting as the anonymous “Guinea Pig No. 1” in his ledger. He died seven days after being bitten. Walter Reed was overwhelmed with guilt because he had not been in Cuba at the time of his colleagues’ self-experimentation. But together the medical doctors of the commission protected Lazear, writes Molly Caldwell Crosby, so his family wouldn’t be denied life insurance due to his “medical suicide.”

  Many involved with the commission had bitter memories of the suffering caused by yellow fever. It was especially personal for Lena Angevine Warner, the chief nurse serving under Reed in Havana. During the Memphis epidemic in 1878, as a young girl, she had lain on her house floor immobilized, sickened by the disease, and watched her siblings and guests and the family servants die. She was alive still as robbers broke into her home and strangled her father.

  Daunted by the loss of Jesse Lazear, Reed presented the commission’s findings and convinced the US government to fund a new facility. The new experimental ground was called Camp Lazear. There, Reed would rule out other means of transmission. One method aimed to dismiss yellow fever as a germ. At first, the “Infected Clothing Building”—a dark, sealed room filled with diarrhea- and vomit-sodden clothes and beddings—sounds as harmless as those red biohazard boxes in a doctor’s examination room. But when you stick people in there, crank the temperature up to 100 degrees Fahrenheit, and keep the door locked for three weeks, the “Infected Clothing Building” seems like a misnomer. At the beginning, volunteers ran outside gagging from the smell percolating from the infested wooden crates. But you’ll be happy to know they survived unharmed—at least physically.

  In Building No. 2, infected mosquitoes shared space with sick and healthy volunteers in beds partitioned by cheesecloth. Another room had no separation. Amazingly, the soldiers involved declined monetary compensation as they nobly thought of the thousands of lives they’d save. They continued receiving bites through December 1900. “My spine felt twisted and my head swollen and my eyes felt as if they would pop out of my head,” said one volunteer. “Even the ends of my fingers felt as though they would snap off.” By January 1901, Walter Reed had confidently established yellow fever’s propagation, and he believed survivors could eventually become immune to the virus.

  Experimentation continued under direction of Carlos Finlay and another doctor at the Havana hospital. It didn’t conclude until public protests sought an end to it after three more people died. Their families were compensated $100 each.

  * * *

  The moral burden of the Yellow Fever Commission is said to have weakened Walter Reed’s immune system. He passed away two years later, in 1902. But the success of the commission changed the world; the first human virus was discovered, and it was confirmed that mosquitoes become pathogenic 12 to 20 days after biting an infected individual. After the discovery, Colonel William Gorgas of the Medical Corps rallied “mosquito hunters” to blitzkrieg Aedes breeding grounds (gutters, water pots) in 1901 and put up window screens across Havana neighborhoods. Because of the bug exterminators, only one city resident died from yellow fever over a four-month period. Word of these tactics spread and were also implemented in Central America, allowing for the completion of the Panama Canal.

  Reed’s legacy was solidified by the Walter Reed Army Institute of Research. Infectious disease research continues there in hopes of fighting off the largely endemic dengue carrier A. aegypti and the sandfly parasites US troops encounter in the Middle East. Across the pond in underground labs at the London School of Hygiene and Tropical Medicine, volunteers still shove their arms into containers with mosquitoes to test repellants. Archaic? Maybe—but we’ve learned that defeating big scourges requires equal parts heresy and obsession. Consider the fact that Swiss chemist Paul Müller mixed 349 concoctions and took four years of research before finding the Insecticide—warranting a capital “I”—known as DDT. One of Müller’s drives was combating the lice-spread typhus epidemic in Russia that wreaked havoc from 1870 to 1940 and killed millions. Until the EPA banned the synthetic in the 1990s for the ecological havoc it wreaked, DDT became the go-to for defeating bed bug epidemics, plagues, malaria, and yellow fever outbreaks. (It’s also been theorized that our TV-watching habits kept us indoors, thus reducing insect interaction.) Strategic use of the compound, such as with air strikes, made the world livable and bug wars winnable. But overexposure rendered many insects resistant—an evolutionary knack bugs have, if you remember from chapter 3, in order to survive in volume.

  In the wake of Reed’s work, in 1937, virologist Max Theiler developed “17D”—a vaccine against yellow fever that the World Health Organization concluded in 2013 gave “lifelong immunity.” Shortly following the vaccine’s creation, a malaria epidemic—caused by a complex multicellular parasite—hit the Americas. One of the top villains behind it? Anopheles gambiae—the most adept African malaria vector, discovered in Brazil by entomologist Raymond Shannon. The mosquito was eradicated shortly before World War II with a highly toxic insecticide called Paris green, applications
of which were carried out by Fred Soper, a man Malcolm Gladwell called the “General Patton of entomology.” Soper would go on to form the Global Malaria Eradication Program. According to the Centers for Disease Control (CDC), all traces of the parasite in the United States were “eliminated” by the early 1950s.

  Sometimes, though, control methods target the incorrect mosquito, making the actual vector more prevalent. This is what happened once during World War II in the South Pacific with two different species of Anopheles. One of these species enjoyed laying eggs on water in shaded areas, so the solution was to hack away the brush.

  “A few weeks later a different Anopheles species came in—one that liked sunlit water,” says our arbovirus expert Mike Turell. That particular species had previously been rare. “The first specie was an inefficient transmitter of malaria. However, the second one was a much better transmitter. By controlling the wrong species, they actually made the disease much worse.”

  Today, the pathogens carried by Anopheles cause 1 million deaths per year. In 2010, the CDC reported 219 million cases of malaria—a parasitic disease with flu-like symptoms—across the world. Some years that number soared as high as 500 million. Normally Anopheles resides in tropical climates, but seafarers changed that. According to Michael Specter’s “Mosquito Solution” article in the New Yorker, “Researchers estimate that mosquitoes have been responsible for half the deaths in human history.” As the toxic control methods of yesteryear are outlawed, research teams look to eliminate malaria-transmitting mosquitoes and other vectors using cutting-edge sterilization and genetic modification programs.

  In the battle to reduce cases of malaria and dengue fever, several solutions lie at the forefront. Two come from North Carolina State University and UC Irvine, and involve lab-raised mosquitoes. Molecular geneticist Anthony James at UC Irvine told one reporter there are two genetic modification strategies: a “bite” method that stops diseases from being transmitted, or a “no-bite” goal that eliminates certain species entirely. The latter is being attempted at NC State with the engineering of flightless females as a means to decrease the A. aegypti species. As for the “bite” method in Irvine, James is taking malaria-destroying genes found in mice and modifying them for mosquitoes so the blood-borne disease will be destroyed in their own bodies. (Parasites are actually stored in the mosquitoes’ salivary glands, which strengthens the pathogen.) After working on it for 15 years, he made a recent breakthrough with the help of colleagues at UC San Diego. Once James’s mosquitoes became resistant to malarial parasites, he needed a gene drive to make the resistance inheritable, transferring the majority (rather than half) of those altered genes to their mosquito offspring. Fortunately, a team at UC San Diego, which had accomplished similar work with gene drives in fruit flies, found out about James’s efforts. By July 2015, the team at UC Irvine produced mosquito larvae with red eyes—a genetic marker that the gene drive had delivered the malaria parasite antibodies. One medical entomologist quoted in a Nature piece argued that “the elimination of Anopheles would be very significant for mankind.”