The Fever: How Malaria Has Ruled Humankind for 500,000 Years (16 page)

Despite the huge toll of malaria in Italy and quinine’s great promise in fighting it, the majority of Italy’s free quinine was never consumed.
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At least not by
Homo sapiens
. Frightened and skeptical, many peasants fed it to their pigs.
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Badly used, misunderstood, and poorly distributed, quinine still prevailed as the world’s sole malaria drug (save for traditional remedies used locally) until the 1940s. And so it might have stayed, too, had it not been for the catastrophic quinine disasters of World War II.

At first, malaria was the least of the concerns of American generals prosecuting the war in the Pacific, even as scores of nonimmune troops pushed deep into the malarial jungles and swamps in New Guinea, the Philippines, and elsewhere. The malariologist Paul Russell, envisaging multiple bloody malaria epidemics, visited with American military leaders in New Guinea to plead for greater attention to malaria prevention. They dismissed his concerns out of hand. “If you want to play with mosquitoes in wartime,” one told him, “go back to Washington and stop bothering me. I’m busy getting ready to fight the Japs.”
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Back in Washington, the U.S. government felt prepared. By the time the country entered the war, six million ounces of quinine sulphate had been stockpiled and plans were in place to fortify the U.S.
quinine supply with new shipments of tablets from both the Kina Bureau and cinchona plantations outside the cartel, such as a new one in the U.S.-controlled Philippines. In 1921, the governor-general of the Philippines paid the Dutch four thousand dollars for a bottle of cinchona seeds from their quinine-rich Ledgeriana trees, which he then planted in the southern Philippines, on the island of Mindanao.
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By 1941, the Mindanao plantations produced around two thousand pounds of quinine a year.
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But then, war being war, Germany invaded the Netherlands. One of their first orders of business: hijack Amsterdam’s stores of quinine and send them to Berlin.
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The crushing of quinine’s queen bee was ominous enough. Then, in 1942, Japan invaded Indonesia and took control of Java’s cinchona plantations (along with its tin, rubber, and other tropical riches).
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Within a matter of months, 95 percent of the world’s quinine had fallen into enemy hands.
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As the flow of quinine ebbed,
Plasmodium
flourished among the nonimmune troops. In Papua New Guinea, malaria laid claim to four times more casualties than the ferocious battles themselves, with more than 70 percent of Australian soldiers down with malaria.
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Every single soldier of the U.S. Americal Division, sent to Guadalcanal in the Solomon Islands in late 1942, came down with malaria, some more than once. According to what General MacArthur told Paul Russell, “one-third of his fighting men were in the throes of malaria, one-third were recovering, and only the final third were truly fit for combat.”
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Overall, malaria sickened 60 percent of Allied troops in Southeast Asia.

Quinine stocks in American shops dried up entirely. “If you require quinine, you must now have a doctor’s prescription,”
Harper’s
magazine complained, “and even with that you will probably get only the ground-bark solution.”
⁸⁵
Malaria cases in India rose precipitously, up to one hundred million by the end of 1942,
The New York Times
reported that year.
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But the most notorious epidemic occurred on the island of Bataan, in the Philippines, where American and Filipino troops had fled
from a Japanese invasion. With 85 percent of the troops sick with malaria, there wasn’t enough quinine for the sick to finish their courses, let alone take the drug prophylactically.
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Under fire, the weakened, emaciated troops—they’d been eating their own horses by then—surrendered to the Japanese. It was the largest surrender in American and Filipino military history. The Japanese took more than fifteen thousand American and sixty thousand Filipino soldiers as prisoners, forcing them to march one hundred miserable kilometers to prison camps.
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It was an outrage, fumed American legislators in Congress.
⁸⁹
Bataan had been lost “not because the ammunition was gone,” as
The New York Times
pointed out, “but because the quinine tablets gave out.”
⁹⁰
The years of reliance on a single highly controlled source for a lifesaving medicine now appeared recklessly foolish. The Kina Bureau had “ruthlessly stifled” competition in the quinine market, a California legislator railed, with “preclusive purchasing, subterranean political activity and indirect economic pressure.”
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Meanwhile, the Japanese, by controlling the Dutch monopoly, “ could have all the bark [they] wanted,” quinine historian Duran-Reynals pointed out, allowing them to conquer mosquito-ridden China unworried by malaria.
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To add to their antimalarial superiority, the Japanese army employed elderly women to perform the job of “net tucker-in” to secure the mosquito nets after the soldiers got in their beds.
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Allied governments quickly ramped up their efforts to stanch malaria by other means. General MacArthur appointed Paul Russell as chief malariologist for the U.S. military,
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and Russell assigned malaria control and survey teams to every combat force present in malarious regions—all in all, more than two hundred units, each of about a dozen people. Their supplies and officers leapt from tenth priority in overseas shipment to first.
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The U.S. Army newspaper reminded troops to keep their sleeves rolled down to avoid mosquito bites. The Armed Forces Radio broadcast so many antimalaria messages that troops called it the Mosquito Network.
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Even the famed author Theodor Seuss Geisel, aka Dr. Seuss, brought his talents to
bear on the malaria problem, producing a cartoon distributed by the U.S. Army in 1943. “This is Ann,” Seuss wrote, under a comic rendering of an
Anopheles
mosquito.

She drinks blood! Ann moves around at night (a real party gal) and she’s got a thirst. No whiskey, gin, beer or rum coke for Ann . . . she drinks G.I. blood . . . Never give her a break. She can make you feel like a combination of a forest fire, a January blizzard, and an old dish mop. She will leave you with about as much pep as a sack of wet sand and now and then she can knock you flat for keeps . . . Bathing and swimming at night where Ann hangs out really is asking for trouble. Head nets, rolled-down sleeves, leggings and gloves may seem like sissy stuff and not so comfortable—BUT, a guy out cold from MALARIA is just as stiff as the one who stopped a hunk of steel. Now IF you really are looking for trouble and you don’t want to miss [out]—just drop down to the nearest native village some evening. The places are lousy with fat little Anns sitting around waiting for you with their bellies full of germs. They stock up on MALARIA bugs from the home-town boys and gals and when they find a nice new sucker they give him the works.
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As the troops digested these morsels of wisdom, scientists back home rushed to screen tens of thousands of compounds in search of a drug that might replace the divine remedy they’d lost. This massive effort at long last ushered in a new chapter in humankind’s fight against malaria, with the development of powerful, easy-to-manufacture synthetic chemicals that could lay waste to malarial mosquitoes and the parasites they harbored.

Ironically, given the greater urgency of the Allied nations’ search for a quinine replacement, German researchers at I.G. Farben were the first to discover the antimalarial drugs quinacrine and chloroquine, which were only later stumbled upon and developed further by American scientists.

Quinacrine persisted in the blood for a week, which could be useful, but it yellowed the skin and could sometimes trigger psychotic reactions. It also wasn’t nearly as effective against vivax malaria as quinine. Quinine-deprived American troops forced to take it during the tail end of the war hated it.
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Chloroquine was another matter. Like quinine, it killed malaria parasites by interfering with their ability to metabolize the iron compounds in red blood cells known as heme.
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But chloroquine departed from its pharmacodynamic cousin in every other way. Where quinine failed, chloroquine excelled. It lasted longer. Its side effects were insignificant. And best of all, it could be churned out in factories as reliably as widgets.

Produced cheaply by drugmakers all over the world, chloroquine exploded into the postwar global marketplace. Elites positioned their bottles of chloroquine prominently on their dinner tables, next to the condiments.
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Troops assembled for “chloroquine parades.”
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The American drug company that started promoting chloroquine in 1947 claimed it was eight to thirty-two times more effective than quinine,
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and people, it seems, took them at their word. In Africa, chloroquine overtook aspirin as the drug of choice for fevers, and even aches and pains. This was encouraged by top malaria experts, remembers WHO’s José Nájera. “Chloroquine, it was said, should be treated as a commodity, not a drug.”
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Why bother even trying to diagnose malaria before taking chloroquine? The pill, experts advised, should be simply taken as soon as a fever comes on, as “presumptive treatment,” by sufferers in their own homes.
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The divine medicine quinine, with its quaint botanical heritage, fell into obscurity. The cinchona plantations in Java were left to wither after the war.
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The German military knocked down the imposing statue erected in Paris commemorating Pelletier and Caventou for their heroic extraction of quinine, melting it down for metal to turn into weapons.
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Under siege, the Kina Bureau’s tactics grew increasingly unhinged. They secretly paid syndicated newspaper writers to propagandize for
quinine. Their collaborators “would not dare write more than eight or nine articles in any one year,” however, “in case the syndicate should become suspicious of their featuring quinine too regularly.”
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The bureau promoted risky self-medication with quinine, even though “this might lay us open to attack by the medical authorities,” as one Kina Bureau promoter put it.
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They also tried to engineer criticism of anti-quinine medical authorities. “The best method of attack . . . must appear on the surface to be a spontaneous protest by some outstanding man in this country,” one noted, “while it is true that I would supply such a man with all the material.” They even toyed, pitiably, with the idea of raising money to rebuild the statue of quinine chemists Pelletier and Caventou.
¹⁰⁹
But for nought. In the giddy celebration of chloroquine, the world’s hunger for quinine steadily declined.

Plasmodium
did not survive for millennia by virtue of some unerring killer instinct, unfailingly homing in on the immunological loopholes and secret hiding places in its prey. It survived by being more adaptable than its hosts. Each species of malaria parasite boasts scores of genetically distinct strains, each with a unique set of strengths and weaknesses. Some parasites may be especially adept at, say, quick reproduction inside the mosquito. Others might be skilled at avoiding capture by immune cells. And the various species hang out together, playing out their rivalries and alliances inside our infected bodies. The human host can, albeit painstakingly, devise a defensive maneuver or two to fight them. But we are single individuals, relatively fixed in our capacities. The parasites infesting us, on the other hand, comprise a rapidly regenerating mini-civilization. Even if some fall prey to our defenses, there will be others who won’t—and whose progeny will rapidly conquer the body.

The parasite’s tremendous adaptability most likely escaped observers during the quinine era, when the drug’s strikes against the parasite remained weak, sparsely distributed, and sporadic. It probably
remained hidden during the 1950s, too, as chloroquine consumption took off. But inside drug-dosed bodies all over the world, parasite populations found themselves under assault. Under those conditions, the few hardy individual parasites that could withstand the toll were suddenly plucked from obscurity.

The first signs that malaria parasites could resist synthetic drugs cropped up during the tail end of World War II, as the Allies dosed their troops with the hated quinacrine.

With widespread distrust and dislike of the drug, General MacArthur had instructed the director of medicine for the Australian army, Neil Hamilton Fairley, to provide solid evidence of quinacrine’s effectiveness, especially under the wartime conditions in which the drug would be used.

This Fairley did, conducting a series of wrenching human experiments in the unlikely locale of the lush Australian highlands west of Cairns.
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He rounded up hundreds of volunteers—Jewish refugees and injured soldiers among them—to be purposely infected with malaria and then rigorously dosed with quinacrine, to show how well the drug worked to prevent illness. But he didn’t stop there. He exposed the volunteers to hundreds of bites from infected mosquitoes, made them march more than two hundred kilometers in a matter of a few days, with minimal breaks for rest and food, injected them with adrenaline and insulin, and herded them into the freezing chamber of the local meat works. Still, quinacrine quelled their experimentally induced malarias. The drug, in other words, worked.
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(“They never told us anything,” recalls one subject who survived the trials. “At first I didn’t realize it was dangerous . . . I thought it would be an adventure and that is why I went,” remembered another.
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)