by Sonia Shah
The two scientists decided that they’d found the microbe responsible for malaria. It was a germ, it lived in the soil and the air, and they called it Bacillus malariae. They announced their findings in 1879.
The scientific method is not infallible, of course, and such mistakes are made, even when the entire economy of a newly formed nation depends on the results.
Counterevidence soon emerged.
In November 1880, Alphonse Laveran, a French surgeon stationed in Constantine, Algeria, peered at a crimson blob on a glass slide. How he found what he did is a bit of a mystery. Most nineteenth-century microscopists soaked their slides in chemicals, their cutting-edge techniques thus unknowingly killing the malaria parasites in their samples and rendering them all but invisible amid the scattered debris of the magnified blood. Those who did examine blood from malaria victims while still fresh, as Laveran did, presumably did so more promptly than he did on this particular day. The blood was still warm when Laveran excused himself from its notice. What precisely he did upon abandoning his slide nobody knows, but whatever it was, it took about fifteen minutes. Maybe it was a cup of coffee.6
In any case, during the lull, the drop of malarial blood on the glass cooled. The change in temperature roused the parasites in the sample, which now considered that they had left the warm-blooded human for the cool environs of a mosquito body. Male forms of the parasite would soon be called upon to fertilize female ones, and each started to sprout long flagella and wave them about, in lascivious preparation. Laveran returned to his microscope expecting yet another static scene. Instead, the shocked surgeon caught sight of tiny spheres propelling themselves with fine, transparent filaments, wrigglingly alive.7
For the first time ever, Plasmodium had been spied by the human eye. Laveran found the creature again and again in his malarial patients, and watched it disappear from their blood after he administered quinine. He knew this was no bacillus, but something else entirely, and he would soon set out to show the world his new discovery, Bacillus malariae or no.8
Meanwhile, on the Mississippi River Delta, an American army surgeon named George Miller Sternberg attempted to replicate Klebs and Tomassi-Crudeli’s results with Bacillus malariae. He collected samples from a notoriously malarial area just as Klebs and Tommasi-Crudeli had done. Back in the lab, he isolated the tiny rods and injected them into rabbits. But the bunnies’ heaving fevers didn’t look like malaria to Sternberg. On a hunch, he decided to inject some other rabbits with an alternative substance to compare their fates. Given an ongoing debate on the infectious capacities of spit, Sternberg decided to use his own saliva. He injected the spit into the bunnies, and it made them sick, too, in the same way as the tiny rods had. So now Sternberg knew that either malaria was caused by both the malaria germ and his own slobber or the erstwhile malarial germ did not exist.9
Laveran went home to Europe to explain his findings, but the discovery of Bacillus malariae had already been adopted by European scientists, business leaders, and the press. “It is a germ,” proclaimed The New York Times, “and is carried by the mist.” After all, the notion of a Bacillus malariae fit well with then-current miasmatic theory. Bacillus malariae found favor, too, among developers eager to drain marginal wetlands and swamps, an activity they could now claim “ventilates the earth . . . and stop[s] the growth of fever germs.” What was not to like?10
Laveran was met with stern disapproval. In Paris, France’s leading malaria authority, Léon Colin, scoffed at the obscure army surgeon’s misinterpretation of white blood cells.11 In Rome, Tommasi-Crudeli proclaimed that Laveran’s creature was just some dead bacilli. The world’s foremost microbiologist, German scientist Robert Koch, similarly rejected Laveran’s claims,12 to which the French army surgeon soon appended yet another wild and unheeded speculation: that his malarial creatures were transmitted by mosquitoes.13
Laveran’s hunch was likely inspired by the work of Scottish physician Patrick Manson, who had discovered, around the same time, the role of the mosquito in transmitting filarial worms and causing the disease known as filariasis. The worms block the flow of the lymph glands, creating huge disfiguring tumors, sometimes as heavy as fifty pounds, particularly on the legs and groin. The disease was endemic in south China, where Manson was stationed with the Imperial Chinese Maritime Customs Service. Neither Chinese nor Western medicine had any treatment to offer filariasis victims, but Manson, unlike his Chinese colleagues, who considered invasive procedures anathema, was willing to lop off the tumors themselves. His amputations freed filariasis patients from their burdens, at least until the tumors grew back.14
After scientists found filarial worms in the blood and urine of filariasis patients in 1874, Manson got to thinking about how the worms survived from generation to generation. He knew filariasis was not contagious—the worms didn’t spew out in coughs and sneezes, or on dirty hands—and yet they had to have some method of leaving the human body and infecting a new one. He started examining blood samples from his patients, which led him to the discovery that the worms presented themselves in the bloodstream only occasionally, and then for only a brief amount of time. The bloodstream, he surmised, must be their escape avenue. Something was coming to whisk them away. Manson deduced, from this, that the worms must be abetted by some kind of bloodsucker. Filariasis was unknown in England, which ruled out fleas, lice, and leeches, which lived “pretty well all over the world.” The vector could, however, be mosquitoes, Manson thought. According to him, mosquitoes were “confined to a limited area of the earth’s surface.”
Manson built a special “mosquito house,” in which he enticed one of his filariasis patients to sleep at night while mosquitoes fed upon the man’s exposed body. In the morning, Manson’s servant collected the blood-filled mosquitoes resting on the walls of the house and dropped them into glass vials for Manson to examine. Manson sliced the bugs open, exposing the young, sausage-shaped worms within and establishing the mosquito as the vector.15
Mosquitoes had been suspected as diseased since early times, in India and parts of Africa as well as in the West. As the first-century Roman agricultural writer Lucius Columella wrote,
during the heat a marsh throws up a noxious poison and breeds animals armed with aggressive little stingers, which fly upon us in very thick swarms . . . whereby hidden diseases are often contracted, the causes of which not even the physicians can ascertain.16
But Manson had read in a natural history book that mosquitoes took but a single blood meal in their lives, before promptly laying eggs and perishing in the water.17 Since a mosquito that bites only once can’t, by its own agency, properly transmit anything, Manson dreamed up a possible modus operandi. The microbes lived in the mosquito, which laid its eggs in the water and then promptly drowned, as per the natural history book’s authority. As the mosquito corpse floated along, slowly decomposing, Manson figured, its microbes seeped into the water. At some point, an unsuspecting human ingested the contaminated water. And the ingested microbes infected the human, who would later be bitten by another mosquito, completing the cycle.18
In fact, mosquitoes take several blood meals, which is why they are reliable carriers for pathogens—they can both pick up and pass on microbes. Manson’s habit of feeding his lab mosquitoes only once reinforced his faulty impression, for they died soon after that single feeding. They probably starved to death.
Manson didn’t have much experimental evidence to offer in support of his theory. He’d performed just a single—and illegal—dissection of a filariasis victim in the same hot, windowless room in which the man had died. The “light was very bad and the heat overpowering,” he admitted later. The doomed autopsy proved inconclusive. According to the Manson biographer Douglas M. Haynes, conviction drove his theory more than deduction.
Collaboration with scientists with better experimental skills and insights into mosquito behavior could have improved Manson’s groundbreaking theory. But rather than seek out collaborators, Manson sought turf. He wan
ted to stake his claim to the theory, promoted fully intact. Technically, his Scottish medical degree held the same status as one from an English university, but in reality, he was all but shut out of the lucrative London medical scene, and he knew it. He’d need a powerful mentor, someone with say-so among the British scientific elites. There were two top filariasis specialists in the British Empire at the time: Thomas Spencer Cobbold, a fellow of the elite Royal Society, based in London, and Timothy Lewis, stationed in the backwaters of the Indian colonies.
Manson appealed to the authority of the heralded London-based Cobbold. “I live in an out-of-the-world place, away from libraries, and out of the run of what is going on,” he wrote to Cobbold deferentially. “I do not know very well the value of my work, or if it has been done before, or better.” Cobbold, in the midst of a nasty fight with Lewis over the primacy of his own findings, rushed Manson’s fantastic tale to The Lancet, establishing himself—with Manson in tow—as the first to discover the disease-carrying capabilities of the mosquito.
Together the two swatted away any inconvenient dissent or counterevidence. Lewis, for example, couldn’t find the embryonic and larval worms that Manson claimed to have found, or in any way confirm that the worm was transmitted into water through the mosquito’s body. Instead of reexamining their theory, Manson and Cobbold attacked Lewis for his “hesitation and scientific caution.” By 1883, “medical and scientific circles in England and on the Continent of Europe” lauded the dead-mosquito-water theory and called the man who came up with it a “keen investigator and accurate observer,” as the British Medical Journal noted.19
The vast majority of people at risk of malaria infection did not have the resources, nor their political leaders the will, to act upon the implications of the latest scientific discoveries. And so these nineteenth-century scientific missteps wouldn’t have made much difference in the grand scheme of things, except that, just then, the French diplomat Ferdinand de Lesseps was planning to build a canal through Panama.
Unlike most of the malarious masses around the globe, De Lesseps had both the resources and the insight to implement the most cutting-edge medical discoveries of the day. He was a famous developer who had already successfully built the Suez Canal. And he knew malaria would pose an obstacle to his new project in Panama. The geographers he sent to survey for the new canal had already suffered waves of dengue, yellow fever, and malaria, which they called Chagres fever, after the river. “The white men withered as cut plants in the sun,” recalled one visitor.20 Cholera epidemics had similarly roiled De Lesseps’s workers during the building of the Suez Canal, and De Lesseps himself had suffered a horrifying week during which disease killed both his wife and son.
And so, before luring some thirteen thousand workers from Jamaica, Colombia, Venezuela, and Cuba to converge upon malarious Panama, De Lesseps would do all he could to prevent epidemics of disease. He built beautiful hospitals to care for the sick, designed to minimize malarial influences as the leading scientists in Europe described them. Patients’ every comfort was considered. Lush gardens surrounded the stately buildings, and scented tropical air wafted freely throughout the wards. The hospital in Colón jutted out over the sea, so that patients could breathe in the fresh sea air. And the legs of each bed were set in small pots of water to repel ants and spiders.21
Soon enough, with tropical downpours washing over the machete-wielding workers, “devoured by mosquitoes” every night (as the painter Paul Gauguin put it, before fleeing for Martinique), three quarters of the hospitals were full of fevered malaria patients.22 “Is M. de Lesseps a Canal Digger or a Grave Digger?” Harper’s Weekly wondered, publishing an illustration of the rotund De Lesseps despondently shoveling a ditch.23
Harper’s charged that the canal company was suppressing the causes of death. But in fact there was no reason for De Lesseps’s managers to suspect that the mosquitoes that rose from the canal site and from his well-watered hospital gardens and pots of standing water had anything to do with the workers trembling in their beds, or that his lovely hospitals themselves had become purveyors of disease. The canal company’s chief surgeon routinely examined the blood of patients in the canal hospitals and found the offending Bacillus malariae.24 American medical consultants called upon to examine progress at the canal concurred.25
By 1889, malaria and yellow fever had killed an estimated twenty-two thousand people working on the canal.26 De Lesseps’s company went bankrupt, abandoning the muddy, corpse-littered gash. In France, enraged investors blamed human, not entomological, malfeasance: the French government collapsed, and three former premiers, two former ministers, two senators, and a hundred deputies and former deputies were accused of corruption. De Lesseps’s son, among others, was tried for bribery.27
Meanwhile, the true nature of the mosquito’s role in malaria transmission had grown even more obscure. Back in London and hoping to establish himself as a malaria expert—London teemed with malarious Brits returned home from the colonies, needy of medical attention—Manson had reprised his celebrated mosquito theory, but this time to explain malaria. “As the problem and conditions are the same for both organisms,” he wrote in 1894, “the solution to the problem may also be the same.” That is, unlucky humans contracted not only filariasis but also malaria by drinking water or inhaling dust contaminated with the corpses of infected mosquitoes.28
There were several obvious flaws in Manson’s theory. For one thing, it required that the malaria parasite survive in the environment on its own for days, or even weeks and months. Scientists such as Laveran—whose discovery of Plasmodium had by then been found acceptable—knew that the parasite was too delicate to survive anywhere independently of a host, whether in water or dust.29 And Italian scientists had established, by feeding swamp water to patients, that water from even the most malarial regions did not infect humans with anything. But Manson stood by his story. Obviously, “the Frenchies and Italians will pooh pooh it at first,” he wrote in a letter, “then adopt it, and then claim it as their own.”30
Debilitated by periodic attacks of gout, Manson himself could not travel to malarial regions to collect mosquitoes and prove the veracity of his theory. He needed an assistant.
Ronald Ross was like many other docs in the British Raj’s Indian Medical Service. He professed no particular interest in public health or medicine, or even India, and wasn’t especially accomplished. He’d studied medicine mostly because his father, an army surgeon stationed in India, had expected him to. He hadn’t done well on his exams, and so qualified only for an Indian Medical Service job in the less desirable Madras branch. But he didn’t really mind. There was steady pay to be had, plenty of sport, and only a few hours of work to be done every day.31 Ross had literary ambitions and spent his days in pleasant distraction, playing sports and writing poetry, while the bloody revolts and epidemics of the Raj swirled around him. He published his first novel in 1889, about the life of a child marooned on an island “not knowing the face of a human being, not knowing the speech of men, nor even their very gestures.”32
A different kind of hidden world was revealed to Ross when he took a course on bacteriology while on furlough from India. Hunched over his microscope, Ross could spend hours lost in a cryptic world full of shapes and shadows and pulsing with cryptic meaning.33 Like every other nineteenth-century microscopist, he didn’t know half of what he was looking at. But he meticulously described the “clusters or chains of very faint, sometimes brownish, little globules,” the “faintest possible indications of a matrix,” “delicate, bluish bodies,” “bubbles of a pale, yellow, luminous substance,” the “flower-like” appearance of “beautiful structures,” and “small, beautifully delicate red corpuscles” he saw through the lens. The mysterious microcosm inside a drop of blood smeared onto a fragile glass slide enchanted the young aesthete. Ross was hooked.34
Ross published his microscopic meditations, one of which caught the attention of Patrick Manson, who soon had Ross under his wing, pr
omising fame and fortune should he produce evidence in support of Manson’s mosquito theory of malaria. “If you succeed in this you will go up like a shot and get any facilities you may ask for,” Manson told him. “Look on it as a Holy Grail and yourself as a Sir Galahad.”
Thus began one of the most famous and fraught scientific collaborations in medical history. Via a long and well-preserved written correspondence, Manson encouraged Ross to feed mosquito-contaminated water and sediment to healthy volunteers. “The mosquito water, or mosquito dust, should be taken or inhaled first thing in the morning and on an empty stomach,” he counseled. “A positive result to such an experiment would be irrefutable.”
But the local Indians mistrusted him, Ross complained repeatedly to Manson. “My two cases ran away,” he told Manson in 1895, “because I pricked their fingers, in spite of my giving them a rupee a prick!”35 “The bazaar people won’t come to me even though I offer what is enormous payment to them . . . 2 & 3 rupees for a single finger prick . . . they think it is witchcraft. Even my own gardener refused to allow me to prick her finger more than once,” he wrote. The mother of a malarial child “fight[s] me about pricking its heathenish little black toe,” he complained. Finally he resorted to deception, wickedly informing one reluctant volunteer that the mosquitoes Ross allowed to feed upon his skin performed the therapeutic function of removing disease.
Ross’s efforts to rear mosquitoes similarly floundered. Like Manson, he knew precious little about mosquitoes. And he didn’t have much regard for those who did—“mere naturalists,” he called them, “fit for nothing but classifications, making pretty pictures & belonging to societies,” he scoffed. He captured and raised the wrong species, whose body was like poison to the parasite. He killed his larvae by placing their bottles in the sun. He couldn’t entice adult mosquitoes to bite. They were “as obstinate as mules,” he complained. The whole business was “vexatious.” Ross once did suspect that the species of mosquito might play some role in malaria transmission, since he frequently found mosquito-ridden places that were malaria free, but Manson set him straight. “The reason for the absence of malaria in certain mosquito-haunted places does not lie in the inefficiency of the mosquito,” Manson advised, “but in the presence of something inimical to the plasmodium in it.”