The Fever: How Malaria Has Ruled Humankind for 500,000 Years (24 page)

Ross published his microscopic meditations, one of which caught the attention of Patrick Manson, who soon had Ross under his wing, promising 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.”

Meanwhile, supported by both state and industry, Italian malariologists were hot on malaria’s trail. The Italians differed fundamentally from Ross and Manson in their approach to the disease. They conducted interdisciplinary research and embraced the insights of naturalists and of malaria sufferers themselves. While Ross described the malarious Indians he experimented upon as “ people who love filth” and “ really nearer a monkey than a man,”
³⁶
the Italian pathologist Amico Bignami considered malaria victims “much better informed about malaria than some medical men.” Visiting malarious areas, he asked locals about their experiences with the parasite, gleaning important clues about its secret ways. “Many precautions which they take against the fever are taken, one would say, to defend them from the sting of insects,” Bignami noted. They avoided going out at night and sleeping outdoors. They closed their leaky windows against insects but not the night breeze, and took “great care of their mosquito curtain,” which they wrapped themselves in every night, regardless of the heat.

All of this led Bignami to hypothesize that it was the bite of the mosquito—not its water or dust or air—that carried
Plasmodium
to its final destination. Bignami and his colleagues backed up their hypothesis with experimentation. They fed volunteers marsh water, let them inhale dust from malarious areas, and injected them with blood from malaria victims. The water and dust did nothing, but the inoculation indeed sickened volunteers.
³⁷

Bignami’s team had made progress on the species of mosquito, too. In 1895, the zoologist Giovanni Battista Grassi had joined Bignami in Rome. Grassi, a highly regarded evolutionary biologist, had described malaria in owls, pigeons, and sparrows, among other birds, finding that each bird species boasted its own unique malaria parasite species. For Grassi, as for any naturalist, the species of the mosquito was as crucial a factor in human malaria transmission as the
species of the host and of the pathogen itself. Grassi had already thoroughly described the distribution of mosquitoes in Italy (there were at least fifty species), and of the six species that frequented malarial areas, he had narrowed the suspects to just three: two
Culex
species and the true
Anopheles
culprit.
³⁸

In 1896, Bignami published his notion that the bite of the mosquito transmitted malaria to humans, and with Grassi, he started experimental work to prove it.
³⁹

Manson and Ross, neither of whom ever achieved much financial success, constantly fretted over securing a living. Manson’s tactic was to try to shame the British government into supporting his and Ross’s work, appealing to its sense of national pride. “It is little to our credit,” he told a medical society gathering in 1894, “that continental nations, whose stake in tropical countries is infinitely smaller than ours, are nevertheless just as infinitely ahead of us in this matter.” Ross agreed: it would be so “annoying” if “the Italians do come in first!”
⁴⁰

Manson and Ross fought the Italian researchers’ findings tooth and nail and clung to their misguided hypotheses to the very end. After all, their very livelihoods were at stake. “Bignami is a pure villain,” Ross raged.

He wants to secrete a mosquito theory of his own . . . He wants to bite into the heart of your theory, suck its juices & then bloat & swell into a discoverer—or rather until he is thought to be one . . . He is quite capable of spreading his six legs over your work & calling it all his own . . . if you have not squelched him already you ought to do it.
⁴¹

Malariology averted the dead end that Ross and Manson urgently steered it into when the two scientists happened upon the same conclusion as Bignami and Grassi, albeit less via methodical inquiry
than through serendipity. First, Ross inadvertently discovered
Anopheles
mosquitoes, hidden deep inside a forest (a local servant pointed them out to him). Because he couldn’t entice any human volunteers—“for several reasons hospital patients . . . are not convenient to work with,” he wrote, “they expect treatment & the papers might talk”
⁴²
—Ross shifted from humans and their malaria to the more easily captured birds and theirs.
⁴³
And while trying to prove Manson’s mosquito-water theory, he encountered a strange, delicate structure inside the torn-off head of a mosquito. “This proved to be a long branching gland of some sort, looking like a coil of large intestine,” he wrote. “I noticed at once that the rods”—sporozoites—“were swarming here & were even
pouring out
from somewhere in streams.” What was this quivering coil, shuddering with tiny squirming parasites? “I still experience, however, the greatest difficulty in dissecting out the gland itself,” Ross wrote.

It appears to lie in front of the thorax close to the head, but breaks so easily in the dissection that I cannot locate it properly. In the second mosquito however there was no doubt, as shown by evident attachment that the duct led straight into the headpiece, probably into the mouth.

In other words it is a thousand to one, it is a
salivary gland
.
⁴⁴

In other words, Bignami had been right all along. But Ross and Manson didn’t see it that way. In London, Manson promptly declared that he and Ross had solved the mystery of malarial transmission, presenting Ross’s work on bird malaria to a meeting of the British Medical Association, enlivening his report with dramatic flourishes such as the reading out of a telegram from Ross on his latest results.
⁴⁵
“The fat is thoroughly in the fire,” Manson reported proudly to Ross afterward.
⁴⁶
“You will be lionized when you get home.”
⁴⁷
“Well, I have become unbearable with conceit,” Ross wrote back. “That was a grand charge! I brag openly about it!”
⁴⁸

Of course, Ross had shown that mosquitoes transmit malaria to
birds
, not humans. Bignami had come out with the correct hypothesis first, and Grassi was the first to experimentally infect a human volunteer with malaria through the bite of an infected mosquito, a result published in 1898. Ross had described some gray, dapple-winged mosquito, while Grassi had fingered
Anopheles
specifically. The month before Manson’s grand announcement, German bacteriologist Koch announced that
he
had discovered malaria’s mosquito vector.
⁴⁹

That is, Ross and Manson’s stake to the nineteenth century’s scientific Holy Grail was as assured as one of those tattered flags flapping on Mount Everest. In the august pages of Britain’s leading medical journal, Bignami and Grassi politely cited Manson and Ross and their “interesting observations” on birds.
⁵⁰
The head of the British Medical Association openly said that the Italians had made the major discoveries in malaria’s transmission. When Ross actually went to Italy to visit with Italian researchers, the local papers downgraded him to “an engineer.”
⁵¹

The Indian Medical Service, which had repeatedly disrupted Ross’s studies, yawned in the face of his fabulous discovery. It forbade him to publish his findings on malaria in birds, and even when it finally gave him time off to complete his investigations, it demanded that he look into other diseases as well as malaria. When he made his big breakthrough, the IMS “congratulated me politely,” he wrote, “but they asked no questions, never sent for me, never ordered anyone to inspect or verify my work, never gave me any assistance.”
⁵²

Back in Britain, Ross struggled to secure a well-paying position.
⁵³
He went on the offensive, writing angry papers defending the primacy of his work, and insulting other scientists who disagreed with or belittled him. “I might have omitted the word
stupid
,” he wrote in his memoirs of one such assault, “but the criticism was quite sound and valuable.”
⁵⁴
“Please don’t believe too much of Grassi & Cos.’ work,” he begged one colleague. “Their actual observations have been
of the slenderest and . . . the rest is eked out by aid of my reports.”
⁵⁵
“The work on human malaria is only of secondary importance,” he added, a “mere detail” of his work on birds.
⁵⁶

Ross’s vitriol worked. In the end, it was he, not Grassi, who was awarded the Nobel Prize in 1902.
⁵⁷
But much time was wasted in the ugliness. “I hate war and publicity of this sort,” Manson complained.
⁵⁸
And in the meantime, the pace of scientific research into the mosquito question—and with it,
Homo sapiens’
first big chance to tackle malaria transmission—ground nearly to a halt.

Public skepticism about the mosquito theory of malaria transmission reigned. The notion that
Anopheles
mosquitoes transmitted malaria, alone, didn’t fully explain common experiences with the disease. Did all species of
Anopheles
carry malaria? And if so, why was it that malaria raged in places where precious few
Anopheles
could be found, and was scarce in places where
Anopheles
rose in giant black flocks? This phenomenon was particularly obvious in Europe, where the malaria vector
Anopheles maculipennis
appeared to have no relation whatsoever to the prevalence of malaria. European malariologists called the conundrum “anophelism without malaria.” Further, was the mosquito the sole vector of malaria? If so, why was it that in places such as the Netherlands and Germany, fevers started in April and May, months before fat and sleepy
Anopheles
awoke from hibernation?
⁵⁹

Ross and Grassi’s discovery shed little light on such questions. As a result, many thinkers held that if the mosquito did transmit malaria, there were other, still-undiscovered factors. According to this way of thinking, Ross and Grassi had found just one route among many, and perhaps not even the most important one at that. (Grassi called the elusive transmitter “Factor X.”
⁶⁰
)

Countertheories abounded. A paper in the
Indian Medical Gazette
argued that “proper, filtered water supply” played a bigger role in malaria transmission than “the mere presence of
Anopheles
.”
⁶¹
The mosquito theory was just a fad, wrote another author, who claimed to be able to prove with statistical certainty that malaria was a waterborne complaint.
⁶²
In fact, according to another, malaria actually was just a “disorder of degenerating white blood corpuscles.”
⁶³

Ross and Manson’s response to the missing pieces in their mosquito theory only inflamed the public’s skepticism. Manson organized some poorly received experiments, which convinced few of anything. Meanwhile, Ross wildly proclaimed that he’d be able to extinguish malaria in every city in the tropics within two years.
⁶⁴

Ross’s exaggerations provoked even more exaggerated dismissals among health officials and scientists, who pointed out the folly of attempting to effect mosquito genocides. “I doubt whether, even if the whole population of India were put to the work of filling up all the puddles during the rains, the results would justify the expense,” maintained a British official at a malaria conference in India.
⁶⁵
Indeed, the chairman of London’s Society of Arts said to Ross, “Mosquitoes are every where. They surround us like the air we breathe.”
⁶⁶