Why has malaria plagued humans for 500,000 years? A ruthless protozoan creature has the answer

Most pathogens mellow as they age. It’s enlightened self-interest, as the theory goes. Diminishing virulence is a superior strategy for survival. It doesn’t make much sense for a pathogen to rapidly destroy its victim – a dead body just means it’s time to move on. Take measles and smallpox, for example. In Europe, when those pathogens first emerged, they were probably reckless killers, taking millions of lives. The survivors learned how to withstand the diseases’ ravages, though, and in time both measles and smallpox settled into being unremarkable childhood illnesses, felling scores only when encountering virgin populations, such as those in the New World of the fifteenth century.

Which begs the question as to malaria’s tenacity and continuing malevolence. Malaria has been plaguing humans in Africa for some five hundred thousand years, with the first encounters between human, mosquito, and malaria parasite probably occurring around the time our ancestors discovered fire. Malaria existed in Africa before then, too, feeding on the birds, chimps, and monkeys that lived in the canopy. We’ve had plenty of time – our entire evolutionary history, in fact – to adapt to malaria, and it to us. Or, at least, to devise tools and strategies to blunt its appetite. And yet, despite the millennia-long battles between us, malaria still manages to infect at least three hundred million of us – that is one out of twenty-one human beings on the planet – and kills nearly one million, year after year. As an extinguisher of human lives, write the malariologists Richard Carter and Kamini Mendis, malaria historically and to this day “has few rivals.” It remains essentially wild and untamed, despite its great antiquity.

One simple reason for malaria’s ferocity is that the protozoan creature that causes the disease is, by definition, a cheater at the game of life.

It is a parasite, a creature that can eke out its livelihood only by depleting others of theirs. The rest of us all do our obscure little part in the drama of life, weaving ourselves deeper into local ecology and strengthening its fabric, the bees pollinating the flowers, predators culling the herds of their weakest members. Parasites don’t help anyone. They’re degenerates.

Take the parasitic barnacle, Sacculina carcini. It is born with a head, mouth, segmented body, and legs, just like any respectable barnacle. But then, because it is a parasite, it stops developing into an independent creature. It burrows into the shells of the crabs off of which it will spend its life feeding. There it loses its segments, its legs, its tail, and even its mouth, devolving into a pulsing plantlike form, little more than a blob with tendrils sucking food from the forlorn crab’s body. It’s the very definition of repellent. In 1883, Scottish lecturer Henry Drummond called parasitism “one of the gravest crimes of nature” and a “breach of the law of Evolution.” Who can blame him?

And yet parasites such as Plasmodium are not anomalous on this earth. According to the science writer Carl Zimmer, one third of all described species practice the parasitic lifestyle. To be fair, for Plasmodium, parasitism arose as an accommodation to newfound opportunities, not because of any intrinsic quality or irreversible mechanism within it. Plasmodium did not start out life hardwired to steal. This killer first emerged on the planet as a plantlike creature, most likely some kind of aquatic algae. We know this because 10 percent of the proteins in modern-day Plasmodium parasites contain vestiges of the machinery of photosynthesis.

Plasmodium’s ancestors probably rubbed shoulders with the eggs and larvae of mosquitoes, similarly floating on sun-dappled waters. When the mosquitoes took wing, malaria’s ancestors likely went quietly along with them. It must have happened, then and again, that when a mosquito pierced a bird or chimp or some other blood-filled creature, malaria’s algae ancestors fell into the wound. Most probably died. But through the blind ticking clock of evolution, one day some subset of the interlopers found themselves thriving in those crimson seas, and a vampiric parasite was born.

Such are the ironies of surviving on this protean planet.

A creature at the very bottom of the zoological scale, a humble being beneficently converting sunlight into living tissue (and thereby providing the basis for the planet’s entire food chain), turns into one of the most ruthlessly successful parasites ever known, commanding two separate spheres of the living world, human and entomological.

Henry Drummond would have been appalled.

Delve into even the most rudimentary scientific literature on malaria and you will soon be confronted with a dizzying range of unpronounceable words. There is “exflagellation”, “erythrocytic schizogony”, and “exo-erythrocytic schizogony”. There are “gametocytes” and “trophozoites” and “sporozoites”. These are not obscure terms for little-discussed facets of the parasite whispered over cluttered lab benches by a few old-school malaria nerds, but rather basic stages in the parasite’s life cycle bandied about by nearly everyone in the malaria world, from ponytailed Harvard undergrads to queenly Cameroonian researchers and grizzled Italian vaccine makers. It is as if scientists had to come up with a whole new language just to talk about malaria.

That’s because during the course of its life, Plasmodium transmogrifies into no fewer than seven different forms, which vary in both morphology and physiology. Its parasitic modus operandi demands such shape-shifting wiliness. After all, in order to survive, the malaria parasite must extort from two different species: the animal whose blood it feeds upon, and the insect who deposits it into that animal’s blood. It’s sort of like robbing a bank while stealing a car. Things get complicated.

The mosquito’s immune system instinctively attacks the parasite, encapsulating the intruder in scabs and bombarding it with toxic chemicals. To survive, the parasite must unleash armies of progeny in such massive numbers that fighting it off becomes more trouble than it’s worth. Male and female forms of the parasite, called gametocytes, then fuse, and the resulting parasites create cysts that cling to the walls of the bug’s gut. (The spasmodic waving of the male gametocyte’s long tail, which precedes the act of fusing with the female – yes, this microbe reproduces sexually as well as asexually – is called exflagellation.) Tens of thousands of slithering threads explode from the cysts and swarm up to the mosquito’s salivary gland. This is the form the parasite must take to infect human beings. Malariologists call it the sporozoite. When the mosquito starts a blood feed, some two dozen slivery sporozoites will escape into their next host.

The parasite’s shtick fails in most of the world’s 3,200 species of mosquito. It works only in a single genus, called Anopheles (rhymes with “enough of peas”), most likely because of that mosquito’s strangely tepid defences.

This restriction doesn’t hinder the parasite terribly, though – there are some 430 known species of Anopheles, distributed in every corner of the planet except for Polynesia, east of Vanuatu. At least 70 species are known to carry malaria.

Outwitting the human body’s defences, though, requires orders of magnitude more cunning. The parasite must conceal its appetite and indeed its very presence inside the body. The object of its desire – the hemoglobin inside red blood cells, which it feasts upon – is particularly precious. Produced from iron in bone marrow, hemoglobin makes it possible for blood cells to attach to oxygen molecules, and thus ferry life-giving oxygen to the body’s tissues. Without hemoglobin, lone oxygen molecules maraud unattached, degrading cells, proteins, and DNA as surely as they brown sliced apples and rust metal, and the body weakens, becomes anemic, and ultimately perishes.

The parasite must hide. First, the sporozoites retreat to the liver, where they spend a few surreptitious days shifting, regenerating, dividing, and generating again, secretly transforming into an army of fifty thousand parasites in a new form capable of infecting red blood cells – the merozoite. In the next stage of the invasion, the merozoites pour into the bloodstream. They are cleverly disguised inside the liver cells they’ve gagged and murdered, but an epic battle ensues nevertheless, and the body’s immune fighters slaughter thousands. It isn’t a perfect victory. If a few stragglers in this marauding horde manage to escape, they latch onto red blood cells, and within moments penetrate the cells’ interior. There, they quietly feast on hemoglobin, and a new round of shifting, regenerating, dividing, and generating ensues. Some transform from tiny ring-shaped beings into fat, rounded creatures and unleash a wave of progeny. When nothing is left of the former oxygen-carrying cell besides a stream of waste and a bulge of fattened parasites, the parasites burst out of the cell and rush out to invade and consume a fresh crop of cells. Others quietly shape-shift into the male and female forms called gametocytes and lie in wait inside their hijacked blood cells. With any luck, they will be picked up by another bloodthirsty Anopheles mosquito.

A creature this protean and multifarious defies easy challenge.

Excerpted with permission from The Fever: How Malaria Has Ruled Humankind For 500,000 Years, Sonia Shah, Penguin Random House India.