Prologue A Vein Is a River

The boy in the bed in front of me was named Justin, and he didn't want to wake up. His bed, a spongy mat on a metal frame, sat in a hospital ward, a small concrete building with empty window frames. The hospital was made up of a few of these buildings, some with thatched roofs, in a wide dusty courtyard. It felt more like a village than a hospital to me. I associate hospitals with cold linoleum, not with goat kids in the courtyard, punching udders and whisking their tails, not with mothers and sisters of patients tending iron pots propped up on little fires under mango trees. The hospital was on the edge of a desolate town called Tambura, and the town was in southern Sudan, near the border with the Central African Republic. If you were to travel out in any direction from the hospital, you would head through little farms of millet and cassava, along winding paths through broken forests and swamps, past concrete-and-brick funeral domes topped with crosses, past termite mounds shaped like giant mushrooms, past mountains covered in venomous snakes, elephants, and leopards. But since you're not from southern Sudan, you probably wouldn't have traveled out in any direction, at least not when I was there. For twenty years a civil war had been lingering in Sudan between the southern tribes and the northerners. When I visited, the rebels had been in control of Tambura for four years, and they decreed that any outsiders who arrived on the weekly prop plane that landed on its muddy airstrip could travel only with rebel minders, and only in the daytime.

Justin, the boy in the bed, was twelve years old, with thin shoulders and a belly that curved inward like a bowl. He wore khaki shorts and a blue-beaded necklace; on the window ledge above him was a sack woven from reeds and a pair of sandals, each with a metal flower on its thong. His neck was so swollen that it was hard to tell where the back of his head began. His eyes bulged in a froglike way, and his nostrils were clogged shut.

"Hello, Justin! Justin, hello?" a woman said to him. There were seven of us there at the boy's bedside. There was the woman, an American doctor named Mickey Richer. There was an American nurse named John Carcello, a tall middle-aged man. And there were four Sudanese health workers. Justin tried to ignore all of us, as if we'd all just go away and he could go back to sleep. "Do you know where you are?" Richer asked him. One of the Sudanese nurses translated into Zande. He nodded and said, "Tambura."

Richer gently propped him up against her side. His neck and back were so stiff that when she lifted him he rose like a plank. She couldn't bend his neck, and as she tried, Justin, his eyes barely open, whimpered for her to stop. "If this happens," she said emphatically to the Sudanese, "call a doctor." She was trying to hide her irritation that they hadn't called her already. The boy's stiff neck meant that he was at the edge of death. For weeks his body had been overrun with a single-celled parasite, and the medicine Richer was giving him wasn't working. And there were a hundred other patients in Richer's hospital, all of whom had the same fatal disease, called sleeping sickness.

I had come here to Tambura for its parasites, the way some people go to Tanzania for its lions or Komodo for its dragons. In New York, where I live, the word parasite doesn't mean much, or at least not much in particular. When I'd tell people there I was studying parasites, some would say, "You mean tapeworms?" and some would say, "You mean ex-wives?" The word is slippery. Even in scientific circles, its definition can slide around. It can mean anything that lives on or in another organism at the expense of that organism. That definition can include a cold virus or the bacteria that cause meningitis. But if you tell a friend with a cough that he's harboring parasites, he may think you mean that there's an alien sitting in his chest, waiting to burst out and devour everything in sight. Parasites belong in nightmares, not in doctors' offices. And scientists themselves, for peculiar reasons of history, tend to use the word for everything that lives parasitically except bacteria and viruses.

Even in that constrained definition, parasites are a vast menagerie. Justin, for example, was lying in his hospital bed on the verge of death because his body had become home to a parasite called a trypanosome. Trypanosomes are single-celled creatures, but they are far more closely related to us humans than to bacteria. They got into Justin's body when he was bitten by a tsetse fly. As the tsetse fly drank his blood the trypansomes poured in. They began to steal oxygen and glucose from Justin's blood, multiplied and eluded his immune system, invaded his organs, and even slipped into his brain. Sleeping sickness gets its name from the way trypansomes disrupt people's brains, wrecking their biological clock and turning day to night. If Justin's mother hadn't brought him to the Tambura hospital, he would certainly have died in a matter of months. Sleeping sickness is a disease without pardon.

When Mickey Richer had come to Tambura four years earlier, there were hardly any cases of sleeping sickness, and people generally thought of it as a disease that was fading into history. That wasn't always the case. For thousands of years, sleeping sickness has threatened people in the range of the tsetse fly: a wide swath of Africa south of the Sahara. A version of the disease also attacked cattle and kept vast regions of the continent free of domesticated animals. Even now, over 4.5 million square miles are off limits to cattle in Africa because of sleeping sickness, and even where people do raise cattle, 3 million die of sleeping sickness each year. When Europeans colonized Africa, they helped trigger giant epidemics by forcing people to stay and work in tsetse-infested places. In 1906, Winston Churchill, who was the colonial undersecretary at the time, told the House of Commons that one sleeping sickness epidemic had reduced the population of Uganda from 6.5 million to 2.5 million.

By World War II, scientists had discovered that drugs effective against syphilis could also eradicate trypanosomes from the body. They were crude poisons, but they worked well enough to make the parasites sink back down to low levels if doctors carefully screened places thick with tsetse flies and treated the sick. There would always be sleeping sickness, but it would be an exception, not the rule. Campaigns against sleeping sickness during the 1950s and 1960s were so effective that scientists talked of eliminating the disease in a matter of years.

But war, crumbling economies, and corrupt governments let sleeping sickness come back. In Sudan the civil war drove away Belgian and British doctors from Tambura County; they had been keeping a careful watch for outbreaks. Not far from Tambura, I visited an abandoned hospital that had had its own sleeping sickness ward; now it is filled with wasps and lizards. As the years passed, Richer watched her load of sleeping sickness cases rise, first to 19, then to 87, then to hundreds. She ran a survey in 1997 and estimated from it that 20 percent of the people in Tambura County— 12,000 Sudanese— carried sleeping sickness.

That year Richer launched a counteroffensive, hoping to fight back the parasite at least in Tambura county. For people who were still in the early stages of the disease, ten days of injections in the buttocks with the drug pentamidine was enough. For those like Justin who had the parasites in their brains, a harsher course was necessary. They needed stronger stuff that could kill the parasite outright in their brain— a brutal potion known as melarsoprol. Melarsoprol is made of 20 percent arsenic. It can melt ordinary plastic IV tubes, so Richer had to have tubes flown in that were as tough as Teflon. If melarsoprol seeps out of a vein, it can turn the surrounding flesh into a swollen, painful mass; then, at the very least the drugs have to be stopped for a few days, and at worst the arm may have to be amputated.

When Justin arrived at the hospital, he already had parasites in his brain. The nurses gave him injections of melarsoprol for three days, and the medicine wiped out a fair number of the trypanosomes in his brain and spine. But as a result, his brain and spine had been flooded with scraps of dead parasite tissue, driving his immune cells from a torpor to a frenzy. They shot out blasts of poisons, which scorched Justin's brain. The inflammation they triggered was squeezing it like a vise.

Now Richer prescribed steroids for Justin to try to bring the swelling down. Justin whimpered remotely as the needleful of steroids went into his arm, his eyes closed as if he were deep in a bad dream. If he was lucky, the steroids would take pressure off his brain. The next day would tell: either he would be better or he would be dead.

Before I arrived at Justin's bedside, I had been traveling with Richer for a few days, watching her at work. We had gone to villages where her staff was spinning blood in centrifuges, looking for the signature of the parasite. We had driven for hours to get to another clinic of hers, where people were getting spinal taps to see if the trypanosomes were on their way to the brain. We had made the rounds of the Tambura hospital, seeing other patients: little children who had to be held down for injections as they screamed, old women bearing up silently as the medicine burned into their veins, a man made so crazy by the medicine that he had taken to attacking people and needed to be tied to a post. And from time to time— and now, as I looked at Justin— I tried to see the parasites inside them. It brought to mind that old movie Fantastic Voyage, in which Raquel Welch and her fellow crewmates climb into a submarine that is then squinched down to microscopic size. They are injected into a vein in a diplomat's body so that they can travel through his circulatory system to his brain and save him from a life-threatening wound. I had to enter that world, made of underground rivers, where the currents of blood follow ever-smaller branches of arteries until they pass back around into the veins, joining up to larger veins until they reach the surging heart. Red blood cells bounced and rolled along, squeezing through capillaries and then rebounding to their original puck shapes. White blood cells used their lobes to crawl into the vessels through lymphatic ducts, like doorways disguised as bookshelves in a house. And among them traveled the trypanosomes. I have looked at trypanosomes under a microscope in a Nairobi laboratory, and they are quite beautiful. Their name comes from trypanon, the Greek word for an augur. They are about twice as long as a red blood cell, silvery under a microscope. Their bodies are flat, like a strip, but as they swim they spin like drill bits.

Parasitologists who spend enough time looking at try panosomes in laboratories tend to fall in love with them. In an otherwise sober scientific paper, I came across this sentence: "Trypanosoma brucei has many enchanting features that have made this parasite the darling of experimental biologists." Parasitologists watch the trypanosomes as carefully as an ornithologist watches ospreys, while the parasites gulp glucose, while they evade the pursuit of immune cells by tossing off their coat and putting on a new one, while they transform themselves into new forms that can survive in the gut of a fly and then transform back into a form perfectly adapted for human hosts.

Trypanosomes are only one of many parasites inside the people of southern Sudan. If you could travel Fantastic Voyage-style through their skin, you would probably come across marble-sized nodules where you'd float past coiled worms as long as snakes and as thin as threads. Called Onchocerca volvulus, these animals, male and female, spend their ten-year-long lives in these nodules, making thousands of babies. The babies leave them and travel within the skin, in the hope that they'll get taken up in the bite of a black fly. In the black fly's gut they can mature to their next stage, and the insect can then inject them in the skin of a new host, where they will form a nodule of their own. As the babies swim through a victim's skin they can trigger a violent attack from the immune system. Rather than kill the parasite, though, the immune system puts a rash of leopard spots on the skin of its host. The rash can get so itchy that people may scratch themselves to death. When the worms wander through the outer layer of the eyes, the immune system's scarring can leave a person blind. Since their larvae are aquatic, black flies tend to stay around water, and the disease has thus earned the name river blindness. There are some places in Africa where river blindness has claimed the eyes of just about every person over forty.

Then there are Tambura's guinea worms: two-foot-long creatures that escape their hosts by punching a blister through the leg and crawling out over the course of a few days. Then there are filarial worms that cause elephantiasis, which can make a scrotum swell up until it can fill a wheelbarrow. Then there are tapeworms: eyeless, mouthless creatures that live in the intestines, stretching as long as sixty feet, made up of thousands of segments, each with its own male and female sex organs. There are leaf-shaped flukes in the liver and the blood. There are single-celled parasites that cause malaria, invading blood cells and exploding them with a fresh new generation hungry for cells of their own. Stay long enough in Tambura, and people around you turn transparent and become glittering constellations of parasites.

Tambura is not as freakish as it might seem. It's just a place where you can find parasites thriving in humans with particular ease. Most people on Earth carry parasites, even if you set aside bacteria and viruses. Over 1.4 billion people carry the snakelike roundworm Ascaris lumbricoides in their intestines; almost 1.3 billion carry blood-sucking hookworms; 1 billion have whipworm. Two or three million die of malaria a year. And many of these parasites are on the rise, not the wane. Richer may be slowing down the spread of sleeping sickness in her little patch of Sudan, but around her it seems to be spreading. It may kill three hundred thousand people a year; it probably kills more people in the Democratic Republic of Congo than AIDS. Parasitically speaking, New York is actually more freakish than Tambura. And if you step back and survey our evolution from an apelike ancestor 5 million years ago, the past century of parasite-free living that some humans have enjoyed is a fleeting reprieve.

I checked in on Justin the following day. He was propped up on his side, eating broth from a bowl. His back was lazily curved along the bed as he ate; his eyes were no longer swollen; his neck was supple again; his nose was clear. He was still exhausted and was far more interested in eating than in talking to strangers. But it was good to see that the fleeting reprieve included him as well.

Visiting places like Tambura, I began to think of the human body as a barely explored island of life, home to creatures unlike anything in the outside world. But when I remembered that we are just one species out of millions on this planet, the island swelled up to a continent, a planet.

A few months after my trip to Sudan, on a night that wavered between muggy and rainy, I walked through a Costa Rican jungle. I held a butterfly net in my hand, and the pockets of my raincoat spilled over with plastic bags. The headlamp on my brow cast a slanted oval on the path in front of me, which a spider crossed twenty feet ahead. Its eight eyes glinted together like a single diamond chip. A giant solitary wasp crawled slowly into its burrow on the side of the path to hide from my glare. The only light beyond my lamp came from distant lightning and the fireflies that glowed for long slow flashes in the trees overhead. The grass gave off the rank odor of jaguar urine.

I walked with seven biologists, led by one scientist named Daniel Brooks. He was about as far from my picture of the intrepid jungle biologist as he could get: heavy frame, a drooping mustache, and big aviator glasses, dressed in a red-and-black jogging suit and sneakers. But as the rest of us passed the time on the walk by talking about how to photograph birds or how to tell the difference between a poisonous coral snake and a harmless mimic, Brooks kept ahead, listening to the peeps and croaks that surrounded us. He stopped suddenly at the side of the path, waving his right hand back and low to shut us up. He moved toward a broad ditch filling with the night's rain and lifted his net slowly. He put one sneaker into the water and then suddenly brought the net down on the far bank. Its pointed end started dancing and punching, and he grabbed the net midway before raising it. With his other hand he took a plastic bag from me and blew it full of air. He transferred a big beige-striped leopard frog into the bag, where it jumped frantically. He knotted the open end of the bag, still fat with air, and wedged the knot under the drawstring of his sweatpants. He started walking down the path again with his bulging frog bag, a transparent sack of gold.

Frogs and toads were everywhere that night. Brooks caught a second leopard frog not far down the path. Tungara frogs drifted in the water, in powerful choruses. Marine toads, some as big as cats, waited until we were close by before taking a single big lazy hop to keep their distance. We walked past blobs of foam as firm as bubble bath, out of which hundreds of tadpoles squirmed into the nearby water. We caught blunt-faced microhylid frogs, with tiny stupid eyes crowded up just over their nostrils and fat low bodies shaped like dollops of chocolate pudding.

For some zoologists, the hunt for their animals would be over at this point. But Brooks wasn't sure yet what he had actually found. He brought the frogs back to the headquarters of the Area de Conservacion de Guanacaste. He left the frogs in their bags overnight, with some water to keep them damp and alive. In the morning, after a breakfast of rice and beans and pineapple juice, he and I went to his lab. The lab consisted of a shed with chicken-wire walls on two sides.

"The assistants here call it thejaula," said Brooks. There was a table in the middle of the shed that held dissecting microscopes, and woolly bears and beetles crawled across its concrete floor. A mud wasp nest hung from the light cord. Outside, beyond the vines that surrounded the shed, a howler monkey roared in the trees. Jaula means "jail" in Spanish. "They say that we have to stay in here or we'd kill all their animals."

Brooks took out a leopard frog from the bag and dispatched it with a sharp thwack on the edge of the sink. It was dead in an instant. He laid it on the table and began snipping its belly open. He used tweezers to pull the guts delicately free of the frog's trunk. He put the organs into a broad petri dish and put the husk of the frog under a microsope. During the previous three summers, Brooks had looked into the insides of eighty species of reptiles, birds, and fish at Guanacaste. He had started making a list of every parasite species that lives in the reserve. There are so many different kinds of parasites within the animals and plants of the world that no one had ever dared such a thing in a place the size of Guanacaste. He adjusted the lights on their long black stalks, two curious snakes looking at the dead frog. "Ah," he said, "here we go."

He had me look: a filarial worm— a relative of guinea worms in humans— had come wandering out of its home in one of the veins in the frog's back. "It's probably transmitted by mosquitoes that feed on the frogs," Brooks explained. He pulled it out intact and dropped it in a dish of water. By the time he had gotten a dish of acetic acid (industrial-strength vinegar) to fix it in, the parasite had exploded into a white froth. But Brooks was able to get another one out untorn and into the acid unexploded, where it straightened out, ready to be preserved for decades.

That was the first of many parasites we looked at. A string of flukes came out, like a writhing necklace, from another vein. The kidneys carried another species that only mature when the frog is eaten by a predator like a heron or a coati. The lungs of this frog were clear, although often the frogs here will have parasites in their lungs as well. They get several malarias in their blood, even get flukes in their esophagus and ears. "Frogs are parasite hotels," Brooks said. He worked apart the intestines, slitting them carefully so that he wouldn't snip any parasites inside. He found another species of fluke, a tiny fleck that swam across the microscope's view. "If you didn't know what to look for, you'd think it was garbage. It goes from a snail to a fly, which is then eaten by a frog." The fluke has to share this particular set of intestines with a trichostrongylid worm that takes a more direct route to get there, burrowing straight into the frog's gut.

Brooks pushed the dish out from under the microscope. "That was real disappointing, guys," he said. I think he was addressing the parasites. I was pretty overwhelmed by all the creatures I'd just seen in one animal, but Brooks knew that a single frog species may have a dozen species inside it, and he wanted me to see as many as I could. He spoke to the frog: "Let's hope your compadre has more."

He reached into the bag for the second leopard frog. This one had two toes missing from its front left foot. "That means he escaped from a predator that wasn't as successful as me," Brooks said, and dispatched it with another swift thwack. When he got its open belly under the microscope, he said "Oh!" with a sudden brightness. "This is nice. Sorry. Relatively speaking, this is nice." He had me look through the eyepieces. Another fluke, this one called a gorgoderid, for its resemblance to the writhing snakes on Medusa's head, was twisting out of the frog's bladder. "They live in freshwater clams. This tells me this frog has been somewhere where there are clams, which need a guaranteed water supply, sandy bottom, calcium-rich soil. And its second host is a crayfish, so the habitat has to support clams, crayfish, and frogs, and do it year round. Where we caught him yesterday is not where he comes from." He moved on to its intestines. "Here's a nice little vignette"— nematodes alongside flukes that form cysts on the frog's skin. When the frog sheds its skin, it eats it, thereby infecting itself. The flukes were acrobatic sacs of eggs.

Cheered up now, Brooks moved on to a blobby microhyalid frog. "Oh my, you've brought me luck," he says, looking inside it. "This thing must have a thousand pinworms. Holy cow, this guy is crawling." In the pinworm soup there were squirming iridescent protozoa, single-celled giants that were almost as big as the multicellular worms.

A few of the parasites we saw already have names, but most are new to science. For now, Brooks went to his computer and typed in vague descriptors— nematode, tapeworm— that would be honed down by himself or some other parasitologist who would come up with a Latin name. The computer carried in it the records of other parasites Brooks had recorded over the years, including some of the ones I had watched dissected over the course of the previous few days. There were the iguanas with their tapeworms, the turtle with an ocean of pinworms. Just before my arrival, Brooks and his assistants had opened up a deer and found a dozen species living in or on it, including nematodes that live only in the deer's Achilles tendon and flies that lay their eggs in the deer's nose. (Brooks calls these last ones the snot bots.)

Even within this one reserve, Brooks was probably not going to be able to count every parasite. Brooks is an expert on the parasites of vertebrates as parasites are traditionally defined— in other words, excluding the bacteria and viruses and fungi. When I visited him, he had identified about three hundred of these parasites, but he estimated there would be eleven thousand in total. Brooks doesn't study the thousands of species of parasitic wasps and flies that live in the forest, devouring insects from within and keeping them alive till the last moment of their feast. He doesn't study the plants that parasitize other plants, stealing the water their hosts pump from the ground and the food they make out of air and sun. He doesn't study fungi, which can invade animals, plants, or even other fungi. He can only hope that other parasitologists will join him. They are spread thin over their subjects. Every living thing has at least one parasite that lives inside it or on it. Many, like leopard frogs and humans, have many more. There's a parrot in Mexico with thirty different species of mites on its feathers alone. And the parasites themselves have parasites, and some of those parasites have parasites of their own. Scientists such as Brooks have no idea just how many species of parasites there are, but they do know one dazzling thing: parasites make up the majority of species on Earth. According to one estimate, parasites may outnumber free-living species four to one. In other words, the study of life is, for the most part, parasitology.

The book in your hand is about this new study of life. Parasites have been neglected for decades, but recently they've caught the attention of many scientists. It has taken a long time for scientists to appreciate the sophisticated adaptations parasites have made to their inner world, because it is so hard to get a glimpse of it. Parasites can castrate their hosts and then take over their minds. An inch-long fluke can fool our complex immune system into thinking it is as harmless as our own blood. A wasp can insert its own genes into the cells of a caterpillar to shut down the caterpillar's immune system. Only now are scientists thinking seriously about how parasites may be as important to ecosystems as lions and leopards. And only now are they realizing that parasites have been a dominant force, perhaps the dominant force, in the evolution of life.

Or perhaps I should say in the minority of life that is not parasitic. It takes a while to get used to that.

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