Parasite Rex

5 The Great Step Inward

There are billion-year-old secrets at the University of Pennsylvania, but they are well hidden from view in the laboratory of a biologist named David Roos. The sunlight of a soft Philadelphia sky flows through high windows into the lab, where Roos’s graduate students are laying flasks of cherry-colored liquids under microscopes, kneading data on computers, clicking pipettes in test tubes, and working in incubator rooms, cool rooms, warm rooms. Overhead, the sunlight strikes the vines and aloe plants on the shelves. The plants take in the summer light, each photon falling onto the surface of a microscopic, blob-shaped structure called a chloroplast. A chloroplast is essentially a solar-powered factory. It uses the energy of the light to manufacture new molecules out of raw materials such as carbon dioxide and water. The new molecules are trundled out of the chloroplasts and used by the plants to sprout new roots, to send out new feelers along the shelf. Below them, Roos’s students work furiously, discovering the hidden biochemistry of a parasite and publishing scientific papers, as if within them the sun were also driving some kind of intellectual photosynthesis. At a time like this, in a place like this, who has time to think about ancient history?

David Roos runs the lab from an office lodged at its center. He’s a young man with a curly mat of black hair and a chipped front tooth. He speaks coolly, comfortingly, his answers rolling out in paragraphs and pages with references ahead and back from the subject at hand, with hardly a pause for collecting thoughts. On the sunny day I visited, he was explaining to me how he came to study the parasite that he carries by the thousands in his own brain: Toxoplasma gondii. Overhead are charcoal drawings of human figures, a reminder of Roos’s days as an art student in college. That came after a stint after high school as a computer programmer—“I thought I wouldn’t go to college, since I was having so much fun and making so much money as a programmer, but that got old fairly quickly”—and before Roos took up biology. When he began studying biology, he contemplated working on parasites. “There’s no more interesting question biologically than how does one organism survive off of another, especially inside another cell? But as a graduate student I looked around and talked to a couple of labs, and the systems just seemed so archaic.”

By this, Roos meant that parasitologists had a harder time with husbandry than other biologists. A lot of scientists who study how animals develop from fertilized eggs, for example, study the fruit fly. If they find an interesting mutation in a fly, they know how to breed a line of them that all carry the same mutation; they have the tools to isolate the mutated gene, to shut that gene down or replace it with a different version. With these tools, biologists can map out the web of interactions that turn a single cell into a noble insect. But parasitologists struggle just to keep parasites alive in a lab, and breeding interesting strains is often impossible. Fruit fly biologists have a giant toolbox at their disposal. Parasitologists have been stuck with a broken hammer and a toothless saw.

The frustration didn’t appeal to Roos, so he went off to work in graduate school on viruses, and later on mammalian cells. His work paid off well, landing him a job at Penn, but by then he wanted something new to study. He learned that in the years he had stayed away from parasites, other researchers had had some early success in using them like fruit flies. One parasite looked particularly promising: Toxoplasma. It might not have the cachet of its close relative Plasmodium—the parasite that causes malaria, a sophisticated creature that can turn a barren red blood cell into a home in a matter of hours—but it seemed to take well to life in the lab. Perhaps it could act as a model for malaria, since many of their proteins worked in similar ways. “I thought, maybe very naively, that one of the reasons people had not worked on Toxoplasma in the past was that it was rather boring,” Roos said. “Like anybody else, biologists like to work on sexy topics. But maybe if this organism is so boring—meaning more or less like things we’re more familiar with—it wouldn’t require completely reinventing the wheel to develop genetic tools.”

Roos started building the tools, and he found success unnervingly simple. “Some people think we have golden hands in my lab, but in truth we work on an easy organism,” he says. His lab learned how to riddle the parasite with mutations, how to switch one gene with a new one, how to see the parasite more clearly than before. Within a few years they were able to start using their tools to ask questions, such as exactly how Toxoplasma invades cells, or why some drugs kill Toxoplasma and Plasmodium, while the parasites manage to resist others.

In 1993, Roos began studying a drug that kills both parasites, called clindamycin. It’s not used to cure malaria, though, because it takes too long to kill Plasmodium; instead, it’s chiefly used against Toxoplasma in AIDS victims who need a drug they can take for years without side effects. “The funny thing about clindamycin,” Roos says, “is that it shouldn’t work.”

Clindamycin is actually used mostly as an antibiotic to kill bacteria, which it does by clogging up the bacteria’s protein-building structures, known as ribosomes. “Eukaryote cells have quite different ribosomes, and clindamycin doesn’t interfere with them, which is good, because otherwise it would kill you. That’s what makes it a good drug. Now Toxoplasma, these guys aren’t bacteria. They have a nucleus, they have mitchondria.” (Mitochondria are compartments where eukaryote cells generate their energy.) “They’re clearly more closely related to you and me than to bacteria.”

And yet, clindamycin kills Toxoplasma, and Plasmodium as well. How it killed them no one knew. Scientists knew that they didn’t affect the regular ribosomes in the parasites. But eukaryotes also carry a few extra ribosomes in their mitochondria that are different from the rest. Mitochondria carry their own DNA, which they use to build their own ribosomes, among other things. Yet, researchers found that clindamycin left the ribosomes of mitochondria unharmed as well.

Roos rememberd that Toxoplasma actually had a third set of DNA. In the 1970s, scientists had discovered a circle of genes that didn’t belong to its nucleus or its mitochondria. This orphan DNA contained the recipe for a third ribosome. Perhaps, Roos thought, clindamycin attacked the third ribosome and killed the parasites in the process. He and his students destroyed the circle of DNA and discovered that indeed Toxoplasma couldn’t survive without it.

But what exactly was this ring of genes? Roos and his students discovered that it sat inside a structure floating close by the parasite’s nucleus. In the past, scientists had given the structure many names—the Spherical Body, the Golgi Adjunct, the Multi-membraned Body—all of which may make you think they knew what it was for. They didn’t.

Roos now knew it was for housing the genes that make Toxoplasma vulnerable to clindamycin. But he didn’t know yet what the ribosome that the genes made was for. To get some insight, he compared the genes to other genes in Toxoplasma and other microbes. The closest match he found was not among the genes inside Toxoplasma’s nucleus or mitochondria. It was the chloroplasts in plants, those solar-powered factories that make the plants on the laboratory shelves grow. “They look for all the world like a green plant,” says Roos.

Roos had hoped to figure out how Toxoplasma and Plasmodium die like bacteria, even though they live like us. Now he had simply traded one puzzle for another: How can malaria be a cousin to ivy?

To nineteenth-century biologists such as Lankester, parasites got to be the way they are now by degeneration. Their evolutions were tales of loss, of the abandonment of all the adaptations that made an energetic, free-living existence possible, of settling for a spoon-fed dinner. In this century, that notion of degeneration has hung on; for decades, evolutionary biologists simply thought that the story of parasite evolution was not worth thinking about compared with sagas like the origin of flight or the enfolding of the brain. Yet, the ability of Trichinella to make its host build itself a nursery in its muscles, of Sacculina to make a male crab into its mother, of blood flukes to become blood-invisible—all of these are adapations produced by evolution. Many parasitologists don’t have evolution as their main business; they study parasites as they live today. And yet, evolution elbows its way into their work.

Such is the case with David Roos: the only way he can understand what Toxoplasma is today, and how it is that malaria is a green disease, is to plunge back hundreds of millions of years. These sorts of histories are just as fascinating as those of free-living animals. They are tangled up with the evolution of the rest of life, going back 4 billion years. In fact, the history of parasites is, to a great extent, the history of life itself.

Reconstructing that history isn’t easy. Parasites tend to be squishy or crunchy—two conditions that don’t augur well for fossils. Every few million years, a parasitic wasp may stumble into a blob of amber, or a male crab feminized by a parasitic barnacle may leave behind its transgendered fossil, but for the most part parasites vanish in the rotting tissues of their hosts. Rocks don’t have a monopoly on clues to life’s history, though. Evolution has formed a vast tree, and biologists today can inspect its leafy tips. By comparing the biological features they find there, they can work their way back to the crooks of branches, to the tree’s base.

Biologists draw the branches of this tree by figuring out which species are most closely related to one another. Their close heritage shows that they must have diverged from a common ancestor more recently than from other species. To see this kinship, biologists look at the similarities and differences among organisms, judging which ones are the result of common descent or the illusions of evolution. A duck, an eagle, and a bat all have wings, but the duck and the eagle are much more closely related. The evidence is in their wings: on birds they consist of feathers hanging from a fused hand; a bat has membranes stretched over long fingers. The fact that bats are hairy, give birth to live young, and nurse them with milk helps show that despite their wings, they’re actually more closely related to us and other mammals than to a bird.

Flesh and bone can say only so much, though. They do not say definitively whether bats are closer cousins to primates or to tree shrews, for instance. And for organisms that don’t have flesh or bone, they say nothing at all. That silence has pushed biologists in the past twenty-five years to compare the protein and DNA of organisms rather than wings or antlers. They have learned how to sequence the genes and compare them with the help of computers. This approach brings its own pitfalls—genes can sometimes create trees as confusing as flesh and bone—but while they may be provisional, they have allowed biologists to look for the first time with one grand sweep of the eye at all of life.

The base of the tree represents the origin of life. Many of the organisms that occupy the branches closest to the base live today in scalding water, often around hydrothermal vents. That suggests that life may have gotten its start in such a place 4 billion years ago. Gene-like molecules may have assembled inside little fatty capsules or perhaps in oily films coating the sides of the vents. After untold millions of years, the first true organisms formed, bacteria-like things that carried genes floating loose inside their walls. Out of these bacterial beginnings, life began to diverge into separate lineages. The Archaea continued a basically bacteria-like kind of life, while a third branch—the eukaryotes with their DNA balled up tight in a nucleus and their power coming from mitochondria—took on a drastically different form.

Parasites, according to the traditional definition of the word (the creatures that cause malaria and sleeping sickness, that cram into guts and livers, that burst out of caterpillars as if their hosts were giant birthday cakes), all sit on branches on the eukaryote part of the tree. They have abandoned a life in the sea or on land for one inside other eukaryotes. They include organisms separated by vast evolutionary gulfs from ourselves—trypanosomes and Giardia branched off on their own separate destinies at the dawn of the age of eukaryotes, over two billion years ago. Among the parasites there are also much closer relatives, such as fungi and plants. Parasitic animals, such as blood flukes and wasps, are practically our kissing cousins. Parasitism is scattered across the eukaryote domain, a way of life that lineages have independently adopted and have found to be immensely profitable for many hundreds of millions of years.

Yet, this tree also makes it clear just how shallow the conventional definition of parasite is. Why should the name be restricted to organisms that are found on one of the three great branches of life? Nineteenth-century biologists were right to call infectious bacteria parasites. Just as some eukaryotes abandoned the free-living life, so did certain bacteria such as Salmonella and Escherichia coli, while other bacteria have kept up their independence in oceans, swamps, and deserts—even under Antarctic ice. The difference is only in genealogy, not lifestyle.

And even this definition of parasites is too parochial. Nowhere on this tree, for instance, can you find a flu virus. That’s because viruses aren’t, strictly speaking, living things. They have no inner metabolism and can’t reproduce on their own. They are nothing more than protein shells, which carry in them the equipment necessary to get into cells and then use the cell’s own machinery to make copies of themselves. Yet, viruses have the same sorts of parasitic hallmarks you could find in creatures like blood flukes—they thrive at their host’s expense, they use some of the same tricks to evade the immune system, and they can sometimes even change their hosts’ behavior to increase their spread.

In the 1970s, the English biologist Richard Dawkins made viruses less of a paradox. Viruses may not be alive in the traditional sense, but they get the basic job of life done: they replicate their genes. Animals and microbes exist, Dawkins argued, to do the same thing. We should think of their bodies, their metabolism, their behavior all as vehicles that genes build in order to get themselves replicated. In that sense, a human brain is no different from the protein coat that allows a virus to slip inside a cell. This view of life is a controversial one, and many biologists believe it downplays the importance of life’s complexity. But it works very well when it comes to parasitism. For Dawkins, parasitism is not what some particular flea or thorny-headed worm does. Parasitism is any arrangement in which one set of DNA is replicated with the help of—and at the expense of—another set of DNA.

That DNA can even be part of your own genes. Huge swaths of human genetic material do nothing for the good of the body they’re in. They don’t make hair, they don’t make hemoglobin, they don’t even help other genes do their job. They consist of little more than the instructions for getting themselves replicated faster than the rest of the genome. Some of them produce enzymes that slice them free and then insert them at another point in your genes. Soon the gap they leave behind is visited by proteins that search for damaged DNA. Because human genes come in pairs, these proteins can use the undamaged copy as a guide, and rebuild the stretch that disappeared. In the end, there are two copies of the jumping DNA.

These chunks of wandering genetic material are sometimes called selfish DNA or genetic parasites. They use their host—their fellow genes—to get themselves replicated. Like more conventional parasites, genetic parasites can harm their host. As they insert themselves at random places in the genome, they can cause diseases. Because genetic parasites can replicate at a faster rate than their fellow genes, they have swamped the genome of many hosts, including humans.

Parents pass their genetic parasites down to their children, and it’s possible therefore to sort selfish DNA into families, descendants of common ancestors that lived within the common ancestors of their hosts. Genetic parasites have their own dynasties that rise and fall. When a founder first turns up in a new host’s DNA, it starts copying itself at an explosive pace, packing its host gene with parasites. (I speak here of an explosion over evolutionary time—perhaps thousands of years.) Genetic parasites are sloppy duplicators, though, and they often make defective copies of themselves. These misfits can’t replicate themselves and simply clog up their host’s DNA. Genetic parasites are thus always risking self-inflicted extinction.

They can escape this dead end with little bursts of evolutionary renewal. Some of them steal genes from their host that allow them to build protein shells. They become viruses that can break free of their own cell and infect other ones. Some of these breakaways can even infect new species. They probably get carried away by parasites (such as mites) that take them to their new host, although some of the jumps are so long that it’s hard to know how they could possibly happen. How is it, for instance, that a freshwater flatworm has the same genetic parasites as a hydra living in the ocean, and a beetle living on land?

Viruses and genetic parasites may be common today, but 4 billion years ago parasitism might have been even more rampant. A typical organism alive today, be it a bacterium or a redwood, carries genes that are organized into powerful coalitions. They can copy themselves accurately into a new generation, and they can put up a fight against cheating genes. But when the Earth was young, some biologists think that genes were barely organized and couldn’t cooperate very well. Genes moved fluidly from one microbe to the next, sliding in and out of genomes through a sort of global microbial network. Any genes that could trick others into replicating them would be rewarded by natural selection and spread. Eventually the coalitions of genes got organized into separate organisms, but they were still trading DNA around so promiscuously that a biologist would have a hard time classifying them into separate species.

In spite of the assaults, true organisms did manage to evolve. Probably their genes evolved to a point where they all worked together well and could shut out cheating genes, and they could faithfully replicate themselves. It was probably at this time that life began to diverge into three great branches: bacteria, Archaea, and eukaryotes. Some of those early microbes found their energy in the chemicals growing along hydrothermal vents. As hundreds of millions of years drifted by, some lineages of bacteria became able to capture the energy of light. Other bacteria scavenged their microbial dung. Others evolved into killers, swallowing up the self-sufficient bacteria. Genetic parasites still lived off these different kinds of microbes, although their hosts had begun to get the upper hand.

But with every level of complexity that life achieved, a new kind of parasite emerged. When true organisms evolved, some of them became parasites. There are a few plausible stories of how they first evolved, and they may all turn out to be true in one case or another. One story begins with microbial predators swallowing what should have been their next meal. They opened up a cavity in their membrane and engulfed their prey; they prepared to carve it up, but for some reason, that was as far as their meals got. The prey sat in the predator’s microbial belly, indigestible.

Now the tables were turned—the prey turned out to be able to get a little nutrition from its failed predator before it was spat out. That extra food, that brief shelter from more successful predators, helped the prey reproduce more quickly than it would have otherwise. Natural selection would make the genes that helped it survive inside the predator became more common. They were joined by other genes that helped the prey actually seek out its predator, to open those cavities in the predator’s membrane by themselves. The prey spent more and more time inside the predator and gradually abandoned its free-living ways. Now it became the predators that had to fight off the prey, putting more and more effort into expelling them. If the cost of trying to fight off the invasion of parasites became too great, it would have benefited some hosts to make their parasites full-time guests. When the host divided, the parasite copied its own DNA and passed it down through the generations.

Once brought together this way, parasite and host can take their relationship in any one of several directions. The parasite may go on making its host’s life miserable, or it may instead become useful to the host, perhaps secreting some protein that the host can use. After many generations together, the lines between parasite and host may begin to blur. Some of the DNA of the parasite is accidentally ferried into the host’s own genes. The parasite itself may shrivel away to a few essential functions. The two organisms become essentially one.

Darwin never imagined this sort of fusion of life. He thought of life as an ever-branching tree, something like the tree shown on page 124. But biologists now recognize that they need to braid some of the branches together.

Scientists are now sequencing the full battery of genes in many microbes, and in them they can see signs of the choices that parasites have taken. Among the fully sequenced species is Rickettsia prowazekii, a bacterium that causes typhus. It invades cells, soaks up their nutrients and consumes their oxygen, multiplies like mad, and bursts its hosts open. Its DNA looks remarkably like the DNA in mitochondria, the organelles that provide every cell in our body with energy. A primordial free-living bacteria must have been the ancestor of both Rickettsia and mitochondria perhaps 3 billion years ago. Some of its descendants ended up passing through the earliest eukaryotes. The branch that led to Rickettsia evolved down the vicious path, while mitochondria’s ancestors eventually settled peacefully inside their hosts. Mitochondria was a fortunate parasite for our ancestors to gain. Photosynthesizing bacteria were gradually filling the atmosphere with oxygen, and mitochondria let eukaryotes breathe it.

Today’s eukaryotes are the product of a slow orgy of feasting and infection. After mitochondria invaded, several branches of eukaryotes all gained more bacteria of their own. These bacteria were photosynthetic, and their hosts stripped them down to their bare sun-harnessing essence, the chloroplast. These eukaryotes gave rise to algae and land plants, which added even more oxygen to the air. We can breathe oxygen, and plants can produce it in vast quantities, thanks to the parasites inside our cells.

This billion-year-old drama explains how malaria came to be a green disease. Some ancient eukaryote swallowed a photosynthesizing bacteria and became a sunlight-gathering alga. Millions of years later one of these algae was devoured by a second eukaryote. This new host gutted the alga, casting away its nucleus and its mitochondria, keeping only the chloroplast. That thief of a thief was the ancestor of Plasmodium and Toxoplasma. And this Russian-doll sequence of events explains why you can cure malaria with an antibiotic that kills bacteria: because Plasmodium has a former bacterium inside it doing some vital business.

It’s hard to know what exactly that ancient parasite did with its newfound chloroplasts. Perhaps it used them to live like a plant by photosynthesis. But that’s not the only possibility, because chloroplasts in plants do more than harness sunlight. They make many compounds, including fatty acids (the sort of molecules that constitute olive oil, for example). David Roos and his colleagues have speculated that in Plasmodium and Toxoplasma, their remnant of a chloroplast still makes these fatty acids and that the parasites use them to enshroud themselves inside their host cells. Clindamycin may be lethal to the parasite because it destroys Plasmodium’s bubble.

One thing is clear, though: that ancestor of Plasmodium and Toxoplasma didn’t live inside animals. A billion years ago, there weren’t any animals yet to parasitize. At the time, single-celled creatures were only just beginning combining into colonies and collectives. Many of the first multicellular creatures were like nothing alive today. Some of them looked like inflatable mattresses or the ornate coins of some ancient kingdom. It wasn’t until about 700 million years ago that the first kinds of animals we see today arose: corals, jellyfishes, arthropods. Meanwhile, algae began organizing into more complicated forms, giving rise to plants, and about 500 million years ago they moved on shore, forming a mossy carpet and later evolving into low-stalked plants, and finally trees. Soon afterward, animals came on shore as well—centipedes and insects and other invertebrates by 450 million years ago, and the first lumbering vertebrates 360 million years ago.

Multicellular organisms created a seductive new world for parasites to explore. They concentrated food into big, dense bodies that were stable homes for weeks or years at a time. The animals of the Cambrian oceans attracted protozoa like Plasmodium as well as bacteria and viruses and fungi. And once again, a new kind of parasite came into existence: animals themselves evolved to live inside other animals. Flatworms made their way into crustaceans, where they diversified into flukes, tapeworms, and other parasites. Crabs, insects, arachnids—at least fifty times other lineages of animals followed suit.

The parasites evolved quickly within their hosts into forms quite unlike their ancestors. Relatives of jellyfish began to parasitize fish, and stripped themselves down into little sporelike shapes, which today plague the trout of American rivers with whirling disease. As their hosts became bigger and more widespread—growing to towering trees, ant colonies millions strong, marine reptiles eighty feet long—parasites enjoyed an ever-expanding habitat. After the first flush of success at the dawn of life, after the brutal clamp-down as hosts became better organized, now came a new golden age for parasites.

Our own lineage, the vertebrates, hasn’t done a very good job at becoming parasites. Among the few that have are some species of catfish in the rivers of Latin America. The most famous one of them is the candiru, a pencil-thin fish. It earns its fame by attacking people who urinate in rivers. It follows the odor of their urine and rams itself into their urethra. Once it sinks its teeth into a penis or a vagina, it’s almost impossible to get out. Attacking people is not how the candiru makes a living, though; it usually feeds on other fish, working its way under their gill flaps and sucking blood from the delicate vessels underneath. After a few minutes it drops off and looks for another fish to make its host. Other species have an even more parasitic way of life. When fish are caught in Latin America, they’re sometimes found with inch-long catfish lodged in their gills. Those little fish may spend most of their lives there, feeding on blood or mucus from their hosts.

No one knows why there aren’t more candirus in the world, but there may be some things about being a vertebrate that make a parasitic life hard. Vertebrates have high metabolisms compared with invertebrates, so they may not be able to get enough food within another animal. To be a parasite, an animal needs to produce a lot of young, because getting into the next host is so difficult and so essential. Vertebrates need to put a lot of energy into each offspring, so they may not be able to meet the challenge. But parasitism, as Richard Dawkins pointed out, doesn’t have to take a conventional form like a tapeworm. Imagine an animal that could somehow trick another animal into raising its young. The tricker would be more likely to pass on its genes, while the trickee would have less time to tend to its own offspring and to its own genetic legacy. In fact, there are many species—both invertebrates and vertebrates—that practice just this sort of social parasitism.

Among the invertebrates, one of the most extreme cases can be found in the Swiss Alps. There you find nests of the ant Tetramorium. If you look for the queen, chances are good you’ll find some pale, strangely shaped ants sitting on her back. They are not a special caste of Tetramorium ant but a different species altogether: Teleutomyrmex schneideri. Teleutomyrmex spends most of its life on a Tetramorium queen’s back, hugging her with specially designed gripping legs. Instead of attacking these aliens, the Tetramorium workers let them eat the food they regurgitate for their queen. The Teleutomyrmex parasites mate inside their host’s nest, and the new queens leave to find a new colony where they can hop on a new host.

The secret to parasitizing ants this way is creating illusions of smell. Ants depend mainly on smells to perceive the world, and they’ve evolved a complicated vocabulary of airborne chemicals to communicate with each other—to lay down food trails, to set off a colony-wide alarm, to recognize each other as nestmates. Teleutomyrmex can fool their hosts into caring for them rather than eating them because they can produce signals that make their hosts perceive them as queens themselves. The reason why Teleutomyrmex can cast these spells is probably that they evolved from their own host, turning their common language against their kin.

But many animals are social parasites of ants that aren’t ants themselves. Some butterflies, for example, can trick ants into rearing their caterpillars. The butterflies lay their eggs on flowers, and when the caterpillars hatch, they drop to the ground, where ants come across them. Normally, ants look at a caterpillar as a gigantic lunch. But if they come across a social parasite, they act as if the caterpillar is a lost larva from own colony. Deceived by the caterpillar’s odors, the ants drag it back to their nest, where they feed it and groom it the way they would any of their own larvae. Sometimes the ants even prefer the parasite to their own young. The caterpillar spends the winter growing in this luxury, after which it forms a cocoon. The ants go on caring for it as it metamorphoses into a winged butterfly. Only when it emerges from its cocoon does it finally occur to the ants that a huge intruder is in their midst and they try to attack it. But the butterfly bolts out of the nest and flies away.

All these social parasites essentially do what any conventional parasite does: they find the weaknesses in their hosts’ defenses and turn them to their own advantage. There are vertebrates that do the same thing. The cuckoo, for instance, lays its eggs in the nests of other birds such as reed warblers. When a young cuckoo hatches, it proceeds to hurl its host’s eggs and nestlings to the ground. The reed warbler feeds the cuckoo anyway, even as it grows so large that it dwarfs its stepparent. Once it is fully grown, the cuckoo flies off to find a mate, leaving the childless reed warbler behind.

Ants perceive their world mainly by smells, but birds depend much more on their eyes and ears. So cuckoos and other parasitic birds don’t create fake smells but fake sights and sounds. The cuckoo egg mimics those of its host species, so the host is unlikely to get the urge to throw it out of the nest. After the cuckoo is born, it tricks the reed warbler into feeding by playing on the signals it uses to feed its young. To figure out how much food to catch, reed warblers look down in their nest, where their babies are holding open their mouths. If they see a lot of pink—the inside of bird mouths—they automatically hunt for more food. At the same time they rely on the sound of their crying babies as a second signal. If the babies are still hungry and are crying, the warbler will find more food.

A single cuckoo starts life much bigger than a warbler, and as it grows it gets even bigger. When the warbler looks down at its nest, it sees one big cuckoo mouth, which registers in its brain the same way a lot of little reed warbler mouths would. At the same time the young cuckoo mimics the calls of baby warblers. But rather than mimic the sound of a single warbler, the cuckoo can sing like an entire nestful. So the cuckoo tricks its host not only into feeding it but into bringing it eight warblers’ worth of worms. There may not be much room inside animals for a vertebrate parasite, but an animal’s nest is another matter.

So is a mother’s womb. When a fertilized egg tumbles down into the uterus and tries to implant itself, it encounters an army of macrophages and other immune cells. The new embryo doesn’t have the same proteins on its cells as its mother, which ought to trigger the immune cells to destroy it. The fetus faces the same troubles as a tapeworm or a blood fluke, and it evades its mother’s immune system in much the same way. The first cells that differentiate in a human embryo, known as trophoblasts, form a protective shield around the rest of its body. They fend off attacking immune cells and complement molecules, and they can send out signals that make the surrounding immune system sluggish. Strangely enough, there’s some evidence that these suppressing signals are made in the trophoblasts by some of the viruses that are lodged permanently in our DNA—just as viruses in parasitic wasp genes let them control the immune systems of their hosts.

If you think of parasitism in terms of Dawkins’s definition of genetic interests, then a fetus is a sort of half-parasite. It shares half its genes with its mother, and the rest belong to its father. Both mother and father have an interest, evolutionarily speaking, in seeing the fetus get born and live a healthy life. But some biologists have argued that parents also have strong conflicts on how the fetus grows. As it develops, it builds its placenta and a network of vessels to draw nourishment out of its mother. It knocks out its mother’s control over her blood vessels near the uterus, so that she can’t restrict the flow of blood to the fetus. It even releases chemicals to raise the concentration of sugar in her blood. But if the mother lets her child take too much, it might take a serious toll on her health. She might not be able to take care of her other children, and it might even threaten her ability to have any more. In other words, the fetus threatens her genetic legacy. Research suggests that mothers struggle against their fetus, releasing counteracting chemicals of their own.

While a fetus can take a heavy toll on its mother, how fast it grows will have no effect on its father’s health. It’s in his genetic interest for the fetus to grow as fast as possible. This conflict plays out within the fetus itself. Research on animals has shown that the genes a fetus inherits from its father and mother do different things, particularly in the trophoblasts. The maternal genes try to slow down the growth of the fetus, to control this parasite within her. Meanwhile, the paternal genes clamp down on these maternal genes and silence them, letting the fetus grow faster and draw more energy from its host.

Whenever two lives come into close contact and genetic conflict—even mother and child—parasitism will turn up.

The feeling of being surrounded by a few million parasites is a hard one to put into words. If you put your face close to a jar filled with a graceful ribbon, a tapeworm pulled from a porcupine, you can’t help admire its hundreds of segments, each with its own set of male and female sexual organs, all brimming with life and caught like a photograph in these preserving spirits. Then, just for a second, you start to worry that the whole creature will twitch a little, suddenly flail, and then break out of the glass.

The National Parasite Collection, run by the Agricultural Research Service of the U.S. Department of Agriculture, is one of the three biggest collections of parasites in the world. (Nobody is quite sure whether the American collection is bigger than the national collections of Russia. After you get up to a few million specimens, you tend to lose count.) It sits in a former guinea-pig barn on a farm the Department of Agriculture has been running in Maryland since 1936. In the distance, corporate headquarters push their cool blue-glass heads just over the trees. My guide through the collection was Eric Hoberg, a parasitologist in the shape of a bear. He studies the parasites of the far north, the nematodes that live only in the lungs of musk oxen, the flukes of a walrus. He led me down a flight of gray-striped stairs, past a couple of small labs, past a high stack of card catalogs a woman was slowly keying into a computer—a century of parasites. Then we went through a thick doorway to the collection.

At first I was a bit disappointed. I’ve followed paleontologists past museum displays and slipped through hidden doors into their collections, and we’ve wandered through corridors lined with high, deep cabinents full of whale skulls and dinosaur vertebrae that haven’t been touched since they were dragged out of the ground. You could fit a little diner into the National Parasite Collection, or maybe a shoe repair shop. Hoberg introduced me to a retired science teacher named Donald Poling. Poling sat at a table, wearing hiking boots and a white lab jacket, rescuing slides of nematodes from preserving fluid that had crystallized over the past hundred years into the consistency of brown sugar. “Keeps me out of the bars,” he said, scraping off a cover slip.

The rest of the room was taken up mainly by metal shelves on rollers that glided open with the turn of a three-pronged wheel. When Hoberg and I started walking among the shelves, browsing through the jars and vials, the disappointment disappeared. The collection surrounded me and became my world. We turned sealed jars around to read the labels that had been written in pencil. “Host: Yellowheaded Blackbird.” Tapeworms from Alaskan reindeer. Liver flukes from elks. Frilly monogeneans that held on to the gills of fish from Korea.

At one point, when Hoberg was showing me a nematode—thick as a finger, long as a riding crop, the color of blood—which was still curled up inside a fox’s kidney, I couldn’t help myself. I said, “Gross.” I had actually come to see Hoberg to learn something, not to continue with my horror marathon, but these things have a way of fighting their way out. Now it was Hoberg’s turn for disappointment. “I get irritated by the yuck factor,” he said. “What’s being missed is how incredibly interesting these are. And it’s tended to hurt parasitology as a discipline. Part of it is that people are put off by that,” he nodded to the kidney. “Parasitologists are retiring and not being replaced by new ones.”

We kept looking. We looked at a jar full of Hymenolepis, the tapeworm that uses beetles to get into rats, a great swirl of rice noodles. A piece of pig flesh with Trichinella running through it like a night of shooting stars. We passed closed trays of slides stacked upright like books on the shelves, hundreds of them, each with dozens of slices of parasites mounted on glass. We passed by the twelve thousand slides of specimens Hoberg collected in the Aleutian islands while he was working on his dissertation—twelve thousand slides he doubts he’ll ever find time to write about before he retires. Hoberg brought the slides with him from the University of Washington when he got the job at the collection in 1989. A decade later, he was still coming across surprises. “Crab-eater seal?” he barked at a jar of tapeworms, picking it up and turning it in his hand. He lifted his glasses to his forehead to study the paper label floating in the fluid and said, “This may have been from Byrd’s last expedition to the Antarctic.” We came across a jar of botfly larvae. As horses walk through fields, adult botflies lay eggs on their hair, and when the horses lick themselves clean, they swallow the eggs. The eggs take the warmth of their mouth as a cue to hatch, and they chew their way into the horse’s tongue. From there they drill down to the horse’s stomach, where they anchor themselves and drink its blood. Once they mature, they let go their grip and are carried out of the horse’s digestive tract. They hit the ground and transform into adult flies. In the jar before us, a swatch of horse stomach lay at the bottom, studded with botfly larvae, a cluster of stony little hives. I was fascinated, but Hoberg flinched. “That’s one thing I can do without.” I was glad to see that even a parasitologist has his limits.

Hoberg’s favorite part of the collection was the slides. He grabbed a few cases and took them up with us to his office, which is dominated by a compound microscope. He focused slides for me to look at, showing sections of tapeworms from puffins, from bearded seals, from killer whales. It’s hard to tell tapeworm species apart. Sometimes the only visual difference is the shape of the chamber that houses their sexual organs. Sometimes only their genes will tell you that two tapeworms are separate species. Yet, by studying their relationships, Hoberg re-creates 400 million years of parasite history without a single fossil to guide him. He does so by finding strange patterns in parasites and their hosts. Why, Hoberg wonders, do these kinds of tapeworms—called tetrabothriids—live only in sea birds and marine mammals? Why do none of them live in humans or sharks? Why does another kind of tapeworm turn up in only two places in the world: in Australia and the thorn forests of Bolivia? The answers to these questions add up to a history of tapeworms, an epic that also carries secrets about the history of their vertebrate hosts, about drifting continents and pulsing glaciers.

A century ago, biologists thought this history was simple and drab. Once parasites surrendered to their inner life, they had reached an evolutionary dead end, since they could live nowhere else. What little evolution they experienced came only when their host dragged them in their wake. Their hosts might divide into new species when a population became isolated on an island or a mountain range, and the parasite, similarly cut off from the rest of its species, formed a new species of its own.

If that were true, you’d expect to see a certain pattern when you compared an evolutionary tree of closely related hosts to the parasites they carried: they would form mirror reflections of each other. Say you dissected four closely related bird species and found tapeworms inside. The lineage of birds that had branched off earliest on their own would have carried away the tapeworms that branch off first among the parasites. Each subsequent branch of host would have carried along its own branch of parasite as well.

It wasn’t until the late 1970s that biologists such as Daniel Brooks of the University of Toronto started actually lining up host and parasite trees in this way. Before long they realized that these twinned histories were actually far more complicated than they had thought. Sometimes the trees looked like perfect mirrors, like the tree above. But other times they looked like the tree on the next page.

Parasites did sometimes follow their hosts into new species, but they could also leap to entirely new hosts (as did tapeworms B, C, and E in this example). Sometimes they split into two new species on a single host without the host splitting as well. And sometimes they vanished from their hosts altogether. Parasites, in other words, have evolutionary stories as stormy and complex as their free-living cousins.

The most important clues to the early history of tapeworms come from the deepest roots in their tree. These primitive tapeworms all live in fish. Two main groups of fishes are alive today: the cartilaginous fishes, such as sharks and rays, and the bony fishes. They branched apart about 420 million years ago. About 400 million years ago, the bony fish lineage split into two branches of its own. One lineage led to ray-finned bony fish: salmon, trout, gar, and thousands of other species. The other led to bony fish with fleshy lobe fins, such as lungfish and coelacanths. It was this lobe-finned branch that eventually produced vertebrates with legs, able to climb on shore—in other words, that became our ancestors.

Tapeworms probably first evolved in the earliest ray-finned fish. That history is reflected in the fact that the most primitive tapeworms alive today live in the most primitive ray fins, such as sturgeon and bowfin. It was in these hosts that tapeworms evolved from a leafy shape to their distinctively long, segmented bodies. From this origin, the tapeworms later colonized sharks and other cartilaginous fish. But apparently they didn’t approach lobe fins. Neither lungfish nor coelacanths are known to carry the parasites.

Yet, tapeworms live inside their closest relatives—the terrestrial vertebrates. In fact, they live in just about every sort of amphibian, bird, mammal, and reptile. Life on land didn’t inherit tapeworms from their aquatic ancestors. The parasites must have invaded them, coming out of the water in some ray-finned fish. Perhaps 50 million years after vertebrates had come ashore, some reptilian creature eating a fish picked up a tapeworm inside its meal, and a new lineage was born. Since then, tapeworms on land have evolved with their hosts as they diverged into new forms, and they’ve continued to hop from branch to branch, shuttling, for instance, from mammals to amphibians and from mammals to birds.

Vertebrates on land had split into reptiles and the forerunners of mammals by about 300 million years ago. By 200 million years ago, the reptile branch had produced dinosaurs, which rapidly became the dominant land animal. Did tapeworms live in dinosaurs? No one can say for sure, but it’s hard to imagine they didn’t, given that their closest relatives, birds and crocodiles, both carry them. And it’s hard to imagine that they wouldn’t have taken advantage of the space inside these giants, growing to lengths of one hundred feet or more. That’s a thought that makes a parasitologist smile. The Santa Barbara parasitologist Armand Kuris has mused about what kind of ecology such a monster would have. The biggest dinosaurs were long-necked plant-eaters called sauropods, which could grow to weigh over one hundred tons. It’s hard to fathom how any predator, even one as big as Tyrannosaurus rex, could have brought them down. Perhaps it only scavenged the big dinosaurs, or perhaps it got some help. Perhaps, Kuris has suggested, the tapeworms turned the sauropods and Tyrannosurus rex into foreshadowings of moose and wolf. The sauropods picked up tapeworm eggs on the plants they ate, and the parasites developed into giant cysts inside them. As they tore up their hosts’ lungs or brains, they might have slowed down the sauropods enough to let Tyrannosaurus rex catch them, and let the tapeworm get into its final host. A dinosaur tapeworm might even have left its mark on the fossil record. The cysts of some tapeworms today get so big, and grow with such force, that they can split open a human skull. If dinosaurs carried cysts so big you’d need a forklift to carry them, paleontologists might be able to recognize their traces.

Over the 400 million years that tapeworms have been alive, Earth has been blasted by four major mass extinctions. The most recent one took place 65 million years ago and was most likely triggered by a ten-mile-wide asteroid that crashed into the Gulf of Mexico. It was powerful enough to kill the dinosaurs as well as 50 percent of all species on Earth. But tapeworms survived. It’s even possible in some parts of the world to find tapeworms still living the way they did when dinosaurs walked the Earth. The thorn forests of Bolivia are home to marsupials such as mouse opossums. They are hosts to a rare group of tapeworms called linstowiids, which need an arthropod as an intermediate host. The only other place on Earth where linstowiid tapeworms live is Australia, where they also live in similar marsupials. Today these parasites are split by thousands of miles of Pacific water, but 70 million years ago, Australia, South America, and Antartica were all joined in a single continental mass. The ancestor of the Australian and Bolivian tapeworms originated in a marsupial on that vanished continent, and host and parasite gradually split apart as the land mass was split by continental drift. But over the 70 million years that have since passed, the ecosystem that supported the tapeworm’s cycle through the mammals has remained intact.

Other tapeworms may have survived the asteroid by abandoning their old hosts. The tetrabothriid tapeworms live only in marine birds like puffins and grebes, and marine mammals like whales and seals. On the face of it, this sort of combination of hosts doesn’t make sense. These animals are too distantly related to share the tapeworms as an heirloom from some common ancestor. Birds evolved from reptiles—probably ground-running dinosaurs over 150 million years ago. Marine mammals invaded the oceans much later. Whales arose from coyote-like mammals about 50 million years ago, and seals from bear-like mammals about 25 million years ago. You have to reach back over 300 million years to find a common ancestor for birds and mammals, and that same ancestor gave rise to many other lineages of vertebrates, ranging from crocodiles to tortoises to cobras to wallabies to humans—none which is a host for tetrabothriids.

The birds and the whales had to get their tapeworms from somewhere. They probably didn’t get them from fish, because the closest relatives of tetrabothriids live in reptiles on land, which aren’t closely related to the birds and the whales. So tetrabothriids must descend from a tapeworm that lived in some group of ancient reptilian hosts. It just so happens that before whales and sea birds existed, there were reptiles in the oceans that played the same ecological roles. If you had sailed across an ocean 200 million years ago, you wouldn’t have seen birds flying overhead but pterosaurs: narrow-headed reptiles that soared on wings of hairy skin, plucking fish to bring back to their rookeries on shore. And breaching the water around you would not have been whales but monstrous reptiles of many pedigrees, such as long-necked plesiosaurs and swordfish-shaped ichthyosaurs.

Between 200 and 65 million years ago, these reptiles dominated the marine food chain. Pterosaurs began sharing the sky with birds, and Hoberg thinks that as a sort of welcoming present, they gave them their tapeworms as the birds ate the fish that served as the parasite’s intermediate host. The extinction 65 million years ago that claimed the big dinosaurs also wiped out the marine reptiles and the pterosaurs. No one knows why birds survived the impact, but it seems that they carried on the cycle of the tetrabothriid. Whales and seals later took up the roles left vacant by the marine reptiles, and the tapeworms colonized them as well. As long as an ecosystem remains intact—even if the animals that constitute it change—parasites will survive.

In the past 65 million years, tapeworms have continued to thrive, and their travels continue to mark the history of their hosts. The tapeworms that live in stingrays in the Amazon, for example, show how the river once flowed backward. If stingrays had colonized the Amazon from the Atlantic, where it flows today, their tapeworms would be most closely related to tapeworms in living Atlantic rays. But the tapeworms are actually more closely related to those in the Pacific. And making matters more puzzling, there are still other tapeworms in the Atlantic and Pacific stingrays that are more closely related to one another than either is to the Amazon tapeworms.

The scenario that reconciles these facts best has stingrays coming upriver 10 million years ago. At that time, the Andes hadn’t yet formed, and the Amazon flowed out of Brazil to the northwest coast of South America. Another big difference in the geography of that time was that the isthmus of Panama hadn’t yet formed, so that the Atlantic and Pacific were joined by a broad channel. Groups of stingrays from the Pacific swam into the Amazon when it flowed in the opposite direction. As the Amazon stingrays adapted to fresh water and became isolated from their ocean-going cousins, the marine stingrays still mingled between the two oceans. By the time Panama had risen out of the ocean, they had shared some new species of tapeworms that the freshwater rays couldn’t pick up.

In the last few million years, tapeworms have discovered yet another host, one that walks on two legs. Hoberg has been studying tapeworms that live in humans. Over the years parasitologists have come up with many ideas for how tapeworms came to live inside us. One has it that ten thousand years ago, when humans domesticated livestock, they picked up the tapeworms that cycled between wild relatives of cattle and their predators. But looking at evolutionary trees, Hoberg doesn’t think that’s the case. He and his colleagues have compared the genes of human tapeworms with their closest relatives and have found they branched off on their own a million years ago, not a few thousand. At that point, our ancestors were hominids who were a long way from farming. The closest thing to a cow or a pig they would have eaten then would have been the scavenged carcasses of wild game that had been killed by lions. Which would explain something else Hoberg discovered: the closest relatives to human tapeworms make lions and hyenas their final host. Hoberg pictures hominids following after lions, scavenging their kills and picking up their tapeworms.

There is more than one way to look back at the dawn of humanity. You can go to Ethiopia and sift the dust for stone tools and scoured bones, but you can also go to the National Parasite Collection, find the right jar, and stare at a fellow traveler.

As tapeworms moved into new hosts they had to evolve new ways to live inside them. They had to adapt to new geographies of intestines; the tapeworms that began living inside rats stumbled across new ways to get flour beetles into their final host’s jaws. Reconstructing the rise of these adaptations is treacherous work because sensible-sounding stories about evolution are easy to make up. You see long tails on a swallow and decree that they must have evolved to let the bird maneuver more precisely, but someone else looks at them and decrees that they have evolved that way because female swallows find them attractive on male ones. Or maybe no adapation is involved at all—maybe most of the swallows that happened to establish this species just happened to have long tails, and it’s been that way ever since.

Consider the journeys of the nematode Strongylus. In one species, for instance, Strongylus vulgaris, the larva crawls to the top of blades of grass and lies in wait for a horse to graze by. Once swallowed, the worm takes a long, seemingly pointless journey. It travels down the horse’s throat to its stomach and then passes on into the gut. From there it chews out into the horse’s abdominal cavity and wanders the arteries of the horse for weeks until it has matured. Thereupon it returns to the intestines, burrows its way back in, and spends the rest of its life there.

Why should a parasite leave the intestines only to return for the rest of its life? Suzanne Sukhdeo has sorted through the close relatives of Strongylus and she has come to a working hypothesis for how this pilgrimage came to be. The ancestor of these nematodes lived in the soil more than 400 million years ago, spending its days burrowing and feeding on bacteria, amoebae, and other microscopic game (as many thousands of species of nematodes still do today). About 350 million years ago, it began to encounter something new—soft-skinned amphibians slithering around in the muck. The nematodes used their burrowing abilities to plow into these hosts and make their way to the gut, where they lived happily on the food that the amphibians ate.

Over the course of tens of millions of years, new kinds of vertebrates evolved on land: upright mammals and reptiles. These animals no longer offered the easy target of a slimy belly hugging the ground—they stood high on tall legs. Some parasitic nematodes adapted to these new hosts by evolving a new entry: by getting eaten rather than burrowing in through the skin. But burrowing, Sukhdeo argues, was too deep in their nature to disappear. Once swallowed, they would take up the flesh-drilling pilgrimage their ancestors had made for millions of years, looping back through their host’s body in order to enter the intestines again.

Sukhdeo suggests that the strange trip of Strongylus is just an evolutionary relic. Some day they may lose this heritage, but for now they still retain a vestige of their first go at parasitism, when bellies and mud stayed in close touch. On the other hand, some researchers think the parasites continue taking this journey because it benefits them. Parasitologists have compared species of nematodes such as Strongylus that wander through tissue with species that stay put in the intestines, and they’ve found a pretty consistent difference: the wanderers actually grow faster and end up bigger and more fertile. A trip through muscle means a respite from the gastric acid of the intestines, the slosh of digested food, the low oxygen levels, and the vicious blasts of the intestine’s powerful immune system. The trip may be a relic, but it’s a useful one.

The puzzle of parasite evolution gets even more confusing when you consider the things that happen to hosts when they are invaded by parasites. Filarial worms, which cause elephantiasis, enter the lymphatic system and start producing thousands of baby worms. Sometimes a person’s immune system reacts violently to the worms, scarring the lymph channels and blocking them up. The lymphatic fluid builds up in the lymph channels, producing elephantiasis—monstrously swollen legs, breasts, or scrotums. There’d be no sense in calling a swollen leg an adaptation of the parasite, since it does no good for the worm. It’s simply the immune system misfiring. It is nothing more than what Richard Dawkins has called a “boring by-product.”

The best way to tell whether a given change to a host is a boring by-product or a true adaptation is to study its evolution. One elegant test of this has been done with insects that make galls on plants. You may sometimes notice cherry-shaped balls hanging from the leaves of oak trees, or a flower’s stem bulging as if it had somehow swallowed a marble. These are galls: bits of plant tissue that have formed into shelters for insect parasites. Hundreds of different insect species live in galls, which can form on flowers, twigs, stems, or leaves. Some species of wasps, for example, lay their eggs on oak leaves, and the cells of the leaf respond to the egg by growing up and around it. The larva is born and becomes buried even deeper in the leaf. The cells multiply into a huge spherical shape, with an inner layer of hairy tissue. Food—starches and sugars, fats and proteins—is pumped into the gall from elsewhere in the plant and fills up the oversized cells in the inner hairs. The wasp larva bursts them open and feeds on the fluid cocktail. As it destroys the inner cells the outer ones divide and become ready to be eaten.

The galls are formed by the plants themselves, not the insects. Are they, as some researchers have suggested, just scars that happen to give the parasites some shelter? Warren Abrahamson of Bucknell University and Arthur Weis of the University of California at Irvine have performed some of the closest studies of galls, focusing on the goldenrod gallflies. The flies lay their eggs in a bud of a goldenrod plant in late spring. A spherical gall forms, growing to half an inch to an inch in diameter, and the fly larva grows inside. Parasitic wasps attack the fly larva, as do beetles. Woodpeckers and black-capped chickadees chip the galls open during the winter to eat them like some kind of delicious hard-shelled nut.

The galls in which these flies live vary in size and shape. Say for the moment that the galls are merely the boring by-product of a fly living within a goldenrod plant. Then you’d expect that any change in their variation from one generation to the next should be linked to changes in the genes plants use to defend themselves against invaders. Abrahamson and Weis have run experiments in which they raised gallflies on goldenrod plants that were all clones. Since their genes were identical, the plant’s defense against the flies should have been identical. Yet, Abrahamson and Weis found that the plants produced very different sorts of galls. That suggests that the flies’ genes are responsible for shaping the galls by taking control of the plant’s own genes. There’s probably some fierce natural selection going on in the flies for these genes, given that 60 to 100 percent of the galls are attacked by parasites. Supporting this, when the biologists observed the gallflies from generation to generation, a given lineage of flies all produced similar galls. The gall is made by the plant and yet is the work of the parasite, shaped by its evolution, not that of its host.

It’s actually surprising just how many things parasites do to their hosts that are not boring by-products but adaptations produced by evolution. Even harm itself is often an adaptation. Closely related parasites can be gentle or brutal to their hosts, or any shade in between. Leishmania can cause a few sores or eat away your face, depending on the species. Until recently, scientists didn’t think about how parasites could have such different effects on their hosts. The doctors were too busy looking for cures, and the evolutionary biologists were more interested in hosts than in parasites. They waved off the differences with a notion that when parasites first hop to a new host species they do a lot of damage. Once they’ve had a chance to fine-tune themselves, the story went, the parasites gradually mellow.

That’s certainly the case when many parasites accidentally find themselves in new hosts. A disease called sparganosis, for example, is caused by a species of tapeworm that uses copepods as its intermediate host and matures inside a frog. If a human should accidentally swallow the copepod in a glass of water, the tapeworm will escape out of the intestines and wander in confusion around the body, with none of the cues and landmarks it uses in a frog. As it zigzags randomly under the skin the tapeworm grows a few inches long, destroying tissue in its wake and inflaming its host into agony. If enough frog tapeworms found themselves inside humans, they might evolve into a new species better adapted to a new host. If they did, the conventional wisdom went, they would be amply rewarded by natural selection for any mutation that caused less harm to their new host. After all, if their host died off, the parasites would die with it. The wisdom of maturity brings gentleness.

It took until the 1990s for biologists to run the first experiments that could actually test this notion. A German evolutionary biologist named Dieter Ebert performed one of them, using water fleas. Water fleas sometimes suffer from a parasitic protozoan called Leistophora intestinalis, which lives in their gut and gives them diarrhea; the diarrhea carries the parasite’s spores with it, spreading them to other water fleas in the same pond. Ebert gathered fleas from England, Germany, and Russia and raised parasite-free colonies of each population. He then infected the colonies with Leistophora but used only the ones that had lived in the English ponds.

According to the conventional ideas about parasites, the English water fleas should have fared best. After all, the English Leistophora had spent untold generations inside the English water fleas and theoretically had come to a mellow coexistence. But Ebert found in fact that the opposite happened. The English fleas became burdened with many more parasites than the German and Russian fleas: they grew more slowly, they laid fewer eggs, and they died in greater numbers. Even though the English parasites had had more time to adapt themselves to English fleas, they had remained vicious.

Ebert’s findings did not come as a surprise to some biologists. They had built mathematical models of the relationship between hosts and parasites, and they had discovered theoretical reasons why familarity could breed contempt. Natural selection favors genes that can get themselves replicated more often than others. Obviously, a gene that makes a parasite instantly fatal to its host won’t go very far in this world. Yet, a parasite that is too well mannered won’t have any more success. Because it takes almost nothing from its host, it won’t have enough energy to reproduce itself and will come to the same evolutionary dead end. The harshness with which a parasite treats its host—what biologists call virulence—contains a trade-off. On one hand, the parasite wants to make use of as much of its host as possible, but on the other hand, it wants its host to stay alive. The balancing point between these conflicts is the optimal virulence for a parasite. And quite often, that optimal virulence is quite vicious.

The way virulence works is nicely illustrated by mites that live on the ears of moths. Moths have to be on constant guard against bats, which seek them out with echolocating shrieks. When moths hear the bats sending out their ultrasonic signals, they immediately start dodging and weaving through the air to avoid an attack. If the mites colonize the full extent of a moth’s ear—on both its outside and its inside—they will have enough room to produce a lot of offspring. But as they root around, damaging the delicate hairs that the moth uses to hear, they leave the moth deaf in that ear. With one ear out of commission, the moth will have a harder time escaping bats. If both ears shut down, the moth is doomed.

Nature has settled on two solutions to this dilemma. Some species of mites take up residence in the entire ear, both on the outside and on the inside. But they live in only one of the moth’s ears, leaving their host with enough hearing to keep it from being devoured. Other species of mites live on the outside of both ears. But because they forgo all the inner-ear real estate, they reproduce less than the deafening mites and are transmitted more slowly from moth to moth.

To test theories of virulence, biologists can make predictions about how real-world parasites behave. In the forests of Central America, several species of parasitic nematodes live inside wasps. These wasps are exceptional creatures: the female lays her eggs inside the flower of a fig tree and dies. The flower transforms into a plump fruit, and the eggs of the wasps hatch, the wasp larvae feeding on the fig. They mature into adult males and females and mate inside the fruit. The females then leave the fig to find a new one to lay their eggs in. As they leave they gather pollen on their bodies, and when they find a new fig flower, they fertilize it, triggering the production of a new seed.

It’s a pleasant symbiosis for both plant and animal: the fig depends on the wasp to let it mate, and the wasp depends on the fig for a place to raise its young. But into this happy scene intrudes the nematode. Some figs are riddled with these parasites, and when an egg-bearing female wasp prepares to leave, a nematode crawls onto her to hitch a ride. By the time the wasp has arrived at a new fig, the nematode has penetrated her body and is devouring her guts. The wasp enters the fig and lays her eggs, but the parasite has laid its own eggs inside her body as well. By the time the wasp has finished laying her eggs, the parasite kills her, and out of her body emerge a half dozen or so new nematodes.

The wasps and nematodes have been living together as host and parasite for over 40 million years—a long, venerable association. From species to species the wasps have different egg-laying habits: some will lay eggs only in a fig untouched by other wasps so that their young will have the fig to themselves. Other species don’t mind laying eggs alongside those of other wasps. Virulence theory makes a prediction about the nematodes that live in fig wasps. Nematodes that infect a wasp that lays its eggs alone must handle their host delicately. If they ravage the wasp too quickly, she may be able to lay only a few eggs, or none at all. The nematode’s own offspring would then have fewer potential hosts in their fig, and they’d have worse chances of surviving.

The same doesn’t hold for parasites of more neighborly wasps. When a nematode’s offspring hatch in a fig, they’re likely to find other wasps there that they can parasitize. What a nematode does to its own host doesn’t pose any risk to its offspring, so you’d expect these parasites to be far nastier. The biologist Edward Herre studied fig wasps and their parasites in Panama for over a decade, and when he looked over his records for eleven species, he found that they did indeed fall into the predicted pattern—a powerful vindication for the theory of virulence.

To study the laws of virulence, parasitologists can work with just about any parasites, whether they are mites, nematodes, fungi, viruses, or even rogue DNA. The host can be a human, a bat, a wasp, an oak tree. The same equations still apply. When scientists look at parasites from this evolutionary point of view, suddenly the walls that traditionally divide them tumble away. Yes, they all occupy different branches of the tree of life; yes, they are all descended from radically different free-living ancestors. But those gulfs make their similarities all the more remarkable. Darwin himself noticed that different lineages can independently evolve toward the same form. A bluefin tuna and a bottlenose dolphin are separated by over 400 million years of divergent evolution. Yet, the dolphin, whose ancestors looked like coyotes only 50 million years ago, has evolved a teardrop-shaped body, a rigid trunk, and a narrow-necked tail shaped like a crescent moon—all of which are possessed by the tuna. Biologists call this coming-together convergence, and parasites are the most spectacularly convergent organisms of all. Free-living nematodes have moved from the soil into the roots of trees, where they have evolved the ability to switch on and off individual genes and turn individual plant cells into comfortable shelters. Another lineage of nematodes produced Trichinella—a parasite that does the same thing to the cells in muscles of mammals. The lancet fluke has evolved chemicals that can force an ant to climb to the top of a blade of grass and clamp itself there. The same feat is accomplished by fungi. To find the last common ancestor of lancet flukes and fungi, you’d have to explore the oceans for some single-celled creature that lived a billion years ago or more. Yet, after all that time, they both managed to come across the same tactic to control their hosts.

The laws of virulence are also built on convergence, and they promise to change the way we fight diseases. A virus such as HIV needs to go from host to host in order to propagate, just as a nematode does. If it becomes easier for a strain of HIV to travel, it can reproduce more quickly in a given host (and cause him or her more harm). That’s how the AIDS epidemic has played out: in populations where people have many sexual partners, the virus destroys its host’s immune system faster. Cholera is caused by a bacterium called Vibrio cholerae, which travels through water and escapes its host by causing diarrhea. In places where water is purified and Vibrio’s odds of infecting a new host are low, the disease is milder. In places without sanitation, the bacteria can afford to be more vicious.

The history of parasites, stretching over billions of years, is just beginning to emerge, but already it has made clear that degeneration isn’t its guiding force. Parasites may indeed have lost some traits over the course of their evolution, but then again, in our own history we have lost tails, fur, hard-shelled eggs. Lankester was appalled at how Sacculina lost its segments and appendages as it matured. He could just as easily have been disgusted by the way he himself had developed the vestiges of gills in his mother’s womb and then lost them as he grew lungs. As parasites colonized Earth’s third great habitat, they did lose some of their old anatomy, but they evolved all sorts of new adaptations that scientists are still trying to understand.

At the end of the day at the National Parasite Collection, after Eric Hoberg and I had spent an afternoon in his office talking and searching slides, I asked if I could go back down to the collection. “Sure. Just let me unlock it for you,” he said. We walked back downstairs, and he opened the door. It was empty now; Donald Poling had finished his slide-scraping for the day and had gone home. As I walked in, Hoberg stood by the door and told me to ask if I needed anything, and then he shut me in. The heavy door closed with more finality than I would have liked. Now I was trapped with the parasites. But after I got used to being shut in with them, the place became meditative. This was the closest thing to a proper museum I could think of for parasites, even though a grand diaspora of parasites was missing—the parasitic wasps and gall makers scattered in entomological collections, the protozoa hidden in schools of tropical medicine, Sacculina in the hands of some Danish expert on barnacles. Someday, I thought, you’ll all be reunited, and maybe in something classier than an old guinea pig barn.