Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease - Sharon Moalem (2007)


For thousands of years a parasitic worm called Dracunculus medinensis—which means “little dragon”—has plagued humans across Africa and Asia. It causes a terrible disease. the larvae of the worm, also known as Guinea worm, are eaten by water fleas that fill ponds and other sources of still water in remote tropical areas. When people drink the water, their digestive system destroys the fleas but not the larvae. Some of the larvae migrate from the small intestine into the body, where they grow and eventually mate with each other. About a year after infection, adult females—now two to three feet long, about the diameter of a piece of spaghetti, and full of new larvae themselves—make their way to the skin of the person carrying them. Once they get to the surface, these female Guinea worms begin to secrete acid, effectively burning themselves an exit tunnel. the first sign of infection is the appearance of a painful blister. Soon after the blister appears it ruptures painfully, and the worm starts to make its way out. the burning caused by the acid drives the human host to seek relief in cooling water. And as soon as the worm senses water it emits a milky fluid full of thousands of larvae to begin the process anew.

Worms can sometimes be removed surgically, but for millennia, the only effective treatment has been to wrap the worm around a stick and slowly, carefully pull it out. The process lasts for many painful weeks or months and can’t be hurried along too quickly—if the worm breaks, the infected person can experience an even more painful and serious reaction, perhaps even death.

Guinea worm has afflicted humanity for centuries. It’s been found in Egyptian mummies and even thought to be the “fiery serpent” that ravaged the Israelites during their forty years in the desert. Some scholars think the Rod of Asclepius—the snake wrapped around a staff that is a symbol of medicine—was originally a simple drawing that early doctors used to show they offered help to remove the worms by wrapping them around a stick.

Today, because we understand how the Guinea worm manipulates its victims to collaborate in the infection of others, the little dragon’s fire is on the verge of being extinguished. Former president Jimmy Carter has led a two-decade effort to spread understanding about the parasite’s method of reproduction to every corner of the world, ensuring that its victims avoid water when looking for relief and that its potential victims avoid water that could be infected. According to the Carter Center, the worldwide incidence of Guinea worm infections had dropped from 3.5 million in 1986 to just 10,674 in 2005. By understanding how the Guinea worm has evolved in relationship to us, we have the chance to protect people from it.

IF YOU’VE COME this far on our journey across the evolutionary landscape, you’ve probably gathered a good sense of the interconnectedness of—well, just about everything. Our genetic makeup has been adapting in response to where we live and what the weather’s like. The food we eat has evolved to cope with the organisms that eat it, and we’ve evolved to cope with that. We’ve looked at the way we’ve evolved to resist or manage the threat posed by specific infectious diseases, like malaria. But what we haven’t discussed—yet—is how all those infectious diseases are evolving right along with us. Make no mistake—they are, and for the exact same reason that we’ve been evolving for millions of years too. At the end of the day, every living thing—bacteria, protozoa, lions, tigers, bears, and your baby brother—shares two hardwired imperatives: Survive. Reproduce.

Now, in order to really understand the relationship between humans and the millions of microbes living beside us, you have to discard the notion that all bacteria are bad, all microbes are marauders, all viruses are villains, all—okay, you get the point. the truth is that we have been evolving in tandem with all of these microscopic organisms—often to our mutual benefit. The way our bodies work today is directly related to our interaction with infectious agents over millions of years. Everything from our senses to our appearance to our blood chemistry has been shaped by evolutionary response to disease. Even sexual attraction has a connection to disease. Why is the scent of someone you find sexually attractive so alluring? It’s often a sign that you have dissimilar immune systems, which will give your children wider immunity than either of their parents.

Of course, it’s not just external organisms we’ve evolved to manage—or that have evolved to manage us. Guess what? You may not have sent any invitations, but as you read this, you’re playing host or hostess to a massive party of microbes. In fact, if your body’s a party and your cells are the guests, you’re outnumbered in your own home. An adult human contains ten times as many “foreign” microbial cells as mammalian cells. If you put them all together, you’d find more than 1,000 different types of microbial creatures weighing about three pounds and numbering somewhere between 10 trillion and 100 trillion. And when it comes to genetic material, it’s not even close; the microbes that make you their home collectively contain 100 times as many genes as your own genome does.

Most of these microbes are found in the digestive system, where they play crucial roles. These intestinal bacteria, or gut flora, help to create energy by breaking down food products we otherwise couldn’t break down; they help to train our immune systems to identify and attack harmful organisms; they stimulate cell growth; and they even protect us against harmful bacteria. In fact, the digestive problems many people experience when taking antibiotics are directly related to the loss of these healthy bacteria. Using broad-spectrum antibiotics is like carpet bombing—they kill everything in their way and can’t tell the difference between enemies, allies, and innocent bystanders. That’s why many doctors recommend eating yogurt when taking antibiotics: the bacteria in yogurt are friendly—probiotic—and they can help to provide some of the digestive assistance and protection that is normally performed by the gut flora until they get back to normal levels.

Not all the bacteria who have made you their home are so friendly—right now, you may be providing a human roof over the metaphoric heads of Neisseria meningitidis, Staphylococcus aureus, and Streptococcus pneumoniae, the bacteria that can cause, respectively, meningitis, toxic shock syndrome, and pneumonia. Fortunately, the millions of microscopic allies in your gut have also taken it upon themselves to keep the bad guys under control.

Th rough what’s called the barrier effect, colonies of gut flora prevent these dangerous bacteria from growing to dangerous levels by dominating the resources in the digestive tract. The helpful bacteria actually work with our own bodies to ensure that harmful bacteria can’t gain a microscopic foothold. To provide a similar effect, some doctors advise women who are prone to yeast infections to take probiotics, either by eating them in foods like yogurt or by taking a supplement. Just as they do in the digestive system, probiotic friendly bacteria act as naturally occurring helpful bacteria and create a barrier effect that inhibits the growth of vaginal yeast. One of the reasons some probiotics are friendly has to do with their taste in metals. Remember how almost every form of life on earth needs iron to survive? Well, one of the exceptions is also one of the most common probiotics, a bacterium called Lactobacillus, which uses cobalt and manganese instead of iron—which means it’s not hunting yours.

Your digestive system is a veritable jungle, with hundreds of species of bacteria competing for survival—most of them working with you, but a few of them ready to work against you if they have the chance. When the relationship between an organism and the host it inhabits is mutually beneficial—as is generally the case with humans and intestinal bacteria—it’s called symbiotic. Often, of course, that’s not the case. The Guinea worm is a pure parasite; it lives off its human host for its own benefit, providing nothing, causing only harm. And when its victim feels the natural urge to plunge the sores the worm causes into cool water (and thus help the worms to spread), the infected person is experiencing a type of host manipulation—the phenomenon that occurs when a parasite provokes its host to behave in a way that helps the parasite to survive and reproduce.

By examining some of the most extreme examples of host manipulation in nature, we can gain a better understanding of how parasites can affect our own behavior. So before we continue our exploration of the relationships among humans, microbes, and our mutual evolution, let’s take a trip back to the actual jungle to examine a real-life Invasion of the Body Snatchers, Spider Body Snatchers, anyway.

PLESIOMETA ARGYRA IS an orb-weaving spider native to Central America. Orb weavers are a large family of spiders, with more than 2,500 different species spinning webs around the world. True to their name, these little guys spin those familiar circular webs with bull’s-eye centers. The fellow we’re concerned with—along with his special relationship to a parasitic wasp called Hymenoepimecis argyraphaga—has been the subject of serious study by a scientist named William Eberhard. Because these insects only have Latin names, let’s call the spider Thane of Cawdor and the wasp Lady Macbeth.

Cawdor lives a happy life in the Costa Rican jungle, spinning orb-shaped webs, hunting the prey that happen to stumble into his home, and wrapping them up for later consumption. Then one day Lady Macbeth flies up, seemingly out of nowhere, and stings him. Cawdor is paralyzed. Now the wasp lays an egg on the spider’s abdomen. Ten to fifteen minutes later, Cawdor awakens and goes about his business—spinning webs and trapping prey. Little does he know that from the moment Lady Macbeth first laid her stinger on him he was as doomed as his namesake. The egg deposited by the adult wasp soon hatches into a larva. The larva—let’s call it Baby Macbeth—makes holes in the spider’s abdomen and slowly feeds off its blood. Over the next few days, the wasp larva lives off the spider and the spider spins on, oblivious.

Then, when the larva is ready to cocoon and begin the final phase of its transformation into an adult, Baby Macbeth injects old Cawdor with chemicals that completely change the spider’s behavior, effectively turning it into the larva’s slave. Instead of building circular webs, the spider now goes back and forth over the same few spokes—retracting its steps as many as forty times, as it builds a special web to protect the larva’s cocoon. Then, near midnight (Mother Nature can definitely lay on the drama) the spider sits down in the center of this special web and doesn’t move. All that’s left is for Baby Macbeth to finish the job.

The larva kills the motionless spider and basically sucks it dry. When it’s finished its meal, it discards the spider’s lifeless husk on the jungle floor. The next night it spins a cocoon around itself, which it hangs from the reinforced webs built by the dead spider, and enters the final phase of its growth. Around a week and a half later, an adult wasp emerges from the cocoon.

Researchers aren’t entirely sure how the larva hijacks the spider’s instinctual web-building behavior. To be clear, it’s not that the spider is behaving in a completely new and different way—the steps it repeats to build the special “cocoon web” are essentially the first two steps of the five basic steps involved in building a normal web; it just repeats them over and over again like some kind of looping music track stuck on repeat. Dr. Eberhard says, “the larva somehow biochemically manipulates the spider’s nervous system causing it to perform one small piece of a subroutine, which is normally only a part of orb construction, while repressing all the other routines.”

Dr. Eberhard’s research also made it clear that, however the biochemical injected by the larva works, it works quickly and lasts awhile. In laboratory studies, when the parasite is removed from the spider after it has started to build the cocoon web but before it has finished—that is, after the larva has asserted mental control but before it kills the spider—our arachnid friend continues to build the cocoon web for days, until it eventually returns to building normal webs.

Nature abounds with examples of host manipulation; generally—no big surprise here—they involve a critical step in the parasite’s efforts to reproduce. In the case of many parasites, that boils down to this—how do I get from this host to the next one? Before we turn back to parasites that manipulate humans, let’s look at a parasite that faces a particularly vexing transportation problem.

DICROCOELIUM DENTRITICUM IS a tiny worm that lives in the livers of sheep and cattle; it’s commonly called a lancet liver fluke. If you and your family lived in a sheep and you didn’t want your entire species to die out when the sheep died, you’d have to find a way to get your kids into the gut of another sheep. When adult flukes lay eggs, those eggs are passed by their hosts in dung where they remain dormant until a land snail comes along to feed on the dung, eating the eggs in the process. Once eaten, the eggs hatch inside the snails, and, eventually, the newborn flukes are excreted from the snail as slime. Ants feed on the slime and become a new ride for the flukes in the process—but there’s still a long road ahead. Think about it—you’re riding in an ant and you need to get into a sheep; what to do?

As the worms being carried by the ant develop, one of them makes its way to the ant’s brain, where it manipulates the ant’s nervous system. Suddenly, the fluke-hosting ant behaves in completely uncharacteristic fashion. Every night, it leaves its colony, finds a nice blade of grass, and climbs to the tip, where it hangs on and, apparently suicidal, waits to be eaten by a grazing sheep as it munches on the grass. If it’s not eaten, it returns to its colony during the day and finds another blade of grass the next night. Eventually, when the ant is eaten along with its blade of grass, the flukes make their way from the digestive system of their new host and colonize another liver.

The parasitic hairworm Spinochordodes tellinii grows to adulthood inside grasshoppers in the south of France. It’s another worm that, like a houseguest that will never leave, makes its host suicidal. As soon as the hairworm larva reaches adulthood it releases specialized proteins that convince the unfortunate French grasshopper to find the nearest pool of water and jump right in, like a drunken sailor docked in Marseille who has forgotten that he can’t swim. Once in the water, while the grasshopper is drowning, the worm slithers out and swims off to find romance and reproduction.

Remember, bugs and worms aren’t the only organisms capable of host manipulation. Viruses and bacteria engage in sophisticated host manipulation all the time. The rabies virus is an interesting example of host manipulation on more than one level. the rabies virus colonizes the salivary glands of its host, making it difficult to swallow. That’s what causes the characteristic foaming at the mouth—the inability to swallow makes the animal’s mouth froth with, not coincidentally, rabies-filled saliva. By the time the animal is foaming at the mouth, the virus will most likely have infected its host’s brain, where it chemically induces the animal to feel higher and higher levels of agitation and aggression. When animals are agitated and aggressive, they bite. When their mouths are foaming with rabies-filled saliva, their bites are infectious. Angry bite plus infected saliva equals new host, which means survival and reproduction for the virus. The origin of “foaming at the mouth” as an idiom for angry and aggressive behavior isn’t the only piece of culture we’ve gotten from rabies. It’s very likely that the werewolf myth, in which one bite transforms the victim into a possessed beast just like the biter, almost certainly has its roots in ancient observations of the rabies virus at work.

Enslaved spiders and suicidal grasshoppers are examples of host manipulation at its most extreme. Janice Moore, a professor of biology at Colorado State University who has studied host manipulation for more than twenty-five years, notes that, in some cases, the change can be so dramatic that the infected host is essentially transformed into another creature:

It is possible that the parasitized animals are frequently so altered compared with their uninfected counterparts that they well may be the functional equivalent of a different species.

On the other hand, many host manipulations are more subtle and at least seem to be natural. Notice, even in the case of the orb-weaving spider and the wasp larva, it’s not that the larva actually assumes complete control of the spider. Rather, through chemical manipulation, it gets the spider to behave in a way that is more to the larva’s benefit than to the spider’s. But the spider is still alive and volitional—the two steps of the web-building routine, after all, belong to the spider, not the wasp. Similarly, when people infected with Guinea worm plunge their hands into a cold pool to relieve the pain, the Guinea worm isn’t actually controlling their minds, of course—but it has evolved to stimulate its host to behave in a way that helps it survive and reproduce.

The good news for us is that we’re a lot smarter than spiders. The more we understand how parasites manipulate their hosts, especially when their hosts are humans, the more we can manage those effects and control the outcome. Sometimes, the only effective option may be to stamp out the behavior that allows the threatening parasite to reproduce—as in the case of the Guinea worm. Sometimes, as you’ll soon see, we may be able to steer the parasite’s evolution in a more benign—or at least less harmful—direction. There’s ample evidence of that in the evolutionary record, after all. Just think about all those bacteria in your stomach helping you to digest that pint of Häagen-Dazs you shouldn’t have eaten for lunch.

TOXOPLASMA GONDII IS a parasite that can infect just about every warm-blooded animal but can reproduce in a way that guarantees its survival only in cats. T. gondii reproduces by copying itself during the life of its host, but it’s only in cats that it undergoes sexual reproduction, producing new oocysts, or spore cells, that can go on to find new hosts. Infected cats distribute oocysts in their droppings. The oocysts are hardy little organisms that can survive for as long as a year in tough conditions. When rodents, birds, or other animals ingest the oocysts, they become infected; animals can also become infected by eating the flesh of an infected animal. Humans can ingest oocysts by eating undercooked meat or poorly washed vegetables or after handling cat litter.

Once an animal is infected, the T. gondii cells are distributed through the body by the bloodstream, where they insert themselves inside muscle and brain cells. It’s a pretty nasty-sounding infection—who wants parasites setting up permanent shop in your brain?—but it’s thought to be generally benign in most people, although more on that shortly. It’s also incredibly common, infecting as much as half the world’s people—and not just where you might think. According to the Centers for Disease Control and Prevention (CDC) in the United States, scientists think more than 20 percent of the population is infected—in France, it’s nearly 90 percent. (Some epidemiologists think there’s a correlation between raw meat consumption and T. gondii infection rates, which might somewhat explain the high level of French infection; tartare is a French word, after all.)

None of which explains how T. gondii gets back into a cat. Well, that’s where the story gets interesting. T. gondii is a master little host manipulator—of mice and rats. When a mouse (or a rat) eats infected cat droppings, the parasite behaves in the usual manner, moving into the mouse’s muscle and brain cells. Once inside the mouse’s brain, in ways that are not completely understood, the parasite has a profound effect on its behavior. First, the mouse becomes fat and lethargic. Then, it loses its natural fear of predators—of cats. In fact, some studies have shown that instead of fleeing areas marked with cat urine, infected mice are actually drawn by its scent. You know what the scientific term is for a fat, slow mouse that is attracted by the smell of cats?

Cat food.

Which gets T. gondii exactly where it wants to go.

We mentioned a moment ago that T. gondii is thought to be largely benign in humans. Well, that is largely the case, but not always the case. First of all, people with severely compromised immune systems, like people living with HIV, are at risk for serious complications, as they are with many infections that people with a fully functioning immune system can manage. Those complications can include blindness, damage to the heart and liver, and inflammation of the brain, called encephalitis, which can lead to death. The other group that has to be on the lookout is pregnant women. Depending upon how far along she is, if a pregnant woman becomes infected, there can be as much as a 40 percent chance the fetus will become infected, and that can cause similar severe complications. This risk doesn’t exist if a woman is already infected, that is, if she became infected at some point before she became pregnant—there’s only a risk to the fetus during the phase of initial infection. But for that reason, pregnant women and people who have compromised immune systems should avoid raw meat and let somebody else empty the litter box.

there is also increasing evidence that past infection with T. gondii (toxoplasmosis) may trigger schizophrenia in some people. E. Fuller Torrey, a renowned psychiatrist and schizophrenia researcher, publicized many of these theories in 2003. It seems clear that there is a higher incidence of T. gondii infections in schizophrenics—although it isn’t yet clear what causes what. T. gondii may be a schizophrenia trigger, but it’s also possible that people with schizophrenia are more likely to engage in behavior that exposes them to T. gondii, like poor hygiene. It’s certainly an area that deserves serious exploration—just a decade ago, scientists dismissed the idea that infections could cause ulcers; today that’s a proven fact. (Of course, the doctor who proved the connection, Dr. Barry Marshall, had to swallow bacteria and give himself an ulcer before the “experts” would take it seriously. Sometimes there is justice, though; Dr. Marshall along with his colleague J. Robin Warren won the Nobel Prize in physiology or medicine in 2005 for their discovery.)

the notion that T. gondii may trigger schizophrenia is supported by recent studies demonstrating that mice that have toxoplasmosis modify their behavior when given antipsychotic medication. Researchers at Johns Hopkins University are now testing whether schizophrenics might be helped with antibiotics that fight toxoplasmosis. If Dr. Torrey is right, and T. gondii infection can trigger schizophrenia, it will add a whole new meaning to the stereotypical picture of the crazy cat lady.

Given T. gondii’s dramatic influence on rodent brain chemistry, it’s not surprising that scientists have looked for evidence that the parasite influences humans as well. And there is evidence that people who have T. gondiiinfections do exhibit some subtle differences in behavior when compared to uninfected people. Again, it’s not clear whether T. gondii is causing the behavior or whether people with these behavioral tendencies are more likely to be exposed to T. gondii—but it is interesting.

One dedicated researcher, Professor Jaroslav Flegr of Charles University in Prague, has discovered that women infected with T. gondii spend more money on clothes and are consistently rated as being more attractive than women without the infection. Flegr summed up his findings this way:

We found they [infected women] were more easy-going, more warm-hearted, had more friends and cared more about how they looked. However, they were also less trustworthy and had more relationships with men.

Flegr found infected men, on the other hand, to be less well groomed, more likely to be loners, and more willing to fight. they were also more likely to be suspicious and jealous and less willing to follow rules.

If it turns out that T. gondii does influence human behavior in any of these ways, it’s likely to be an accidental effect of the parasite’s evolved manipulation of rodents. That’s part of the reason why the possible effects in humans seem so much subtler than the effect in rodents—the manipulation is designed to get rodents to be eaten by cats, because that’s where T. gondii’s primary life cycle occurs. The infection of humans and other animals is more or less gravy for the parasite. the chemicals T. gondii evolved in order to affect the behavior of rodents may also have an effect on our brains. But whatever effect they do have isn’t host manipulation in the evolutionary sense, because it doesn’t do anything for the parasite—unless you know about a species of cats that only eats well-dressed women.

MOST PEOPLE THINK of sneezes as symptoms—but that’s really only half the story. A normal sneeze occurs when the body’s self-defense system senses a foreign invader trying to get in through your nasal passages and acts to repel the invasion by expelling it with a sneeze. But sneezing when you’ve got a cold? there’s obviously no way to expel the cold virus when it’s already lodged in your upper respiratory tract. That sneeze is a whole different animal—the cold virus has learned to trigger the sneezing reflex so it can find new places to live by infecting your family, your colleagues, and your friends.

So yeah, sneezes are symptoms—but when they’re caused by a cold, they’re symptoms with a purpose, and the purpose isn’t yours. That’s true for many of the things we think of as symptoms of infectious disease—they’re actually the product of host manipulation as whatever bacteria or virus has infected us works to engage our unconscious assistance in making the jump to its next host.

As many people who have children know, pinworm infection is one of the most common infections contracted by children in North America. the CDC believes that somewhere around 50 percent of American kids probably have pinworms at any given point in time. Adult pinworms are no more than half an inch long and look more or less like a small piece of white thread. Pinworms grow to maturity in the large intestine, where they feed on digestive matter and eventually mate. During the night, pregnant females make their way out of the large intestine (the same way everything else does) and deposit their microscopic eggs on the skin of the infected child. At the same time, they deposit allergens that cause serious itching. they don’t usually cause any damage except the itching—but those worms definitely want your child to scratch that itch.

When a child who has pinworms scratches his or her bottom, the eggs get lodged underneath his or her fingernails. Without serious scrubbing every morning, including underneath fingernails, it’s easy for those eggs to get around. They’re sticky little things and they easily make their way from fingers to everything the child touches—doorknobs, furniture, toys, even food. When other children touch those surfaces, they pick up some eggs. Eventually, those curious fingers make their way into mouths and some eggs are ingested orally, worms hatch in the small intestine, migrate to the large intestine, and begin the cycle again. Pinworms live only in humans—contrary to popular belief, they can’t be caught from any other animal (although their eggs could easily be picked up from the fur of a pet that had been touched by a person with eggs on his or her fingers). Their survival requires movement from human host to human host, and they’ve evolved a simple and efficient method of host manipulation to help them make the trip—scratch and spread.

Other diseases cause symptoms that manipulate us in more passive ways, all in the name of easing their ability to spread and reproduce. Cholera is a waterborne disease that causes severe diarrhea. In serious cases, the persistent diarrhea can cause dehydration and death. But like the itching caused by pinworms and the sneeze caused by the cold, the diarrhea caused by cholera isn’t just a symptom—it’s a transmission channel. It’s how the disease makes it into the water supply and ensures its ability to find new hosts.

Malaria manipulates human hosts too—in its case, by incapacitating us. People with malaria experience a terrible cycle of fever and chills, accompanied by debilitating weakness and fatigue—and when you’re lying in bed too tired even to lift an arm, you’re a pretty helpless target for mosquitoes. Mosquitoes bite infected humans and pick up a load of malaria-causing protozoa, and then these bugs carrying bugs fly away to infect someone else.

The study of host manipulation in humans is very young, but it’s already revealing some surprising insights that promise new insights into the causes—and potential cures—of an enormous range of disease. We’ve discussed the possibility that when T. gondii jumps from cats to cat owners, it may sometimes trigger schizophrenia. Recent, although controversial, research shows the possibility of a connection between obsessive-compulsive disorders and streptococcal infections in children.

The family of streptococcal bacteria is responsible for a wide range of human disease—from strep throat to scarlet fever, bacterial pneumonia, and rheumatic fever. Many types of streptococcal bacteria exhibit a phenomenon called molecular mimicry in which they display characteristics of human cells in order to trick the immune system. The cells these bacteria mimic include cells found in the heart, the joints, and even the brain. When you have a bacterial infection, your immune system produces antibodies to attack the invaders. When the invaders are partially disguised through molecular mimicry, they can cause an autoimmune disorder. the immune system recognizes the threat posed by bacterial invaders, but the antibodies it produces attack all the cells that resemble the bacteria—including the body’s own cells. That’s how some children who have rheumatic fever end up with heart problems—antibodies attack the heart valve because the infecting bacteria resembles it in some ways.

Dr. Susan Swedo, a researcher at the National Institute of Mental Health, believes that certain strep infections can trigger an autoimmune disorder that leads to an antibody-led attack on the basal ganglia, the part of the brain believed to control movement. Researchers call this condition PANDAS—pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. Parents of children with PANDAS describe heartbreaking transformations, often overnight. Shortly after infection, children suddenly display repetitive tics and uncontrolled touching, as well as serious anxiety.

It’s not clear that this is actual host manipulation—that depends on whether the change in behavior helps the bacteria to spread. Theoretically, of course, it’s not hard to imagine how uncontrolled, repetitive touching of toys, furniture, and other kids would help the virus to spread. It’s also possible that there is a relationship between obsessive-compulsive disorder and strep infections that isn’t host manipulation itself, but the by-product of the bacteria’s effort to fool the immune system.

One thing is clear—we are just beginning to understand the myriad ways our behavior is affected by infectious agents. One very new avenue of research is exploring the striking possibility that sexually transmitted diseases may actually influence sexual behavior. Now, I’m not suggesting that this kind of influence will transform a happily married man into an insatiable cheat. In fact, that wouldn’t necessarily be in the virus’s (or fungus’s or bacteria’s) interest. Too much promiscuity on the part of the host could disable it with other, potentially more damaging, diseases. And that would leave the parasite stuck in a host that couldn’t get around. From the sexually transmitted parasite’s point of view, it may want you to have more sex—but not too much sex.

As far as diseases influencing human sexual behavior, some researchers are examining the possibility that genital herpes may affect human sexual feeling in a way that could influence behavior. Two researchers at the Department of Anatomy and Neurobiology at the University of California at Irvine, Carolyn G. Hatalski and W. Ian Lipkin, have speculated that the herpes virus may heighten sexual feeling because it is so intertwined with the nerves that carry those feelings. they wrote:

It is intriguing to speculate that the ganglion infection may modulate sensory input to sex organs leading to increased sexual activity and enhanced probability of virus transmission.

In other words, sometimes the herpes virus may want you to get some action.

HOST MANIPULATION OCCURS when a parasite or disease affects our behavior for its own ends. But that’s not the only way disease affects human behavior, of course—there are thousands of ways in which personal, cultural, and social standards have evolved in order to help us avoid or manage disease. Some behavior is instinctual, like the sense of disgust at certain sights and smells, which prompts us to avoid animal waste or spoiled food—things that are usually ripe with infectious material. Others are learned behavior and social pressure—covering your nose and mouth when you sneeze is a good example. Washing your hands before a meal is another. All of these reactions to disease are called behavioral phenotypes—the observable actions of an organism that result from its attempts to manage the interaction between its genetic makeup and its environment for its own benefit.

A few evolutionary psychiatrists (scientists who study human behavior in the context of evolution and look to see whether specific behavior conferred an evolutionary advantage) have even suggested that humankind’s instinctual fear of strangers may have its roots in disease avoidance. The theory is rooted in the notion that in humans two of our basic biological imperatives—survival and reproduction—have fostered in us a core social concern for the health and safety of our children and close relatives. This concern means that, in certain circumstances, evolution might actually push us to sacrifice our own survival for the sake of our children’s survival, or even that of close relatives. And the more relatives you could save through your sacrifice, so the theory goes, the more likely you’d be to act. From an evolutionary perspective, it makes perfect sense—let a single carrier of your genes die (that is, you) in order to let your larger gene pool of close relatives and extended family survive.

So what happens when you’re sick with a deadly—and contagious—infection? Some researchers believe that the sick primate that is abandoned by its community may actually be partly responsible, wandering away to protect its kin from infection. This phenomenon has been documented in cliff swallows and flour beetles; when they’re infected with parasites, members of both species appear to migrate away from their kin.

There’s also evidence that some species have evolved mechanisms to avoid their brethren when they become infected with a dangerous parasite. Researchers at Old Dominion University, in Norfolk, Virginia, studied Caribbean spiny lobsters, usually gregarious critters that normally live together in communal dens. The researchers found that when otherwise healthy lobsters become infected with a lethal pathogenic virus they are shunned by their den mates—the uninfected lobsters pick up and leave. What’s really amazing is that the uninfected lobsters make for the underwater highway before the diseased lobster shows any symptoms. Which means the behavior is likely to involve some chemical sensor and trigger.

Here’s where it all comes together as far as this theory is concerned. If certain infections drive organisms away from their own group in order to protect their kin, how will other groups respond when an unknown individual comes wandering over the hill? Xenophobia, which is the formal name for the fear of outsiders, appears to be a nearly universal instinct in human culture. It’s possible that xenophobia has its roots in some deeply buried instinct to protect one’s own group from outside threats to health and survival, including infectious disease. Of course, if that is the case, understanding its origins will give us another powerful tool in fighting an instinct—if it even is one—that has long outlived its usefulness.




You’ve seen the headlines. they’ve probably frightened you. And it’s true—just as we’ve been evolving to survive disease, all the organisms that cause disease have been evolving right along with us. You’ve seen how parasites have evolved very specialized abilities to navigate seemingly impossible challenges to survival—like traveling from a sheep to a snail to an ant in order to get to another sheep. And small organisms, because they multiply so rapidly and so frequently, sometimes cycling through hundreds of generations in just days, have one big evolutionary advantage over us—they evolve faster. Take Staphylococcus aureus, which doctors call staph for short. Staph is a very common bacteria; it may be living on your skin or in your nose right now. It can cause pimples—and it can cause deadly infections like meningitis and toxic shock syndrome. It’s also the bug behind many of those terrifying reports of antibiotic-resistant infections plaguing hospitals and, more recently, professional and college sports teams.

When penicillin was accidentally discovered by Alexander Fleming in 1928, it was actually inhibiting the growth of staph—that’s what was in the petri dish. Fourteen years later, when penicillin was first used to treat infections in humans, there were virtually no reports of penicillin-resistant staph. But just eight years later, in 1950, 40 percent of all staph infections were penicillin-resistant. By 1960, that number had climbed to 80 percent. Treatment switched to a specialized relative of penicillin called methicillin, which was introduced in 1959—and two years later, the first incident of methicillin-resistant staph, known as MRSA, was reported. MRSA is now firmly entrenched in hospitals, and treatment has moved to a different class of antibiotics, usually with one called vancomycin. the first case of VRSA—yes, vancomycin-resistant staph—was reported in 1996 in Japan.

All of this sounds frightening—as if we’re in an arms race where the other side has vastly superior technology. But that’s not the whole story—they’re faster, but we’re smarter. We can think about how evolution works and try to use that to our advantage—they can’t think at all. Now, remember that the biological imperatives driving bacteria are survival and reproduction, just like the biological imperatives that drive everything else. So what if we made it easier for a given type of bacteria to survive in a healthy human than to survive in a sick human—wouldn’t that create evolutionary pressure against behavior that harms us?

That’s what Paul Ewald thinks.

PAUL EWALD ISone of the pioneers of evolutionary biology, especially the evolution of infectious diseases and how pathogens select for—or against—traits that harm their hosts. The degree to which an organism destroys its host is called virulence. The range of virulence found in pathogens that infect humans is enormous—from all-but-harmless (pinworms) to unpleasant but hardly dangerous (the common cold) to rapidly, horribly fatal (Ebola). So why does one microbe evolve toward massive virulence while another is content to leave you up and running? Ewald believes the key factor that determines virulence is how a given parasite gets from host to host.

When you remember that every infectious agent has the same goal—to survive and reproduce by infecting new hosts—that starts to make a lot of sense. Let’s look at the three basic ways a microbe moves from one host to another:

·        Close proximity that allows for transmission through the air or physical contact—diseases transmitted this way include the common colds and sexually transmitted diseases (STDs)

·        Hitching a ride on an intermediate organism, usually a mosquito, fly, or flea—this category includes malaria, African sleeping sickness, and typhus

·        Traveling through contaminated food or water—cholera, typhoid fever, and hepatitis A are all transmitted this way

Now let’s think about what that means in terms of virulence. According to Ewald, diseases in the first category face evolutionary pressure against virulence. These microbes rely on their hosts to carry them around and introduce them to new hosts. That means they need their hosts to be relatively healthy—certainly healthy enough to be mobile. That’s why you can almost always get up and go to work when you’ve got a cold, even if you’re miserable the whole time. The cold virus leaves you well enough to get on the subway and go to work, sneezing and coughing all the way. Ewald believes the cold virus has hit the evolutionary jackpot; it’s evolved to a level of virulence that guarantees our mobility and its survival. In fact, he believes it may never evolve to kill or seriously incapacitate us.

On the other hand, when an infectious agent doesn’t need its host to get around, things can really heat up. As we mentioned, malaria has evolved to incapacitate us—it doesn’t need our help to meet new hosts; instead, it wants us vulnerable to attack by its blood-sucking buddies, mosquitoes. In fact, there is an evolutionary advantage for the malaria parasite to push its hosts toward the brink of death. The more parasites swarming through our blood, the more parasites the mosquito is likely to ingest; the more parasites the mosquito ingests, the more likely it will cause an infection when it bites someone else.

Cholera is similar—it doesn’t need us moving around to find new hosts, so there’s no reason for the bacteria to select against virulence. It spreads easily through unprotected water supplies when soiled clothes or bed linens are washed in rivers, ponds, and lakes, or through sewage runoff. And again, cholera actually has an advantage in evolving toward virulence—as the bacteria reproduces ruthlessly, causing more and more diarrhea, the infected person may excrete as many as a billion copies of the organism, increasing the likelihood that some bacteria finds its way to a new host.

The bottom line is this—if an infectious agent has allies (such as mosquitoes) or good delivery systems (such as unprotected water supplies), peaceful coexistence with its host becomes a lot less important. In those cases, evolution is likely to favor versions of the parasite that best exploit its host’s resources, allowing the parasite to multiply as much as possible—all of which spells bad news for the host.

But not necessarily bad news for humanity: Ewald believes that we can use this understanding to influence the evolution of parasites away from virulence. The basic theory is this—shut down the modes of transmission that don’t require human participation and suddenly all the evolutionary pressure is directed at allowing the human host to get up and get out.

Let’s look at how this would apply to a cholera outbreak. According to Ewald’s theory, the virulence of a cholera outbreak in a given population should be directly related to the quality and safety of that population’s water supply. If sewage flows easily into rivers that people wash in or drink from, then the cholera strain would evolve toward virulence—it can multiply freely, essentially using up its hosts, relying on its access to the water supply for transmission. But if the water supply is well protected, the organism should evolve away from virulence—the longer it remains in a more mobile host, the better its chance of transmission.

A series of cholera outbreaks that began in Peru in 1991 and spread across South and Central America over the next few years provide compelling evidence that Ewald is on to something. The water supply systems from country to country ranged from relatively advanced to seriously rudimentary. Sure enough, when the bacteria invaded nations with poorly protected water supplies, such as Ecuador, the virus became more harmful as it spread. But in countries with safe water supplies, such as Chile, the bacteria evolved downward in virulence and killed fewer people.

The implications of this are huge—instead of challenging bacteria to become stronger and more dangerous through an antibiotic arms race, we could essentially challenge them to get along with us. Think about the application of this theory just in terms of waterborne diseases like cholera. If we clean up water supplies, it will certainly mean fewer people will get infected because fewer people will consume contaminated water. But if Ewald is right, every dollar spent on protecting water supplies—and thus, controlling the transmission channel of the disease—will also steer the evolution of the disease itself toward a less harmful incarnation. As Ewald said:

We should be taking control of the evolution of those disease organisms, favoring those mild strains and thereby essentially domesticating those disease organisms, making them into mild versions of what was there before. With a mild version, most people won’t even know they’re infected. It’ll be almost like those people having a free, live vaccine.

If every malaria patient were covered in mosquito netting or stayed indoors, we might push P. falciparum, the malaria-causing protozoa, in a similar direction. If mosquitoes didn’t have access to bedridden malaria patients, the microbe would be under evolutionary pressure to evolve in a way that allowed the infected person to remain mobile, increasing the opportunity for it to spread.

Of course, Ewald knows that his theory isn’t always applicable. Some parasites complicate the picture because they are capable of survival outside a host for a very long time. A pathogen that can lie in wait for years until a potential host happens upon it isn’t very reliant on transmission pressure. Anthrax is one of these patient predators. The deadly bacteria can exist outside a host for more than ten years in some situations. In these cases, it’s hard to affect virulence by reducing the pathogen’s transmission channels, because its ability to survive outside a host makes it less concerned with transmission from an evolutionary perspective.

WE ALREADY KNOW that humans can affect the evolution of bacteria. The evolution of all those antibiotic-resistant strains of staph is conclusive proof of that. But Ewald’s theory takes the notion that bacterial evolution gives bacteriaan advantage over us and turns it on its head:

Not by getting involved in some kind of arms race in which we’re using one antibiotic weapon against the organism, and [the organism] evolve[s] a defensive weapon against that antibiotic, and then we have to shift to another, and so on, indefinitely. Instead, we have a sense of where we want evolution to end, and we adjust the environment so that the organism freely evolves to that endpoint, which is in its interest and also in our interest.

By understanding how the organisms that cause infectious disease have evolved among us, next to us, and inside us—affecting their evolution even as they affect ours—we gain new insight into how those diseases influence us, and into how they can be controlled for our benefit. Already, that understanding is giving us the opportunity to interrupt the transmission channel of horrible aff ictions like the Guinea worm. And it suggests powerful ways to change the course of diseases—like cholera and malaria—that have plagued humankind for longer than there has been a history to record it.

When it comes down to it, everything that’s alive wants to do two things: survive and reproduce. The Guinea worm wants to, the malaria protozoa wants to, the cholera bacteria wants to—and so, of course, do we. The difference—our big advantage—comes down to one thing.

We know it.