4. THE RISE OF PATHOGENS When I was a medical student.I spent the summer assisting a doctor whose job was to examine workers in a West Virginia Job Corps program.It was a great experience,because it was intensely clinical.I learned to do careful physical exams on a large number of basically healthy young people.My teacher,Dr.Fred Cooley,was practical,smart,and funny.My job with him ended at about one in the afternoon,so I could head over to the hospital and work with other doctors seeing all kinds of patients.They didn't have many medical students,so they welcomed me with open arms,a trainee with lots of questions. One afternoon,we were called to see an eleven-year-old boy who had become acutely ill and was hospitalized.He lived in a small,very conservative,Baptist community.He had been perfectly well until about two days earlier,when he began to feel achy:he developed a fever and an upset stomach.The next day his fever worsened,and he had a headache.On the third day,he developed small purplish dots all over his body.His parents were scared and brought him to the hospital, which was a good thing The emergency room doctors quickly diagnosed Rocky Mountain spotted fever,a disease caused by a bite from a tick infected with a type of bacteria called rickettsia.Although first discovered in the Bitterroot Valley in Montana,hence its name,it is much more common in the eastern half of the country. The bacterium multiplies within cells lining blood vessels,invoking a vigorous immune response.That explains the rash,since the blood vessels get inflamed and break.And it explains the headache,since the brain's blood vessels are involved causing a form of encephalitis.The boy was started on tetracycline,a life-saving antibiotic.If treatment isn't given immediately,or is started too late,RMSF is fata in up to 30 percent of people. Iaccompanied the doctors up to see him.His hospital room was darkened because light hurt his eyes,indicating that his brain was affected.His body was covered in purple spots,more than I have seen in anyone since.Some of the spots ran together,producing big blackish purple patches.His hair was matted.He was 37
4. THE RISE OF PATHOGENS When I was a medical student, I spent the summer assisting a doctor whose job was to examine workers in a West Virginia Job Corps program. It was a great experience, because it was intensely clinical. I learned to do careful physical exams on a large number of basically healthy young people. My teacher, Dr. Fred Cooley, was practical, smart, and funny. My job with him ended at about one in the afternoon, so I could head over to the hospital and work with other doctors seeing all kinds of patients. They didn’t have many medical students, so they welcomed me with open arms, a trainee with lots of questions. One afternoon, we were called to see an eleven-year-old boy who had become acutely ill and was hospitalized. He lived in a small, very conservative, Baptist community. He had been perfectly well until about two days earlier, when he began to feel achy; he developed a fever and an upset stomach. The next day his fever worsened, and he had a headache. On the third day, he developed small purplish dots all over his body. His parents were scared and brought him to the hospital, which was a good thing. The emergency room doctors quickly diagnosed Rocky Mountain spotted fever, a disease caused by a bite from a tick infected with a type of bacteria called rickettsia. Although first discovered in the Bitterroot Valley in Montana, hence its name, it is much more common in the eastern half of the country. The bacterium multiplies within cells lining blood vessels, invoking a vigorous immune response. That explains the rash, since the blood vessels get inflamed and break. And it explains the headache, since the brain’s blood vessels are involved, causing a form of encephalitis. The boy was started on tetracycline, a life-saving antibiotic. If treatment isn’t given immediately, or is started too late, RMSF is fatal in up to 30 percent of people. I accompanied the doctors up to see him. His hospital room was darkened because light hurt his eyes, indicating that his brain was affected. His body was covered in purple spots, more than I have seen in anyone since. Some of the spots ran together, producing big blackish purple patches. His hair was matted. He was 37
drenched in sweat as he thrashed from side to side,his hands tied to the bed rails so he would not hurt himself and others.He was yelling at the top of his lungs, hallucinating,completely incoherent.From time to time,a recognizable word would emerge,but they were all curses:"shit,fuck,you fucking bastard,tits,cunt, fuck."This went on continuously.In the corner of the room,his parents were cowering.Where had he learned these words?We knew that the encephalitis was causing his lack of inhibition. Fortunately,with treatment,he turned the corner,gradually got better,and was discharged from the hospital five days later to complete his treatment at home.He didn't remember anything that happened,but I am sure his parents never forgot it, not just the horror of his illness but the miracle of his cure Pathogens like rickettsia are microbes that make you ill.They bring the fevers, chills,pains,and aches that keep you bedridden for days.They can kill you slowly or rapidly.You might die alone or alongside thousands of others.We usually call them germs and have,since their discovery about 150 years ago,done everything in our power to kill them.For the past 70 years we have waged an aggressive war against pathogenic bacteria using a slew of antibiotics,saving millions of lives worldwide.But to our chagrin,this battle seems to have no end. Bacteria mutate with lightning speed and have developed resistance against some of our most effective antibiotics.Even more worrisome,the battle we wage against pathogens has led to serious unintended consequences for our health and well- being But before we look at those consequences,let's get to know what we are fighting.Other than potentially harming us,pathogens differ in many ways,for example,their biological nature-are they bacteria or viruses?Do they produce a toxin that injures our cells while they live offshore,in the middle of the gastrointestinal tract,like a battleship lobbing in shells along the coastline?Or are they like the marines,aggressively coming onshore and inflicting damage that way? It's tempting to think of pathogens as intrinsically evil,but they're not.Just like Yellowstone's wolves,they are predators.More often than not,by pursuing their own survival,pathogens inflict terrific damage on the hosts they inhabit.Sometimes the damage is accidental,the pathogen's cost of doing business.But for pathogens that are well adapted to their host,the damage serves a purpose.For example,the bacteria that cause tuberculosis make people cough,thereby spreading themselves around and infecting other people.Similarly,the rabies virus attacks the part of the brain involved with aggressive biting behavior and is spread via saliva in infected animals. David Quammen,in his book Spillover,about emerging infectious diseases. notes that we think of predators as big beasts that eat their prey from the outside, whereas pathogens are small beasts that eat their prey from within.It's an apt description. 38
drenched in sweat as he thrashed from side to side, his hands tied to the bed rails so he would not hurt himself and others. He was yelling at the top of his lungs, hallucinating, completely incoherent. From time to time, a recognizable word would emerge, but they were all curses: “shit, fuck, you fucking bastard, tits, cunt, fuck.” This went on continuously. In the corner of the room, his parents were cowering. Where had he learned these words? We knew that the encephalitis was causing his lack of inhibition. Fortunately, with treatment, he turned the corner, gradually got better, and was discharged from the hospital five days later to complete his treatment at home. He didn’t remember anything that happened, but I am sure his parents never forgot it, not just the horror of his illness but the miracle of his cure. Pathogens like rickettsia are microbes that make you ill. They bring the fevers, chills, pains, and aches that keep you bedridden for days. They can kill you— slowly or rapidly. You might die alone or alongside thousands of others. We usually call them germs and have, since their discovery about 150 years ago, done everything in our power to kill them. For the past 70 years we have waged an aggressive war against pathogenic bacteria using a slew of antibiotics, saving millions of lives worldwide. But to our chagrin, this battle seems to have no end. Bacteria mutate with lightning speed and have developed resistance against some of our most effective antibiotics. Even more worrisome, the battle we wage against pathogens has led to serious unintended consequences for our health and wellbeing. But before we look at those consequences, let’s get to know what we are fighting. Other than potentially harming us, pathogens differ in many ways, for example, their biological nature—are they bacteria or viruses? Do they produce a toxin that injures our cells while they live offshore, in the middle of the gastrointestinal tract, like a battleship lobbing in shells along the coastline? Or are they like the marines, aggressively coming onshore and inflicting damage that way? It’s tempting to think of pathogens as intrinsically evil, but they’re not. Just like Yellowstone’s wolves, they are predators. More often than not, by pursuing their own survival, pathogens inflict terrific damage on the hosts they inhabit. Sometimes the damage is accidental, the pathogen’s cost of doing business. But for pathogens that are well adapted to their host, the damage serves a purpose. For example, the bacteria that cause tuberculosis make people cough, thereby spreading themselves around and infecting other people. Similarly, the rabies virus attacks the part of the brain involved with aggressive biting behavior and is spread via saliva in infected animals. David Quammen, in his book Spillover, about emerging infectious diseases, notes that we think of predators as big beasts that eat their prey from the outside, whereas pathogens are small beasts that eat their prey from within. It’s an apt description. 38
The Inuit believe that "the wolves keep the caribou healthy."A healthy caribou can easily ward off wolves,whereas wolves spot weaker members of the herd rush in,and tear them apart for dinner.They thin the herd.It's the same with pathogens.Seven billion people live in today's world,often existing in squalid, crowded conditions.Malnourished,weak,and often without access to modern drugs,impoverished humans can be easy prey for the pernicious pathogens discussed in this chapter.I'm not saying that thinning the human herd is a good thing Just that it has always happened and assuredly will happen again. There are pathogens that simply get under your skin through cuts and scrapes When a wound is not properly cleaned,you can get an infection,but it is treatable if mild,just with cleansing,a band-aid,and a kiss;if more severe,then with deep cleansing.Sometimes antibiotics are needed.These cases are pure accidents.The pathogens almost never spread to another person. Organisms that ordinarily are not very pathogenic (disease-causing)can evolve extraordinary levels of virulence and can also kill robust,healthy individuals in a very short time.Most of us carry E.coli in our intestine,and most strains don't harm us at all.But in 2011 there was a huge outbreak of E.coli infections in Germany when people ate contaminated sprouts.At least two E.coli strains exchanged genetic material,producing an extremely virulent organism that infected more than four thousand people,damaged the kidneys of more than eight hundred of them,some permanently,and killed fifty Communicable diseases are caused by microrganisms that colonize your body, multiply out of control,and make you ill.They can be viruses that cause the flu bacteria that cause whooping cough,fungi that grow in the lining of your mouth,or a variety of free-living single-cell organisms called protists,such as a nasty amoeba that causes dysentery and bloody diarrhea.More than fourteen hundred human pathogens are currently recognized.They can be high or low grade.The rickettsia that caused spotted fever in the previously healthy young boy is a high-grade pathogen,whereas the kinds of organisms affecting people with chronic lung diseases can be low grade,meaning they are less virulent.They cause illness when a person is compromised and are less likely to make a perfectly healthy person ill. Ultimately all communicable disease-causing microbes come to us from our primate cousins,from our domesticated animals,and in other ways that are increasingly dangerous,including from wild animals.Some"jumped"from animals to humans so far back in the past that we can't be sure of their origins.But other diseases can be traced:plague from the fleas that live on rodents,rabies from bats influenza from birds,Lyme disease also from rodents but now via ticks.Some of the deadliest pathogens are rogue viruses that have emerged much more recently Ebola,SARS,Hantavirus,Marburg virus,swine and bird flu.They are virtually impossible to eradicate because we humans can come into contact with the animals in which they live in all sorts of ways.When intermediate vectors like mosquitoes 39
The Inuit believe that “the wolves keep the caribou healthy.” A healthy caribou can easily ward off wolves, whereas wolves spot weaker members of the herd, rush in, and tear them apart for dinner. They thin the herd. It’s the same with pathogens. Seven billion people live in today’s world, often existing in squalid, crowded conditions. Malnourished, weak, and often without access to modern drugs, impoverished humans can be easy prey for the pernicious pathogens discussed in this chapter. I’m not saying that thinning the human herd is a good thing. Just that it has always happened and assuredly will happen again. There are pathogens that simply get under your skin through cuts and scrapes. When a wound is not properly cleaned, you can get an infection, but it is treatable: if mild, just with cleansing, a band-aid, and a kiss; if more severe, then with deep cleansing. Sometimes antibiotics are needed. These cases are pure accidents. The pathogens almost never spread to another person. Organisms that ordinarily are not very pathogenic (disease-causing) can evolve extraordinary levels of virulence and can also kill robust, healthy individuals in a very short time. Most of us carry E. coli in our intestine, and most strains don’t harm us at all. But in 2011 there was a huge outbreak of E. coli infections in Germany when people ate contaminated sprouts. At least two E. coli strains exchanged genetic material, producing an extremely virulent organism that infected more than four thousand people, damaged the kidneys of more than eight hundred of them, some permanently, and killed fifty. Communicable diseases are caused by microrganisms that colonize your body, multiply out of control, and make you ill. They can be viruses that cause the flu, bacteria that cause whooping cough, fungi that grow in the lining of your mouth, or a variety of free-living single-cell organisms called protists, such as a nasty amoeba that causes dysentery and bloody diarrhea. More than fourteen hundred human pathogens are currently recognized. They can be high or low grade. The rickettsia that caused spotted fever in the previously healthy young boy is a high-grade pathogen, whereas the kinds of organisms affecting people with chronic lung diseases can be low grade, meaning they are less virulent. They cause illness when a person is compromised and are less likely to make a perfectly healthy person ill. Ultimately, all communicable disease–causing microbes come to us from our primate cousins, from our domesticated animals, and in other ways that are increasingly dangerous, including from wild animals. Some “jumped” from animals to humans so far back in the past that we can’t be sure of their origins. But other diseases can be traced: plague from the fleas that live on rodents, rabies from bats, influenza from birds, Lyme disease also from rodents but now via ticks. Some of the deadliest pathogens are rogue viruses that have emerged much more recently: Ebola, SARS, Hantavirus, Marburg virus, swine and bird flu. They are virtually impossible to eradicate because we humans can come into contact with the animals in which they live in all sorts of ways. When intermediate vectors like mosquitoes 39
help transmit disease,as with malaria,the picture gets especially complicated. Some of the most successful human pathogens no longer need their original animal reservoirs.Somewhere along the line,the smallpox,polio,and measles viruses evolved to specialize in humans;they affect us exclusively (and thus are vulnerable to elimination once and for all from humans-like smallpox).But the 800-pound gorilla of recent pathogens,HIV,which jumped to humans from chimpanzees,is now transmitted from person to person through sexual intercourse and contaminated blood.From occasional chance events,over 100 million people are now infected.As I will discuss in chapter 15,I am concerned that we are creating the conditions favorable for the spread of other pandemic microbes by the combination of easier global travel and the lowering of our defenses For the vast majority of human history and prehistory,the pathogens behind the world's great epidemic diseases-smallpox,measles.influenza.plague.polio. cholera,typhoid,scarlet fever,and diphtheria-did us no harm.They did not kill us.The reason has to do with population size.When our ancestors were hunter- gatherers in central Africa,they lived in small groups-maybe thirty to sixty individuals-and were widely dispersed across the vast savanna They lived this way for about 2 million years before Homo sapiens arose,about two hundred thousand years ago.Our existence in civilizations going back about eight or ten thousand years is just a punctuation point on our enormous prehistory.That long period shaped who we are today. Our ancestors were self-sufficient.When times were plentiful,males brought home enough game to nourish the group;females foraged for fruits,nuts,and plants. But when food was scarce,people suffered.Hunters exhausted themselves trying to find game.Malnourished women stopped menstruating or lactating Worst of all. when severe droughts persisted,entire groups died out,leaving no trace.Hyenas and vultures picked their bones clean. But from our modern perspective,this precarious existence had one good thing going for it:there were no epidemics.Our ancestors suffered from common infections,such as parasitic worms and yaws,which are chronic,nonfatal disorders.There were no epidemic diseases because these tiny bands were totally isolated,with no neighbors to bring harmful bacteria or viruses into their communities.If by happenstance a lone individual with a contagious disease stumbled into their settlement,the outcome could go one of several ways:nothing happened,everyone became ill and died,or a few became ill and the rest became immune.But after that,the pathogen had nowhere to go.There were no new hosts to infect.It was marooned and died out But the hunter-gatherers did have to contend with latency.Eons ago tuberculosis and several other well-known pathogens developed this strategy- 40
help transmit disease, as with malaria, the picture gets especially complicated. Some of the most successful human pathogens no longer need their original animal reservoirs. Somewhere along the line, the smallpox, polio, and measles viruses evolved to specialize in humans; they affect us exclusively (and thus are vulnerable to elimination once and for all from humans—like smallpox). But the 800-pound gorilla of recent pathogens, HIV, which jumped to humans from chimpanzees, is now transmitted from person to person through sexual intercourse and contaminated blood. From occasional chance events, over 100 million people are now infected. As I will discuss in chapter 15, I am concerned that we are creating the conditions favorable for the spread of other pandemic microbes by the combination of easier global travel and the lowering of our defenses. * * * For the vast majority of human history and prehistory, the pathogens behind the world’s great epidemic diseases—smallpox, measles, influenza, plague, polio, cholera, typhoid, scarlet fever, and diphtheria—did us no harm. They did not kill us. The reason has to do with population size. When our ancestors were huntergatherers in central Africa, they lived in small groups—maybe thirty to sixty individuals—and were widely dispersed across the vast savanna. They lived this way for about 2 million years before Homo sapiens arose, about two hundred thousand years ago. Our existence in civilizations going back about eight or ten thousand years is just a punctuation point on our enormous prehistory. That long period shaped who we are today. Our ancestors were self-sufficient. When times were plentiful, males brought home enough game to nourish the group; females foraged for fruits, nuts, and plants. But when food was scarce, people suffered. Hunters exhausted themselves trying to find game. Malnourished women stopped menstruating or lactating. Worst of all, when severe droughts persisted, entire groups died out, leaving no trace. Hyenas and vultures picked their bones clean. But from our modern perspective, this precarious existence had one good thing going for it: there were no epidemics. Our ancestors suffered from common infections, such as parasitic worms and yaws, which are chronic, nonfatal disorders. There were no epidemic diseases because these tiny bands were totally isolated, with no neighbors to bring harmful bacteria or viruses into their communities. If by happenstance a lone individual with a contagious disease stumbled into their settlement, the outcome could go one of several ways: nothing happened, everyone became ill and died, or a few became ill and the rest became immune. But after that, the pathogen had nowhere to go. There were no new hosts to infect. It was marooned and died out. But the hunter-gatherers did have to contend with latency. Eons ago, tuberculosis and several other well-known pathogens developed this strategy— 40
latency-which permits them to infect one generation,lie low,and then infect later generations,thus avoiding the problem of what happens when no new susceptible hosts are around Another example of latency occurs with chickenpox.If,like many children,you breathed in the varicella-zoster virus you would have soon developed a fever and then broken out in a rash,with blisters all over your body.After a few days,the rash would have faded.In two weeks,you'd be back to normal.With rare exceptions,a child who contracts chickenpox develops lifelong immunity to varicella-zoster.That is the end of the story,or so it might seem.But the virus is clever.It sequesters itself in nerve cells along the spine and in equivalent locations in the head.The virus endures like this for decades,silently,stealthily,causing no discomfort Until one day,when you are in your sixties,seventies,or eighties,you might feel a tingling sensation under a rib on one side of your body.The next day,you notice a rash following the contour of your rib.Upon close inspection,you see that the rash has blisters similar to those you had as a child with chickenpox,only this time it is localized.You now have the shingles,which doctors call herpes zoster In general,the older you are,the more likely you are to get shingles.For decades your immune system is able to hold the virus in check,but as your system weakens with age,the virus is no longer suppressed and out it pops- -as zoster And when the zoster blisters break from their elderly host,the virus spills out into the air,where it can infect a child who has not yet acquired immunity. And so the cycle repeats.In this way,varicella-zoster can skip entire generations.Although there may be no cases of acute infections in a small community for decades,the virus can"come alive"at any point and then infect a whole new group of susceptible people who were born in the years since the last active transmission.The virus,well adapted to humans,has two opportunities for transmission:from a child with chickenpox or from an aged relative who had chickenpox long before and now has shingles.Contagious,latent,contagious- this is a strategy that optimized success during the long period when our ancestors lived in small bands as hunter-gatherers in the African savannahs. The bacterium that causes tuberculosis is transmitted similarly,both acutely and after reactivation of a latent infection,usually in an elderly person,which optimized its survival in the small isolated populations that dominated our prehistory.But when human populations later expanded,tuberculosis took off like a rocket Small populations are now the exception.About ten thousand years ago,the invention of agriculture made food supplies secure.Populations soared.Trade flourished.Towns grew into cities and crowding was commonplace.And that's when epidemic diseases began to take off. Measles is the best-known example for illustrating the working of these so- 41
latency—which permits them to infect one generation, lie low, and then infect later generations, thus avoiding the problem of what happens when no new susceptible hosts are around. Another example of latency occurs with chickenpox. If, like many children, you breathed in the varicella-zoster virus, you would have soon developed a fever and then broken out in a rash, with blisters all over your body. After a few days, the rash would have faded. In two weeks, you’d be back to normal. With rare exceptions, a child who contracts chickenpox develops lifelong immunity to varicella-zoster. That is the end of the story, or so it might seem. But the virus is clever. It sequesters itself in nerve cells along the spine and in equivalent locations in the head. The virus endures like this for decades, silently, stealthily, causing no discomfort. Until one day, when you are in your sixties, seventies, or eighties, you might feel a tingling sensation under a rib on one side of your body. The next day, you notice a rash following the contour of your rib. Upon close inspection, you see that the rash has blisters similar to those you had as a child with chickenpox, only this time it is localized. You now have the shingles, which doctors call herpes zoster. In general, the older you are, the more likely you are to get shingles. For decades your immune system is able to hold the virus in check, but as your system weakens with age, the virus is no longer suppressed and out it pops—as zoster. And when the zoster blisters break from their elderly host, the virus spills out into the air, where it can infect a child who has not yet acquired immunity. And so the cycle repeats. In this way, varicella-zoster can skip entire generations. Although there may be no cases of acute infections in a small community for decades, the virus can “come alive” at any point and then infect a whole new group of susceptible people who were born in the years since the last active transmission. The virus, well adapted to humans, has two opportunities for transmission: from a child with chickenpox or from an aged relative who had chickenpox long before and now has shingles. Contagious, latent, contagious—this is a strategy that optimized success during the long period when our ancestors lived in small bands as hunter-gatherers in the African savannahs. The bacterium that causes tuberculosis is transmitted similarly, both acutely and after reactivation of a latent infection, usually in an elderly person, which optimized its survival in the small isolated populations that dominated our prehistory. But when human populations later expanded, tuberculosis took off like a rocket. Small populations are now the exception. About ten thousand years ago, the invention of agriculture made food supplies secure. Populations soared. Trade flourished. Towns grew into cities and crowding was commonplace. And that’s when epidemic diseases began to take off. Measles is the best-known example for illustrating the working of these so- 41