Infection is an inescapable part of life. All creatures feast on other creatures and in turn are feasted upon, in a kind of Escheresque food chain. When humans are the meal, we call it infectious disease. This book is about today’s new and emerging infections—those that have increased in attack rate or geographic range, or threaten to do so. It explores why these infections are materializing now and why they will never go away. And it tells the stories of scientists racing to catch up with invisible adversaries superior in speed and guile. Each chapter will look at a different threat: animal- and insectborne diseases, foodborne pathogens, antibiotic resistance, pandemic influenza, infectious causes of chronic disease, and bioterrorism.

The list is not unique. Any slice of time yields a catalog of infectious disease, new and old. The mid-1970s to the early 1980s were

especially fecund. First came the swine flu debacle of February 1976, when the U.S. government pulled out all stops preparing for a repeat— which never occurred—of the deadly 1918 influenza pandemic. Summer of 1976 brought a bona fide novelty, Legionnaires’ disease, which struck in Philadelphia, killed 34 people, and stumped the nation’s top infectious disease experts for nearly six months. As other outbreaks followed in short order, a new vocabulary arose: Lyme disease, toxic shock syndrome, E. coli O157:H7, STDs, Ebola virus. In June 1981 came the now-landmark report from the Centers for Disease Control and Prevention (CDC). Nine brief paragraphs described a strange cluster of fatal symptoms among five gay men in Los Angeles: acquired immunodeficiency syndrome, or AIDS, which had already silently infected 250,000 in the United States.

The same tricks of biology and convergence of habits and slips of surveillance that brought us AIDS are constantly drawing agents into our midst. As the world was grimly marking the twentieth anniversary of that CDC report, other infections were quietly exacting a toll. In the upper Midwest, a commonplace staph infection had turned inexplicably virulent, impervious to one of the most powerful drugs used to treat it; four healthy children and a strapping college student suddenly died, and hundreds were infected. E. coli killed a little girl who indulged in watermelon slices at a Sizzler restaurant in Milwaukee, one of 5,000 annual deaths from foodborne pathogens. Mosquitoes and birds carried West Nile virus from New York City to the Deep South and beyond. Nature lovers and suburban homeowners were catching tickborne Lyme disease. In the terror-filled autumn of 2001, deliberately planted anthrax spores killed and infected Americans, and U.S. public health officials girded for the return of smallpox.

As bacteriologist and historian Hans Zinsser wrote in 1934, “However secure and well-regulated civilized life may become, bacteria, Protozoa, viruses, infected fleas, lice, ticks, mosquitoes, and bedbugs will always lurk in the shadows ready to pounce when neglect, poverty, famine, or war lets down the defenses. And even in normal times they prey on the weak, the very young and the very old, living along with us, in mysterious obscurity waiting their opportunities.”

Through media coverage and sometimes sensationalistic reportage and fiction, Americans have awakened to the emerging infection threat. But our anxieties often focus on the trivial. The CDC has had to contend with bogus reports of imported bananas carrying flesh-eating bacteria, drug addicts placing HIV-infected needles in pay phone coinreturn boxes, virus-soaked sponges arriving with the mail. Late in 2001, the rumors were of war—germ war. Perhaps because we increasingly feel at the mercy of a world out of control, bizarre fictional health threats quickly take root. But these fantasies mask more likely—and commonplace—sources of danger.

To offer a local view of a universal and authentic peril, this book focuses on the United States. In truth, the distinction between national and global threats is artificial. Infectious agents need no visas. Secret agents shadow ecological change everywhere, and the pace of change is speeding up. U.S. health officials scan the terrain beyond our national borders in part because many of those infections can be transported, in people or goods or animals, to this country. Scientists must also keep apprised of pathogens abroad because related organisms may already be here, lying in wait. When a deadly pulmonary syndrome turned up for the first time in the Southwest in 1993, for example, researchers were at first baffled—until diagnostic tests developed decades earlier by the Defense Department, to identify a related virus in Korea that caused a very different pattern of disease, provided the first laboratory evidence that they were dealing with the genus Hantavirus.

What we face today is what we have always faced: one plague (the word comes from the Greek for “blow” or “strike”) after another, and usually several at once. A 2000 report from U.S. intelligence agencies described infectious diseases as a “nontraditional” threat. But history shows emerging infections to be the most traditional threat, both to individuals and to nations.

Before the recent headline accounts of avian flu, a silent hepatitis C epidemic, parasite-contaminated water slides, new variant

Creutzfeldt-Jakob disease, and anthrax, we had smallpox, typhus, polio, cholera, rabies, and the Black Death. We still have them. None have been consigned to history; in some cases, they are lethally intractable today. Even grisly reports of flesh-eating bacteria are nothing new. In the fifth century BC, Hippocrates described a condition in which “Flesh, sinews and bones fell away in large quantities . . . There were many deaths. The course of the disease was the same to whatever part of the body it spread.”

Small human populations suffer the oldest diseases of humankind: those that are either chronic, such as leprosy or herpes, or that have reservoirs in animals or the soil, such as yellow fever, the virus of which circulates in monkeys. Only when a community is dense and filthy enough to keep spreading germs and big enough to keep supplying new susceptibles do such infections as measles, smallpox, typhoid, and influenza—crowd diseases, or “zymotics”—stay in circulation.

The shattering “plagues” of history (some of which actually were plague) bespoke Homo sapiens’s immunological naiveté. In AD 79, an outbreak believed to be malaria contributed to the Roman Empire’s fall. The plague of Antoninus (AD 166–180), probably smallpox, killed between one-fourth and one-third of Italy’s population. The plague of Justinian (AD 542–543), one of the first documented cases of ratborne bubonic plague, was “a pestilence by which the whole human race came near to being annihilated,” in the words of Byzantine historian Procopius, killing 10,000 people daily in Constantinople and eventually spreading as far north as Denmark.

Over the next centuries, wave upon wave of emerging infections shaped human history. Between 1346 and 1350, one-third of Europe’s population died of bubonic plague, spread from Asia to Europe by Mongol armies, whose retinues of rodents carried infected fleas that subsequently bit humans. In the sixteenth and seventeenth centuries, slave ships from West Africa brought yellow fever and its mosquito vector, Aedes aegypti, to the New World. Smallpox, transported to the Americas by Spanish conquistadors, killed one-third of the relatively disease-free native population, and was followed by a similarly lethal

onslaught of measles. Diseases introduced from Europe killed an estimated 95 percent of the pre-Columbian Native American population. To a far lesser extent, exotic infections attacked in the other direction too. European colonials succumbed to malaria, yellow fever, and other endemic infections in tropical Africa, India, Southeast Asia, and New Guinea. Syphilis, a bacterial scourge that relies on a mobile population and indiscriminate sexual contact, appeared in 1494—perhaps with Columbus’s returning soldiers.

The Industrial Revolution of the nineteenth century amplified such diseases as tuberculosis, an ancient bacterial infection that thrives in squalid close quarters. Illnesses from contaminated food and water, such as typhoid and cholera, also went on a spree. Nevertheless, life expectancy rose during the nineteenth century—perhaps, as some say, because a biological equilibrium between our bodies and ever-present pathogens was achieved. The twentieth-century British physician and historian Thomas McKeown argued that the improvement stemmed from better nutrition, which built stronger resistance, and from sanitation measures such as sewage disposal, which reduced our exposure to disease-causing microbes. More recently, scholars have suggested that personal health practices, such as boiling drinking water and isolating sick relatives, may have made some difference.

Beginning in the late 1870s, the new discipline of bacteriology found the agents that caused cholera, tuberculosis (TB), gonorrhea, typhoid, and scarlet fever. “We no longer grope after some mysterious, intangible thing, before which we must bow down or burn something, as if it were some demon which we would exorcize,” wrote a physician in 1890. By 1900 scientists widely agreed that microorganisms—spread by casual contact, food and water contamination, insects, and even (in the cases of typhoid and TB) healthy human carriers—caused communicable diseases. These discoveries spurred expansion of government health initiatives such as water purification, food inspection, and rodent control, as well as more awareness of individual hygiene measures such as covering a cough or washing hands before eating. The years 1890 to 1930 were seen as the golden era of the American public health

movement. As a 1924 Scientific American editorial put it, “the natural outcome of the struggle between mankind and microbe has always favored man.”

Medicine soon targeted the discrete organisms behind infectious disease. In the 1930s and 1940s came specific antimicrobial therapies such as sulfa compounds and penicillin. By the mid-1960s, hundreds of new antibiotics were available to treat such afflictions as gonorrhea, syphilis, pneumonia, TB, bacterial meningitis, typhoid fever, even bubonic plague, while new vaccines prevented epidemics of measles, rubella, and polio. The study of infectious disease became unfashionable. Ambitious young doctors were advised not to specialize in it. In his classic 1962 text The Natural History of Infectious Disease, the Australian Nobel laureate Sir MacFarlane Burnet mused that “to write about infectious disease is almost to write of something that has passed into history.”

Between 1970 and 1975, as the National Institutes of Health budget increased 100 percent, the budget for its infectious disease arm rose only 30 percent. Cancer and heart disease seemed the last unconquered frontiers. Public health officials assumed that proper hygiene, sanitation, vaccination, antibiotic use, and good hospital care would keep the bugs at bay. The New Yorker medical writer Berton Roueché could afford a tone of amused detachment; infectious disease was ripe for elegy.

The belief that enlightened policies would finally wipe out infections peaked in 1978, when United Nations members signed the Health for All 2000 accord, which predicted that even the most cash-strapped nations would undergo a health transition before the millennium. That assumption was rooted in the public health concept of the “epidemiological transition”: as nations develop, life expectancy increases and deaths due to pestilential infections give way to deaths caused by heart disease, malignancies, and other chronic afflictions of old age. Now, at the beginning of the twenty-first century, the notion of a neat “before”

and “after” pattern of disease tethered to “progress” seems hollow. “A hundred years from now,” suggests Columbia University virologist Steve Morse, “we may still be worried about tuberculosis while having managed to get rid of most of the underlying causes of heart disease. That’s really turning the conventional wisdom on its head. Could you imagine a well-fed society that has got all the right interventions—even a little nanotechnology to clean out the arteries—and another HIV comes along?”

When HIV came along for the first time, government leaders were looking the other way; in the early 1980s, too, public health agencies had stopped surveillance for drug-resistant tuberculosis just as the disease started to rise (it soon became endemic in New York City, bred by poverty, a surge of immigration, urban crowding, and the concomitant AIDS epidemic). “The national public health capacity was allowed to lapse during the eighties and early nineties,” says Jim Hughes, director of the CDC’s National Center for Infectious Diseases. “We’re still scrambling and playing catch-up.” That indifference translated into numbers. In the two decades after 1980, the U.S. infectious disease mortality rate jumped 58 percent; even after removing AIDS from the tally during that period, the United States saw a 22 percent rise in infectious disease deaths. Public health requires long-range planning and strong commitment demonstrated by steady funding, because surveillance and response focus on improbable biological events that happen inevitably, though unpredictably. In 1998, the CDC issued a detailed five-year plan to prepare the nation for emerging infections, but congressional funding has lagged. In fiscal year 2001, though the agency estimated it would need $260 million, it received only $139 million.

The microbiologist René Dubos described life itself as “emergence,” a perpetual process of evolution and adaptation. In this sense, emerging infections are merely chapters in a Darwinian saga stretching over eons. Conditions ceaselessly shift—temperatures rise and fall,

habitats flourish and perish, food supplies grow lush and dwindle— and all living things transform themselves or die.

In the perpetual drama of emerging infections, nature’s undercover operatives are the same: viruses, bacteria, fungi, protozoa—a crew collectively known as “microorganisms” (colloquially, “microbe” refers only to bacteria). Nor has the plot changed. Just as all mystery writing draws on five or six plotlines, so biologists have found only a handful of pathogenic strategies, breathtakingly elaborated.

Microorganisms play the survival game exceedingly well. For one thing, they adapt far more quickly than do humans to the scene shifts around them. Humans crank out a new generation every 20 years or so; bacteria do it every 20 to 30 minutes, and viruses even faster. Richard Krause, former director of the National Institute of Allergy and Infectious Diseases (NIAID), calls this microbial pace “a millennium in a fortnight.” Natural selection—the process by which genetically better-adapted individuals leave more progeny and thus transmit those desirable characteristics—operates far more efficiently in the microbial world. And because they assemble in enormous numbers, viruses and bacteria can support considerable variety in their communities, including the mutated oddballs that may shine when circumstances change. A billion bacteria inhabiting a thimble can be virtually wiped out on Monday and be back in full force by Tuesday.

“When you look at the relationship between bugs and humans, the more important thing to look at is the bug,” says NIAID medical epidemiologist David Morens. “When an enterovirus like polio goes through the human gastrointestinal tract in three days, its genome mutates about two percent. That level of mutation—two percent of the genome—has taken the human species eight million years to accomplish. So who’s going to adapt to whom?” Pitted against such nimble competition, the human capacity to evolve “may be dismissed as almost totally inconsequential,” adds Joshua Lederberg, professor emeritus at Rockefeller University, whose discoveries about genetic recombination in bacteria earned him the Nobel Prize in 1958.

With microorganisms, less is more. Consider their simplicity. A

virus—the word comes from a Latin term for “poisonous substance”— is nothing more than nucleic acid, DNA or RNA, surrounded by a shell made of protein and sometimes also of fatty materials called lipids. The biologist Peter Medawar once observed that a virus is “a piece of bad news wrapped in protein.” Viruses are tiny, ranging in size from about 20 to 400 nanometers in diameter—millions can fit in the period at the end of this sentence—and visible only through an electron microscope. Some are rod-shaped, others round and 20-sided, and yet others have fanciful forms with multisided “heads” and cylindrical “tails.” Outside a living cell, a virus is a dormant particle, lacking the raw materials for synthesis. Only when it enters a congenial host cell does it explode into action, hijacking the cell’s metabolic machinery to produce copies of itself that may burst out of infected cells or simply bud off a cell membrane. This squatter’s existence means that viruses cannot be cultured in artificial media; they can only be propagated in live cells, fertilized eggs, tissue cultures, or bacteria. Scientists believe that viruses were originally fragments of genetic material derived from cellular organisms—perhaps bare nucleic acid, or pieces of DNA from bacteria or higher animals.

Viruses make us sick by killing host cells or by skewing the cells’ function. Our bodies often respond with fever (heat inactivates many viruses), the secretion of a chemical called interferon (which blocks virus replication), or by marshaling the immune system’s antibodies and other cells targeted to the invader. But viral infections are hard to fight once the process is under way because our immune responses usually kick in too late to subdue them. The virus that causes AIDS is especially clever, targeting the immune system itself. And because viruses commandeer the machinery of living cells to replicate, it’s been hard to develop drugs that combat the infection without also harming our cells. Only a small number of antivirals are available for particular infections. Doctors generally treat viral infections by trying to ease specific symptoms, such as fever or dehydration. In other words, although their symptoms can be treated, viruses themselves are so far undefeated in their ongoing war with human medicine.

Bacteria are about 1,000 times larger than viruses and more self-sufficient. One-celled organisms that are generally visible under a light microscope, bacteria are known as “prokaryotic”—so primitive, they lack a membrane-bound nucleus with neatly linear chromosomes inside. Instead, bacteria usually carry a tangled necklace of DNA joined at the ends, and sometimes smaller rings of DNA known as plasmids, which contain genes that enable a bacterium to manufacture proteins beyond its usual repertoire. Unlike more advanced organisms, bacteria carry one set of chromosomes instead of two, an arrangement that means that every gene counts and every selective advantage must be conserved. By taking in new genetic material instead of slowly adapting over millions of years, they evolve in quantum bursts. Bacteria come in three name-conferring shapes: spherical (coccus), rodlike (bacillus), and curved (vibrio, spirillum, or spirochete). Reputed to be the most ancient organisms, imprinted in fossils more than three billion years old, bacteria have evolved a vast range of behaviors over a vast range of habitats.

Over eons, bacteria have learned tricks to help them cleave to cells, make paralyzing poisons, elude or suppress our bodies’ defenses, and shrug off drugs and antibodies. They can pick up genes from almost everywhere: from other bacteria, from viruses, from plants, even from yeasts, in a round-the-clock flea market that’s a source of impressive plasticity. The pneumococcus bacterium, which causes pneumonia and other ills, soaks up DNA that has spilled out of dead or dying brethren—inheritance by cannibalism that has imparted, among other things, antibiotic resistance. When a virus picked up a toxin gene from a deadly Shigella dysenteriae and inserted it into a harmless E. coli, it created E. coli O157:H7, a mean bacterial hybrid that clings to mucosal surfaces in the human intestine and produces toxins that trigger hemolytic uremic syndrome, the most common cause of acute kidney failure in children. Such mixing-and-matching is “an exquisite example of genetic engineering carried out in the wild,” according to Stanford University molecular biologist Lucy Shapiro. Bacteria even employ a stealth tactic known as phase variation, hiding their immunity-provok-

ing surface proteins and sugars to fool the body’s defenses. According to Joshua Lederberg, “That says they’ve got a memory. They’re carrying about pieces of their evolutionary history in unexpressed forms, waiting to be expressed.”

Bacteria inflict damage in a different way than viruses. Sometimes they multiply so rapidly they crowd out host tissues and disrupt normal function. Sometimes they kill cells and tissues outright. Sometimes they manufacture toxins that can paralyze, destroy metabolic pathways, or generate a massive immune reaction that is itself toxic. Drug-resistant bacteria often make an enzyme that destroys antibiotics or spits them out. Special virulence factors enable bacteria to penetrate cells, gather nutrients for growth and survival, and evade the host’s defenses by jamming or slipping in under the immune system’s radar. Furthermore, bacteria don’t attack until their numbers are high enough to establish an infection. This wireless communication system, called “quorum sensing,” enables microbes to coordinate their activities. The bacteria that congregate in the slimy biofilms such as dental plaque actually assume individual specialized tasks. Despite these feints and stratagems, bacteria remain easier to treat than viruses. Because they are free-living, and because their structure differs from that of mammalian cells, they are more susceptible to drugs delivered via the bloodstream.

A more mysterious class of infectious agents—the newly discovered triggers of animal and human brain diseases such as bovine spongiform encephalopathy (BSE, or mad cow disease) and its human counterpart, new variant Creutzfeldt-Jakob disease—apparently repeal the laws of biology. Called prions (pronounced pre´-ons), these proteins are folded in an abnormal way; when they come in contact with other proteins, they turn them into prions, setting off a chain reaction that eventually riddles the brain with holes. A cow can contract BSE by eating one gram of prion-infected tissue—the size of a peppercorn—from another cow. Unlike viruses or bacteria, prions can’t reproduce and evoke no immune response. More frightening, they resist heat, ultraviolet light, radiation, and sterilization.

The traditional wisdom about emerging pathogens is that they are noxious because they are new—that is, ill adapted to a human host. Indeed, their destructive power is supposedly a tip-off to their recent arrival and to a bad biological fit. Animal viruses, such as the Ebola virus or the Sin Nombre virus that causes hantavirus pulmonary syndrome, can trigger lavish and bizarre symptoms—from hemorrhagic breakdown to acute respiratory failure—because our immune response has not evolved with the virus. Over the long haul, microorganisms and humans usually reach a subtle accommodation. Humans acquire resistance to the infectious agent while the parasite becomes milder, permitting us to survive its assault and permitting it to transmit its genes to someone else. Microorganisms need their hosts to survive; a dead host is a dead-end. The reason the lethal spore-forming bacillus Clostridium botulinum—the cause of botulism—hasn’t leveled our species is because when it kills us with its toxins, it kills its prospects for spread.

In unlocking microbes’ secrets, scientists have gained respect for these hidden adversaries. Humans, they agree, are an encumbered species, composed of too many working parts, fragile when stressed. Bacteria, having evolved for more than three billion years, are supremely well adapted and elegantly stripped down. “I am in awe of these minute creatures,” says Stanford University microbiologist Stanley Falkow. “They know more about the biology of the human cell than most cell biologists. They know how to tweak it and how to exploit it.”

Viruses may be more clever yet. “Some viruses are enormous, and have large numbers of genes that do a lot of things. But other viruses are streamlined, and those are the ones that I really admire,” says molecular biologist and composer Jeffery Taubenberger, who has studied the 1918 influenza virus. “These viruses are so tightly packaged that several different genes can be coded from the same sequence by starting at different places—the sequences actually overlap to conserve space. Genetically, they work like a Bach fugue. In a purely biological sense, they’re incredibly beautiful.”

As far back as the second century AD, in one of his philosophical Table Talks, the historian Plutarch argued that new classes of disease arise because of profound changes in the way we live. This is no less true today. If you want to know where emerging infections come from and how they gain a foothold, take a look at your own life. Virtually every aspect of American culture—from where we live to where we play, from how we raise livestock to how we raise children—is changing. Change creates new markets, you might say, for pathogens. And these agents have a knack for leveraging the slimmest advantage.

The story of emerging infections is like the story of a dangerous intersection that needs a stop sign. Every time two cars collide, bystanders shake their heads and wonder why it doesn’t happen more often. In the case of emerging infections, the collision is between pathogens and people. These crashes take place partly because there’s so much snarling traffic—not only of humans, but of animals, plants, seeds, insects, and all manner of life. Every day, more than two million people worldwide cross national borders. Every year, more than 1.5 billion people travel by air. The United States alone hosts 47 million visitors yearly. “In the old days, our neighbors were Canada and Mexico,” says CDC director Jeffrey Koplan. “Nowadays, with the frequency and speed of air travel, our neighbors are Sri Lanka and Paraguay and you name it.”

Just as, in the nineteenth century, cholera traveled on steamships to Europe and Africa, so in the early 1990s cholera reached the oyster beds of Mobile Bay by stowing away in the bilgewater of ships from Latin America. Though trucks, freighters, and airplanes may have replaced caravans and steamships, the results are the same. Look in your shopping cart. Today’s international cornucopia has included Cyclospora-tainted raspberries from Guatemala, Shigella-contaminated green onions from Mexico, Salmonella-saturated alfalfa sprouts from the Netherlands, E. coli-covered carrots from Peru, and other invisibly poisoned fare. Mike Osterholm, former Minnesota state epidemiologist and an esteemed disease sleuth, describes the clinical

sequelae as “classic traveler’s diarrhea for individuals who never leave home.”

Any pathogen, not just those present in food, can be virtually anywhere within 48 hours. In 1998, a Ukrainian émigré on a Paris-to-New York airplane flight infected 13 other passengers with drug-resistant tuberculosis. In 2001, an Ontario hospital went on red alert when a Congolese woman arrived with what looked to be a hemorrhagic virus such as Ebola. Though she was eventually diagnosed with malaria, public health officials were once again reminded of the ticketless travel arrangements of exotic pathogens. The scenario they most dreaded was a brand-new disease that couldn’t be diagnosed.

Microbes also mix it up when we settle down—especially at the margins of the wild. Lyme disease came to us courtesy of nineteenthcentury deforestation in the Northeast, followed by patchy and less diversified second-growth forests. These nurtured deer populations that, without natural predators, exploded, coinciding with an exurban surge toward the idyllic fringes of “nature.” Coastal population growth has led to contamination of shellfish beds with human waste, fostering the transmission of viral and bacterial pathogens. Human encroachment on the tropical rainforest may open the way for hemorrhagic fever viruses and perhaps even HIV’s mysterious retroviral cousins; in Africa, HIV-like organisms have turned up in more than a dozen species of primates hunted for bush meat or kept as pets.

But communing with nature isn’t the only path to pathogens: microbes also love crowds. In 1900, only 5 percent of the population lived in cities of over 100,000 residents. By the year 2025, 65 percent of the population in developing regions will inhabit cities. Dense urban enclaves will be simultaneously magnets for infections from isolated rural areas and launch pads that allow pathogens to reach other fastgrowing populations. Overwhelmed by unsafe water, poor sanitation, and widespread poverty, tomorrow’s megacities will become cauldrons for new infections.

The devastating 1998–1999 Nipah virus outbreak in Malaysia that killed nearly a third of infected people probably sprang from intensive

pig raising, which permitted a novel virus (probably carried by fruit bats) to propagate and then jump to farmers. Pig farms acted as megacities for the deadly agent, and pig farmers became sentinel cases. In industrialized countries, day care centers are notably noxious settings in which the combination of frequent infections, susceptible children, poor hygiene, and high antimicrobial use breeds diarrheal diseases and antibiotic-resistant microbes such as Streptococcus pneumoniae, a common cause of ear infections and pneumonia.

Keeping ourselves alive longer also, paradoxically, increases our susceptibility to infection. In 1900 only 4 percent of the U.S. population was over 65; in 2040 it will reach almost 25 percent. Elderly people, with their fading immunity, are at the mercy of microorganisms that are normally benign. While chemotherapy and other immunosuppressive treatments have enabled people to live with cancer and other illnesses, they also increase our susceptibility to such ubiquitous pathogens as cytomegalovirus, which can cause pneumonia and eye infections, as well as to new threats such as West Nile virus.

Modern technologies intended to make our lives easier may also

make life easier for microbes. Take Legionnaires’ disease. The bacterium, normally a habitué of moist soil and lakes, not only thrives in water of a narrowly warm temperature range, but also must be misted into tiny particles in order to penetrate deep into human lungs—and so is neatly accommodated by cooling towers, whirlpool spas, and even, according to a recent news account, the hot-water pipes in the Queen’s shower at Buckingham Palace. More futuristically, organ transplants from pigs—contemplated as treatments for diabetes and Parkinson’s disease, among other illnesses—could infect humans with porcine endogenous retroviruses, or PERVs, which are in the same class as HIV; critics fear that such viruses, which are insinuated in the donor pig’s DNA, could interact with human viruses to create new, potentially dangerous species that might spread to the general population.

Bugs themselves are changing, often with a human assist. In 1954 the United States produced two million pounds of antibiotics. Today, it makes tens of millions of pounds per year, half or more administered to livestock. As a result, 70 percent of bacteria that cause the infections patients acquire in hospitals are resistant to at least one antibiotic, and the animals we eat have become factories for drug-resistant microbes. Our newest foe in the antibiotic wars—vancomycin-intermediate Staphylococcus aureus, or VISA—defies medicine’s most powerful antibiotic; should VISA infections become common (five have been reported so far in the United States), simple scrapes could become mortal wounds, and surgery could be as dangerous as it was a century ago—a nightmare vision that has prompted some scientists to speak of a “post-antibiotic era.” “It takes us seventeen years to develop an antibiotic,” says David Morens. “But a bacterium can develop resistance virtually in minutes. It’s as if we’re putting our best players on the field, but the bench is getting empty, while their side has an endless supply of new players.”

Finally, microorganisms may have a much broader reach than we have understood to this point. New DNA-based methods have revealed infectious agents behind diseases that in the past were blamed on lifestyle or the environment. Researchers have reason to be looking for infectious elements in atherosclerosis, Type I diabetes, multiple

sclerosis, Crohn’s disease, Guillain-Barré syndrome, Tourette’s syndrome, even kidney stones. Someday, your annual physical may include a quick survey of “endogenous microflora” in the mouth, on the skin, and in the bowel, to predict current and future medical problems.

Using equally sophisticated epidemiological tools, could science pick up the next HIV before it spreads? The CDC is betting on it, with a project that scrutinizes sudden unexplained deaths and life-threatening illnesses among previously healthy people. The centers hope to pick up odd, sporadic infections and piece them together like a jigsaw puzzle before the illnesses spiral into public health emergencies.

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In recent decades, our attention to infectious disease has pulsed on and off, following the signals of government interest and political fortitude. But for bugs, the beat goes on. “Let your guard down for a minute,” says Joe McDade, deputy director of the National Center for Infectious Disease, “and the microbes are still there.”

What many biologists fear most is a new deadly virus. Viruses are harder to fight with drugs, intimately entangled as they are with the genes and metabolic machinery in our cells. Viruses also seem to stimulate our immune systems more violently and self-destructively than do bacteria. And unlike with bacteria, which have known virulence factors, it’s harder to predict whether a particular virus will radiate quickly or will be especially savage. “If you wanted to think of an Andromeda strain, you would think of, say, a virus with a short incubation period that’s rapidly transmitted from person to person through aerosol, with potential for a high fatality rate and which could move very rapidly,” says McDade, who in 1976 discovered the cause of Legionnaires’ disease. Influenza currently fits the bill—but so could something else, such as a hypothetically mutated Ebola virus that spreads through the air.

Back during the Great Depression, when life seemed at a standstill, Hans Zinsser wrote that “Infectious disease is one of the few genu-

ine adventures left in the world.” Modern adventurers like to up the ante, but even the most extreme sports wouldn’t produce the adrenaline of a race against pandemic influenza or a cloud of anthrax at the Super Bowl. In the field of infectious disease, reality is stranger than anything a writer could dream up. The most menacing bioterrorist is Mother Nature herself.