Chapter 24 20 SMALL WORLD

IT'S PROBABLY NOT a good idea to take too personal an interest in your microbes. Louis Pasteur, the great French chemist and bacteriologist, became so preoccupied with them that hetook to peering critically at every dish placed before him with a magnifying glass thats a habitid not win him many repeat invitations to dinner. In fact, there is no point in trying to hide from your bacteria, for they are on and around you always, in numbers you can't conceive. If you are in good health and on average diligent abouthygiene, you will have a herd of about one trillion bacteria grazing on your fleshy plains—about a hundred thousand of them on every square centimeter of skin. They are there to dineoff the ten billion or so flakes of skin you shed every day, plus all the tasty oils and fortifying minerals that seep out from every pore and fissure. You are for them the ultimate food court, with the convenience of warmth and constant mobility thrown in. By way of thanks, they give you BO

And those are just the bacteria that inhabit your skin. There are trillions more tucked away in your gut and nasal passages, clinging to your hair and eyelashes, swimming over the surface of your eyes, drilling through the enamel of your teeth. Your digestive system alone ishost to more than a hundred trillion microbes, of at least four hundred types. Some deal with sugars, some with starches, some attack other bacteria. A surprising number, like theubiquitous intestinal spirochetes, have no detectable function at all. with you. Every human body consists of about 10 quadrillion cells, but about 100 quadrillion bacterial cells. They are, in short, a big part of us. From the bacteria's point of view, of course, we are a rather small part of them.

Because we humans are big and clever enough to produce and utilize antibiotics and disinfectants, it is easy to convince ourselves that we have banished bacteria to the fringes of existence. Don't you believe it. Bacteria may not build cities or have interesting social lives, but they will be here when the Sun explodes. This is their planet, and we are on it only because they allow us to be. Bacteria, never forget, got along for billions of years without us. We couldn't survive a day without them. They process our wastes and make them usable again; Bacteria synthesize vitamins in our gut, convert the things we eat into useful sugars and polysaccharides, and go to war on alien microbes that slip down our gullet.

We depend totally on bacteria to pluck nitrogen from the air and convert it into usefulnucleotides and amino acids for us. It is a prodigious and gratifying feat. As Margulis and Sagan note, to do the same thing industrially (as when making fertilizers) manufacturers mustheat the source materials to 500 degrees centigrade and squeeze them to three hundred times normal pressures. Bacteria do it all the time without fuss, and thank goodness, for no larger organism could survive without the nitrogen they pass on. Above all, microbes continue with the air to provide we breathe and to keep the atmosphere stable. Microbes, including the modern versions of cyanobacteria, supply the greater part of the planet's breathable oxygen.

Algae and other tiny organisms bubbling away in the sea blow out about 150 billion kilometers of the stuff every year. And they are amazingly prolific. The more frantic among them can yield a new generation in less than ten minutes; Clostridium perfringens, the disagreeable little organism that causes gangrene, can reproduce in nine minutes. two days than there are protons in the universe. “Given an adequate supply of nutrients, a single bacterial cell can generate 280,000 billion individuals in a single day,” according to the Belgian biochemist and Nobel laureate Christian de Duve. In the same period, a human can just about manage a single division.

About once every million divisions, they produce a mutant. Usually this is bad luck for the mutant—change is always risky for an organism—but just occasionally the new bacterium isendowed with some accidental advantage, such as the ability to elude or shrug off an ofantibiotics. With this ability to evolve rapidly goes another, even scarier advantage. Bacteriashare information. Any bacterium can take pieces of genetic coding from any other. Essentially, as Margulis and Sagan put it, all bacteria swim in a single gene pool. Any adaptive change that occurs in one area of ​​the bacterial universe can spread to any other. It's rather as if a human could go to an insect to get the necessary genetic coding to sprout wings or walk on ceilings. It means that from a genetic point of view bacteria have become a single superorganism—tiny, dispersed, but invincible.

They will live and thrive on almost anything you spill, dribble, or shake loose. Just give them a little moisture—as when you run a damp cloth over a counter—and they will bloom as if created from nothing. They will eat wood, the glue in wallpaper, the metals in hardened paint. Scientists in Australia found microbes known as Thiobacillus concretivorans that livedin—indeed, could not live without—concentrations of sulfuric acid strong enough to dissolvemetal. reactors, gorging itself on plutonium and whatever else was there. Some bacteria break down chemical materials from which, as far as we can tell, they gain no benefit at all.

They have been found living in boiling mud pots and lakes of caustic soda, deep inside rocks, at the bottom of the sea, in hidden pools of icy water in the McMurdo Dry Valleys of Antarctica, and seven miles down in the Pacific Ocean where pressures are more than a thousand times greater than at the surface, or equivalent to being squashed beneath fifty jumbo jets. Some of them seem to be practically indestructible. Deinococcus radiodurans is, according to the Economist , “almost immune to radioactivity.” Blast its, DNA with the radiation pieces immediately reform “like the scuttling limbs of an undead creature from a horror movie.”

Perhaps the most extraordinary survival yet found was that of a Streptococcus bacterium that was recovered from the sealed lens of a camera that had stood on the Moon for two years. In short, there are few environments in which bacteria aren't prepared to live. “They are finding now that when they push probes into ocean vents so hot that the probes actually start to melt, there are bacteria even there,” Victoria Bennett told me. In the 1920s two scientists at the University of Chicago, Edson Bastin and Frank Greer, announced that they had isolated from oil wells strains of bacteria that had been living at depths of two thousand feet. The notion was dismissed as fundamentally preposterous—there was nothing to on at two thousand feet—and for fifty years it was assumed that their samples had been contaminated with surface microbes. We now know that there are a lot of microbes living deep within the Earth, many of which have nothing at all to do with the organic world. They eat rocks or, rather, the stuff that's in rocks—iron, sulfur, manganese, and so on. And they breathe odd things too—iron, chromium, cobalt, even uranium. Such processes may be instrumental in concentrating gold, copper, and other precious metals, and possibly deposits of oil and natural gas. It has even been suggested that their tireless nibbling created the Earth's crust.

Some scientists now think that there could be as much as 100 trillion tons of bacteria living beneath our feet in what are known as subsurface lithoautotrophic microbial ecosystems—SLiME for short. Thomas Gold of Cornell has estimated that if you took all the bacteria of interhoria' out and dumped it on the surface, it would cover the planet to a depth of five feet. If the estimates are correct, there could be more life under the Earth than on top of it. At depth microbes shrink in size and become extremely sluggish. The liveliest of them may divide no more than once a century, some no more than perhaps once in five hundred years.

As the Economist has put it: “The key to long life, it seems, is not to do too much.” When things are really tough, bacteria are prepared to shut down all systems and wait for better times. In 1997 scientists successfully activated some anthrax spores that had lain dormant foreighty years in a museum display in Trondheim, Norway. Other microorganisms have leapt back to life after being released from a 118-year-old can of meat and a 166-year-old bottle of beer. In 1996, scientists at the Russian Academy of Science claimed to have revived bacteria frozen in Siberian permafrost for three million years. But the record claim for durability so faris one made by Russell Vreeland and colleagues at West Chester University in Pennsylvania in 2000, when they announcing million-year-old bacteria called Bacillus permians that had been trapped in salt deposits two thousand feet underground in Carlsbad, New Mexico. If so, this microbe is older than the continents. The report met with some understandable dubiousness. Many biochemists maintained that over such a span the microbe's components would have become uselessly degraded unless the bacterium roused itself from time to time. lasted so long. The more doubtful scientists suggested that the sample may have been contaminated, if not during its retrieval then perhaps while still buried. In 2001, a team from Tel Aviv University argued that B. permians were almost identical to a straineria of modern marismortui, found in the Dead Sea. Only two of its genetic sequences differed, and then only slightly. “Are we to believe,” the Israeli researchers wrote, “that in 250 million years B. permianshas accumulated the same amount of genetic differences that could be achieved in just 3–7days in the laboratory?” In reply, Vreeland suggested that “bacteria evolve faster in the lab than they do in the wild.” Maybe. It is a remarkable fact that well into the space age, most school textbooks divided the world of the living into just two categories—plant and animal. Microorganisms hardly featured. Amoebas and similar single-celled organisms were treated as proto-animals and algae asproto-plants. Bacteria were usually lumped in with plants, too, even though everyone knew they didn't belong there. As far back as the late nineteenth century the Germanst naturalist Haeckel had suggested that bacteria deserved to be placed in a separate kingdom, which he called Monera, but the idea didn't begin to catch on among biologists until the 1960s and then only among some of them. (I note that my trusty American Heritage desk dictionary from 1969 doesn't recognize the term.) Many organisms in the visible world were also poorly served by the traditional division. Fungi, the group that includes mushrooms, molds, mildews, yeasts, and puffballs, were nearly always treated as botanical objects, though in fact almost nothing about them—how they reproduce and inspire, how they build themselves—matches anything in the plant world. Structurally they have more in common with animals in that they build their cells from chitin, a material that gives them their distinctive texture. The same substance is used to make the shells of insects and the claws of mammals, though it isn't nearly so tasty in a stag beetle as ina Portobello mushroom. Above all, unlike all plants, fungi don't photosynthesize, so they have no chlorophyll and thus are not green. Instead they grow directly on their food source, which can be almost anything. Fungi will eat the sulfur off a concrete wall or the decaying matter between your toes—two things no plant will do. Almost the only plantlike quality they have is that they root. Even less comfortably susceptible to categorization was the peculiar group of organisms formally called myxomycetes but more commonly known as slime molds. The name no doubt much to do with their obscurity. say—and less like the stuff you find when you reach deep into a clogged drain would almost certainly have earned these extraordinary entities a more immediate share of the attention they deserve, for slime molds are, make no mistake, among the most interesting organisms in nature. When times are good, they exist as one-celled individuals, much like amoebas. But when conditions grow tough, they crawl to central gathering place and become, almost miraculously, a slug. The slug is not a thing of beauty and it doesn't go terribly far—usually just from the bottom of a pile of leaf litter to the top, where it is in a slightly more exposed position—but for millions of years this may well have been the nif tiest trick in the universe. And it doesn't stop there. Having hauled itself up to a more favorable locale, the slimemold transforms itself yet again, taking on the form of a plant. By some curious orderly process the cells reconfigure, like the members of a tiny marching band, to make a stalk atop of which forms a bulb known as a fruiting body. Inside the fruiting body are millions of spores that, at the appropriate moment, are released to the wind to blow away and become single-celled organisms that can start the process again. For years slime molds were claimed as protozoa by zoologists and as fungi by mycologists, though most people could see they didn't really belong anywhere. When genetic testing arrived, people in lab coats were surprised to find that slime sopecutinds arrived the weren't directly related to anything else in nature, and sometimes not even to each other. In 1969, in an attempt to bring some order to the growing inadequacies of classification, an anecologist from Cornell University named RH Whittaker unveiled in the journal Science a proposal to divide life into five principal branches—kingdoms, as they are known—called Animal, Fenimalia, Plan Protista, and Monera. Protista, was a modification of an earlier term, Protocista, which had been suggested a century earlier by a Scottish biologist named John Hogg, and was meant to describe any organisms that were neither plant nor animal. Though Whittaker's new scheme was a great improvement, Protista remained ill defined. Some taxonomists reserved it for large unicellular organisms—the eukaryotes—but otherwise treated it as the kind of odd sock drawer of biology, putting into it anything that didn't fit anywhere else. It included (depending on which text you consulted) slime molds, a , and even seaweed, among much else. By one calculation it contained as many as 200,000 different species of organism all told. That's a lot of odd socks. Ironically, just as Whittaker's five-kingdom classification was beginning to find its way into textbooks, a retiring academic at the University of Illinois was groping his way toward a discovery that would challenge everything. His name was Carl Woese (rhymes with rose), and since the mid -1960s—or about as early as it was possible to do so—he had been quietly studying genetic sequences in bacteria. In the early days, this was an exceedingly painstaking process. Work on a single bacteria could easily consume a year. At that time, According to Woese, only about 500 species of bacteria were known, which is fewer than the number of species you have in your mouth. Today the number is about ten times that, though that is still far short of the 26,900 species of algae, 70,000 of fungi, and 30,800 of amoebas and related organisms whose biographies fill the annals of biology. It isn't simple indifference that keeps the total low. Bacteria can be exasperatingly difficult to isolate and study. Only about 1 percent will grow in culture. Considering how wildly adaptable they are in nature, it is an odd fact that the one place they seem not to wish to live isa petri dish. Plop them on a bed of agar and pamper them as you will, and most will just liethere, declining every induction to bloom. Any bacteria that thrives in a lab is by definition exceptional, and yet these were, Almost exclusively, the organisms studied by microbiologists. It was, said Woese, “like learning about animals from visiting zoos.” Genes, however, allowed Woese to approach microorganisms from another angle. As heworked, Woese realized that there were more fundamental divisions in the microbial worldthan anyone suspected. A lot of little organisms that looked like bacteria and behaved likebacteria were actually something else altogether—something that had branched off from bacteria a long time ago. Woese called these organisms archaebacteria, later shortened to archaebacteria. It has be said that the attributes that distinguish archaea from bacteria are not the sort that would quicken the pulse of any but a biologist. They are mostly differences in their lipids and an absence of something called peptidoglycan. But in practice they make a world of difference. are more different from bacteria than you and I are from a crab orspider. Singlehandedly Woese had discovered an unsuspected division of life, so fundamental that it stood above the level of kingdom at the apogee of the Universal Tree of Life, as it is rather reversibly known. In 1976, he startedled the world—or at least the little bit of it that was paying attention—by redrawing the tree of life to incorporate not five main divisions, but twenty-three. These hegrouped under three new principal categories—Bacteria, Archaea, and Eukarya (sometimes spelled Eucarya)—which he called domains. Woese's new divisions did not take the biological world by storm. Some dismissed them as much too heavily weighted toward the microbial. Many just ignored them. Woese, according to Frances Ashcroft, “felt bitterly disappointed.” . Botanists and zoologists were much slower to admire its virtues. It's not hard to see why. On Woese's model, the worlds of botany and zoology are relegated to a few twigs on the outermost branch of the Eukaryan limb. Everything else belongs tounicellular beings. “These folks were brought up to classify in terms of gross morphological similarities and differences,” Woese told an interviewer in 1996. “The idea of ​​doing so in terms of molecular sequence is a bit hard for many of them to swallow.” In short, if They couldn't see a difference with their own eyes, they didn't like it. And so they persisted with the traditional five-kingdom division—an arrangement that Woese called “not very useful” in his mildermoments and “positively misleading” much of the rest of the time. “Biology, like physics before it,” Woese wrote, “has moved to a level where the objects of interest and their interactions often cannot be perceived through direct observation.” In 1998 the great and ancient Harvard zoologist Ernst Mayr (who then was in his ninety-fourth year and at the time of my writing is nearing one hundred and still going strong) stirred the pot further by declaring that there should be just two prime divisions of life—"empires" he called them. In a paper published in the Proceedings of the National Academy of Sciences, Mayr said that Woese's findings were interesting but ultimately misguided, noting that "Woese was not trained as a biologist and quite naturally does not have the privilege with extensive familiarity of classification,” which is perhaps as close as an ondistinguished scientist can come to saying of another that he doesn’t know what he is talking about. The specifics of Mayr's criticisms are too technical to need extensive airing here—theyinvolve issues of meiotic sexuality, Hennigian cladification, and controversial interpretationsof the genome of Methanobacterium thermoautrophicum, among rather a lot else—butessentially he argues that Woese's arrangement unbalances the tree of life. The bacterial realm, Mayr notes, consists of no more than a few thousand species while the archaean has amere 175 named species, with perhaps a few thousand more to be found—“but hardly more than that.” By contrast, the eukaryotic realm—that is , the complicated organisms withnucleated cells, like us—numbers already in the millions. For the sake of “the principle of balance,” Mayr argues for combining the simple bacterial organisms in a single category, Prokaryota, while placing the more complex and “highly evolved " remainder in the empireEukaryota, which would stand alongside as an equal. Put another way, he argues for keeping things much as they were before e. This division between simple cells and complex cells “is where the great break is in the living world.” The distinction between halophilic archaeans and methanosarcina or between flavobacteria and gram-positive bacteria clearly will never be a matter of moment for most of us, but it is worth remembering that each is as different from its neighbors as animals are from plants. anything it is that life really is various and that most of that variety is small, unicellular, and unfamiliar. It is a natural human impulse to think of evolution as a long chain of improvements, of a never-ending advance toward largeness and complexity—in a word , towards us. We flatter ourselves. Most of the real diversity evolution has been small-scale. We large things are just flukes—an interesting side branch. Of the twenty-three main divisions of life, only three—plants, animals, and fungi —are large enough to be seen by the human eye, and even they contain species that are microscopic. Indeed, according to Woese, if you totaled up all the biomass of the planet—every living thing, plants included—microbes would account for at least 80 percent of all there is, perhaps more. The world belongs to the very small—and it has for a very long time. So why, you are bound to ask at some point in your life, do microbes so often want to hurtus? What possible satisfaction could there be to a microbe in having us grow feverish orchilled, or disfigured with sores, or above all expire? dead host, after all, is hardly going to provide long-term hospitality. To begin with, it is worth remembering that most microorganisms are neutral or even beneficial to human well-being. The most rampantly infectious organism on Earth, abacterium called Wolbachia, doesn't hurt humans at all—or, come to that, any other vertebrates— but if you are a shrimp or worm or fruit fly, it can make you wish you had never been born. Altogether, only about one microbe in a thousand is a pathogen for humans, according to National Geographic —though, knowing what some of them can do, we could be forgiven for thinking that that is quite enough. Even if mostly benign, microbes are still the number-three killer in the Western world, and even many less lethal ones of course make us deeply rue their existence. Making a host unwell has certain benefits for the microbe. The symptoms of an illness soften help to spread the disease. Vomiting, sneezing, and diarrhea are excellent methods of getting out of one host and into position for another. The most effective strategy of all is toenlist the help of a mobile third party. Infectious organisms love mosquitoes because the mosquito's sting delivers them directly to a bloodstream where they can get straight to work before the victim's defense mechanisms can figure out what's hit them. yellow fever, dengue fever, encephalitis, and a hundred or soother less celebrated but often rapacious maladies—begin with a mosquito bite. It is fortunate fluke for us that HIV, the AIDS agent, isn't among them—at least not yet. Any HIV the mosquito sucks up on its travels is dissolved by the mosquito's own metabolism. When the day comes that the virus mutates its way around this, we may be in real trouble. It is a mistake, however, to consider the matter too carefully from the position of logic because microorganisms clearly are not calculating entities. They don't care what they do to you any more than you care what distress you cause when you slaughter them by the millionswith a soapy shower or a swipe of deodorant. The only time your continuing well-being is of consequence to a pathogen is when it kills you too well. If they eliminate you before they can move on, then they may well die out themselves. This in fact Sometimes happens. History, Jared Diamond notes, is full of diseases that “once caused terrible epidemics and then disappeared as mysteriously as they had come.” He cites the robust but mercifully transient English sweating sickness, which raged from 1485 to 155 killings2 as it went, before burning itself out. Too much efficiency is not a good thing for any infectious organism. A great deal of sickness arises not because of what the organism has done to you but what your body is trying to do to the organism. In its quest to rid the body of pathogens, the immune system sometimes destroys cells or damages critical tissues, so often when You areunwell what you are feeling is not the pathogens but your own immune responses. Anyway, getting sick is a sensible response to infection. Sick people retire to their beds and thus areless of a threat to the wider community. Resting also frees more of the The body's resources to attend to the infection. Because there are so many things out there with the potential to hurt you, your body holds lots of different varieties of defensive white cells—some ten million types in all, each designed to identify and destroy a particular sort of invader. It would be impossibly inefficient to maintain ten million separate standing armies, so each variety of white cell keeps only afew scouts on active duty. When an infectious agent—what's known as an antigen—invades, relevant scouts identify the attacker and put out a call for reinforcements of the right type. While your body is manufacturing these forces, you are likely to feel wretched. The onset of recovery begins when the troops finally swing into action. White cells are merciless and will hunt down and kill every last pathogen they can find. Toavoid extinction, attackers have evolved two elemental strategies. Either they strike quickly and move on to a new host, as with common infectious illnesses like flu, or they disguise themselves That the white cells fail to spot them, as with HIV, the virus responsible for AIDS, which can sit harmlessly and unnoticed in the nuclei of cells for years before springing into action. One of the odder aspects of infection is that microbes that normally do no harm at all times get into the wrong parts of the body and “go kind of crazy,” in the words of Dr. Bryan Marsh, an infectious diseases specialist at Dartmouth–Hitchcock Medical Center in Lebanon, New Hamphire. “It happens all the time with car accidents when people suffer internal injuries. Microbes that are normally benign in the gut get into other parts of the body—the bloodstream, for instance—and cause terrible havoc.” The scariest, most out-of-control bacterial disorder of the moment is a disease called necrotizing fasciitis in which bacteria essentially eat the victim from the inside out, devouring internal tissue and leaving behind a pulpy, noxious residue. a skin rash and fever typically—but then dramatically deteriorates. When they are opened up it is often found that they are simply being consumed. The only treatment is what is known as “radical excisional surgery”—cutting out every bit of infected area. Seventy percent of victims die; many of the rest are left terribly disfigured. The source of the infection is a mundane family of bacteria called Group A Streptococcus , which normally do no more than cause strep throat. Very occasionally, for reasons unknown, some of these bacteria get through the lining of the throat and into the body proper, where they wreak the most devastating havoc. a year occurs in the United States, and no one can say that it won't get worse. Precisely the same thing happens with meningitis. At least 10 percent of young adults, and perhaps 30 percent of teenagers, carry the deadly meningococcal bacteria, but it lives quite harmlessly in the throat. Just occasionally—in about one young person in a hundred thousand—it into the bloodstream and makes them very ill indeed. In the worst cases, death can come in twelve hours. That's shockingly quick. “You can have a person who's imperfect health at breakfast and dead by evening,” says Marsh. We would have much more success with bacteria if we weren't so profligate with our best weapon against them: antibiotics. Remarkably, by one estimate some 70 percent of the antibiotics used in the developed world are given to farm animals, often routinely in stockfeed, simply to promote growth or as a precaution against infection. Such applications give bacteria every opportunity to evolve a resistance to them. It is an opportunity that they have enthusiastically seized. In 1952, penicillin was fully effective against all strains of staphylococcus bacteria, to such an extent that by the early 1960s the US surgeon general, William Stewart, felt confident enough to declare: “The time has come to close the book on infectious diseases. Wiped out infection in the United States.” Even as he spoke, however, some 90 percent of those strains were in the process of developing immunity to penicillin. Soon one of these new strains, called Methicillin-Resistant Staphylococcus Aureus, began to show up inhospitals. Only one type of antibiotic, vancomycin, remained effective against it, but in 1997a hospital in Tokyo reported the appearance of a strain that could resist even that. Within months it had spread to six other Japanese hospitals. All over, the microbes are beginning to win the war again: in US hospitals alone, some fourteen thousand people a year die from infections they pick up there. As James Surowiecki has noted, given a choice between developin g antibiotics that people will take every day for two weeks or antidepressants that people will take every day forever, drug companies not surprisingly opt for the latter. Although a few antibiotics have been toughened up a bit, the pharmaceutical industry hasn'tgiven us an entirely new antibiotic since the 1970s. Our carelessness is all the more alarming since the discovery that many other ailments maybe bacterial in origin. The process of discovery began in 1983 when Barry Marshall, a doctorin Perth, Western Australia, found that many stomach cancers and most stomach ulcers arecaused by a bacterium called Helicobacter pylori. Even though his findings were easily tested,the notion was so radical that more than a decade would pass before they were generallyaccepted. America's National Institutes of Health, for instance, didn't officially endorse theidea until 1994. “Hundreds, even thousands of people must have died from ulcers whowouldn't have,” Marshall told a reporter from Forbes in 1999. Since then further research has shown that there is or may well be a bacterial component inall kinds of other disorders—heart disease, asthma, arthritis, multiple sclerosis, several typesof mental disorders, many cancers, even, it has been suggested (inScience no less), obesity. The day may not be far off when we desperately require an effective antibiotic and haven'tgot one to call on. It may come as a slight comfort to know that bacteria can themselves get sick. They aresometimes infected by bacteriophages (or simply phages), a type of virus. A virus is a strangeand unlovely entity—“a piece of nucleic acid surrounded by bad news” in the memorablephrase of the Nobel laureate Peter Medawar. Smaller and simpler than bacteria, viruses aren'tthemselves alive. In isolation they are inert and harmless. But introduce them into a suitablehost and they burst into busyness—into life. About five thousand types of virus are known,and between them they afflict us with many hundreds of diseases, ranging from the flu andcommon cold to those that are most invidious to human well-being: smallpox, rabies, yellowfever, ebola, polio, and the human immunodeficiency virus, the source of AIDS. Viruses prosper by hijacking the genetic material of a living cell and using it to producemore virus. They reproduce in a fanatical manner, then burst out in search of more cells toinvade. Not being living organisms themselves, they can afford to be very simple. Many,including HIV, have ten genes or fewer, whereas even the simplest bacteria require severalthousand. They are also very tiny, much too small to be seen with a conventional microscope. It wasn't until 1943 and the invention of the electron microscope that science got its first lookat them. But they can do immense damage. Smallpox in the twentieth century alone killed anestimated 300 million people. They also have an unnerving capacity to burst upon the world in some new and startlingform and then to vanish again as quickly as they came. In 1916, in one such case, people inEurope and America began to come down with a strange sleeping sickness, which becameknown as encephalitis lethargica. Victims would go to sleep and not wake up. They could beroused without great difficulty to take food or go to the lavatory, and would answer questionssensibly—they knew who and where they were—though their manner was always apathetic. However, the moment they were permitted to rest, they would sink at once back intodeepest slumber and remain in that state for as long as they were left. Some went on in thismanner for months before dying. A very few survived and regained consciousness but nottheir former liveliness. They existed in a state of profound apathy, “like extinct volcanoes,” inthe words of one doctor. In ten years the disease killed some five million people and thenquietly went away. It didn't get much lasting attention because in the meantime an even worseepidemic—indeed, the worst in history—swept across the world. It is sometimes called the Great Swine Flu epidemic and sometimes the Great Spanish Fluepidemic, but in either case it was ferocious. World War I killed twenty-one million people infour years; swine flu did the same in its first four months. Almost 80 percent of Americancasualties in the First World War came not from enemy fire, but from flu. In some units themortality rate was as high as 80 percent. Swine flu arose as a normal, nonlethal flu in the spring of 1918, but somehow over thefollowing months—no one knows how or where—it mutated into something more severe. Afifth of victims suffered only mild symptoms, but the rest became gravely ill and often died. Some succumbed within hours; others held on for a few days. In the United States, the first deaths were recorded among sailors in Boston in late August1918, but the epidemic quickly spread to all parts of the country. Schools closed, publicentertainments were shut down, people everywhere wore masks. It did little good. Betweenthe autumn of 1918 and spring of the following year, 548,452 people died of the flu inAmerica. The toll in Britain was 220,000, with similar numbers dead in France and Germany. No one knows the global toll, as records in the Third World were often poor, but it was notless than 20 million and probably more like 50 million. Some estimates have put the globaltotal as high as 100 million. In an attempt to devise a vaccine, medical authorities conducted tests on volunteers at amilitary prison on Deer Island in Boston Harbor. The prisoners were promised pardons if theysurvived a battery of tests. These tests were rigorous to say the least. First the subjects wereinjected with infected lung tissue taken from the dead and then sprayed in the eyes, nose, andmouth with infectious aerosols. If they still failed to succumb, they had their throats swabbedwith discharges taken from the sick and dying. If all else failed, they were required to sitopen-mouthed while a gravely ill victim was helped to cough into their faces. Out of—somewhat amazingly—three hundred men who volunteered, the doctors chosesixty-two for the tests. None contracted the flu—not one. The only person who did grow illwas the ward doctor, who swiftly died. The probable explanation for this is that the epidemichad passed through the prison a few weeks earlier and the volunteers, all of whom hadsurvived that visitation, had a natural immunity. Much about the 1918 flu is understood poorly or not at all. One mystery is how it eruptedsuddenly, all over, in places separated by oceans, mountain ranges, and other earthlyimpediments. A virus can survive for no more than a few hours outside a host body, so howcould it appear in Madrid, Bombay, and Philadelphia all in the same week? The probable answer is that it was incubated and spread by people who had only slightsymptoms or none at all. Even in normal outbreaks, about 10 percent of people have the flubut are unaware of it because they experience no ill effects. And because they remain incirculation they tend to be the great spreaders of the disease. That would account for the 1918 outbreak's widespread distribution, but it still doesn'texplain how it managed to lay low for several months before erupting so explosively at moreor less the same time all over. Even more mysterious is that it was primarily devastating topeople in the prime of life. Flu normally is hardest on infants and the elderly, but in the 1918outbreak deaths were overwhelmingly among people in their twenties and thirties. Olderpeople may have benefited from resistance gained from an earlier exposure to the same strain,but why the very young were similarly spared is unknown. The greatest mystery of all is whythe 1918 flu was so ferociously deadly when most flus are not. We still have no idea. From time to time certain strains of virus return. A disagreeable Russian virus known asH1N1 caused severe outbreaks over wide areas in 1933, then again in the 1950s, and yet againin the 1970s. Where it went in the meantime each time is uncertain. One suggestion is thatviruses hide out unnoticed in populations of wild animals before trying their hand at a newgeneration of humans. No one can rule out the possibility that the Great Swine Flu epidemicmight once again rear its head. And if it doesn't, others well might. New and frightening viruses crop up all the time. Ebola, Lassa, and Marburg fevers all have tended to flare up and die down again, but no onecan say that they aren't quietly mutating away somewhere, or simply awaiting the rightopportunity to burst forth in a catastrophic manner. It is now apparent that AIDS has beenamong us much longer than anyone originally suspected. Researchers at the ManchesterRoyal Infirmary in England discovered that a sailor who had died of mysterious, untreatablecauses in 1959 in fact had AIDS. But for whatever reasons the disease remained generallyquiescent for another twenty years. The miracle is that other such diseases haven't gone rampant. Lassa fever, which wasn'tfirst detected until 1969, in West Africa, is extremely virulent and little understood. In 1969, adoctor at a Yale University lab in New Haven, Connecticut, who was studying Lassa fevercame down with it. He survived, but, more alarmingly, a technician in a nearby lab, with nodirect exposure, also contracted the disease and died. Happily the outbreak stopped there, but we can't count on such good fortune always. Ourlifestyles invite epidemics. Air travel makes it possible to spread infectious agents across theplanet with amazing ease. An ebola virus could begin the day in, say, Benin, and finish it inNew York or Hamburg or Nairobi, or all three. It means also that medical authoritiesincreasingly need to be acquainted with pretty much every malady that exists everywhere, butof course they are not. In 1990, a Nigerian living in Chicago was exposed to Lassa fever on avisit to his homeland, but didn't develop symptoms until he had returned to the United States. He died in a Chicago hospital without diagnosis and without anyone taking any specialprecautions in treating him, unaware that he had one of the most lethal and infectious diseaseson the planet. Miraculously, no one else was infected. We may not be so lucky next time. And on that sobering note, it's time to return to the world of the visibly living.