A Short History of Nearly Everything

by Bill Bryson

  And it doesn't stop there. Having hauled itself up to a more favorable locale, the slime mold 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 molds were so distinctive and peculiar that they 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 ecologist from Cornell University named R. H. Whittaker unveiled in the journal Science a proposal to divide life into five principal branches--kingdoms, as they are known--called Animalia, Plantae, Fungi, Protista, and Monera. Protista, was a modification of an earlier term, Protoctista , 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 others 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, amoebas, 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 bacterium 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 is a petri dish. Plop them on a bed of agar and pamper them as you will, and most will just lie there, declining every inducement to bloom. Any bacterium 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 he worked, Woese realized that there were more fundamental divisions in the microbial world than anyone suspected. A lot of little organisms that looked like bacteria and behaved like bacteria were actually something else altogether--something that had branched off from bacteria a long time ago. Woese called these organisms archaebacteria, later shortened to archaea.

  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. Archaeans are more different from bacteria than you and I are from a crab or spider. 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 reverentially known.

  In 1976, he startled 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 he grouped 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." But slowly his new scheme began to catch on among microbiologists. 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 to unicellular 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 milder moments 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 an extensive familiarity with the principles of classification," which is perhaps as close as one distinguished 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--they involve issues of meiotic sexuality, Hennigian cladification, and controversial interpretations of the genome of Methanobacterium thermoautrophicum , among rather a lot else--but essentially 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 a mere 175 named specimens, with perhaps a few thousand more to be found--"but hardly more than that." By contrast, the eukaryotic realm--that is, the complicated organisms with nucleated 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 empire Eukaryota, which would stand alongside as an equal. Put another way, he argues for keeping things much as they were before. 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. If Woese's new arrangement teaches us 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, toward us. We flatter ourselves. Most of the real diversity in 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 hurt us? What possible satisfaction could there be to a microbe in having us grow feverish or chilled, or disfigured with sores, or above all expire? A 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, a bacterium 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 often 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 to enlist 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. This is why so many grade-A diseases--malaria, yellow fever, dengue fever, encephalitis, and a hundred or so other less celebrated but often rapacious maladies--begin with a mosquito bite. It is a 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 millions with 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 terrifying 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 1552, killing tens of thousands 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 are unwell 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 are less of a threat to the wider community. Resting also frees more of 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 a few 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. To avoid 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 so 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 sometimes 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. Patients often come in with comparatively mild complaints--a skin rash and fever typically--but then dramatically deteriorate. 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. They are completely resistant to antibiotics. About a thousand cases a year occur 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 bacterium, but it lives quite harmlessly in the throat. Just occasionally--in about one young person in a hundred thousand--it gets 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 in perfect 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 stock feed, 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 U.S. surgeon general, William Stewart, felt confident enough to declare: "The time has come to close the book on infectious diseases. We have basically 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 in hospitals. Only one type of antibiotic, vancomycin, remained effective against it, but in 1997 a 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 U.S. hospitals alone, some fourteen thousand people a year die from infections they pick up there. As James Surowiecki has noted, given a choice between developing antibiotics that people will take every day for two weeks or antidepress
ants 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't given us an entirely new antibiotic since the 1970s.

  Our carelessness is all the more alarming since the discovery that many other ailments may be bacterial in origin. The process of discovery began in 1983 when Barry Marshall, a doctor in Perth, Western Australia, found that many stomach cancers and most stomach ulcers are caused 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 generally accepted. America's National Institutes of Health, for instance, didn't officially endorse the idea until 1994. "Hundreds, even thousands of people must have died from ulcers who wouldn'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 in all kinds of other disorders--heart disease, asthma, arthritis, multiple sclerosis, several types of mental disorders, many cancers, even, it has been suggested (in Science no less), obesity. The day may not be far off when we desperately require an effective antibiotic and haven't got one to call on.