Koch's Postulates

For his successful determination of the bacterium that causes tuberculosis, Mycobacterium tuberculosis, Koch was awarded the Nobel Prize in Physiology or Medicine in 1905. Koch formulated his famous set of criteria for establishing a causative link between an infectious agent and a disease (Fig. 1.17). These four criteria are known as Koch's postulates:
            1. The microbe is found in all cases of the disease but is absent from healthy individuals.
            2. The microbe is isolated from the diseased host and grown in pure culture.
            3. When the microbe is introduced into a healthy, susceptible host (or animal model), the same disease occurs.
            4. The same strain of microbe is obtained from the newly diseased host. When cultured, the strain shows the same characteristics as before.    

Koch's postulates continue to be used to determine whether a given strain of microbe causes a disease. Mod-em examples include Lyme disease, a tick-borne infection that has become widespread in New England and the Mid-Atlantic states; and hantaviral pneumonia, an emerging disease particularly prevalent among Native Americans in the Southwest. Nevertheless, the postulates remain only a guide; individual diseases and pathogens may confound one or more of the criteria. For example, tuberculosis bacteria are now known to cause symptoms in only 10% of the people infected. If Koch had been able to detect these silent bacilli, they would not have fulfilled his first criterion. In the case of AIDS, the concentration of HIV virus is so low that initially no virus could be detected in patients with fully active symptoms. It took the invention of the polymerase chain reaction (PCR), a method of producing any number of copies of DNA or RNA sequences, to detect the presence of HIV. Another difficulty with AIDS and many other human diseases is the absence of an animal host that exhibits the same disease. In the case of AIDS, even chimpanzees, our closest relatives, are not susceptible, although they exhibit a similar disease from a related pathogen, simian immunodeficiency virus (SIV). Experimentation on humans is prohibited, although in rare instances researchers have voluntarily exposed themselves to a proposed pathogen. For example, Australian researcher Barry Marshall ingested Ileiicobacter pylori to convince skeptical col-leagues that this organism could colonize the extremely acidic stomach. II. pylori turned out to be the causative agent of gastritis and stomach ulcers, conditions that had long been thought to be caused by stress rather than infection. For the discovery of H. pylori, Marshall and col-league Robin Warren won the 2005 Nobel Prize in Physiology or Medicine.

Growth of Microbes in Pure Culture

Unlike Pasteur, who was a university professor, Koch took up a medical practice in a small Polish-German town. To make space in his home for a laboratory to study anthrax and other deadly diseases, his wife curtained off part of his patients' examining room. Anthrax interested Koch because its epidemics in sheep and cattle caused economic hardship among local farmers. Today, anthrax is no longer a major problem for agriculture, as its transmission is prevented by effective environmental controls and vaccination. It has, however, gained notoriety as a bioterror agent because anthrax bacteria can survive for long periods in the dormant, desiccated form of an endospore. In 2001, anthrax spores sent through the mall contaminated post offices throughout the northeastern United States, as well as an office building of the United States Senate, causing several deaths. To investigate whether anthrax was a transmissible disease, Koch used blood from an anthrax-infected carcass to inoculate a rabbit. When the rabbit died, he used the rabbit's blood to inoculate a second rabbit, which then died in turn. The blood of the unfortunate animal had turned black with long, rod-shaped bacilli. Upon introduction of these bacilli into healthy animals, the animals became ill with anthrax. Thus, Koch demonstrated an important principle of epidemiology: the chain of infection, or transmission of a disease. In retrospect, his choke of anthrax was fortunate, for the microbes generate disease very quickly, multiply in the blood to an extraordinary concentration, and remain infective outside the body for long periods.
        Koch and his colleagues then applied their experimental logic and culture methods to a more challenging disease: tuberculosis. In Koch's day, tuberculosis caused one-seventh of reported deaths in Europe; today, tuberculosis bacteria continue to infect millions of people worldwide. Koch's approach to anthrax, however, was less applicable to tuberculosis, a disease that develops slowly after many years of dormancy. Furthermore, the causative bacteria, Mycobacterium tuberculosis, are small and difficult to distinguish from human tissue or from different bacteria of similar appearance associated with the human body. How could Koch prove that a particular bacterium caused a particular disease? What was needed was to isolate a pure culture of microorganisms, a culture grown from a single "parental" cell. This had been done by previous researchers using the laborious process of serial dilution of suspended bacteria until a culture tube contained only a single cell. Alternatively, inoculation of a solid surface such as a sliced potato could produce isolated colonies, distinct populations of bacteria, each grown from a single cell. For M. tuberculosis, Koch inoculated serum, which then formed a solid gel after heating. Later he refined the solid-substrate technique by adding gelatin to a defined liquid medium, which could then be chilled to form a solid medium in a glass dish. A covered version called the petri dish (also called a petri plate) was invented by a colleague, Julius Richard Petri (1852-1921). The petri dish consists of a round dish with vertical walls covered by an inverted dish of slightly larger diameter. Today, the petri dish, generally made of disposable plastic, remains an indispensable part of the microbiological laboratory. Another improvement in solid-substrate culture was the replacement of gelatin with materials that remain solid at higher temperatures, such as the gelling agent agar (a polymer of the sugar galactose). The use of agar was recommended by Angelina Hesse (1850-1934), a microscopic and illustrator, to her husband, Walther Hesse (1846-1911), a young medical colleague of Koch (Fig.1.16). Agar comes from red algae (seaweed), which is used by East Indian birds to build nests; it is the main ingredient in the delicacy "bird's nest soup." Dutch colonists used agar to make jellies and preserves, and a Dutch colonist from Java introduced it to Angelina Hesse. The Hesses used agar to develop the first effective growth medium for tuberculosis bacteria. (Pure culture is discussed further in Chapter 4.) Note that some kinds of microbes cannot be grown in pure culture without other organisms. For example, viruses can be cultured only in the presence of their host cells. The discovery of viruses is explored at the end of this section

Medical Microbiology

Over the centuries, thoughtful observers, such as Fracastoro and Bassi (see Table 1.2), noted a connection between microbes and disease. Ultimately, researchers developed the germ theory of disease, the theory that many diseases are caused by microbes. The first to establish a scientific basis for determining that a specific microbe causes a specific disease was If all life on Earth shares descent from a microbial ancestor, how did the first microbe arise? The earliest fossil evidence of cells in the geological record appears in sedimentary rock that formed as early as 3.8 billion years ago. Although the nature of the earliest reported fossils remains controversial, it is generally accepted that "microfossils" from over 2 billion years ago were formed by living cells. Moreover, the living cells that formed these microfossils looked remarkably similar to bacterial cells today, forming chains of simple rods or spheres (Fig. 1). The exact composition of the first environment for life is controversial. The components of the first living cells may have formed from spontaneous reactions sparked by ultraviolet absorption or electrical discharge. American chemists Stanley Miller (1930-2007) and Harold C. Urey (1893-1981) argued that the environment of early Earth contained mainly reduced compounds compounds that have a strong tendency to donate electrons, such as ferrous iron, methane, and ammonia. More recent evidence has modified this view, but it is agreed that the strong electron acceptor oxygen gas (02) was absent until the first photosynthetic microbes produced it. Today, all our cells are composed of highly reduced molecules that are readily oxidized (accept electrons from 02). This seem ingly hazardous composition may reflect our cellular origin in the chemically reduced environment of early Earth. In 1953, Miller attempted to simulate the highly reduced conditions of early Earth to test whether ultraviolet absorption or electrical discharge could cause reactions producing the fundamental components of life (Fig. 2A). Miller boiled a solution of water containing hydrogen gas, methane, and ammonia and applied an electrical discharge (comparable to a lightning strike). The electrical discharge excites electrons in the molecules and causes them to react. Astonishingly, the reaction produced a number of amino acids, including glycine, alanine, and aspartic acid. A similar experiment in 1961 by Spanish-American researcher Juan Or (1923-2004) (Fig. 2B) combined hydrogen cyanide and ammonia under electrical discharge to obtain adenine, a fundamental component of DNA and of the energy carrier adenosine triphosphate (ATP). How could early cells have survived the heat and chemically toxic environment of early Earth? Clues may be found in the survival of archaea that thrive under habitat conditions that we consider extreme, such as solutions of boiling sulfuric acid. The specially adapted structures of such microbes may resemble those of the earliest life-forms.

Spontaneous Generation: Do Microbes Have Parents?

The observation of microscopic organisms led priests and philosophers to wonder where they came from. In the eighteenth century, scientists and church leaders intensely debated the question of spontaneous generation, the theory that living creatures such as maggots could arise spontaneously, without parental organisms. Chemists of the day tended to support spontaneous generation, at it appeared similar to the changes in matter that could occur when chemicals were mixed. Christian church leaders, however, supported the biblical view that all organisms have "parents" going back to the first week of creation. The Italian priest Francesco Redi (1626-1697) showed that maggots in decaying meat were the offspring of flies. Meat kept in a sealed container, excluding flies, did not produce maggots. Thus, Redi's experiment argued against spontaneous generation for macroscopic organisms. The meat still putrefied, however, producing microbes that seemed to arise "without parents." To disprove spontaneous generation of microbes, another Italian priest, Lazzaro Spallanzani (1729-1799), showed that a sealed flask of meat broth sterilized by boiling failed to grow microbes. Spallanzani also noticed that microbes often appeared in pairs. Were these two parental microbes coupling to produce offspring, or did one microbe become two? By long and tenacious observation, Spallanzani watched a single microbe grow in size until it split in two. Thus, he demonstrated cell fission, the process by which cells arise by the splitting of preexisting cells. Even Spallanzani's experiments, however, did not put the matter to rest. Proponents of spontaneous generation argued that the microbes in the priest's flask lacked access to oxygen and therefore could not grow. The pursuit of this question was left to future microbiologists, including the famous French microbiologist Louis Pasteur (1822-1895) (Fig. 1.14A). In addressing spontaneous generation and related questions, Pasteur and his contemporaries laid the foundations for modern microbiology.
     Louis Pasteur reveals the biochemical basis of microbial growth. Pasteur began his scientific career as a chemist and wrote his doctoral thesis on the structure of organic crystals. He discovered the fundamental chemical property of chirality, the fact that some organic molecules exist in two forms that differ only by mirror symmetry. In other words, the two structures are mirror images of one another, like the right and left hands. Pasteur found that when microbes were cultured on a nutrient substance containing both mirror forms, only one mirror form was consumed. He concluded that the metabolic preference for one mirror form was a fundamental property of life. Subsequent research has confirmed that most biological molecules, such as DNA and proteins, occur in only one of their mirror forms. As a chemist, Pasteur was asked to help with a widespread problem encountered by French manufacturers of wine and beer. The production of alcoholic beverages is now known to occur by fermentation, a process by which microbes gain energy by converting sugars into alcohol. In the time of Pasteur, however, the conversion of grapes or grain to alcohol was believed to be a spontaneous chemical process. No one could explain why some fermentation mixtures produced vinegar (acetic acid) instead of alcohol. Pasteur discovered that fermentation is actually caused by living yeast, a single-celled fungus. In the absence of oxygen, yeast produces alcohol as a terminal waste product. But when the yeast culture is contaminated with bacteria, the bacteria outgrow the yeast and produce acetic acid instead of alcohol. (Fermentative metabolism is discussed further in Chapter 13.) Pasteur's work on fermentation led him to test a key claim made by proponents of spontaneous generation. The proponents claimed that Spallanzani's failure to find spontaneous appearance of microbes was due to lack of oxygen. From his studies of yeast fermentation, Pasteur knew that some microbial species do not require oxygen for growth. So he devised an unsealed flask with a long, bent "swan neck" that admitted air but kept the boiled contents free of microbes (Fig. 1.148). The famous swan-necked flasks remained free of microbial growth for many years; but when a flask was tilted to enable contact of broth with microbe containing dust, growth occurred immediately. Thus, Pasteur disproved that lack of oxygen was the reason for the failure of spontaneous generation in Spallanzani's flasks. But even Pasteur's work did not prove that microbial growth requires preexisting microbes. The Irish scientist John Tyndall (1820-1893) attempted the same experiment as Pasteur, but sometimes found the opposite result. Tyndall found that the broth sometimes gave rise to microbes, no matter how long it was sterilized by boiling. The microbes appear because some kinds of organic matter, particularly hay infusion, arecontaminated with a heat resistant form of bacteria called endospores (or spores). The spore form can be eliminated only by repeated cycles of boiling and resting, in which the spores germinate to the growing, vegetative form that is killed at 100°C. It was later discovered that endospores could be killed by boiling under pressure, as in a pressure cooker, which generates higher temperatures than can be obtained at atmospheric pressure. The steam pressure device called the autoclave became a standard method for the sterilization of materials required for the controlled study of microbes. (Microbial control and antisepsis are discussed further in Chapter 5.) Although spontaneous generation has been discredited as a continual source of microbes, at some point in the past the first living organisms must have originated from nonliving materials. The origin of life is explored in Special Topic 1.1, and discussed further in Chapter 17.

Microscopes Reveal the Microbial World

 The seventeenth century was a time of growing inquiry and excitement about the "natural magic" of science and patterns of our world, such as the laws of gravitation and motion formulated by Isaac Newton (1642-1727). Robert Boyle (1627-1691) performed the first controlled experiments on the chemical conversion of matter. Physicians attempted new treatments for disease involving the application of "stone and minerals" (that is, the application of chemicals), what today we would call chemotherapy. Minds were open to consider the astounding possibility that our surroundings, indeed our very bodies, were inhabited by tiny living beings.

  Robert Hooke observes the microscopic world.

 The first micros copist to publish a systematic study of the world as seen under a microscope was Robert Hooke (1635-1703). As curator of experiments for the Royal Society of London, Hooke built the first compound microscopea magnifying instrument containing two or more lenses that multiply their magnification in series. With his microscope, Hooke observed biological mate-rials such as nematode "vinegar eels," mites, and mold filaments, illustrations of which he published in Micrographia (1665), the first publication that illustrated objects observed under a microscope (Fig. 1.12). Hooke was the first to observe distinct units of living material, which he called "cells." Hooke first named the units cells because the shape of hollow cell walls in a slice of cork reminded him of the shape of monks' cells in a monastery. But his crude lenses achieved at best 30-fold power (30 x), so he never observed single celled organisms.

Antonie van Leeuwenhoek observes bacteria with a single lens.

Hooke's Micrographia inspired other microscopists, including Antonie van Leeuwenhoek (1632-1723), who became the first individual to observe single-celled microbes (Fig. 1.13A). As a young man, Leeuwenhoek lived in the Dutch city of Delft, where he worked as a cloth draper, a profession that introduced him to magnifying glasses. (The magnifying glasses were used to inspect the quality of the cloth, enabling the worker to count the number of threads.) Later in life, he took up the hobby of grinding ever stronger lenses to see into the world of the unseen. Leeuwenhoek ground lenses stronger than Hooke's, which he used to build single-lens magnifiers, complete with sample holder and focus adjustment (Fig. 1.13B). First he observed insects, including lice and fleas; then the relatively large single cells of protists and algae; then ultimately bacteria. news on Microscopes Reveal the Microbial World One day he applied his microscope to observe matter extracted from between his teeth. He wrote, "To my great surprise [I] perceived that the aforesaid matter contained very many small living Animals, which moved themselves very extravagantly." Over the rest of his life, Leeuwenhoek recorded page after page on the movement of microbes, reporting their size and shape so accurately that in many cases we can determine the species he observed (Fig. 1.13C).
          He performed experiments, comparing, for example, the appearance of "small animals" from his teeth before and after drinking hot coffee. The disappearance of microbes from his teeth after drinking a hot beverage suggested that heat killed microbes a profoundly important principle for the study and control of microbes ever since. Ironically, Leeuwenhoek is believed to have died of a disease contracted from sheep whose bacteria he observed. Historians have often wondered why it took so many centuries for Leeuwenhoek and his successors to determine the link between microbes and dis-ease. Although observers such as Agostino Bassi de Lodi (1773-1856) noted isolated cases of microbes associated with pathology (see Table 1.2), the very ubiquity of microbes most of them actually harmless may have obscured their more deadly roles. In addition, it was hard to distinguish between microbes and the single-celled components of the human body, such as blood cells and sperm. It was not until the nineteenth century that human tissues could be distinguished from microbial cells by the application of differential chemical stains (discussed in Chapter 2).

Microbes Shape Human History

Throughout most of human history, we were unaware of the microbial world. Microorganisms have shaped human culture since our earliest civilizations. latest new science news on Microbes Shape Human History  Yeasts and bacteria have made foods such as bread and cheese (Fig. 1.9A), as well as alcoholic beverages (discussed in Chapter 16). "Rock-eating" bacteria known as lithotrophs leached copper and other metals from ores exposed by mining, enabling ancient human miners to obtain these metals. The lithotrophic oxidation of minerals for energy generates strong acid, which accelerates breakdown of the ore. Today, about 20% of the world's copper, as well as some uranium and zinc, is produced by bacterial leaching. Unfortunately, microbial acidification also consumes the stone of ancient monuments (Fig. 1.9B) a process intensified by airborne acidic pollution. Management of microbial corrosion is an important field of applied microbiology. As humans became aware of microbes, our relationship with the microbial world changed in important ways (Table 1.2, pages 14-15). Early microscopists in the seventeenth and eighteenth centuries formulated key concepts of microbial existence, including their means of reproduction and death. In the nineteenth century, the "golden age" of microbiology, key principles of disease pathology and microbial ecology were established that scientists still use today. This period laid the foundation for modern science, in which genetics and molecular biology provide powerful tools for scientists to manipulate microorganisms for medicine and industry.

Microbial Disease Devastates Human Populations

Throughout history, microbial diseases such as tuberculosis and leprosy have profoundly affected human demo-graphics and cultural practices (Fig. 1.10). The bubonic plague, which wiped out a third of Europe's population in the fourteenth century, was caused by Yersinia pestis, a bacterium spread by rat fleas. Ironically, the plague-induced population decline enabled the social transformation that led to the Renaissance, a period of unprecedented cultural advancement. In the nineteenth century, the bacterium Mycobacterium tuberculosis stalked overcrowded cities, and tuberculosis became so common that the pallid appearance of tubercular patients became a symbol of tragic youth in European literature. Today, societies throughout the world have been profoundly shaped by the epidemic of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV). More than 36 million people are living with HIV infection today, and each year 2 million die of AIDS.
           Historians traditionally emphasize the role of war-fare in shaping human destiny; and the brilliance of leaders or the advantage of new technology, in determining which civilizations rise or fall. Yet the fate of human societies has often been determined by microbes. For example, much of the native population of North America was exterminated by smallpox introduced by European invaders. Throughout history, more soldiers have died of microbial infections than of wounds in battle. The significance of disease in warfare was first recognized by the British nurse and statistician Florence Nightingale (1820-1910) (Fig.1.11A). Better known as the founder of professional nursing, Nightingale also founded the science of medical statistics. She used methods invented by French statisticians to demonstrate the high mortality rate due to disease among British soldiers during the Crimean War. To show the deaths of soldiers due to various causes, she devised the "polar area chart" (Fig. 1.11B). Blue wedges represent deaths due to infectious disease, red wedges represent deaths due to wounds, and black wedges represent all other causes of death. Infectious disease accounts for more than half of all mortality. Before Nightingale's study, no one understood the impact of disease on armies, or on other crowded populations, such as cities. Nightingale's statistics convinced the British government to improve army living conditions and to upgrade the standards of army hospitals. In modern epidemiology, statistical analysis continues to serve as a crucial tool in determining the causes of disease.

Microbial Genomes Are Seqenced

Our understanding of microbes has grown tremendously through the study of their genomes. A genome is the total genetic information contained in an organism's chromosomal DNA (Fig. 1.6). By determining the sequence of genes in a microbe's genome, we learn a lot about how that microbe grows and associates with other species. For example, if a microbe's genome includes genes for nitrogenase, a nitrogen-fixing enzyme, that microbe probably can fix nitrogen from the atmosphere into compounds that plants can assimilate into protein. And by comparing DNA sequences, we can measure the degree of relatedness between different species based on the time since they diverged from a common ancestor. Historically, the first genomes to be sequenced were those of viruses. The first genome whose complete DNA sequence was determined was that of a bacteriologic (a virus that infects bacteria), bacteriologic +X174. The DNA sequence of 0174 was determined in 1977 by Fred Sanger (Fig. 1.7A), who shared the 1980 Nobel Prize in Chemistry with Walter Gilbert and Paul Berg for developing the method of DNA sequence analysis. The genome of bacteriophage 40074 includes over

From Germ tom Genome: WhatIs a Microbe?

From early childhood, we hear that we are surrounded by microscopic organisms, or "germs," that we can not see. What are microbes? Our modern concept of a microbe has deepened through two major research tools: advanced microscopy and the sequencing of gnomic DNA. Microscopy is covered in Chapter 2, and microbial genetics and genomics are presented in Chapters 7-12.

A Microbe Is a Microscopic Organism

A microbe is commonly defined as a living organism that requires a microscope to be seen. Microbial cells range in size from millimeters (mm) down to 0.2 micrometer (pm),

and viruses may be tenfold smaller (Table 1.1). Some microbes consist of a single cell, the smallest unit of life, a membrane-enclosed compartment of water solution containing molecules that carry out metabolism. Each microbe contains in its genome the capacity to reproduce its own kind. Our simple definition of a microbe, however, leaves us with contradictions.

■ Super-size microbial cells. Most single-celled organisms require a microscope to render them visible and thus fit the definition of a microbe. Nevertheless, some species of protists and algae, and even some bacterial cells, are large enough to see with the naked eye. The marine sulfur bacterium Thiomargarita namibiensis, called the sulfur pearl of Namibia, grows as large as the head of a fruit fly (Fig.1.4). Even more surprising, a single-celled plant, the "killer alga" Caulerpa taxifolia, spreads through the coastal waters of California. The single cell covers many acres with its leaflike cell parts.

 ■ Microbial communities. Many microbes form complex multi cellular assemblages, such as mushrooms, kelp's, and boffins. In these structures, cells are differentiated into distinct types that complement each others function, as in multi cellular organisms. And yet, some multi cellular worms and arthropods
require a microscope to see but are not considered microbes.

 ■ Viruses. A virus consists of a non cellular particle containing genetic material that takes over the metabolism of a cell to generate more virus particles. Some viruses consist of only a few molecular parts, whereas others, such as the Mimi virus infecting amebas (also spelled "amoebae"), show the size and complexity of a cell. Although viruses are not fully functional cells, the Mimi virus genome shows that it evolved from a cell.

In practice, our definition of a microbe derives from tradition as well as genetic considerations. In this book, we consider microbes to include prokaryotes (cells lacking a nucleus, including bacteria and archaea) as well as certain classes of eukaryotes (cells with a nucleus) that include simple multi cellular forms: algae, fungi, and protists (Fig. 1.5). The bacteria, archaea, and eukaryotes known as the three domains diverged from a common ancestral cell. We also discuss viruses and related infectious particles (Chapters 6 and 11).

ORIGIN AND DISCOVERY

Life on Earth began early in our planet's history with microscopic organisms, or microbes. Microbial life has since shaped our atmosphere, our geology, and the energy cycles of all ecosystems. A human body contains ten times as many microbes as it does human cells, including numerous tiny bacteria on the skin and in the digestive tract. Throughout history, humans have had a hidden partnership with microbes ranging from food production and preservation to mining for precious minerals. Yet throughout most of our history, humans were unaware that microbes even existed. To study these unseen organisms required a microscope, first developed in the 1600s. In the nineteenth century the "golden age" of microbiology microscopes revealed the tiny organisms at work in our bodies and in our ecosystems. The twentieth century saw the rise of microbes as the engines of biotechnology. Microbial discoveries led to recombinant DNA and revealed the secrets of the first sequenced genomes.         In 2008, the Phoenix Mars lander arrived at the north pole of the planet Mars (Fig. 1.1). The lander carried scientific instruments to study the history of water in Martian soil and search for evidence of microbial life. Its robotic instruments tested the soil for life-supporting elements such as carbon, nitrogen, phosphorus, and hydrogen. The discovery of surface water in the form of frost supported the possible existence of living microbes. Why do we care whether microbes exist on Mars? The discovery of life beyond Earth would fundamentally change how we see our place in the universe. The observation of Martian life could yield clues as to the origin of our own biosphere and expand our knowledge of the capabilities of living cells on our own planet. As of this writing, the existence of microbial life on Mars remains unknown, but here on Earth, many terrestrial microbes remain as mysterious as Mars. Barely 0.1% of the microbes in our biosphere can be cultured in the laboratory; even the digestive tract of a newborn infant contains species of bacteria unknown to science. Our "exploration rovers" for microbiology include, for example, new tools of microscopy and the sequencing of microbial DNA. On Earth, the microscope reveals microbes through out our biosphere, from the super heated black smoker vents at the ocean floor to the subzero ice fields of Antarctica. Bacteria such as Escherichia coli live in our intestinal tract, while algae and cyanobacteria turn ponds green (Fig. 1.2). Protists are the predators of the microscopic world. And viruses such as influenza virus cause disease, as do many bacteria and protists. Yet before microscopes were developed in the seventeenth century, we humans were unaware of the unseen living organisms that surround us, that float in the air we breathe and the water we drink, and that inhabit our own bodies. Microbes generate the very air we breathe, including nitrogen gas and much of the oxygen and carbon dioxide. They fix nitrogen for plants, and they make vitamins, such as vitamin B12. In the ocean, microbes produce biomass for the food web that feeds the fish we eat; and microbes consume toxic wastes such as oil from the Deepwater Horizon spill in 2010. At the same time, virulent pathogens take our lives. Despite all the advances of modern medicine and public health, microbial disease remains the number one cause of human mortality. history of fresh news on ORIGIN AND DISCOVERY In the twentieth century, the science of microbiology exploded with discoveries, creating entire new fields such as genetic engineering. The promise and pitfalls were dramatized by Michael Crichton's best selling science fiction novel and film The Andromeda Strain (1969; filmed in 1971). In The Andromeda Strain, scientists at a top-secret laboratory race to identify a deadly pathogen from outer space or perhaps from a biowarfare lab (Fig. 13A). The film prophetically depicts the computerization of medical research, as well as the emergence of pathogens, such as the human immunodeficiency virus (HIV), that can yet defeat the efforts of advanced science.
       Today, we discover surprising new kinds of microbes deep underground and in places previously thought uninhabitable, such as the hot springs of Yellowstone National Park (Fig. 1.3B). These microbes shape our biosphere and provide new tools that impact human society. For example, the use of heat-stable bacterial DNA polymerase (a DNA-replicating enzyme) in a technique called the polymerase chain reaction (PCR) allows us to detect minute amounts of DNA in traces of blood or fossil bone. Microbial technologies led us from the discovery of the double helix to the sequence of the human genome, the total genetic information that defines our species. In Chapter 1, we introduce the concept of a microbe and the question of how microbial life originated. We then survey the history of human discovery of the role microbes play in disease and in our ecosystems. Finally, we address the exciting century of molecular microbiology, in which microbial genetics and genomics have transformed the face of modern biology and medicine.