SECTION OBJECTIVES
How have microbes changed the course of human history? Before microscopes were developed by Hooke and Leeuwenhoek (Section 1.1), 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. Yet microbes have molded human culture since our earliest civilizations. Yeasts and bacteria made foods such as bread and cheese, as well as alcoholic beverages (Figure 1.4A). “Rock-eating” bacteria known as lithotrophs leached copper and other metals from ores exposed by mining, enabling ancient human miners to obtain these metals. Today, bacterial leaching produces about 20% of the world’s copper. Unfortunately, microbial acid consumes the stone of ancient monuments (Figure 1.4B), a process intensified by airborne acidic pollution.
A photo of Roquefort cheese rounds ripening in France from the productive activity of microbes. Numerous pale yellow to white cheese rounds are arranged in a stone cellar. A scientist checks the quality of one of the rounds. The scientist is wearing a white lab coat and a hair net.
A photo of decay on the hair of a statue from the destructive activity of microbes. The photo is focused on a region of the statue’s head, showing one eye, an ear, and the hair. The statue is carved from smooth light grey to white rock. Dark spots mottle the outer surface. One region of the hair is orange and roughened where advanced decay has set in.
As we became aware of microbes, our relationship with the microbial world changed in important ways (Table 1.1). Early scientists in the seventeenth and eighteenth centuries used microscopes to discover the existence of microbes and revealed 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.
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Table 1.1 Microbes and Human History |
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Date |
Microbial Discovery |
Discoverer(s) |
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Microbes Impact Human Culture without Detection |
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10,000 BCE |
Food and drink are produced by microbial fermentation. |
People of Africa and Asia |
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1500 BCE |
Tuberculosis, polio, leprosy, and smallpox are evident in mummies and tomb art. |
People of Africa and Asia |
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1000 CE |
Smallpox immunization is accomplished by transfer of secreted material. |
People of Africa and Asia |
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1025 CE |
Quarantine was invented to prevent spread of disease. |
Avicenna, or Ibn Sina (Persia) |
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1300–1400 CE |
The Black Death (bubonic plague) kills 17 million people in Europe and Asia. |
Saint Catherine of Siena nursed plague victims (Italy). |
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Early Microscopy and Microbial Disease |
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1676 |
Microbes are observed under a microscope. |
Antonie van Leeuwenhoek (Netherlands) |
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1717 |
Smallpox is prevented by inoculation of pox material, a rudimentary form of immunization. |
Lady Montagu brought from Turkey to England, and Onesimus brought from Africa to New England |
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1765 |
Microbes fail to grow after boiling in a sealed flask; evidence against spontaneous generation. |
Lazzaro Spallanzani (Padua) |
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1798 |
Cowpox vaccination prevents smallpox. |
Edward Jenner (England) |
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“Golden Age” of Microbiology as Science |
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1847–1867 |
Antisepsis prevents patient death during surgery and childbirth. |
Ignaz Semmelweis (Hungary) and Joseph Lister (England) |
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1855–1867 |
Statistics show that poor sanitation leads to mortality (Crimean War). |
Florence Nightingale (England) |
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1857–1881 |
Microbial fermentation produces lactic acid or alcohol. Microbes fail to appear spontaneously, even in the presence of oxygen. The first artificial vaccine is developed (against anthrax). |
Louis Pasteur (France) |
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1877–1884 |
Bacteria are a causative agent in developing anthrax. The first pure isolate, Mycobacterium tuberculosis, is cultured on a solid medium. Koch’s postulates demonstrate the microbial cause of diseases (anthrax and tuberculosis). |
Robert Koch (Germany) |
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1884 |
Gram stain is devised to distinguish bacteria from human cells. |
Hans Christian Gram (Denmark) |
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1889–1899 |
The concept of a virus is proposed to explain tobacco mosaic disease. |
Martinus Beijerinck (Netherlands) |
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Biochemistry, Genetics, and Medicine |
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1900 |
Yellow fever is shown to be transmitted by mosquitoes. |
Walter Reed (USA) and Carlos Finlay (Cuba) |
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1908 |
Antibiotic Salvarsan is synthesized to treat syphilis (chemotherapy). |
Paul Ehrlich (USA) and Sahachirō Hata (Japan) |
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1911 |
Cancer in chickens can be caused by a virus. |
Francis Peyton Rous (USA) |
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1918 |
Influenza A pandemic kills 50 million people worldwide. |
Worldwide |
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1928 |
Streptococcus pneumoniae bacteria are transformed by a genetic material from dead cells. |
Frederick Griffith (England) |
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1929 |
Penicillin, the first widely successful antibiotic, is made by a fungus. |
Alexander Fleming (Scotland), Howard Florey (Australia), and Ernst Chain (Germany) |
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1941 |
One gene encodes one enzyme in Neurospora (bread mold). |
George Beadle and Edward Tatum (USA) |
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1941 |
Poliovirus is grown in human tissue culture. |
John Enders, Thomas Weller, and Frederick Robbins (USA) |
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1944 |
DNA is the genetic material that transforms Streptococcus pneumoniae. |
Oswald Avery, Colin MacLeod, and Maclyn McCarty (USA) |
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1948 |
Protein structure of the alpha helix is discovered by X-ray crystallography. |
Herman Branson, Linus Pauling, and Robert Corey (USA) |
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1952 |
DNA is injected into a cell by a bacteriophage. |
Martha Chase and Alfred Hershey (USA) |
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Molecular Biology and Medicine |
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1953 |
The overall structure of DNA is a double helix, based on X-ray crystallography. |
Rosalind Franklin and Raymond Gosling (England) |
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1953 |
Double-helical DNA consists of antiparallel chains connected by the hydrogen bonding of AT and GC base pairs. |
James Watson (USA) and Francis Crick (England) |
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1961 |
Biochemical energy is stored in a proton gradient across the membrane of bacteria, mitochondria, and chloroplasts. |
Peter Mitchell and Jennifer Moyle (England) |
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1968 |
Serial endosymbiosis explains the evolution of mitochondria and chloroplasts. |
Lynn Margulis (USA) |
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1969 |
Retroviruses contain reverse transcriptase, which copies RNA to make DNA. |
Howard Temin, David Baltimore, and Renato Dulbecco (USA) |
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1953–1971 |
Oral rehydration therapy (ORT) is developed for dehydration due to diarrhea and cholera, saving millions of lives. |
Hemendra Chatterjee and Dilip Mahalanabis (India); Robert Phillips (USA) |
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1973 |
A recombinant DNA molecule is made in vitro (in a test tube). |
Annie Chang, Stanley Cohen, Robert Helling, and Herbert Boyer (USA) |
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1977 |
A DNA sequencing method is invented and used to sequence the first genome of a virus. |
Frederick Sanger, Walter Gilbert, and Allan Maxam (USA) |
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1977 |
Archaea are a third domain of life, the others being Bacteria and Eukaryotes. |
Carl Woese (USA) |
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1979 |
Smallpox is declared eliminated—the culmination of worldwide efforts of immunology, molecular biology, and public health. |
World Health Organization |
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Genomics and Medicine |
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1981 |
The polymerase chain reaction (PCR) makes available large quantities of DNA. |
Kary Mullis (USA) |
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1981–1983 |
AIDS pandemic begins (continues into present). Human immunodeficiency virus (HIV) is discovered as the cause of AIDS. |
Françoise Barré-Sinoussi and Luc Montagnier (France), Robert Gallo (USA), and others |
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1993 |
Gene therapy using a vector derived from HIV succeeds in treating severe combined immunodeficiency disorder (SCID). |
Donald Kohn and others (USA) |
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1995 |
The first bacterial genome is sequenced: Haemophilus influenzae. |
Craig Venter, Hamilton Smith, Claire Fraser, and others (USA) |
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1988–2013 |
Fecal microbiota transplant cures intestinal infections of drug-resistant Clostridioides difficile (CDI). |
Thomas Borody and others (Australia and USA) |
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2014 |
Human Microbiome Project releases first compilation of microbes associated with healthy human bodies. |
National Institutes of Health (USA) |
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2019 |
CRISPR gene editing is used to treat human patients for multiple myeloma, a cancer of white blood cells. |
University of Pennsylvania |
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2019–2023 |
COVID-19 coronavirus is discovered and causes pandemic respiratory illness. |
Li Wenliang (China) |
Historians traditionally emphasize the role of warfare in shaping human history. Yet throughout history, more soldiers have died of microbial infections than of wounds in battle. Microbes have often determined the fate of human societies. For example, smallpox, carried by European invaders, exterminated much of the Native population of North America.
Throughout history, microbial diseases such as tuberculosis and leprosy have profoundly affected human demographics and cultural practices (Figure 1.5). 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, we fight this ancient disease by using modern antibiotics, chemicals that kill or slow growth of bacterial pathogens. But M. tuberculosisevolves to resist every antibiotic we use (discussed in Section 20.3). The emergence of multidrug-resistant (MDR) strains of disease-causing microbes is just one of the microbial challenges faced by health professionals.
A medieval painting of a church procession to ward off the Black Death or bubonic plague. Three people stand at the front of the procession with staffs and a flag. Several men in skirts and black hats follow behind, the first holding a crucifix.
A photo of the A I D S memorial quilt spread across the Washington Monument lawn. There are many quilts laid out, each panel memorializing an individual who died of A I D S. No gaps are left between the quilts and the conglomeration reaches into the distance with no end in sight.
Despite all the advances of modern medicine and public health, microbial infections remain the world’s leading cause of death in children. During the twentieth century, societies throughout the world were profoundly shaped by the pandemic of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV); in 2023, more than 38 million people worldwide were living with HIV. In 2019, a new pandemic pathogen emerged: the SARS-CoV-2 coronavirus, the cause of a pandemic viral disease now called COVID-19.
Before the nineteenth century, the role of microbes as infectious agents was unknown. But people had a sense that those suffering from diseases such as plague and leprosy were to be avoided. The rare individuals who chose to nurse such people were considered spiritual heroes. A prominent example is Catherine of Siena (1347–1380), who served God by nursing the sick (Figure 1.6). When a wave of bubonic plague swept the Italian city of Siena, Catherine and her followers stayed to care for the ill and bury the dead. After her death, Catherine of Siena was canonized and became known as the patron saint of nurses. In modern times, nursing continues to require personal courage—for instance, during our epidemics of AIDS and COVID-19, when populations of ill patients overwhelmed hospitals.
A historic painting of Catherine of Siena, patron saint of nurses. Catherine is pictured with a neck cloth and white veil and is holding a white flower. Her facial expression makes her look wise and dignified.
The observation of microscopic organisms led priests and philosophers to wonder where these organisms came from. In the eighteenth century, scientists and church leaders intensely debated the question of spontaneous generation, the theory that living microbes can arise spontaneously, without parental organisms. Some chemists supported spontaneous generation, arguing that microbes appear the same way chemicals precipitate from a solution. Christian church leaders, however, argued the biblical view that all organisms have “parents” going back to the first week of creation.
The Italian priest Lazzaro Spallanzani (1729–1799) sought to disprove the spontaneous generation of microbes. Spallanzani showed that a sealed flask of meat broth sterilized by boiling failed to grow microbes. The priest also noticed that microbes often appeared in pairs. Were these two parental microbes coupling to produce offspring, or did one microbe become two? Through long observation, Spallanzani watched a single microbe grow until it split in two. Thus he demonstrated cell fission, the process by which cells arise by the splitting of preexisting cells.
Spallanzani’s experiments, however, did not put the matter to rest. Supporters 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; Figure 1.7A). In addressing spontaneous generation and related questions, Pasteur and his contemporaries laid the foundations for modern microbiology.
A historic portrait photo of Louis Pasteur. Pasteur is seated and is wearing a formal suit and bowtie. His hair is neatly combed back. He has a dark, groomed beard cut short and close to his chin. A lab notebook sits open in his lap. He has a neutral expression on his face.
A labeled photo of Pasteur’s swan necked flask. The spherical shaped flask has a hollow tube connected to the top. The thin glass tube is bent into an S shape and is open to air. There is growth medium filling up about half of the spherical flask. The S shape of the tube excludes dust and microbes and keeps the growth medium free from microbial contamination, after boiling, despite access to air.
Pasteur began his career as a chemist. He was asked to help with a chemical problem encountered by French manufacturers of wine and beer. Alcoholic beverages are made by fermentation, a process by which microbes gain energy by converting sugars to alcohol. In the time of Pasteur, however, the role of microbes was unknown. 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.
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 a 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 (Figure 1.7B). The famous swan-necked flasks remained free of microbial growth for many years. Yet, when a flask was tilted to enable contact of broth with microbe-containing dust, microbes immediately grew. As a result, 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 appeared because some kinds of organic matter, particularly hay infusion (broth of dried grass, boiled), are contaminated 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 (212°F).
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 use of a steam pressure device called the autoclave became a standard way to sterilize materials required for the controlled study of microbes and for surgical procedures. (Microbial control and antisepsis are discussed further in Chapter 13.)
If all life on Earth shares descent from a microbial ancestor, how did the first microbe arise? 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 earliest fossil evidence of cells in the geological record appears in sedimentary rock that formed over 2 billion years ago.
The components of the first living cells may have formed from spontaneous reactions sparked by ultraviolet absorption or electrical discharge. Such “early-Earth” conditions were simulated in 1953 during famous experiments by chemist Stanley Miller (1930–2007). Miller combined hydrogen gas, methane, and ammonia and applied an electrical discharge (comparable to a lightning strike), which generated simple amino acids such as glycine and alanine. Similar experiments conducted in 1961 by Spanish-American researcher Joan Oró (1923–2004) combined hydrogen cyanide and ammonia under electrical discharge to obtain adenine, a fundamental component of DNA and of the energy carrier, adenosine triphosphate (ATP). These small organic molecules are also found in meteorites. Thus, chemical reactions both on Earth and in outer space could have generated the fundamental components of life—but how they assembled into living cells remains a mystery.
SECTION SUMMARY