Textbook of Microbiology Surinder Kumar
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1General Bacteriology2

Historical Development of MicrobiologyCHAPTER 1

History is bunk—(Henry Ford 1863–1947)
In the field of observation, chance favors only prepared minds–Louis Pasteur
 
INTRODUCTION
Microbiology is the study of living organisms of microscopic size. Medical microbiology is the subdivision concerned with the causative agents of infectious disease of man, the response of the host to infection and various methods of diagnosis, treatment and prevention. The term microbe was first used by Sedillot in 1878, but now is commonly replaced by microorganisms.
 
INFECTION AND CONTAGION
 
Ancient Belief
Among ancient peoples, epidemic and even endemic diseases were believed to be supernatural in origin, sent by the gods as punishment for the sins of human kind. Sacrifices and lustrations to appease the anger of the gods were sought for the treatment and, more important, the prevention of disease. There was never any difficulty in finding particular sets of sins to justify a specific epidemic since humans are wilful and wantom by nature.
 
Concept of Contagion
Long before microbes had been seen, observations on communicable diseases had given rise to the concept of contagion: The spread of disease by contact, direct or indirect. This idea was implicit in the laws enacted in early biblical times to prevent the spread of leprosy.
 
Invisible Living Creatures Produced Disease
Varro in the second century BC later recorded the principle of contagion by invisible creatures. Roger Bacon, in the thirteenth century more than a millennium later, postulated that invisible living creatures produced disease. Fracastorius (1546), a physician of Verona concluded that communicable diseases were caused by living agents (germs) ‘seminaria’ or ‘seeds’. Kircher (1659) reported finding minute worms in the blood of plague victims, but with the equipment available to him, it is more likely that what he observed were only blood cells. von Plenciz (1762) suggested that each disease was caused by a separate agents.
 
DISCOVERY OF MICROORGANISMS
Even before microorganisms were seen, some investigators suspected their existence and responsibility for disease. Among others, the Roman philospher Lucretius (about 98-55 BC) and the physician Girolamo Fracastoro (1478–1553) suggested that disease was caused by invisible living creatures.
 
First Observation of Microorganisms
As microbes are invisible to the unaided eye, direct observation of microorganisms had to await the development of the microscope.
 
Antony van Leeuwenhoek (1632–1723)
The credit for having first observed and reported bacteria belongs to Antony van Leeuwenhoek. Antoni van Leeuwenhoek, the Dutchman, was a draper and haberdasher in Delft, Holland. He had little education, but great patience and curiosity. His hobby was grinding lenses and observing diverse materials through them. He was the amateur microscopist and was the first person to observe microorganisms (1673) using a simple microscope. In 1683 he made accurate descriptions of various types of bacteria and communicated them to the 4Royal Society of London. Their importance in medicine and in other areas of biology came to be recognized two centuries later.
 
Contributions of Antony von Leeuwenhoek
  1. He constructed the first microscope: Consisted of a single biconvex lens that magnified about x200.
  2. The first person to observe microorganisms: Microorganisms were first seen by Antony van Leeuwenhoek (1673) and he found many microorganisms in materials such as water, mud, saliva and the intestinal contents of healthy subjects, and he recognized them as living creatures (animalcules) and to Leeuwenhoek the world of “little animalcules” represented only a curiosity of nature.
  3. Accurate description of bacteria: He first accurately described the different shapes of bacteria as cocci (spheres), bacilli (rods) and spirochetes (spiral filaments) and communicated them to Royal Society of London in 1683.
 
CONFLICT OVER SPONTANEOUS GENERATION
 
Spontaneous Generation (Abiogenesis)
From earliest times, people had believed in spontaneous generation (abiogenesis) that living organisms could develop from nonliving matter. Even great Aristotle (384-322 BC) thought animal could originate from the soil. This view was finally challenged by the Italian physician Francesco Redi (1626–1697) and proved that gauze placed over jar containing meat prevented maggots forming the meat. Similar experiments by others helped discredit the theory for larger organisms.
 
Evidence Pro
Some proposed that microorganisms arose by spontaneous generation though larger organisms did not. John Needham (1713–1781 the English priest) in 1745, published experiments purporting the spontaneous generation (abiogenesis) of microorganisms in putrescible fluids. Felix Pouchet (1859), the French naturalist, claimed to have carried out experiments conclusively proving that microbial growth could occur without air contamination. This claim provoked Louis Pasteur (1822–1895) to settle the matter once and for all.
 
Evidence Con
Spontaneous Generation Experiment: Lazzaro Spallanzani (1729–1799), an Italian priest and naturalist opposed this view who boiled beef broth for an hour, sealed the flasks, and observed no formation of microbes. Franz Schulze (1815–1873), Theodore Schwann (1810–1882), Georg Friedrich Schroder and Theodor von Dusch attempted to counter such arguments.
Louis Pasteur (1822–1895) settled the matter once and for all. In a series of classic experiments, Pasteur proved conclusively that all forms of life, even microbes, arose only from their like and not de novo. Pasteur was able to filter microorganisms from the air and concluded that this was the source of contamination and finally, in 1859, in public controversy with Pouchet, prepared boiled broth in flasks with long narrow gooseneck tubes that were open to the air. Air could pass but microorganisms settled in the gooseneck, and no growth developed in any of the flasks. If the necks were broken, growth commenced immediately. Pasteur had not only resolved the controversy by 1861 but also had shown how to keep solution sterile.
Tyndallization—John Tyndall (1820–1893): John Tyndall (1820–1893), the English physicist finally, dealt a final blow to spontaneous generation in 1877. He completed the story by proving that dust did not indeed carry germs and that if dust was absent, broth remained sterile if directly exposed to air. He was able to explain satisfactorily the need for prolonged heating to eliminate microbial life from infusions.
Heat stable form and a heat-sensitive form—He exposed infusions to heat for varying time and concluded that bacteria existed in two forms: a heat stable form and a heat-sensitive form. Heat-stable forms were destroyed either by prolonged or intermittent heating. Intermittent heating, now called tyndallization, killed both forms since the heat-stable forms changed to heat-sensitive forms between periods of heat treatment. This method of ‘tyndallization’ served to eliminate many of anomalies reported by the advocates of heterogenesis.
 
Heat-Resistant Forms as Spores
Ferdinand Cohn (1828–1898), the German botanist, discovered the evidence of heat-resistant forms as spores. Spores as well as vegetative forms were responsible for the appearance of microbial life in inadequately heated infusions.
 
ROLE OF MICROORGANISMS IN DISEASE
A firm basis for the casual nature of infectious disease was established only in the latter half of the nineteenth century. Fungi, being larger than bacteria, were the first agents to be recognized Agostino Bassi (1773–1856) demonstrated in 1835 that a silkworm disease called muscardine was due to a fungal infection. MJ Berkeley (1845) proved that the great potato blight of Ireland was caused by a fungus. Following his success with the study of fermentation, Pasteur was asked by French government to investigate the pebrine disease of silkworm that was disrupting the silk industry. He showed that the disease was due to a protozoan parasite after several years of work.
 
Empirical Observations
The etiologic role of bacteria was first established with anthrax. Pollender(1849) and Davaine (1850) observed anthrax bacilli in the blood of animals dying of the disease.5
Indirect transmission was recognized in the 1840s, when American poet-physician Oliver Wendell Holmes(1843) in Boston, USA and Ignaz Semmelweis in Vienna (1846) had independently concluded that puerperal sepsis was contagious. They blamed obstetricians moving with unwashed hands from one patient to the next for the prevalence of puerperal sepsis in hospitals.Semmelweis also identified its mode of transmission by doctors and medical students attending on women in labor in the hospital and had prevented it by the simple measure of washing hands in an antiseptic solution. But those pioneers encountered enormous resistance from the insulted physicians. Semmelweis was persecuted by medical orthodoxy and driven insane for the service to medicine and humanity.
Relationship of a Spirillum to relapsing fever—Obermeier (1872) discovered the relationship of a Spirillum to relapsing fever and demonstrated for the first time the presence of a pathogenic microorganism in the blood of a human being.
 
SCIENTIFIC DEVELOPMENT OF MICROBIOLOGY
The development of microbiology as a scientific discipline dates from Louis Pasteur, perfection on microbiological studies by Robert Koch, the introduction of antiseptic surgery by Lord Lister and contributions of Paul Ehrlich in chemotherapy.
 
Louis Pasteur (1822–95)
Louis Pasteur (1822–95) was born in the village of Dole, France on December 27, 1822 the son of humble parents. His father was a tanner. He was originally trained as a chemist, but his studies on fermentation led him to take interest in microorganisms. His discoveries revolutionized medical practice, although he never studied medicine.
Father of microbiology—Louis Pasteur (Fig. 1.1) is known as “Father of microbiology”because his contribution led to the development of microbiology as a separate scientific discipline.
 
Contributions of Louis Pasteur in Microbiology (Box 1.1)
  1. Coined the term microbiology.
  2. Proposed germ theory of disease.
  3. Disapproved theory of spontaneous generation.
  4. Developed sterilization techniques.
  5. Developed methods and techniques for cultivation of microorganisms.
  6. Studies on pebrine (silk worm disease), anthrax, chicken cholera and hydrophobia.
  7. Pasteurization.
  8. Coined the term vaccine.
  9. Discovery of attenuation and chicken cholera vaccine.
  10. Developed live attenuated anthrax vaccine.
    zoom view
    Fig. 1.1: Louis Pasteurt
  11. Developed rabies vaccine.
  12. Noticed Pneumococci.
 
Joseph Lister (1827–1912)
Joseph Lister was a professor of Surgery in Glasgo Royal Infirmary. He was impressed with Pasteur's study on the involvement of microorganisms in fermentation and putrefaction.
  • Developed a system of antiseptic surgery—He developed a system of antiseptic surgery designed to prevent microorganisms from entering wounds. The approach was remarkably successful and transformed surgery after Lister published his findings in 1867. It also provided strong evidence for the role of microorganism in disease because phenol, which killed bacteria, also prevented wound infections.
  • Father of modern surgery—He established the guiding principle of antisepsis for good surgical practice and was milestone in the evolution of surgical practice from the era of ‘laudable pus’ to modern aseptic techniques. For this work he is called the “Father of modern surgery”
 
Robert Koch (1843–1910)
Robert Koch (Fig. 1.2) was the German physician. The first direct demonstration of the role of bacteria in carrying disease came by the study of anthrax by Koch. Winner of the Nobel Prize in 1905, Robert Koch is known as “Father of bacteriology”.
 
Contributions of Robert Koch
  1. Staining techniqes: He described methods for the easy microscopic examination of bacteria in dried, fixed films stained with aniline dyes (1877).
  2. Hanging drop method: He was the first to use hanging drop method by studying bacterial motility.
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  1. Methods for isolating pure cultures of bacteria: He devised a simple method for isolating pure cultures of bacteria by plating out mixed material on a solid culture medium and to isolate pure cultures of pathogens.
  2. Discoveries of the causal agents of anthrax (1876), tuberculosis (1882), and cholera (1883).
  3. Koch's postulates: It was necessary to introduce criteria for proving the claims that a microorganism isolated from a disease was indeed causally related to it. Robert Koch proved that microorganisms cause disease. Koch used the criteria proposed by his former teacher, Jacob Henle (1809–1885), to establish the relationship between Bacillus anthracis and anthrax and published his findings in 1876. (Fig. 1.3). His criteria for proving the causal relationship between a microorganism and a specific disease are known as Koch's postulates (1876), which are used today to prove that a particular microorganism causes a particular disease (Box 1.2).
  4. Koch's phenomenon: Koch (1890) observed that a guinea pig already infected with the bacillus responded with an exaggerated response when injected with the tubercle bacillus or its protein. This hypersensitivity reaction is known as Koch's phenomenon.
zoom view
Fig. 1.2: Robert Koch
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Important Discoveries by other Scientists
Koch began to gather round him the group of followers who were destined to introduce his methods into many laboratories throughout the world. Hansen (1874) described the leprosy bacillus; Neisser (1879) discovered the gonococcus in the pus discharge from urethra; Eberth (1880) observed the typhoid bacillus; Alexander Ogston (1881) described the staphylococci in abscess and suppurative lesions; Loeffler (1884) observed and described the diphtheria bacillus; Nicolaier (1884) observed the tetanus bacillus in soil; Rosenbach (in 1886) demonstrated the tetanus bacillus with round terminal spore; Fraenkel (1886) described the pneumococcus; in 1887 Weichselbaum described and isolated the meningococcus from the spinal fluid of a patient; in 1887 Bruce identified the causative agent of malta fever; in 1905 Schaudin and Hoffman discovered the syphilis.
 
GOLDEN ERA OF MEDICAL BACTERIOLOGY
Koch's postulates permitted Koch and his students to identify many of the causes of the most infectious diseases of humans and animals. Koch had now assembled the techniques needed to investigate the bacterial causes of many communicable diseases. The powerful methodology developed by Koch introduced the “Golden era of medical bacteriology”. By 1882 Koch had used these techniques to isolate bacillus of tuberculosis. There followed a golden era of 30 to 40 years in which most of the major bacterial pathogens were isolated.
zoom view
Fig. 1.3: Demonstration of Koch's postulates
 
PAUL EHRLICH (1854–1915)
Paul Ehrlich, an outstanding German Scientist and genius of extraordinary activity also known as “Father of chemotherapy”.
 
Contributions of Paul Ehrlich
  1. Stains to cells and tissues: He applied stains to cells and tissues for the purpose of revealing their function.
  2. Acid-fastness of tubercle bacillus: He reported the acid-fastness of tubercle bacillus.
  3. Methods of standardizing toxin and antitoxin: He introduced methods of standardizing toxin and antitoxin and coined the term minimum lethal dose.
  4. Side chain theory of antibody production: He proposed side chain theory of antibody production.
  5. Salvarsan introduction: He introduced salvarsan, an arsenical compound, sometimes called the ‘magic bullet’. It was capable of destroying the spirochete of syphilis with only moderate toxic effects. He continued his experimentation until 1912 when he announced the discovery of neosalvarsan. Thus 8he created a new branch of medicine known as chemotherapy.
 
GOLDEN AGE OF MICROBIOLOGY (1854–1914)
For about 60 years, beginning with the work of Pasteur, there was an explosion of discoveries in microbiology. The period from 1854 to 1914 has been appropriately named the Golden Age of Microbiology. During this period, rapid advances, spearheaded mainly by Pasteur and Robert Koch, led to the establishment of microbiology as a science.
 
DISCOVERY OF VIRUSES
As a science, virology evolved later than bacteriology. Although the physical nature of viruses was not fully revealed until the invention of the electron microscope, the infections they cause have been known and feared since the dawn of history.
 
Infectious Agents Smaller than Bacteria
The existence of viruses became evident during the closing years of the nineteenth century, the infectious agents of numerous diseases were being isolated and many infectious diseases had been proved to be caused by bacteria. But there remained a large number of diseases for which no bacterial cause could be established until it was realized that the responsible agents were smaller than bacteria.
 
Various Infections
 
Rabies in Dogs
Pasteur had suspected that rabies in dogs could be caused by a microbe too small to be seen under the microscope.
 
Tobacco Mosaic Disease
Iwanowski (1892), Russian scientist and Martinus Beijrinck(1898) in Holland, attributed the cause of tobacco- mosaic disease to the infectious agents in bacteria-free filtrates to be living, but fluid—contagium vivum fluidum and introduced the term virus (Latin for ‘poison’) for such filterable infectious agents.
 
Foot and Mouth Disease of Cattle
Friedrich Loeffler and Paul Frosch at the same time in 1898 in Germany found that foot and mouth disease of cattle was also caused by a similar filter-passing virus.
 
Yellow Fever
The discovery of first human disease proved to have a viral etiology was yellow fever. The US Army Yellow Fever Commission under Walter Reed in Cuba (1902) showed that this human disease (yellow fever) was not only a filterable virus, but also transmitted through the bite of infected mosquitos.
 
Electron Microscope
Viruses could not be visualized under the light microscope or grown in culture media so investigation of viruses and the disease caused by them was rendered difficult. Larger viruses could be seen under light microscope after appropriate staining, but their detailed morphology could only be studied by electron microscope by Ruska (1934).
 
Cultivation of Viruses
The technique of growing them on chick embryos was developed by Goodpasture in 1930s. The use of living human and animal tissue cells for the in vitro culture of viruses was developed by John Enders (1949) and others.
 
Virus infection and malignancy
 
Leukemia
Vilhelm Ellerman and Oluf Bang (1908) in Copenhagen put forth the possibility that virus infection could lead to malignancy by reporting that leukemia could be transmitted between chickens by cell-free filtrates.
 
Sarcoma in Fowls
Peyton Rous(1911) three years later isolated a virus causing sarcoma in fowls. Several viruses have been blamed to cause natural and experimental tumors in birds and animals. Viruses also cause malignant transformation of infected cells in tissue culture.
 
Viral Oncogenesis
The discovery of viral and cellular oncogenes have put forth the possible mechanisms of viral oncogenesis. Positive proof a virus causing of human malignancy was established when the virus of human T-cell leukemia was isolated in 1980.
 
Bacteriophages
Frederick W Twort (1915) and Felix d’ Herelle (1917) independently discovered a lytic phenomenon in bacterial cultures. The agents responsible were termed bacteriophages (virus that attack bacteria). The discipline of molecular biology owes it origin largely to studies on the genetics of bacteriophages and bacteria.
 
IMMUNITY AND IMMUNIZATION
 
Ancient Knowledge
It was known from ancient times since the time of the ancient Greeks that people who have suffered from a distinctive disease, such as smallpox, measles, plague, yellow fever and various other infectious diseases, resisted it on subsequent exposures and rarely contract it second time. The practice of producing a mild form of smallpox intentionally (variolation) was prevalent in India, China and other ancient civilizations from time immemorial.
 
Edward Jenner (1749–1823)
The first scientific attempts at artificial immunizations in the late eighteenth century by Edward Jenner (1749–1823) from England. He observed the immunity to smallpox in milkmaids who were exposed to 9occupational cowpox infection, introduced the technique of vaccination using cowpox material (1796). It was on May 14, 1796, that Jenner extracted the contents of a pustule from the arm of a cowpox-infected milkmaid, Sarah Nelmes, and injected it into the arm of eight- year-old James Phipps. Jenner's vaccination paved the way for the ultimate eradication of smallpox. Edward Jenner is known as the “Father of immunology”.
 
Live Vaccines
Further work on immunization was carried out by Louis Pasteur and derived attenuated (reduced in virulence) live vaccines for fowl cholera, anthrax, swine erysipelas and rabies. He called them vaccine in honor of Jenner's work with cowpox or vaccinia (Latin vacca for cow). In 1881 he made a convincing controlled trial of his anthrax vaccine. Today, attenuated live vaccines are used with outstanding success against such diseases as tuberculosis, poliomyelitis, measles and yellow fever.
 
Vaccine for Hydrophobia
Pasteur's development of a vaccine for hydrophobia made the greatest impact in medicine. This was acclaimed throughout the world. The Pasteur Institute, Paris was built by public contributions and similar institutions were established soon in many other countries for the preparation of vaccines and for the investigation of infectious diseases.
 
Antibodies and Complement
Nuttal (1888) observed that defibrinated blood had a bactericidal effect and Buchner (1889) noticed that this effect was abolished by heating the sera for one hour at 55°C. This heat-labile bactericidal factor was termed ‘alexine’. The first step in elucidating the mechanisms of acquired immunity was the discovery of antibodies by Emil von Behring and Shibasaburo Kitasato (1890) in the sera of animals which had received sublethal dose of diphtheria or tetanus toxoid. Pfeiffer (1893) demonstrated bactericidal effect in vivo by injecting live cholera vibrios intraperitoneally in guinea pigs previously injected with killed vibrios. Bordet (1895) proved the humoral nature of such activity. He defined two components in this reaction, the first being heat stable substance ‘antibody’ found in the immune sera and the second being heat labile identical with Buchner's alexine, subsequently named ‘complement’.
 
Cellular Concept of Immunity
Elie Metchnikoff (1883) discovered the phenomenon of phagocytosis and developed the cellular concept of immunity. Paul Ehrlich hypothesized that immunity could be explained by presence of noncellular components of blood. Wright (1903) discovered opsonization, in which antibodies and phagocytic cells act in conjunction. Both Metchnikoff and Ehrlich shared a Nobel Prize in 1908 for their contributions to the emerging science of immunology. The pioneering work of Landsteiner laid the foundation of immunochemistry.
 
Allergy
Koch's phenomenon: Koch (1890) had noticed that when the tubercle bacillus or its protein was injected into a guinea pig already infected with the bacillus, an exaggerated response took place—a hypersensitivity reaction known as Koch's phenomenon.
Anaphylaxis: Portier and Richet (1902), studying the effect of the toxic extracts of sea anemones in dogs made the paradoxical observation that dogs which had prior contact with the toxin were, abnormally sensitive to even minute quantities of it subsequently. This phenomenon was termed anaphylaxis and led to the development of the discipline of allergy.
 
Selection Theory of Antibody
In 1955, Jerne proposed the ‘natural selection theory’ of antibody synthesis. Burnet (1957) modified this into clonal selection theory.
 
Immunological Surveillance
Burnet (1967) developed the concept of immunological surveillance based on the original suggestion of Thomas (1959), according to which the primary function of the immune system is to preserve the integrity of the body, seeking and destroying all ‘foreign antigens’. Malignancy was thought to be a failure of this function.
 
Transplantation
Another aspect of this role of immunity is in the rejection of homografts. Understanding of the immunological basis of transplantation, largely due to the work of Medawar and Burnet, made successful transplants possible by elective immunosuppression and proper selection of donors based on histocompatibility.
 
SEROTHERAPY AND CHEMOTHERAPY
 
Antisera
The work of Behring and Kitasato led to the successful use of antisera raised in animals for the treatment of patients with diphtheria, tetanus, pneumonia and other diseases. Antisera were the only specific therapeutic agents available for the management of infectious diseases till Domagk (1935) initiated scientific chemotherapy with the discovery of prontosil.
 
Magic Bullet
Ehrlich (1909) discovered salvarsan (arsphenamine),sometimes called the ‘magic bullet’ was capable of destroying the spirochete of syphilis with only moderate toxic effects. In 1912 he announced the discovery of neosalvarsan. This gave him the title, “Father of chemotherapy”.
 
Antibiotics—A Fortunate Accident
The modern era of antibiotics developed only after Gerhard Domagk (1895–1964) found that prontosil 10(the forerunner of sulfonamides) had a dramatic effect on streptococcal infection in 1935. Sir Alexander Fleming (1881–1955) made accidental discovery that the fungus Penicillium notatum produces a substance which destroys staphylococci. In the 1940s, Florey and Chain and their associates demonsrates its clinical value. This was the beginning of the antibiotics era. Selman Waksman exploited the potential for antibiotic production among soil microorganisms in the 1940s. Within 25 years of these discoveries, most of the major groups of antimicrobial agents had been recognized and more recent developments have chiefly involved chemical alteration of existing molecules.
 
Microbes Control is Far more Difficult
The global eradication of smallpox inspired visions of similar campaigns against other major pestilences. But it was realized that controlling microbes was a far more difficult than was imagined when new infectious diseases began to appear. Unceasing vigilance appears essential to protect man from microbes because of problems of emergence of drug resistance and appearance of new agents of infectious disease. The most notorious of these is undoubtedly the human immunodeficincy virus (HIV), the causative agent of acquired immune deficiency sndrome (AIDS). The rise and fall of AIDS produces a sobering reminder of the potential impact of microbial disease.
 
DEVELOPMENT OF MOLECULAR BIOLOGY AND MOLECULAR GENETICS
 
Molecular Biology
Oswald Avery with Colin Macleod and Maclyn Mc-Carty in 1944 showed that deoxyribonucleic acid (DNA) transformed nonvirulent pneumococci to virulent organisms. This discovery of chemical nature of hereditary material heralded the beginning of the merger of microbiology and molecular biology
 
Recombinant DNA Technology
In the 1970s new discoveries in microbiology led to the development of recombinant DNA technology and genetic engineering from work in microbial genetics and molecular biology.
 
NOBEL PRIZES AWARDED FOR RESEARCH IN MICROBIOLOGY
The number of Nobel laureates in Medicine and Physiology for their contribution in microbiology is evidence of the positive contribution made to human health by the science of microbiology. About one-third of these have been awarded to scientists working on microbiological problems (Table 1.1).
KNOW MORE
  • Microbes, also called microorganisms, are minute living things that individually are usually too small to be seen with the unaided eye. The group includes bacteria, fungi (yeasts and molds), protozoa, and microscopic algae). It also includes viruses, those noncellular entities sometimes regarded as being at the border between life and nonlife.
Antony von Leeuwenhoek (1632–1723): His observational report were enthusiastic and accurate and created some interest at the time, but unfortunately Leeuwenhoek treated these investigations as a hobby and did not really found as a science because he kept his methods secret and left no students to continue his work.
  • Although Fracastoro and others had suggested that invisible organisms produced disease, most believed that disease was due to causes such as supernatural forces, poisonous vapors called miasmas, and imbalances between the four humors thought to be present in the body.
 
 
 
 
KEY POINTS
  • Microbiology is the study of living organisms of microscopic size.
  • Antony van Leeuwenhoek was the first person to describe microorganisms.
  • The spontaneous generation of microorganisms was disproved by Spallanzani, Pasteur, Tyndall, and others.
  • The work of Bassi, Pasteur, Koch, and others supported the germ theory of disease. Lister provided indirect evidence with his development of antiseptic surgery.
  • Louis Pasteur: Pasteur showed that fermentations were caused by microorganisms and that some microorganisms could live in the absence of oxygen. He is known as “Father of Microbiology”. Contributions of Louis Pasteur in Microbiology a re very important.
  • Joseph Lister developed a system of antiseptic surgery. For this work he is called the F ather of modern surgery”
  • Robert Koch
    1. Koch developed the techniques required to grow bacteria on solid media and to isolate pure cultures of pathogens.
    2. Koch's postulates are used to prove a direct relationship between a suspected pathogen and a disease.
  • Paul Ehrlich is known as “Father of chemotherapy”.
  • The existence of viruses became evident during the closing years of the nineteenth century.
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Table 1.1   Nobel laureates for research in microbiology
Year
Nobel laureates
Contribution
1901
Emil A von Behring
Developed a diphtheria antitoxin.
1902
Ronald Ross
Discovered how malaria is transmitted.
1905
Robert Koch
Tuberculosis—discovery of causative agent.
1907
CLA Laveron
Discovery of malaria parasite in an unstained preparation of fresh blood.
1908
Paul Ehrlich and Elie Metchnikoff
Developed theories on immunity.
Described phagocytosis, the intake of solid materials by cells.
1913
Charles Richet
Anaphylaxis.
1919
Jules Bordet
Discovered roles of complement and antibody in cytolysis, developed complement fixation test.
1928
Charles Nicolle
Typhus exanthematicus
1930
Karl Landsteiner
Described ABO blood groups; solidified chemical basis for antigen-antibody reactions.
1939
Gerhardt Domagk
Antibacterial effect of prontosil.
1945
Alexander Fleming, Ernst Chain, and Howard Florey
Discovered penicillin.
1951
Max Theiler
Yellow fever vaccine
1952
Selman A Waksman
Development of streptomycin. He coined the term ‘antibiotic’.
1954
John F Enders, Thomas H Weller, and Frederick C Robbins
Cultured poliovirus in cell cultures.
1960
Sir Macfarlane Burnet and Sir Peter Brian Medawar
Immunological tolerance, clonal selection theory
1962
James D Watson, Frances HC Crick, And Maurice AF Wilkins
Double helix structure of deoxyribonucleic acid (DNA).
1966
Francois Jacob, Andre Lwoff and Jacques Monod
Regulatory mechanisms in microbial genes (concept of ‘lac operon’).
1966
Peyton Ross
Viral oncogenes (avian sarcoma)
1968
Robert Holley, Har Gobind Khorana, and Marshall
W Nirenberg
Genetic code
1969
Max Delbruck, AD Hershey and Salvador Luria
Mechanism of virus infection in living cells
1972
Gerald M Edelman and Rodney R Porter
Described the nature and structure of antibodies.
1975
David Baltimore, Renato Dulbecco and Howard M Temin
Interactions between tumor viruses and genetic material of the cells.
1977
Rosalyn Yalow
Developed inmmunoassay
1980
Baruj Benacerraf, Jean Dausset and George Snell
HLA antigens
1984
Cesar Milstein, Georges Kohler Neils Jerne
Developed hybridoma technology for production of monoclonal antibodies.
1987
S Tonegawa
Described the genetics of antibody production.
1989
J Michael Bishop and Harold E Varmus
Discovered cancer-causing genes called oncogenes.
1990
Joseph E Murray and E Donnall Thomas
Performed the first successful organ transplants by using immunosuppressive agents.
1993
Kary B Mullis
Discovered the polymerase chain reaction (PCR) to amplify DNA.
1996
Peter C Doherty and Rolf M Zinkernagel
Cell mediated immune defences
1997
Stanley B Prusiner
Prion discovery
2001
Leland H Hartwell, Paul M Nurse, and R Timothy Hunt
Discovered genes that encode proteins regulating cell division
2005
Barry J Marshall and J Robin Warren
Helicobacter pylori and its role in gastritis and peptic ulcer disease
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2007
Mario R Capecchi, Oliver Smithies and Sir Martin J Evans
Creation of knockout mice for stem cell research
2008
Luc Montagnier and Francoise Barre-Sinoussi Herald zur Hausen
Discovery of human immunodeficiency virus
Human papillomaviruses causing cervical cancer
  • Vaccines against anthrax and rabies were made by Pasteur; von Behring and Kitasato prepared antitoxins for diphtheria and tetanus.
  • Edward Jenner is known as the “Father of immunology”.
  • Ehrlich is given the title, “Father of chemotherapy”.
  • In the twentieth century microbiology contributed greatly to the fields of biochemistry and genetics. It also helped stimulate the rise of molecular biology.
  • The positive contribution has been made to human health by the science of microbiology.
IMPORTANT QUESTIONS
  1. Write short notes on:
    1. Contributions of Antony van Leeuwenhoek
    2. Contributions of Louis Pasteur
    3. Contributions of Robert Koch
    4. Koch's postulates
    5. Contributions of Edward Jenner
    6. Contributions of Paul Ehrlich
    7. Name four Nobel laureates in Microbiology
FURTHER READING
  1. Benacerraf B, et al. A history of bacteriology and immunology. William Heinemann,  London:  1980.
  1. Brock TD. Milestones in microbiology. American Society for Microbiology,  Washington,  DC, 1999.
  1. Bulloch W. The history of bacteriology, London Oxford University Press,  1938.
  1. Collard P. The development of microbiology. Cambridge University Press,  1976
  1. deKruif P. Microbe Hunters. Hutchison,  London:  1958.
  1. Foster WD. A history of medical bacteriology and immunology. Cox and Wyman,  London:  1970.
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