Supplemental Lecture (98/03/28 update) by Stephen T. Abedon (abedon.1@osu.edu)

  1. Chapter title: Germ Theory of Disease
    1. A list of vocabulary words is found toward the end of this document
    2. The germ theory of disease is the single most important contribution by the science of microbiology to the general welfare of the world's people, perhaps the single most important contribution of any modern scientific discipline. It also is the single most important contribution to the practice of modern medicine, essentially defining the term with the invention of antimicrobial chemotherapeutics. To gain a fuller appreciation of how far we have come, in this lecture we will briefly consider the history of the science of microbiology and the concurrent development of the germ theory of disease.
  2. Important Early Microbiologists
    1. van Leeuwenhoek, Anton (1670s)
    2. Semmelweis, Ignaz (1840s)
    3. Pasteur,Louis (1860s)
    4. Lister, Joseph (1860s)
    5. Koch, Robert (1870s)
    6. Iwanowski, Dmitri (1890s)
    7. Fleming, Alexander (1920s)
  3. Germ theory of disease
    1. Microorganisms cause disease:
      1. The theory that microorganisms may be the cause of some or all disease.
      2. The reason medical personnel have to take courses in microbiology.
    2. Foundation of modern medicine:
      1. Germ theory of disease is the single most important contribution to medical science and practice, ever.
      2. See Chapter 10 of Ewald, 1994 for a historical overview.
  4. Spontaneous generation
    1. Key to developing the germ theory of disease was a refutation of the concept of spontaneous generation.
    2. Spontaneous generation is the idea that, in modern times, living things can arise from non-living things (a violation of basic cell theory).
    3. Of course, what was really being observed was the appearance of visible organisms or populations of organisms which were initially microscopic contaminants.
    4. "As long as (individuals) believed that microorganisms could arise from nonliving substances, scientists saw no purpose in considering how diseases were transmitted or how they could be controlled." (p. 9, Black, 1996)
  5. van Leeuwenhoek, Anton (1670s)
    1. First microbiologist:
      1. First observation of individual, live microorganisms (used simple microscope).
      2. "It was Anton van Leeuwenhoek, a Dutch cloth merchant and amateur lens grinder, who first made and used lenses to observe living microorganisms. The lenses Leeuwenhoek made were of excellent quality; some gave magnifications up to 300x and were remarkably free of distortion. Making these lenses and looking through them were the passions of his life." (p. 8, Black, 1996)
  6. Pasteur, Louis (1860s)
    1. Anti-spontaneous generation experiments:
      1. Pasteur definitively demonstrated that microorganisms are present in air but not created by air.
      2. This was critical for refutation of the concept of spontaneous generation and the for development of germ theory of disease.
    2. No contamination when air is withheld:
      1. Sterilized broth by boiling.
      2. Exposure of sterilized broth to air resulted in contamination of broth by microorganisms (i.e., the broth became turbid).
      3. Protection from air, by sealing, prevented contamination.
    3. Contamination due to air-borne particles:
      1. Curved neck flasks allowed contact with air but inhibited movement of non-gaseous particles.
      2. Contamination was prevented (microdes stuck to neck of flask, did not reach broth)---air alone was not sufficient to induce contamination, must be something carried by air.
    4. Vaccine discoverer:
      1. Pasteur played key roles in the discovery and development of vaccines such as the rabies vaccine.
      2. "In gratitude for Pasteur's development of vaccines, people from around the world contributed to the construction of the Pasteur Institute in Paris, France." (p. 10, Prescott et al., 1996)
    5. Microorganisms responsible for fermentation:
      1. Fermentations are such things as the formation of alcohol or acetic acid in grape juice to form wine or vinegar.
      2. Demonstrated that fermentations occur as a consequence of the actions of micoorganisms.
  7. Aseptic technique
    1. Specific aseptic techniques are employed to avoid microbial contamination (e.g., Pasteur's experiments).
    2. "Modern aseptic techniques are among the first and most important things that a beginning microbiologist learns." (p. 8, Tortora et al., 1995)
  8. Pasteurization
    1. Method of prevention of spoilage of liquid foodstuffs (milk, wine, beer) which utilizes heating.
    2. Trade-off between applying enough heat (high enough temperature for long enough) to kill most microorganisms present (and delay or prevent spoilage) and applying so much heat that foodstuff is negatively altered.
  9. Semmelweis, Ignaz (1840s)
    1. Hand washing/childbirth fever:
      1. Demonstrated that hand washing prevented the spread of childbirth fever.
      2. At the time (early 19th century) doctors would deliver babies without first washing their hands and, worse, would do so after performing autopsies on patients who had died from childbirth fever. This not only assured transmission, but biased that transmission so that the most virulent forms of the organism (i.e., those that killed women while they were still in the hospital) would be transmitted.
  10. Lister, Joseph (1860s)
    1. Chemical inhibition of infection:
      1. Connected and applied Semmelweis' and Pasteur's work to develop and popularize the chemical inhibition of infection during surgery.
      2. Washed surgical wounds with phenol (a.k.a., carbolic acid)
      3. Lister is considered to be the father of antiseptic surgery.
  11. Koch, Robert (1870s)
    1. Developed Koch's Postulates which are a sequence of experimental steps for directly relating a specific microbe to a specific disease.
    2. Koch discovered:
      1. Bacillus anthracis
      2. Mycobacterium tuberculosis
      3. Vibrio cholera
    3. Technique developer:
      1. In addition to Koch's postulates, Koch played an important role in the developement of the use of agar as solid medium.
      2. Koch also invented nutrient broth and nutrient agar.
  12. Iwanowski, Dmitri (1890s)
    1. Dmitri Iwanowski discovered the first virus, tobacco mozaic virus.
  13. Chemotherapy [chemotherapeutic agent]
    1. Treatment with chemicals that have anti-microbial action. The chemicals employed are chosen because of a tendency to be more toxic to microorganism than to host.
    2. e.g., antibiotics:
      1. Chemotherapeutics may divided into two types, synthetic drugs and antibiotics.
      2. In practice this distinction is often ignored with synthetic drugs referred to as antibiotics.
  14. Synthetic drug
    1. A synthetic drug is a laboratory synthesized chemotherapeutic agent.
  15. Antibiotic
    1. Not wholly synthetic chemotherapeutic:
      1. An antibiotic is an anti-microbial chemotherapeutic agent produced by microorganisms, isolated, and purified for use by humans, e.g., penicillin.
      2. There also exist semi-synthetic drugs which are synthesized starting with products produced by microorganisms.
    2. natural growth inhibitors:
      1. Operationally, an antibiotic is a substance produced by one microorganism that in very small amounts inhibits the growth of a second microorganism.
  16. Fleming, Alexander (1920s)
    1. Penicillin/first antibiotic:
      1. Fleming discovered that a mold accidentally growing on one of his petri dishes had anti-bacterial activity.
      2. The mold was producing penicillin.
      3. This was the first antibiotic discovered.
    2. Because of problems with mass production, the use of penicillin did not become widespread until the 1940s (p. 11, Tortora et al., 1995).
  17. Vocabulary
    1. Antibiotic
    2. Aseptic technique
    3. Chemotherapy
    4. Chemotherapeutic agent
    5. Germ theory of disease
    6. Pasteurization
    7. Spontaneous generation
    8. Synthetic drug
  18. Practice questions
    1. When doing microbiology there are a number of procedures that prevent not only contamination of the microorganisms being worked with, but the laboratory environment as well. Collectively these procedures are called __________ (single word or phrase)? [PEEK]
    2. True or False, pasteurization = sterilization (circle correct answer)? [PEEK]
    3. True or False, the germ theory of disease has had a significant impact on the practice of medicine (circle correct answer)? [PEEK]
    4. Who was the first to observe individual, live microorganisms? (circle correct answer) [PEEK]
      1. Fleming
      2. Iwanowski
      3. Koch
      4. Leeuwenhoek
      5. Lister
      6. Pasteur
      7. Semmelweis
      8. all of the above
      9. none of the above
    5. In what way is the germ theory of disease relevant to public health? [PEEK]
    6. Some proponents of spontaneous generation believed that air is necessary for life. They thought that Spallanzani did not really disprove spontaneous generation because he hermetically sealed his flasks to keep air out. How did Pasteur's experiments address the air question without allowing the microbes in the air to ruin his experiment? [PEEK]
    7. The contributions of Leeuwenhoek, Semmelweis, Pasteur, Lister, and finally Koch (plus others) contributed to the formulation of what concept which even today is central to the practice of modern medicine.[PEEK]
    8. What was Ignaz Semmelweis' contribution to the elucidation of the germ theory of disease? [PEEK]
    9. Describe three ways by which sterile broth may be isolated from air-borne contaminants (hint: Pasteur's experiments). [PEEK]
    10. What was the significance of the curved necks on the flasks in Pasteur's spontaneous generation-discrediting experiments? [PEEK]
    11. To be an effective treatment of disease, an antibiotic must possess two properties. One is an ability to kill the pathogen causing the disease. What is the other property? [PEEK]
  19. Practice question answers
    1. Aseptic technique
    2. False. Pasteurization fails to kill all of the organisms present (the definition of sterilization).
    3. True. It is perhaps the single most important concept in public health short of "don't explode nuclear weapons over populated areas."
    4. iv, Leeuwenhoek
    5. prior to the invention of practices which intervene in the occurrence of disease caused by microbial replication, the dominant cause of human morbidity and mortality was the result of microbial (i.e., germ) infection.
    6. He employed various means to trap or filter microbes from the air prior to their coming into contact with the sterilized media. In that way air, but not the contaminating agent found in air, could come into contact with the media.
    7. germ theory of disease.
    8. argued that washing hands between patients would reduce the incidence of nosocomial infections.
    9. The container holding the sterile broth, in addition to being at least initially sterile, must be sealed to air, contain a solid stopper, be plugged with cotton at its opening, or have a narrow, curved (swan-shaped) neck.
    10. The curved necks on Pasteur's flasks selectively allowed contact between unadulterated air (not filtered, not heated) but nevertheless could selectively exclude microorganisms suspended in the air.
    11. A low level of toxicity to the individual receiving the treatment.
  20. References
    1. Black, J.G. (1996). Microbiology. Principles and Applications. Third Edition. Prentice Hall. Upper Saddle River, New Jersey. pp. 0-25.
    2. Prescott, L.M., Harley, J.P., Klein, D.A. (1996). Microbiology. Third Edition. Wm. C. Brown Pub. Dubuque, Iowa. pp. 3-16.
    3. Tortora, G.J., Funke, B.R., Case, C.L. (1995). Microbiology. An Introduction. Fifth Edition. The Benjamin/Cummings Publishing, Co., Inc., Redwood City, CA, pp. 2-22.