The History of the Germ Theory of Disease

The History of the Germ Theory of Disease

Man first thought disease to be punishment from God, then brought on by foul vapors (miasma) (malaria for instance)



Aristotle 350 BC Taught Alexander the Great to boil drinking water & bury feces to prevent disease.


Fracastorius 1546 (1478-1553) Theory of contagion: disease infection can be caused by minute bodies (“germs”) capable of self-replication, transmitted from infector to infected. Said to have named syphilis.

Leeuwenhoek 1670s improved microscope, first to observe bacteria.

Agostino Bassi 1834 First to show that a microorganism could cause disease in case of a fungal disease of silkworms: contagious and could be transmitted naturally by direct contact or infected food, or experimentally by means of a pin previously sterilized in a flame


Oliver Wendle Holmes 1843 Noted that it was safer to give birth at home than in hospital, postulated something present in hospital is causing disease (nosocomial disease)

M.J. Berkeley 1845 Showed Irish potato blight caused by a fungus

Ignaz Semmelweis 1848 (1818-1865) In charge of lying-in hospital in Vienna. Childbirth death rate: Ward II midwives = 3%, Ward I, medical faculty: ~10%. Phys. friend died of autopsy wound, S&S same as puerperal fever. Proposed etiology: “cadaveric particles.” Smell not removed by hand washing, but calcium hypochlorite: Ca(OCl)2 did. Chloride of lime washing reduced puerperal fever death rate 12.4% to 1.27%. Iatrogenic disease.

John Snow 1854 (1813-1858) deduced contaminated Broad Street Pump caused cholera epidemic in London


Joseph Lister 1860s (1827-1912) Introduced use of antiseptic during surgery: phenol in surgical dressings and sprayed into the air. Wound infections dropped dramatically, thus due to bacteria.


Louis Pasteur 1865 Demonstrated that spoilage of wine was due to abnormal microorganisms. Then asked by French gov to study PEBRINE: (pa-breen) another disease of silkworms, caused by a protozoan. Could be halted by identifying diseased worms, removing and destroying.

Davaine 1850 observed little thread-like bodies in blood of anthrax-killed animals


Henle proposed that diseases might be directly caused by microorganisms. His student, Robert Koch

Robert Koch 1876 (1843-1910) Rival of Pasteur, raced to find the cause of anthrax (coal, burning coal, from pustules & carbuncles in affected animals) disease of sheep and cattle. First to demonstrate bacillary agent to be pathogen: Used criteria suggested by his teacher, Henle, now called Koch’s postulates: (in study of etiology of anthrax)

KOCH’S POSTULATES are criteria by which a bacterium may be said to cause a disease.
1 microscopic examination found bacillus in blood of all animals with anthrax.
2 single colony-isolated bacillus on solid media. The idea for isolating pure cultures came from his observation of a spoiling cut potato. Also required, as developed in his lab:
Loeffler developed nutrient broth and stains.
Walter Hesse’s wife suggested using agar to solidify.
Petri developed shallow dishes for culture.
3 injected pure culture into healthy animals, they got anthrax.
4 isolated same organism from animals experimentally given anthrax.

Chamberland 1884 Showed that tobacco mosaic disease was caused by “filterable’ agent (i.e., not bacteria) therefore. called virus.

PREVENTION, CURE OF DISEASE: vaccination, therapeutic agents:


Edward Jenner 1798 Saw peasants do this in Turkey. Inoculated susceptible person with pus from cowpox lesion, conferred resistance to Small Pox. Vaccination comes from vache, cow in French.

Pasteur 1880 Cultured chicken cholera repeatedly, it lost its virulence but could still confer immunity when injected. Attenuated [towards thinness] strain = vaccine


Erlich 1910 Searched for “magic bullet” would poison pathogen but not patient. Developed salvarsan, an arsenic compound against syphilis.

Flemming 1928 (1881-1955) Noted inhibition of Staphylococcus growth on plate contaminated with Penicillium notatum. Discovered penicillin.

History of Microbiology

Reference Texts: Page numbers in TFC’s 8th: pp 1- 17, Black’s 6th: 1-10

tigris-euphrat-regulation map

Ancient Practical Arts:
Birth of civilization between Tigris and Euphrates: grain, yeast for bread, beer, wine.
Bacterial cultures for making cheese. Knew technology, but not science

Significance of microbes?
Prior to 20th century: 30% of world’s inhabitants died of TB
Almost 50% children died fr infect. disease
Today: 50% child mortality due to infectious diseases

(recognition depended on new technology of microscope)

Robert Hooke
1665 English, used a compound microscope, noted pores in cork: called cells, slide from Micrographia

Anton van Leeuwenhoek
1673 major improvements in his microscope Looked at “sediments” from his teeth: more ‘animalcules’ in his mouth “moving in the most delightful manner” than in all of Holland. peppercorn infusions. (p. 9) (Leeuwenhoek uses his microscope.)


Matthias Jakob Schleiden and Theodor Schwann 1838-39
(bot and zool.), deduced that all living matter composed of cells. UNIFIED CELL THEORY.



5th C BC Proposed miasma (foul gas) caused putrefaction. The code of Aesculapius guided early physicians


325 BC thought that life arose spontaneously

van Helmont 1577-1644
formula for mice: dirty rags, wheat bran, place in dark open barrel, 2 weeks – 1 month would have mice. i.e., Maggots arose “spontaneously” from decaying meat.


Francesco Redi
1668 (p 11) Italian, first true scientific experiment, tested spontaneous generation hypothesis: sealed three jars tightly with meat, left three jars unsealed. Open jars produced maggots, sealed did not. But critics thought that fresh air was required. He repeated expt so that air could get in, using gauze to keep out flies, deduced that maggots appeared only when flies preceded.

John T. Needham
1745 heated infusion of chicken broth and corn, poured into covered “clean” flasks. Soon contaminated (turbid: Latin, confused, disordered, crowd). Said could only be due to spontaneous generation


Lazzaro Spallanzani
1765 modified Needham’s experiment: the fluid was sealed in the flasks, and then boiled. noted that they did not show contamination if sterilized in the sealed flask


Laurent Lavoisier
1743-1794 Discovered oxygen in air. Many thought this could be the “vital principle.”


Nicolas Appert
1810 Invented canning. Perfected autoclave: placed food in thick bottles, boiled for 5 hrs, sealed with cork and wax. Used by Napoleon, lent strength to his army.

Rudolf Virchow
1858 German: biogenesis; all cells came from cells: Omnis cellula e cellula.


Louis Pasteur
1861 (p 12) filled long-necked flasks with beef broth. Bent necks of some into S shape, other straight. Reasoned that S trapped airborne contamination. Boiled to sterilize. Deduced that micro organisms ubiquitous, can be destroyed by heating. Blocking access to medium will prevent growth.

[means “not putrid”] The elimination of microbes, and maintenance of the resulting sterility.

[Ferment means “to rise up”.]

1857 French vintners plagued by spoilage. Current theory was that air acted on grape juice turn to wine. Pasteur found that yeast on surface of grapes performed fermentation. Etymology: fermentum: to cause to rise up, fervere: to boil

1864 Why does wine spoil (sour to vinegar)? Showed due to bacteria, only in presence of air, making acetic acid. Block out oxygen with an air lock, it will not turn to vinegar.

By heating beer or wine (etc), can kill most bacteria except the thermodermic classic: 63° C (145°F), 30 min now: High Temperature Short Time: HTST: 72° C (163°F), 15 sec
1668 (p 11) Italian, first true scientific experiment, tested spontaneous generation hypothesis: sealed three jars tightly with meat, left three jars unsealed. Open jars produced maggots, sealed did not. But critics thought that fresh air was required. He repeated expt so that air could get in, using gauze to keep out flies, deduced that maggots appeared only when flies preceded.