Last revised: Tuesday, January 21, 2003
Reading: Ch. 2 in text
Effects of Disease on Civilization
- Infectious diseases have played major roles in shaping human history
- Bubonic Plague epidemic of mid 1300's, the "Great Plague", reduced population of western Europe by 25%. Plague bacterium was carried by fleas, spread from China via trade routes and poor hygiene. As fleas became established in rat populations in Western Europe, disease became major crisis.
For further reading, see "Lecture 29. Satan Triumphant: The Black Death", from The History Guide: Lectures on Ancient and Medieval European History. - Smallpox and other infectious diseases introduced by European explorers to the Americas in 1500's were responsible for decimating Native American populations. Example: In the century after Hernan Cortez's arrival in Mexico, the Aztec population declined from about 20 million to about 1.6 million, mainly because of disease.
- Infectious diseases have killed more soldiers than battles in all wars up to WW II. Example: in U. S. Civil war, 93,000 Union soldiers died in direct combat; 210,000 died as a result of infections.
- Until late 1800's, no one had proved that infectious diseases were caused by specific microbes, so the possibility of prevention or treatment had no sound empirical base.
- To see microbes, you need a microscope. The first microscope was invented by Antony van Leeuwenhoek (1632-1723), a Dutch businessman. See photo.
- Leeuwenhoek took up lens grinding to make magnifiying glasses so he could examine fine weave of fabrics. In testing his lenses, he discovered many small creatures he called "animalcules" in samples such as pond water. His best lenses could magnify 300-500X.
- Leeuwenhoek microscopes were crude, relied on a single lens held in a metal plate. See examples.
- Leeuwenhoek described many previously unseen life forms, including different forms of bacteria, mold spores, etc. See examples; also see text p. 31.
- Leeuwenhoek reported discoveries to Royal Society from 1670's on, firmly established existence of microbes. Nevertheless, the significance of this discovery was not apparent for almost 200 years.
- Where did microbes come from? Many believed they arose from simple materials by process of spontaneous generation. This notion had been posited by Aristotle (382-322 B.C.) and other Greek philosophers to explain decay and appearance of animals such as flies and frogs, and was widely held as common sense even in 1700's and 1800's.
- Francisco Redi (1626-1697) demonstrated that flies did not arise spontaneously from rotting meat by simple experiment. If jar of meat was covered by fine muslin, maggots did not arise. See Redi Experiment .
- However, the simpler life forms discovered by Leeuwenhoek lacked visible complexity, and most people still belived these could arise spontaneously. Example: John Needham (1731-1781), a Scottish clergyman and naturalist, showed that mirobes grew in soups exposed to air. Claimed existence of a "life force" present in inorganic matter that could cause spontaneous generation. One of his more convincing demonstrations was to boil some soup (briefly), pour into clean flasks with cork lids, and show that microbes would soon arise.
- Lazzaro Spallanzani (1729-1799) claimed Needham's organisms came from heat-resistant microbes. If flasks were boiled long enough (1-2 h), nothing grew. But Needham countered that prolonged heating destroyed the "life force". See diagram of experiment.
- Louis Pasteur (1822-1895) was passionate believer that life only originated from previous life, developed several experiments that finally deflated claims for spontaneous generation. Pasteur filtered air through cotton to trap airborne materials, then dissolved the cotton and examined the particulate matter under a microscope; many bacteria and spores of other life forms such as molds were present. Since most skeptics kept arguing that overheating killed the life force present in air, Pasteur developed and ingenious experiment using a swan neck flask that allowed fresh air to remain in contact with boiled materials. The long passageway prevented airborne microbes from reaching the nutrient liquid, without impeding access to air. See diagram of this experiment. One of Pasteur's flasks is still sterile after 100+ years of being exposed to the air (Pasteur Institute, Paris).
Pasteur's swan neck flask.
- Robert Koch (1843-1910) was the first to rigorously demonstrate that a specific disease was caused by a specific microorganism.
- Koch worked on anthrax, a disease mainly of animals. Koch noticed that cattle that died of anthrax all seemed to have a certain rod-shaped bacterium in blood, not found in healthy animals. Koch was able to isolate the bacterium in pure culture, put it back into healthy cows, and reproduce the disease.
- Koch's Postulates: a logical way to identify the microbe causing a disease
- A specific microbe must be present in all disease cases
- Microbe must be cultivated outside host in a pure culture
- When pure culture of microbe is inoculated into healthy hosts, disease symptoms identical to those of initial host must be reproduced
- Microbe can be isolated again in pure culture from this experimentally inoculated host.
- Initial attempts to isolate microbes used sliced potatoes or nutrient media containing gelatin -- not ideal media. Then Fannie Hesse (wife of lab worker) suggested agar, a gelling agent used in cooking. Agar rapidly became the standard gelling agent for microbial isolation because it is relatively inert (only some marine microbes have enzymes to digest agar). Agar only melts at high temperatures (100oC); once melted, it remains liquid until about 45oC, at which point it gels. See photo of Petri plate with agar-gelled medium.
- Koch's success at identifying anthrax with bacterium Bacillus anthracis led both Koch and Pasteur to identify the causes of many diseases -- cholera, tuberculosis, plague, etc. -- over the next few decades (late 1880's) -- the "Golden Age of Microbiology" (~ 1870-1920). Note that many microbiologists would regard the present as a new "Golden Age", since the development of molecular biological techniques, PCR, molecular phylogeny, and other developments have revealed many new insights and opened a world of new research directions and ways of understanding microbes.
- Martinus Beijerinck (1851-1931) developed enrichment culture technique, a way to isolate microbes with certain growth preferences. Basic idea: create a laboratory simulation of any environment from which you wish to isolate microbes, then inoculate with microbes from such an environment. Example: suppose you want to find a microbe that breaks down oil sludge and grows at high temperatures. Design a culture medium with oil as the only C-source, other basic nutrients, and incubate at high temperature. This is an enrichment medium that will favor growth of the kind of organism you want. (Note: we will use enrichment media in MCB 229 labs to isolate several interesting microbes).
- Using enrichment media, it was possible to isolate enormous variety of bacteria with different physiological capabilities and different growth ranges. This demonstrated the impressive variety of microbial lifestyles, much broader than that of animals or plants.
- Sergei Winogradsky (1856-1953) extended awareness of microbial diversity. He discovered bacteria capable of autotrophic ("self-feeding") growth using inorganic compounds such as H2S as their only energy source, and CO2 as their only C-source. This was the first discovery that organisms other than green plants or algae could exist without consuming organic matter. Also discovered groups of photosynthetic bacteria that do not produce oxygen as their waste product. Developed culture technique known as Winogradsky column, in which mud and water are left in glass tube exposed to light. Over time, different microbial communities grow and interchange waste products and nutrients. View Winogradsky column (scroll down to see more).