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Author(s): Nancy Moreno, PhD, Barbara Tharp, MS, Deanne Erdmann, MS, Sonia Rahmati Clayton, PhD, and James Denk, MA.

Milestones in Microbiology

Very little attention was paid to the world of microbes until the 1600s, when Robert Hooke developed a primitive compound microscope (one which uses two lenses in sequence) and described tiny organisms that he observed with it. Even more detailed observations of microscopic organisms were made by Anton van Leeuwen­hoek, who developed precise techniques for grinding magnifying lenses. Van Leeuwenhoek observed numerous small, swimming organisms in pond water and named them “animalcules.”

It was not until the mid-1800s that scientists had enough tools to begin serious studies of microbes. In the 1850s, Louis Pasteur studied the fermentation of wine, which he found to be caused by yeast cells. He proposed that microorganisms also could cause disease, and later developed the process of pasteurization to remove harmful bacteria from food. 

Pasteur’s work stimulated that of Robert Koch, a physician who studied anthrax (a disease of cattle and sheep). Koch is credited with developing many culture techniques, including the use of nutrient agar for growing bacteria. He also established a set of rules to guide decisions about whether a given microbe actually caused a disease. These rules are known as “Koch’s Postulates” (see PDF). 

Much later, in the 1930s, Walter Fleming accidentally discovered that substances produced by a common fungus, Penicillium, could kill Staphylococcus bacteria in cultures. His work led to the development of penicillin, the first antibiotic. 

Since viruses are so much smaller than bacteria, most research on viruses and viral diseases began later than work on other microbes. In the 1890s, two investigators working separately, Martinus Beijerinck and Dmitrii Ivanowski, studied juices extracted from the leaves of plants infected with what is now known to be tobacco mosaic virus. They filtered the juices to remove bacteria and found that even when highly diluted, the liquid still could cause infection in plants. Ivanowski concluded that an infectious agent other than a bacterium—a filterable “virus”—led to the disease. Beijerinck called the substance “contagious living fluid.”

Neither investigator was able to observe or grow the hypothesized disease-causing agents. Later, in the 1930s, Wendell Stanley isolated crystals of tobacco mosaic virus. The invention of the transmission electron microscope by Ernst Ruska in 1933 made it possible to observe viruses for the first time at magnifications of 10,000 times or more. For this, Ruska received the Nobel prize in physics. 

The process by which microbiology knowledge has accumulated is typical of how science proceeds. Often a critical tool, such as the microscope, is needed before questions even can be asked. Progress occurs unevenly, with one critical discovery suddenly opening entire new areas of investigation. 


1. Ask students a question about how one discovery or invention can lead to another, such as, Which came first, the wheel or the cart? Or Would a light bulb be of any value if ways to utilize electricity had not been invented? Discuss students’ responses. 

2. Distribute the Discovery Readings sets to each group. Tell students that they will use clues from each reading to figure out the historical order in which events described in the articles occurred. Have each student select a highlighter and one article from the group’s set. Instruct students to highlight words that provide clues related to the order of events. 

3. When a student finishes an article, he or she should pass it to another group member until all members have read and marked all of the articles. If a word or phrase already has been highlighted and the next reader agrees with the marking, that reader should draw a line with his or her highlighter above the mark.

4. Next, have each group discuss and determine the most likely order of events and discoveries. 

5. At the bottom of each reading, have each group list major clues that might help others recreate the order of events. 

6. Distribute the Timeline sheets. Have groups cut out the sections and tape the timeline together. 

7. Tell students to paper clip (not tape) the articles in order along the top of the timeline. Have each group share its results with the class. Discuss any differences among the groups’ timelines. If there is a disagreement, let students present their cases. Lead the class toward consensus. Ask, Why do all of the groups have the same article first on the timeline? (microscope) What is the most logical second event? (agar plates) Ask, Why is the development of this technique important? (It provided a reliable way to grow bacteria for study.)

8. Based on the readings, it will be difficult for students to decide whether “The Discovery of Penicillin” or “Contagious Living Fluid” came first. Ask, What additional information might help us to make a decision? You may want to ask students to research these topics on their own.

9. Finally, have groups calculate the number of years between events and discuss the possible reasons for the varying time intervals between discoveries. You may wish to discuss why related discoveries sometimes occur close together in history. 

10. Allow students time to add this information to their concept maps.

Funded by the following grant(s)

Science Education Partnership Award, NIH

Grant Number: 5R25RR018605