Today we will discuss the history of microbiology as a Science and the use and influence of microbes over the ages. I want you to pay attention to the history but also to the ideas that I bring up. We will revisit many of these ideas as the course goes on. History is just one way to learn to understand the process and results of science.

Obviously humans have had to deal with microbes even before the dawn of recorded history. The first records of humans using microbes comes from ancient tablets from the Mid East.

Babylonians were using yeast (a type of fungus) to make beer over 8000 years ago and acetic acid bacteria to make vinegar over 6000 years ago.

Detailed instructions for making beer can also be found in 6000 year-old hieroglyphics in Egypt.

The oldest records of wine making date to about 5000 years ago in Persia (now Iran). It may seem odd to some that beer and wine were such a priority in ancient times, but you must realize that beer (and wine) were originally thought of as ways to preserve food. Grape juice left open to the air soon rots beyond recognition. Grape juice sealed away from air ferments into wine which keeps for years because the alcohol in the wine acts like a preservative (i.e. it is toxic to most forms of life). You will learn the details of fermentations in a few weeks.

The Romans (and probably other cultures) had Gods that were specific for microorganisms. The Roman God of Mold and Mildew was "Robigus" or "Robigo" which also means "crop rust" (rusts are one type of plant pathogenic fungus). Robigus was greatly feared, probably because of crop losses due to fungal plant pathogens. The festival of the Robigalia was celebrated on April 25th to honor and appease this god. The date for this festival makes sense because spring is a time when fungal diseases can be especially devastating (due to the moist spring conditions). During the Robigalia a procession took place on the Via Claudia to the grove of Robigus at the 5th mile stone. There they sacrificed a red dog and a sheep to keep blight from the growing grain. For more information on this topic listen to this clip from National Public Radio.

In the realm of medicine, there are records of many diseases going way back in Chinese, Greek and other cultures. Some of these records indicate that ancient peoples realized that certain diseases could be transmitted via contaminated clothing and that humans could develop immunity to some diseases. About 2000 years ago Varro (Roman) even proposed that diseases were caused by tiny animals. Then came the dark ages a time when fundamentalist religions had a strangle hold on human progress.

Let's jump forward in time and discuss the development of microbiology in more modern times. Knowledge of microbes was initially very limited by the fact that they are too small to be seen with the unaided eye. Starting in the 1600's people began making crude microscopes.

Robert Hooke (1635-1700) was one maker of microscopes (30x magnification). One of his discoveries was that cork consists of many tiny compartments or cells (from the Latin cellulae, meaning small rooms). He is also credited with being the first to observe microscopic fungi.

Antony van Leeuwenhoek lived during the same age (1632-1723) and was an amateur glass grinder (lens maker) and microscope maker. He was evidently very meticulous and skilled, because he made microscopes that could magnify 300x. His best scopes were evidently fitted with single pieces of ground sand grains. Leeuwenhoek was the first to describe protozoa and bacteria (see figure 1.1 in book). Some of the first bacteria that he looked at were from the plaque of his own teeth! He was way ahead of his time and many scientists didn't believe him.

Also around this time some folks started to question the age-old idea of "spontaneous generation". Going way back in time people believed that life could arise spontaneously (most of the ancient Greek philosophers were convinced that spontaneous generation occurred). For example, it was thought that maggots arose spontaneously via a recombination of matter in rotting materials. The idea of spontaneous generation (SG) held up progress in science and medicine for many years because people thought that, for example, disease causing organisms were the result of disease and not the cause..........

Theologians also had big problems with spontaneous generation because it contradicted their belief that only God could create life. So it isn't so surprising that it was a priest, Francesco Redi (Italian, 1626-1697), who dealt one of the first blows against SG.

Describe his meat experiment...........This is a good example of a controlled experiment.......

Even with evidence like that, many learned folks still believed that microorganisms arose spontaneously. They argued that microbes were so simple that they didn't have to arise from other microbes. Many priests and scientists did experiments to disprove that microbes could arise spontaneously. Early experiments were quite simple and showed that when heated food was hermetically sealed it did not rot or spontaneously produce microbes. But critics of these experiments claimed that there was some "vital force" in air that was needed in order for SG to occur. Others claimed that oxygen was needed in order for SG to occur.

These criticisms eventually led to a bunch of clever experiments by a wide range of scientists including Spallanzani, Schulze and Pasteur (1822-1895). For simplicity I will only describe some of Pasteur's experiments..................................................

1. Swan-necked flask, fruit juice etc. (see figure 1.3)

2. cotton wool as a filter to concentrate microbes from the air then dissolved the cotton and showed that it was loaded with microbes.

Not only did Pasteur help put an end to the idea that there was some "vital force" in air, but he also was the first to show that some bacteria don't even need oxygen. He coined the term anaerobes (literally, without air) to describe these organisms (as opposed to aerobes which can use O2 in their metabolism).

Please note that some of Pasteur's experiments were conducted almost 200 years after those of Redi!!!! (Pasteur also made many other discoveries including the first vaccine for rabies).

It was pretty obvious by this time that some liquids could be sterilized by boiling or even by heating below the boiling point (Pasteurization) - BUT it was also known that it was hard to sterilize certain things especially if they had touched soil (e.g. hay infusions).......Tyndall (1820-1893) was one of the first scientist to make this observation.

Ferdinand Cohn (1828-1898) also studied non-sterilizable infusions and noticed that the organisms that could survive boiling had odd morphologies - draw normal and endospore containing cell...............The Bacteria that form endospores are Gram positive organisms most of which are in the genera Bacillus (aerobes) and Clostridium (anaerobes). The discovery of these organisms led to the development of new ways to sterilize fluids such as the autoclave and pressure cooker. Both of these inventions are pressurized so that they can heat fluids above the boiling point of water. Another method for sterilizing fluids is called "Tyndallization" (or intermittent sterilization). In this process fluids are heated and cooled several times (Can you explain how and why this process works?).

Soil is notoriously hard to completely sterilize because of the large concentration of endospores in most soils. Even a single autoclave run of 90 minutes will not sterilize most soils. In contrast, most liquids are completely sterile after 20 minutes of autoclaving. A standard method for sterilizing soil is to autoclave it for 90 minutes and then let the soil cool over night (allowing endospores to germinate) before re-autoclaving it for 90 minutes the next day.

Martinus Beijerinck (1851-1931)

N2-fixing bacteria and many other discoveries.

Enrichment culture technique......

Sergi Winogradsky (1856-1953)

Winogradsky was the first to describe sulfur oxidizing bacteria such as Beggiatoa. These organisms are chemoautotrophs (fix CO2 without photosynthesis and use inorganic chemicals as their source of energy).

Let's go a little bit into the modern era. In 1922 A.J. Kluyver replaced Beijerinck at the University of Delft and ushered in the modern era of comparative biochemistry. Kluyver and his student C.B. van Niel proposed that all respiratory reactions (aerobic and anaerobic) could be summarized using the simple formula:

They also summarized all photosynthetic reactions with:

We will come back to these reactions in a few weeks.

And now for some history of medical microbiology.
Disease-causing microorganisms have played a major role in the outcomes of history - leading to the downfall of empires and the defeat of large armies. This was especially true prior to World War II - because in earlier wars soldiers usually lived in close quarters under unsanitary conditions where disease could spread rapidily. Many historians think that diseases and infections have killed far more soldiers than actual battles over the ages. We will discuss the historical implications of diseases when we talk about specific diseases later in the course.

Some Famous Names in Medical Microbiology:

R. Koch (1843-1910)

Koch was a country doctor who was given a microscope by his wife. He was looking at the blood of an ox that had died of anthrax and noticed that, besides blood cells, there were a lot of little stick-like things in the fluid (he never saw these sticks in blood from healthy animals). He later grew these sticks in some fluid from the eye of an ox and then injected them into a mouse and the mouse died of anthrax. When he looked at the blood of the dead mouse he again saw the sticks and he was able to culture the sticks from the mouse's blood. This was the first clear experimental evidence showing that a bacterium can cause a disease. This early experiment and many later ones led to what we now call Koch's postulates. Koch's postulates are a set of rules to prove that a specific organism causes a specific disease...........

Koch's Postulates:

1) A specific microorganism is always present in organisms (hosts) with a specific disease.

2) The organism must be cultured away from the host.

3) Inoculation of a new host must lead to the same disease

4) The microbes must be re-cultured from the inoculated host.

......

Koch also determined that the organism that causes anthrax (now called Bacillus anthracis) had a life cycle that included a very resistant spore (endospore) that could survive for years in soil.

Koch went on to study other diseases and many of his students and colleagues made important discoveries in microbiology. Table 1.2 shows some of the diseases that were figured out by Koch and others in the late 1800s.

Koch's lab was also the birth place of pure culture microbiology, especially after Fannie Hesse discovered that agar could be used as a solidifying agent for bacteriological media in 1882.

Another of Koch's co-workers, Paul Ehrlich, is credited as being the discoverer of chemotherapy. Ehrlich noticed that bacteria picked up certain stains more readily than did mammalian tissue. This led him to believe that microbes might also be more susceptible to certain toxins than humans. His first success was with an arsenic-containing compound (Salvarsan) that killed Trypanosomes and the bacterium that causes syphilis (Treponema pallidum). These early chemo-therapeutic agents sometimes had nasty side effects. It wasn't until the mid-1900s that very specific antibiotics were developed (more about that later).

Link to more information on the history of microbiology.