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• Robert Hooke developed the first compound microscope (x20-x50), published 'Micrographia' in 1665, where he first used 'cells' when observing the stem of the cork plant and the spore structure of the fungi on leather.
• Antonie van Leeuwenhoek was an amateur and protective over his invention so wouldn't share his technology. Developed a simple microscope (x200) for examining cloth, fine cottons and other fine materials. He wrote to the Royal Society in London observing 'Animalcules' in a drop of drain water and was the first to describe structure of bacteria.
• Microscope types: confocal, scanning electron, cryo-electron, atomic force.
• Took 100 years after microscope was discovered to associate bacteria with causing infections.
• Hippocrates (400 BC) developed the miasma theory - people believed that diseases were spread from 'bad air' and vapours from decomposing matter. No hygiene and lack of sewage removal meant bad smell and conditions for disease.
• Aristotle believed that life arises spontaneously from non-living materials.
• Francesco Redi (1668) was the first to refute spontaneous generation with a meat experiment. Experiment: open container had maggots, cork-sealed container had no maggots, gauze-covered container had maggots on gauze instead of the meat. Original thought: organism arise out of decomposition of foods. Afterwards: decomposition attracts flies who cause the maggots on meat.
• Louis Pasteur demonstrated that heat could sterilise media (sterilisation). Pasteur flask experiment showed that particulates necessary for contamination (1864). He knew that boiled extracts from meat/yeast remain sterile, if not boiled there'll be contamination and microbial growth.
• Pasteur's Experiment:

  1. Heat neck of flask
  2. Bend neck to create 'swan neck'
  3. Create replicas
  4. Both flasks heated to sterilise media
  5. Cool the flask and leave out so dust and microorganisms are trapped in neck
  6. Tip one flask so the media goes into the neck and comes in contact with dust and microbes
  7. Analyse the flasks - tipped flask has contamination, not tipped flask has no contamination
  8. Conclude that contamination is caused by trapped microorganisms
• In the 19th century, Robert Koch was the first to provide experimental evidence that microorganisms cause disease. He developed Koch's postulates, a criteria for proving that a specific microorganism causes a specific disease. This criteria is still used to prove a particular organism is associated with a particular disease, regarded to as the 'gold standard'.
• Koch's Experiment:

  1. Look at blood of anthrax infected mice, bacterium in blood smears
  2. Look at healthy mice, no bacteria present
  3. Take diseased blood and isolate bacteria
  4. Streak and grow the bacteria in Petri dishes - culture
  5. Repeat for healthy mice - unable to culture bacteria
  6. Take isolated bacteria from the diseased mice and inject it into healthy mice
  7. Observe - healthy mice get disease
  8. Conclude - bacteria cause infection
• Koch's Postulates:

  1. The suspected pathogenic organism must always be present in animals suffering from the disease and should not be present in healthy individuals
  2. The organism must be cultivated in pure culture away from the animal body
  3. Cells from a pure culture of the suspected organism should cause disease in a healthy animal
  4. The organism should be reisolated and shown to be the same as the original
• Koch demonstrated transmission of anthrax in animals. He also discovered Mycobacterium tuberculosis as the cause of tuberculosis. However, it's not always possible to satisfy all postulates for every infectious disease e.g. if there's no animal model or if you can't culture the organism in-vitro.
• Martinus Beijerinck discovered microbial enrichment through an experiment that showed absence of a nutrient such as NH4+ forces cells to fix N2 while also being able to use NH4+ if available. Bacteria grown in a medium with no supplement - bacteria is able to grow on plates with supplement and no supplement as it's able to synthesise own ammonia. Bacteria grown in a medium with supplement - bacteria is only able to grow on plates with supplement as the mixture isn't enriched in bacteria that can grow in the absence of supplement.
• Joseph Lister developed Germ Theory, which postulated that surgical infections were caused by microorganisms. At the time pus was seen as healing, re-using aprons was common in surgery, no anaesthetics or painkillers used and, death from sepsis and infection was very high.
• In 1910, Paul Ehrlich discovered the first antibiotic - Salvarsan used to treat syphilis. Arsenic is toxic but the compound reduced toxicity and initially targeted syphilis more effectively. He searched for chemicals, called magic bullets, that would kill a microorganism but leave the host unaltered.
• Alexander Fleming discovered that Penicillum notatum prevented growth of Staphylococcus aureus. He left plates with Staphylococcus aureus over the weekend and noticed one plate had fungal contamination. Bacteria closest to the fungi was not growing as well as colonies that were further away. From this, he deduced that there was a molecule produced by the fungi that could kill the bacteria and isolated that molecule, called Penicillin. In 1945, he was awarded a Nobel Prize with Chain and Florey, who refined the process to manufacture penicillin for medical use.
• In 1788, Edward Jenner noticed that milkmaids with cowpox didn't get infected with smallpox during an outbreak in Gloucestershire. He took material from pustules of milkmaids and inoculated a child. Then in 1798, he published 'An inquiry into the causes and effects of the Variolae caccinae' (postulates).
• Modern vaccines take many forms including killed whole organisms, attenuated, protein components, and RNA vaccines (COVID-19).
• Advances in modern microbiology has decreased death and serious illness caused by microbes. In 1900s microorganisms caused most deaths whereas now, microorganisms cause a lot less deaths but the over use of antibiotics has led to an increase in antibiotic resistance and created the need to discover new antibiotics.