Lesson 2 - Microbes Shape Human History

When did we find out about Microbes?

• All the way 10,000 BCE (12,000 years ago ish)!

• Various food and drink products were produced by microbial fermentation

What is the correlation between microbes and disease?

• For most of history, infectious disease has been the leading cause of mortality worldwide

• Used to devastate human populations

• Major turning points occurred with increased sanitation and hygiene and later, antimicrobial drugs and vaccines

The Bubonic Plague

• Caused by bacterium Yersinia pestis

• Reoccurred from 6th-17th century!

• Wiped out a third of Europe’s Population

• Spread by fleas and rodents, related to poor sanitation, causes infection of the lymph nodes

  • Major European epidemic from ~1345-1355

    • Black Death (Caused by Bubonic Plague): ~100-200 million deaths in ~10 years; ~45-50% of European population died in 4-year period)

    • Appr. 7 million COVID-19 deaths as of April 2024

Smallpox

• Caused by Variola virus

• Causes small skin lesions, highly contagious, airborne

• Infects multiple organs, ~30% mortality

• Leading cause of death in 18th century Europe, ~400,000 people died from the disease per year

• Evidence of smallpox from Egyptian mummies (~3000 years ago)

• Believed responsible for death of ~90-95% of Indigenous people after European contact; decimated native American communities (no immunity)

Cholera

• Caused by bacterium Vibrio cholerae

• Causes infection of small intestine, severe diarrhea, vomiting and dehydration

• Transmission through contaminated food and water

• Major worldwide epidemics throughout 19th and early 20th Century, ~50 million deaths over first 3 epidemics

Who created the microscope and the term “cell”?

• Architect Robert Hooke (1635–1703)

• Built the first compound lens microscope (~30x magnification);

• First to ‘see’ and record eukaryotic microbes; gave birth to Microbiology…revealed the microscopic world!

• Coined the term “cell” from Latin cella, which means small room after observing cork tissue

Who refined the microscope and what else did he discover?

• Antonie van Leeuwenhoek (1632-1723) experimented magnifying lenses, up to 500X magnification

• He mounted single lenses on sample holder and focus adjustment

• Became the first person to observe single-celled organisms, he called them “Animalcules”

What was the Spontaneous Generation Theory?

• Where did (microscopic) life come from? Do microbes have parents?

• Spontaneous generation: the theory that living creatures could arise without parents

• For example, people believed maggots came from rotting meat and microorganisms arose from decaying material.

• By late 1600s/early 1700s there is evidence to disprove this, though not widely accepted → Redi and later Pasteur provided evidence against it

• Still no evidence links microbes to infectious diseases

Miasma Theory

• Miasma theory stated that diseases (cholera, plague) were caused by “bad air” or “night air”

• Prevailing theory until 19th Century

What theory arose in the 19th Century?

• Germ Theory and Sanitation!

• Germ theory states that some diseases are caused by microorganisms

• Gained widespread acceptance in 19th

• Century; contributors:

  • Louis Pasteur

  • Joseph Lister

  • Florence Nightingale

• Solidify Germ Theory and promoted the ideas of sanitation and hygiene by end 19th century

Who was Florence Nightingale?

• British nurse better known as founder of professional nursing

• Also, founder of medical statistics

• 1855; tracked causes of deaths during Crimean war

• Found more soldiers died of microbial infections than of battle wounds

• Shows statistical correlation of sanitation with mortality

• Convinced British government to improve living conditions for soldiers

Louis Pasteur

• Major contributor to medical microbiology and immunology

• As a French chemist and microbiologist, Pasteur discovered microbial fermentation produces lactic acid or alcohol (1857)

• He showed microbes fail to appear spontaneously using swan-necked flasks (1864)

• Disproved Spontaneous Generation Theory

• Major evidence in support of Germ Theory

• Development of first artificial vaccine (against anthrax; 1881)

• Developed pasteurization techniques for milk

What was Robert Koch the founder of?

• German physician; Founder of the scientific method of microbiology

• Developed Koch’s Postulates (still in use today!)

• Used blood from an anthrax-infected cow carcass to infect a rabbit; when that died, he infected another. The blood was black with long, rod-shaped bacilli

• First to use an animal model system

• Developed the pure-culture technique

• Used these techniques to prove that tuberculosis (TB) is caused by Mycobacterium tuberculosis;

• Nobel prize in 1905

• Discovers the specific agents (bacteria) responsible for TB, anthrax, and cholera

What did Koch depend on for his expirements?

• Koch depended on discoveries by:

  • Julius Petri; discovered and developed the culture plate (dish) used to this day (Petri Dish/Petri plate)

  • Angelina & Walther Hess

    • First to develop solid medium to culture bacteria

Who was Joseph Lister and what discovery did he make?

• Sterilization

• Surgeon

• Realized gangrene and death after surgery was due to infection

• 1860-1870; pioneer antiseptic practice during surgery, using carbolic acid (phenol) spray to sterilize surgical instruments, clean wounds

• Made surgeons wash hands in diluted phenol and wear gloves

Now since the cause of disease was discovered… how do we treat it?

• Identifying the cause of disease is the first step, next comes treatment

• In Asia and Africa, the incidence of smallpox was decreased through inoculation of children with material from pustules

• Lady Montagu, a smallpox survivor, introduced the approach to Europe in 1717

• Variolation: Deliberately exposing a healthy person to material from a smallpox pustule (usually by introducing it into a small cut) to try to give them a milder form of smallpox and future protection.

• The concept is that the virus is attenuated when outside the body, but still stimulated the immune system. Material taken from a pustule and exposed to the environment might be less capable of causing severe disease than a fresh infection

• Carried risks

Edward Jenner and Early Vaccines

• Early 19th Century, English physician Edward Jenner (1749-1823) finds milkmaids exposed to cowpox (vaccinia virus) are immune to the more severe smallpox

• Tests this by inoculating a child with pus from cowpox blisters, develops the first smallpox vaccine

• First person to provide scientific evidence for the deliberate use of vaccination to control an infectious disease

• Cowpox inoculation was called ‘vaccination’, after the virus, which was derived from the Latin word for cow (vacca)

The Discovery of Viruses

• 1892: Dmitri Ivanovsky discovered a disease-causing agent so small that it passed though 0.1 μm pores in a filter

• Martinus Beijerinck proposed the filtrable agent was not a bacterium; it was a novel unknown microbe coined ‘virus’ (latin for poison)

• Wendell Stanley (1904-1971) later purified & crystallized the agent, identifying the Tobacco Mosaic Virus (TMV) (Nobel Prize in Chemistry, 1946)

Summary of Microbe History

• Early Visualizations: Robert Hooke (first compound microscope, eukaryotic microbes, "cell") and Antonie van Leeuwenhoek (high-power simple microscope, discovery of single-celled bacteria/"animalcules").

• The Debate on Spontaneous Generation: Francesco Redi (flies & maggots) → Lazzaro Spallanzani (boiled sealed broth) → Louis Pasteur (swan-necked flasks definitively proving biogenesis).

• Miasma vs. Germ Theory & Antiseptics: Moving away from "bad air" via Florence Nightingale's medical statistics (sanitation vs. battle deaths) and Joseph Lister's carbolic acid (phenol) antiseptic surgery.

• Pure Culture & Koch's Postulates: Robert Koch establishing causality for anthrax, TB, and cholera with help from Julius Petri (Petri dish) and Walther & Angelina Hesse (agar medium).

• Immunization: Variolation (Lady Montagu) → Cowpox/Smallpox vaccination (Edward Jenner) → Attenuation vaccines for anthrax and rabies (Louis Pasteur).

• Subcellular & Genomic Horizons: Discovery and crystallization of viruses (Ivanovsky, Beijerinck, Stanley) up to Sanger sequencing and the first cellular genome (Haemophilus influenzae, 1995).