Unit 3: Infectious Disease and Humans

Necrotizing Fasciitis

• flesh-eating disease after drinking contaminated water

• causes rapid skin necrosis and extreme hemorrhaging

• usually caused by bacteria

10,000 BCE

Food and drink are produced by microbial fermentation - discoverers: Egyptians, Chinese, and others

1500 BCE

Tuberculosis, polio, leprosy, and smallpox are evident in mummies and tomb art - discoverers: Egyptians

50 BCE

copper is recovered from mine water acidified by sulfur-oxidizing bacteria - discoverers: roman metal workers under Julius Caesar

1362 CE

plague transmission is observed - discoverers: Ibn al-Khatib (Granada)

1546 CE

Syphilis and other diseases are seen to be contagious - discoverer: Girolamo Fracastoro (Padua)

Discovery of tetracycline antibiotic use by Ancient Nubians

• Bone analysis showed heavy ____ deposits

• like an antibiotic

• First reported (and disbelieved) in 1981

• 2010 study confirmed high amounts of deposits, even in children’s bones, suggesting intentional and prolonged use

  • Dissolved bones in acid and then extracted the _____ compounds

  • Quantified via mass spec

who used tetracycline antibiotics?

Ancient Nubians

How did scientists determine that the tetracycline residue wasn't just contamination from bacteria?

Dissolved bones in acid and then used mass spec to identify the compounds

Humoral Theory

• Prevailing medical theory from the ancient world until 19th century

  • Hipocrates and galen of pergamon

  • Heath and diseased is caused by the balance of the four humors (fluids) in the body

• Combined with theories of elements and personalities/behaviors

• The imbalance of humors, or dyscrasia, was thought to be the direct cause of all diseases

• Disease could also be the result of “corruption” of one or more of the humors, which could be caused by environmental circumstances, dietary changes, or any other factors

• goal of treatment was to rid the body of some of the excess humor through techniques like purging, bloodletting, catharsis, diuresis, and others

Humoral theory → practice

• PBDD

  • Puking, bleeding, drooling, diarrhea

• Use of poisons/toxins to stimulate PBDD symptoms:

  • Calomel - Mercury

    • Violent gastrointestinal effects

    • Drooling

  • Antimony

    • Violent vomiting

  • Enemas

Miasma Theory

• From Ancient world until 1880s

• Disease is caused by a poisonous vapor or mist filled with particles from decomposed matter (miasmata)

• Diseases could also be the product of environmental factors such as contaminated water, foul air, and poor hygienic conditions

• Infections were not passed between individuals but would affect individuals within the locale that gave rise to such vapors. It was identifiable by its foul smell

• Many people avoided breathing night air by going indoors and keeping windows and doors shut. There was also a general fear that cold or cool air spread disease

• Cultural beliefs about getting rid of odor also made the clean-up of waste a high priority for cities. It also encouraged the construction of well-ventilated hospital facilities, schools, and other buildings

Miasma Theory → Practice

• Cleaning up waste

• Ventilation

• Plumbing

• Fear of ‘slums’ and people who lived in them

Germ Theory

microorganisms can cause disease

Girolamo Fracastoro

• an Italian physician, poet, and scholar in 1546 who proposed early form of Germ Theory

  • ‘Seeds of disease’ theory - epidemic diseases are caused by transferable tiny particles of “spores” that could transmit infection

• Proposed that rabies was transmitted from dog saliva getting into skin

• ‘Syphilis’ word derived from one of his poems

Marko Anton Plencic (1705-1786)

• Slovenian physician

• Published a book that described his theory that “animalcula minima” that lived in the human body were the cause of disease and that they could be spread

The Scandal of Germ Theory

• ideas were vehemently opposed and ridiculed by the wider European scientific and medical establishment in favor of humor and miasma

• The availability of the early microscope led to many challenges to ideas about spontaneous generation during the 1700s and 1800s 

Spontaneous generation

the idea that living creatures arise from non-living matter (dust → fleas)

John Snow (1813-1858)

• English physician 

• Leader in development of anesthesia and medical hygiene

• Exposed to squalid conditions as a child

• Studied ether, chloroform, and other substances and their safe use during surgery, but especially childbirth

• his study was a major event in the history of public health and geography

• Sometimes called the ‘Father of Epidemiology’

• Became one of Queen Victoria’s physicians, assisting with the medicated birth of two of her children

• After his death, he’d be proven right by the discovery of Vibrio cholerae

Pasteur - Key findings

• Airborne dust contained microorganisms which develop and multiply 

• Liquids remained unadulterated if kept away from air (and hence these microorganisms) after heating

• Studying fermentation, discovered organisms that can grow without air (called anaerobic) in contrast to those that require air to grow (aerobic)

• Recommended aseptic procedures (sterilizing linen and wound dressings) to reduce disease

• disproved spontaneous generation

pasteurization

Heating liquids to certain temperatures would kill organisms and preserve them/prevent spoiling

Joseph Lister

develops antiseptic medicine

• High mortality rate of surgery - sepsis

• he applied Pasteur’s germ theory to surgery 

  • Must prevent microbes from entering wounds

  • Methods: 

    • Heating

    • Filtration

    • Chemical

•  Used wound dressings soaked in carbolic acid

  • Slowed uptake

• Reduced mortality rates from major operations from around 40% to <3% by 1910

Semmelweis

• noticed that midwives wards had lower death rates than physician wards

  • Midwives washed their hands and did not deal with dead bodies

  • Physicians refused to wash their hands and were offended at the suggestion

• Proposed washing hands in chlorinated lime water before deliveries. Deaths decreased. But he couldn't explain why

• He was mocked, his colleagues did not adopt the practice

• He suffered a nervous breakdown and was committed to an asylum, where he was beaten, and died two weeks later

Robert Koch

• MD in 1866, followed by more study in Berlin

• Developed methods (along with his assistant and colleagues) to visualize, isolate, and grow bacteria in pure culture

  • Staining

  • Culture broth/media

  • Agar and petri dishes

• Anthrax was a common disease of livestock

• A bacterium had previously been isolated from animals who died from anthrax but this was not accepted as the cause of the disease

• working in a room in his apartment that he used as a lab, he inoculated mice with spleens of dead animals with anthrax → mice died

  • When he did this with spleens from healthy mice → mice survived

Koch’s Postulates

1. The microorganism must be found in abundance in all organisms suffering from the disease but should not be found in healthy organisms

2. The microorganisms must be isolated from a diseased organism and grown in pure culture

3. The cultured microorganism should cause disease when introduced into a healthy organism

4. The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent

Koch’s 1st Postulate

The microorganism must be found in abundance in all organisms suffering from the disease but should not be found in healthy organisms

Koch’s 2nd Postulate

The microorganisms must be isolated from a diseased organism and grown in pure culture

Koch’s 3rd Postulate

The cultured microorganism should cause disease when introduced into a healthy organism

Koch’s 4th Postulate

The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent

Exception to 1st Postulate

Exceptions: asymptomatic carriers (common with viral diseases)

• E.g. cholera, HIV/AIDS, polio, herpes simplex, COVID-19

Exception to 2nd Postulate

Exception: Viruses cannot grow in pure culture. They require a host to grow

Exception to 3rd Postulate

Exception: sometimes exposure to an infectious agent does not result in successful infection

• Examples: tuberculosis, cholera

Other Exceptions to Koch’s Postulates

• Some pathogens can cause several diseases

  • Examples: 

    • Varicella-zoster virus causes both chickenpox and shingles

    • Meningitis can be caused by a variety of bacterial, viral, fungal, and parasitic organisms

• Viruses break a lot of the rules we learned from bacteria

  • honey badgers of the microbial world

What does the debt of discovery require from us?

Every medical and scientific advancement is bought with the lives of those who did not have access to them