DISEASE E&E (History and Causation)

Question 1

Plagues in medieval Europe:

Answer 1

-life expectancy then was 33 years
-many babies, children and teenagers died from infectious diseases
-causes were unknown and people were mostly helpless against disease
-many believed that plagues were punishment by God

Question 2

Common diseases in medieval Europe:

Answer 2

-dysentery
-malaria
-diphtheria
-flu
-typhoid
-smallpox
-leprosy
-bubonic plague

Question 3

Edward Jenner:

Answer 3

-English doctor and scientist
-developed the smallpox vaccine (the world’s first vaccine)
-father of Immunology

Question 4

Edward Jenner’s work:

Answer 4

-“saved more lives than the work of any other human”

Question 5

Smallpox

Answer 5

-two variants (variola major and minor)
-characteristic fluid-filled blisters
-transmission between people via contaminated objects
-mortality rate of 30% in infected individuals
-killed hundreds of millions over the centuries
-eradicated in 1980 by WHO via vaccination

Question 6

Smallpox in Whistlebury:

Answer 6

-Jenner observed that milkmaids were less likely to acquire smallpox
-key observation that the prevalence differed among people with different professions
>lead to development of a smallpox vaccine

Question 7

Cowpox

Answer 7

-caused by cowpox virus
-causes lesions on udders of cows
-in humans, infection causes localized pustular lesions on the hands
-not dangerous and eventually cleared by the immune system
*exposure causes cross-protection against smallpox

Question 8

James Phipps and Edward Jenner

Answer 8

-test whether exposure to cowpox against smallpox
-Jenner exposed 8year old boy , James to cowpox
-6 weeks later, he exposed him to smallpox (had no effect)
-inoculated him more than 20x
*unethical to deliberately expose humans to a deadly disease

Question 9

What was the major obstacle to the scientific understanding of infectious diseases in the 19th century?

Answer 9

-science hadn’t discovered micro-organisms
-causative agent for infectious disease was unknown (pathogen corner had not been discovered)
-miasma theory was the dominant idea
-development of germ theory

Question 10

Development of germ theory:

Answer 10

-would revolutionize medicine and public health

Question 11

Miasma theory of infectious disease:

Answer 11

-was the predominant theory of disease transmission
-“bad air” from rotting organic matter
-diseases by environmental factors (water, foul air, poor hygienic conditions)
-no transmission between individuals (no microscopic disease agent)
-disease prevention: avoid locations with poisonous vapours
-replaced by germ theory at end of 19th century

Question 12

Germ theory of infectious disease:

Answer 12

-many scientists contributed to it
>major contributors were Louis Pasteur and Robert Koch

Question 13

Louis Pasteur:

Answer 13

-French biology, microbiologist and chemist
*pasteurization

Question 14

Robert Koch:

Answer 14

-German physician and microbiologist
*Koch postulates

Question 15

Pasteurization of milk:

Answer 15

-growth of microorganisms was responsible for spoiling beverages such as beer, wine, and milk
>lead to economic losses
-heated liquids (60-100 C) and killed most bacteria and fungi (*pasteurization)

Question 16

Pasteurization prevented:

Answer 16

-prevent wine, beer and milk from spoiling
*showed that “diseases” of beverages were caused by micro-organisms
*suggested that human disease could also be caused by micro-organisms

Question 17

Spontaneous generation:

Answer 17

-air can spontaneously cause genesis of life in liquids

Question 18

Pasteur disproved spontaneous generation:

Answer 18

-used experiments with broth and heat
-boiled broth with open neck seeded by micro-organisms=spoiled
-broiled broth with swan neck=did not spoil despite being in contact with air
*micro-organisms came from outside rather than SG in the broth

Question 19

Micro-organisms killed by heat:

Answer 19

-critical for the development of medicine and public health
*have an agency to kill micro-organisms

Question 20

Robert Koch: characterized important bacterial pathogens

Answer 20

-Bacillus antracis: causes anthrax
-vibrio cholerae: causes cholera
-myobacterium tuberculosis: causes tuberculosis

Question 21

Nobel prize: Robert Koch:

Answer 21

-physiology and medicine
-work on tuberculosis
*showed the importance of spores for bacterial survival in the environment

Question 22

Bacillus anthracis: agent of anthrax disease

Answer 22

-formation of spores that would remain dormant under specific conditions
-under optimal conditions, the spores were activated and caused disease (ex. eaten or from soil)
-multiplication of bacilli and sporulation

Question 23

Causative agent of anthrax:

Answer 23

-dry-fixed bacterial cultures onto glass slides
-used dyes to stain the cultures
-observed them through a microscope
*first to link a specific microorganism with a specific disease

Question 24

Koch’s postulates:

Answer 24

1. Microorganism must be found in abundance in all individuals suffering from the disease, but not in healthy individual’s
2. Microorganism must be isolated from a diseased individual and grown in pure culture
3. Cultured microorganism should cause disease when introduced into a healthy individual
4. Microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent

Question 25

Exceptions to Koch’s postulates:

Answer 25

-not all infected individual’s show disease (asymptomatic carriers)
-not all pathogens can be cultured (ex. prions, viruses must be co-cultured with host cells)
-not all organisms exposed to an infectious agent will acquire the infection

Question 26

Discovery of viruses;

Answer 26

-germ theory was centered on bacteria, viruses too small for the light microscope
-research on TMB led to discovery of viruses
>naïve plants exposed to infected material=infected with TMD
>material passed through filter still caused disease: small bacteria or toxin
>dilution experiment: infectious agent could replicate and was not a toxin
*’virus’ to describe this new type of infectious disease

Question 27

TMD and TMV

Answer 27

-tobacco mosaic disease
-tobacco mosaic virus

Question 28

Electron microscope (EM):

Answer 28

-invented in 1931

Question 29

Viruses and the electron microscope:

Answer 29

-demonstration that TMV was made of protein and nucleic acid (later shown to be RNA)
-protein crystallography to show that TMV was a particle
-first EM image of TMV made in 1939
-invention of EM was critical for virology

Question 30

1918 influenza pandemic:

Answer 30

-caused by H1N1 influenza A virus
-first documented case was March 1918 in Kansas
-500 million people infected in 4 successive waves
-estimate of 17-50million people died
-cause remained unknow until 1930s

Question 31

Richard Pfeiffer:

Answer 31

-German physician and bacteriologist (studied under Robert Koch)
-isolated Haemophilus influenza from influenza patients
>most believed H. influenza caused influenza
-many flu patients didn’t have H. influenza (BLAMED poor culture skills)
-antisera and vaccines against H. influence did NOT help flu patients
*his stature obstructed progress

Question 32

Richard Shope: influenza in pigs

Answer 32

-influenza like disease in pigs in Iowa (1918 and 1929)
-swine influenza=severe pneumonia
-infected pigs contained Haemophilus influenza suis (HIS) and filterable agent

Question 33

HIS:

Answer 33

-caused no disease

Question 34

Filtrable agent:

Answer 34

-caused weak symptoms

Question 35

HIS + filtrable agent:

Answer 35

-reproduced severe pneumonia in pigs
-HIS is commensal in healthy pigs
*difficult to demonstrate causality if an infection disease is caused by combination of pathogens
>viral pathogen knocks out immune system so secondary bacteria can do opportunistic infection

Question 36

Virus causes human influenza:

Answer 36

-sample pharyngeal secretions from human influenza patients
-used ferrets as animal model
-filterable virus form human produced influenza-like disease in ferrets
-developed antibody response that protected them from re-infection
-researcher accidently was exposed to sneezing ferret and developed the flu

Question 37

Lessons learned from 1918 influenza pandemic and Koch’s postulates:

Answer 37

-influenza virus caused secondary infection in H. influenza in human patients
-Pfeiffer incorrectly identified H. influenza as the cause
-important to communicate between medical doctors and veterinarians
-difficult to satisfy Koch’s postulates disease with multiple infectious agents
-human-adapted pathogens may not establish infection in animals models

Question 38

Viruses and Koch postulates:

Answer 38

-did not meet Koch’s postulates
-Thomas Rivers adapted them
-“blind adherence of them may act as a hinderance instead of an aid”

Question 39

Viruses and culture:

Answer 39

-can be cell cultured but not in lifeless media

Question 40

Disease:

Answer 40

-can have multiple etiological agents
Ex. virus and bacterium

Question 41

Infected animals:

Answer 41

-develop antibody responses to pathogens
>include antibody responses as evidence for a causal relationship

Question 42

Incubation period:

Answer 42

-interval between exposure and appearance of disease
-some have long incubation periods (years)
-determining causation is more difficult for long incubation periods

Question 43

BSE:

Answer 43

-pathogen: prion
-incubation 4-6 years in cattle, 12 years in humans

Question 44

Cancer:

Answer 44

-pathogen: oncoviruses
-incubation is years

Question 45

Oncoviruses:

Answer 45

-are viruses that cause cancer in their host
-integrate their genome into host genome
-can cause cancer by 2 mechanisms

Question 46

Oncoviruses examples:

Answer 46

> papilloma viruses
hepatitis viruses
herpesviruses
retroviruses
MMTV
FeLV

Question 47

2 mechanisms for oncoviruses:

Answer 47

1. Viral genome contains cancer promoting oncogenes
2. Integration of viral genome into host genome disrupts cancer-suppressing oncogens

Question 48

Johne’s disease:

Answer 48

-pathogen: MAP
-incubation 2-5years in cattle

Question 49

AIDS:

Answer 49

-pathogen: HIV
-incubation 10 years in humans (in absence of treatment)

Question 50

ASLV and RSV: (oncoviruses

Answer 50

-causes sarcomas and lymphomas in chickens
>injection with tumor filtrate caused cancer in healthy chickens
*idea that infectious agents cause cancer was “utter nonsense”

Question 51

Lessons learned form oncoviruses:

Answer 51

-incubation period for some diseases can take years
-infection with oncovirus can result in cancer years later
-infectious agents can cause unexpected diseases
-many types of cancers have a viral organ
-dogmatic thinking impedes progress