????? (8) A Brief History of Medicine

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????? (8) A Brief History of Medicine

• ??????? ? ?
• Zhejiang University School of Medicine

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?????????(2) Battles to Infectious
Diseases(2)
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Infectious disease in Chinese Medicine

• ?disease, illness, more individually
• ????Disease prevention
• ?Epidemic, communicable disease, more population
  based (?? plague)
• ??Epidemic prevention
• ??Immunity, Vaccination
• ??Vaccine

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How did we win the battles

• Identify the pathogens - Germ Theory
• Effective therapy Vaccine and Antibiotics
• Prevention and control - Public Health System

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Establishment of Germ Theory

• De Contagione et Contagiosis Morbis (On infection
  and infectious diseases,1546)
• He proposed that epidemic diseases are caused by
  transferable tiny particles or "spores" that
  could transmit infection by direct or indirect
  contact or even without contact over long 
  distances.

Girolamo Fracastoro 1478-1553
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Establishment of Germ Theory
A Dutch cloth merchant used new method for
grinding and polishing tiny lenses of great
curvature which gave magnifications up to 270
diameters First to see and describe bacteria as
animalcules, Leeuwenhoek became the pioneer of
microbiology
Antonie van Leeuwenhoek 1632-1723
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Establishment of Germ Theory

• Created germ theory of disease, (germ theory vs
  miasma theory and spontaneous generation)
• Created the first vaccine for rabies 
• Invented Pasteurizaion
• Is regarded as one of the three main founders
  of microbiology, together with Ferdinand
  Cohn and Robert Koch.

??? 1822-1895 Louis Pasteur
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Germ Theory vs Spontaneous Generation Theory "Do
not put forward anything that you cannot prove by
experimentation"
swan-neck flask experiment
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Establishment of Germ Theory

• Heinrich Hermann Robert Koch (1843-1910)
• German physician
• Isolating Bacillus anthracis (1877),
  the Tuberculosis bacillus (1882) and the Vibrio
  cholera (1883)
• Development of Kochs postulates
• He was awarded the Nobel Prize in Physiology or
  Medicine for his tuberculosis findings in 1905.

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Pure culture of bacteria
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Kochs postulates
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Kochs postulates
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Kochs postulates
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Discovery of Viruses
tulips breaking virus
1619 (a morbid beauty)
tobacco mosaic virus
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Discovery of Viruses

• The very first virus discovered is credited to
  the St. Petersburg Academy of Science on the 12th
  February 1892 by Dmitri Iwanowsky a Russian
  botanist. While studying mosiac tobacco disease,
  he found that the agent causing the disease was
  small enough for pass though ceramic filter that
  are small enough to trap all bacteria. This is
  generally accepted as the beginning of Virology.

?????????? (1864-1920),
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Discovery of Viruses

• 1898, Dutch scientist Martinus Beijernick
  confirmed Iwanowski's results on tobacco mosaic
  virus.
• He developed with the term "contagium vivum
  fluidum" which means soluble living germ as
  first the idea of the virus.

 Martinus Beijernick (1851-1931)
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Dimensions of viruses
about 20 nm to about 250nm in diameter
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just for comparison Leukocyte
10 µm
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just for comparison Leukocyte Bacillus
subtitlis
1
m
10 µm
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just for comparison Leukocyte Bacillus
subtitlis Herpesvirus
1
m
10 µm
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Discovery of Viruses
TYMV (Tomato yellow mosaic virus)

• 1898 German scientist Loeffler and Frosch
  discovered Foot-and-mouth disease virus
• 1911, Rous discovered Rous sarcoma virus
• 1915-1917, Twort and dHerelle discovered
  bacteriophage

TMV(Tobacco mosaic virus)
phage
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Shapes of Viruses

• Spherical
• Rod-shaped
• Brick-shaped

Tadpole-shaped Bullet-shaped Filament
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Bacteriophage
1
3
2
4
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Bacteriophage (Replication of DNA virus )
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Influenza Virus (Replication of RNA virus )
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HIV (Replication of retrovirus)
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Invention of Vaccine
In the 10th Century Chinese invented variolation
(blow the scab of smallpox skin lesion)
In 1796 English doctor Edward Jenner invented
cowpox vaccine against human smallpox
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Invention of vaccines
Chicken cholera bacteria
placed
1880,Pasteur first invented chicken cholera live
attenuated vaccine
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Development of vaccines
1881, Pasteur developed anthrax vaccines, which
were based on live-attenuated cultures
of Bacillus anthracis and effectively protected
livestock from the disease
anthrax
Live-attenuated anthrax vaccine
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Invention of rabies vaccine
Negri body
Rabies virus
545
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Rabies vaccine was first used on 9-year
old Joseph Meister, on July 6, 1885
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Invention of vaccines
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Diphtheria antitoxin
At that time in Germany alone 50,000 children
died from diphtheria every year. 1891 Von Behring
cured first case of diphtheria with antitoxin,
thousands of life have been saved since he
developed serum therapy
Diphtheria toxin and antitoxin
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Diphtheria antitoxin

• Roux and Yersini discovered diphtheria toxin
  which is responsible for the symptoms of the
  disease
• Von Behring and his co-worker Kitasato discovered
  the diphtheria antitoxin which lay foundation of
  serum therapy

????? Kitasato Shibasaburo 1852-1931
Emil Adolf von Behring 1854-1917
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Tetanus antitoxin

• With the same principle Von Behring and Kitasato
  developed tetanus antitoxin
• Von Behring won the first Nobel Prize in
  Physiology or Medicine in 1901 for developing
• serum therapy against 
• diphtheria and tetanus

opisthotonus????
dorsal, ventral
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Poliomyelitis (infantile paralysis) Poliovirus
Poliomyelitis 18th Dynasty (1580-1350 BC)
Equinus clubfoot
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Three American scientist John Enders, Thomas
Weller and Frederick Robbins discovered method to
culture polio virus using non-nervous tissue,
they won Nobel Prize in 1954
Jonas Salk invented live polio vaccine in 1954
Franklin Roosevelt himself was a victim of polio,
launched the March of Dimes to raise the National
fund for polio prevention in 1938
Albert Sabin invented oral live-attenuated
vaccine (pills)
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Chemotherapy for Syphilis
Before chemotherapy introduced, mercury used be
the only cure for syphilis, but the harm of
mercury poisoning is more serious than the
disease itself A night in the arms of Venus leads
to a lifetime on Mercury ????? ?????
Treponema pallidum
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Chemotherapy for Syphilis

• Paul Ehrich intended to find the magic bullet
  against microorganism from chemical dyes
• In 1909 he and his student  Hata Sahachiro
  (????) developed a arsenical compounds Salvarsan
  (Arsphenamine ,606), which is effective
  against syphilis
• Ehrlich received the Nobel Prize for Medicine
  together with Mechnikov in 1908

Paul Ehrlich(1854-1915) and Hata Sahachiro
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Discovery of antibiotics and the therapeutic
revolution

• Domagk found f red dye Prontosil and its derivant
  sulfonamide to be effective against streptococcus,
  and treated his own daughter Alice with it,
  saving her the amputation of an arm.
• Prontosil became the first commercially available
  antibacterial agent

Gerhard Domagk 1895-1964
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Discovery of antibiotics and the therapeutic
revolution

• Afterward a series of sulfonamides were
  synthesized and sulfonamides became a
  revolutionary weapon at the time, but were later
  replaced by penicillin
• Domagk received the 1939 Nobel Prize in
  Physiology or Medicine

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Discovery of antibiotics and the therapeutic
revolution

•  Flaming discovered the antibiotic
  penicillin from the fungus Penicillium notatum in
  1928, and published in 1928

Alexander Flaming 1881-1955
staphylococci
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Sir Alexander Fleming Twice Saved Churchill's
Life
(A false story)
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Discovery of antibiotics and the therapeutic
revolution

• 1939, biochemist Ernst Chain (1906-1979)and
  pathologist Howard Florey (1898-1968) took up
  researching and mass producing it with funds from
  the U.S and British governments.
• They started mass production after the bombing of
  Pearl Harbor. When D-day arrived they had made
  enough penicillin to treat all the wounded allied
  forces.
• Feb 12,1941, penicilline was first applied
  clinically
• Penicillin was referred as one of three major
  invents during the World War II (Atom bomb, Radar
  and Penicillin)

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??????-??????
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Discovery of antibiotics and the therapeutic
revolution

• Waksman performing research in soil bacteriology
  in Rutgers University
• Waksman and his team discovered
• several antibiotics, including actinomycin
• clavacin, streptomycin, neomycin and
  others. 
• Of these streptomycin was the first
• antibiotic that could be used to cure
• the disease tuberculosis
• (1943)

Selman Waksman 1888-1973
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(No Transcript)
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Dispute about discovery

• The details and credit for the discovery of its
  use as the antibiotic streptomycin were strongly
  contested by one of Waksman's graduate
  students, Albert Schatz, and resulted in
  litigation. The litigation ended with a
  substantial settlement for Schatz and the
  official decision that Waksman and Schatz would
  be considered co-discoverers of streptomycin.
  Schatz made the discovery while working in
  Waksman's basement lab, and using Waksman's
  equipment

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Discovery of antibiotics and the therapeutic
revolution

• After the discovery of penicillin and
  streptomycin, more antibiotics were isolated from
  the soil, upon 1960s more than 600 antibiotics
  were available in practice
• Thanks of discovery and application of
  antibiotics severe bacterial infection has no
  longer a incurable disease and the average life
  expectancy increased by 10 year leading to the
  therapeutic revolution.?

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Public Health System

• Early religions attempted to regulate behavior
  that specifically related to health, from types
  of food eaten, to regulating certain indulgent
  behaviors, such as drinking alcohol or sexual
  relations. 
• Romewater supply and sewage system, public bath
  and public toilet
• After plague outbreak in Middle Ages clearance,
  sanitation, removing bodies of the dead, burning
  parts of the city and quarantine system
• 1848 passed British Public Health Act
• 1946 CDC was founded in US (Communicable Disease
  Center-1980 Centers of Disease Control)

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August 1854 cholera outbreak in London Soho,
140,000 infected and 618 died. John Snow surveyed
the cause and transmission of the disease
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Public Health System

• An English social reformer, noted for his work to
  reform the Poor Laws and improve sanitary
  conditions and public health
• 1842, Chadwick proposed 'Report into the Sanitary
  Conditions of the Labouring Population of Great
  Britain'
• 1848 British parliament passed the British Public
  Health Act
• People found him rude and dictatorial. Some said
  that they would rather take their chance with
  cholera than be told what to do by Chadwick!

Sir Edwin Chadwick 1800-1890
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Public Health System

• Public health is the science and art of
  preventing disease, prolonging life and promoting
  health through the organized efforts and informed
  choices of society, organizations, public and
  private, communities and individuals. (1920, C.
  E.A. Winslow)
• The goal of public health is to improve lives
  through the prevention and treatment of disease.
  The WHO defines health as "a state of complete
  physical, mental and social well-being and not
  merely the absence of disease or infirmity."

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Functions of Public Health

• Prevention of infectious diseases and other
  diseases through primary, secondary, tertiary
  prevention
• Changing health behavior, improving diet and
  nutrition through health education and health
  promotion
• Improving environment including living
  environment and occupational environment
• Reproduction health
• Epidemilogical survey, disease surveillance,
  statistics, research and education

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Changing the Leading Causes of Death
Leading causes of death in US comparison of 1990
and 1997 1990??1997?????????
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Public Health System
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The End