Transcript Discovery of Viruses

医学史简论 （8）
A Brief History of Medicine
浙江大学医学院 余 海
Zhejiang University School of Medicine
人类与传染病的斗争(2)
Battles to Infectious Diseases (2)
Infectious disease in Chinese Medicine

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病：disease, illness, more individually
疾病预防：Disease prevention
疫：Epidemic, communicable disease, more
population-based (瘟疫 plague)
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防疫：Epidemic prevention
免疫：Immunity
免疫学：Immunology
疫苗：Vaccine
预防接种 Vaccination （Inoculation）
How did we win the battles

Identify the pathogens - Germ Theory 病原理论
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Effective therapy – Vaccine and Antibiotics 疫苗
和抗菌素

Prevention and control - Public Health System
公共卫生
Establishment of Germ Theory
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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
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 小动物，
Leeuwenhoek
became the
pioneer of
microbiology
Antonie van Leeuwenhoek
1632-1723
Establishment of Germ Theory
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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.
巴斯德 1822-1895
Louis Pasteur
Germ Theory vs Spontaneous Generation Theory
"Do not put forward anything that you cannot prove by experimentation"
broth
broth
swan-neck flask experiment
Establishment of Germ Theory

The Nobel Prize in Physiology or
Medicine 1905
"for his investigations and
discoveries in relation to
tuberculosis"
He discovered Mycobacterium tuberculosis
in March 24，that day is designated as
World Tuberculosis Day“世界结核病日”
科赫 Robert Koch
1843－1910
Establishment of Germ Theory
Heinrich Hermann Robert Koch
(1843-1910）
 German physician
 Isolating Bacillus anthracis (1877),
Mycobacterium tuberculosis (1882)
and Vibrio cholera (1883)
 Invented pure culture of bacteria
 Development of Koch’s postulates
Pure culture of
bacteria
Koch’s postulates
Koch’s postulates
Koch’s postulates
The Nobel Prize in Physiology or Medicine 2005
Barry Marshall and
Robin Warren from
Australia won 2005
Nobel Prize in
Physiology or
Medicine：
"for their discovery of
the bacterium
Helicobacter pylori
and its role in gastritis
and peptic ulcer
disease"
Barry J. Marshall
b. 1951
J. Robin Warren
b. 1937
１９８２，Marshall
and Warren discovered
Helicobacter pylori (Hp)
and approved its
relationship with gastritis,
peptic ulcer and
duodenal ulcer ，
The bacteria secrete urease, that
hydrolyse urea to produce
ammonia （C13 breath test）
March 27 2006年 Barry Marshall was awarded as
Honorary Professor of Zhejiang University, and
delivered a speech: An usual disease and unusual
discovery.
Discovery of Plasmodium malariae
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1880 French doctor Charles
Laveran found protozoon from
the blood of a malaria patient
in Algeria and named it as
Plasmodium malariae
1897 British military doctor
Ronald Ross discovered the
oocyst in stomach of mosquito
and approved that malaria is
transmitted by mosquito.
疟疾 Malaria

The Nobel Prize in
Physiology or Medicine
1907
"in recognition of his work on
the role played by protozoa in
causing diseases"
Charles Laveran
拉费兰 1845-1922
疟原虫的发现

The Nobel Prize in
Physiology or
Medicine 1902
"for his work on malaria, by
which he has shown how it
enters the organism and
thereby
has
laid
the
foundation for successful
research on this disease and
methods of combating it“
(1894 met Patrick Manson, 1897.8.20
discovered）
Ronald Ross 18571932
Anopheles sinensis
疟原虫生活史
Plasmodium vivax
Lifecycle
1812 Napoleon’s Invasion of Russia
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June 1812 Napoleon
mobilized 500,000 French
and allied troopers to
invade Russia, retreated on
December with less than
10,000 men remained. Who
defeated Napoleon?
Marshall Kutuzov?
Cold winter in Moscow?
Who defeated Napoleon? Endemic Typhus
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Fatal epidemics of typhus
outbroke among French
soldiers, resulting severe
depletion of troopers, when
Napoleon entered Moscow
only 90,000 men left.
斑疹伤寒 Typhus (Trench
Fever or Jail Fever)
Caused by Rickettsia
transmitted by louse or flea.
Rickettsia Prowazekii
Discovery of pathogen of typhus

The Nobel Prize in
Physiology or Medicine
1928 was awarded to
Danish scientist Charles
Nocolle "for his work
on typhus“
（Pasteur Institute）
Charles Nicolle
1866－1936
Discovery of pathogen of typhus

Two scientists Howard
Ricketts and Howard
Ricketts were credited for
discovery of pathogen of
typhus and both died
from the disease infected
in the laboratory. The
pathogen of typhus was
named after them
(Rickettsia prowazekii).
Stanislav Von
Prowazek
(1875–1912)
Howard Ricketts
1871-1910
Discovery of Viruses
病毒的发现
tobacco mosaic virus
tulips breaking virus
1619 (a morbid beauty)
Discovery of Viruses

Ивановсқий
(1864-1920),
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.
Discovery of Viruses
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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
Martinus Beijernick
(1851-1931)
virus.
Dimensions of viruses
about 20 nm to about 250nm in diameter
… just for comparison
Leukocyte
10 µm
… just for comparison
Leukocyte
Bacillus subtitlis
1 m
10 µm
… just for comparison
Leukocyte
Bacillus subtitlis
1 m
10 µm
Herpesvirus
Discovery of Viruses
TYMV (Tomato
yellow mosaic virus)
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1898 German scientist
Loeffler and Frosch
discovered Foot-and-mouth
disease virus
TMV
（Tobacco
mosaic virus)
1911, Rous discovered Rous
sarcoma virus
1915-1917, Twort and
d’Herelle discovered
bacteriophage
phage
Shapes of Viruses
Spherical
Rod-shaped
Brick-shaped
Tadpole-shaped
Bullet-shaped
Filament
Bacteriophage
1
3
2
4
Bacteriophage
(Replication
of DNA virus ）
Influenza Virus
（Replication of RNA virus ）
HIV
（Replication of retrovirus)
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The Nobel Prize in
Physiology or
Medicine 1976
virology
"for their discoveries
concerning new
mechanisms for the origin
and dissemination of
infectious diseases“
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Blumberg discovered
antigen of hepatitis B virus
(HBsAg）
Gajdusek discovered the
causation of Kuru disease
Baruch S. Blumberg
(1925-2011.4.5)
D. Carleton Gajdusek
(1923-2008.12.12)
Kuru Disease
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Prevalent in Native Fore people
from Fore Islands of New Guinea in
2050s. Among 35000 local
inhabitants 80% had the disease
particularly in women and children.

Symptoms: tremble, ataxia,
dementia, disability of moving,
died in 3-6 months.
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After long-term survey Gajdusek
discovered that the endemic was
associated with eating the brain of
the dead in funeral. This practice
was banned and the disease no
longer occurred.
Discovery of Prions
The Nobel Prize in Physiology
or Medicine 1997
"for his discovery of Prions - a
new biological principle of
infection“
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Prusiner proposed that the
cause of transmissible
spongiform encephalopathy
(TSE）was a type of infectious
protein (Prions）
Stanley B. Prusiner University
of California School of Medicine
b. 1942
Cellular prion PrPc
Viral prion PrPsc
Prion Diseases

Human disease associated with
Prion as a cause：
Kuru Disease，Creutzfeldt-Jakob
disease (CJD), GerstmannStraussler-Scheinker (GSS) disease
and Fatal familial insomnia (FFI)
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Animal diseases：
scrapie （sheep） Spongiform
Encephalopathy （mad cow
disease)
The Nobel Prize in Physiology or Medicine
2008
"for his discovery of
human papilloma viruses
causing cervical cancer"
Harald zur Hausen
Germany Cancer Research
Center , Heidelberg, b 1936
"for their discovery of human immunodeficiency
virus"
Francoise Barre-Sinoussi
Regulation Retroviral Infections
Unit, Virology Department,
Institut Pasteur, b 1947
Luc Montagnier
World Foundation for
AIDS Research and
Prevention, b 1932
October 13 Zu Housen was
awarded the honorary
professorship of Zhejiang
University and dilivaryed a
speech.
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
Invention of vaccines
Chicken cholera bacteria 鸡霍乱
Attenuated
1880,Pasteur first invented
chicken cholera live
attenuated vaccine
Development of vaccines
1881, Pasteur
developed anthrax 炭疽
vaccines, which were
based on live-attenuated
cultures of Bacillus
anthracis and effectively
protected livestock from
the disease
anthrax
Live-attenuated anthrax vaccine
Invention of rabies vaccine 狂犬病
Negri body
Rabies virus
545
Rabies vaccine was first used on 9-year
old Joseph Meister, on July 6, 1885
Invention of vaccines
Diphtheria antitoxin 白喉抗毒素
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
Diphtheria antitoxin
•Roux and Yersini
discovered diphtheria
toxin which is responsible
for the symptoms of the
disease
•Von Behring and his coworker Kitasato
discovered the diphtheria
antitoxin which lay
foundation of serum
therapy
北里柴三郎
Kitasato Shibasaburo
1852-1931
Emil Adolf von Behring
1854－1917
Tetanus antitoxin 破伤风
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With the same principle Von
Behring and Kitasato developed
tetanus antitoxin
serum therapy against
diphtheria and tetanus
opisthotonus
角弓反张
dojingrsal，
ventral
Invention of serum therapy
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The Nobel Prize in
Physiology or Medicine
1901
"for his work on serum therapy,
especially its application against
diphtheria, by which he has opened
a new road in the domain of
medical science and thereby placed
in the hands of the physician a
victorious weapon against illness
and deaths“
（Pasteur died 1895，Nobel Laureate
could be)
Emil Adolf von Behring
1854- 1917
Poliomyelitis (infantile paralysis) ＆
Poliovirus 脊髓灰质炎 （小儿麻痹症）
Poliomyelitis
18th Dynasty (1580-1350 BC)
Equinus clubfoot
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 liveattenuated
vaccine (pills)
Chemotherapy for Syphilis 梅毒
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
风流一夜情 水银伴终生
Treponema pallidum
Chemotherapy for Syphilis
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Paul Ehrlich intended to find the magic bullet
against microorganism from chemical dyes

In 1909 he and his student Hata Sahachiro
(秦佐八郎） developed a arsenical
compounds Salvarsan (Arsphenamine ，606
）, which was effective against syphilis

Ehrlich received the Nobel Prize in Medicine
together with Mechnikov in 1908
Paul Ehrlich(1854－1915)
and Hata Sahachiro
Discovery of antibiotics and the therapeutic
revolution
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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
Discovery of antibiotics and the therapeutic
revolution
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Afterward a series of
sulfonamides 磺胺 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
Discovery of antibiotics and the therapeutic
revolution
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Flaming discovered
the antibiotic penicillin 青
霉素 from the
fungus Penicillium
notatum in 1928, and
published in 1928
Alexander Flaming
1881-1955
staphylococci
Sir Alexander Fleming Twice Saved Churchill's Life
(A false story)
Discovery of antibiotics and the
therapeutic revolution
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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)
抗菌素的发现－治疗学的革命
Discovery of antibiotics and the
therapeutic revolution
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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链霉素was the first
antibiotic that could be used to cure
the disease tuberculosis
(1943)
Selman Waksman
1888-1973
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
Discovery of antibiotics and the
therapeutic revolution
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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.。
Public Health System 公共卫生系统
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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.
Rome：water 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)
August 1854 cholera outbreak
in London Soho, 140,000
infected and 618 died. John
Snow surveyed the cause and
transmission of the disease
Public Health System
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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
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."
Functions of Public Health
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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 as well as law and regulation
Improving environment including living environment and occupational
environment
Reproduction health
Epidemilogical survey, disease surveillance, statistics, research and
education
Changing the Leading Causes of Death
Leading causes of death in US: comparison of 1990
and 1997 1990年和1997年美国主要死因比较
Public Health System
婴幼儿死亡率
平均期望寿命
再
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