1. 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

2. Battles to Infectious Diseases (2)
人类与传染病的斗争(2)
Battles to Infectious Diseases (2)

3. Vocabulary of Infectious disease
疾病，病：disease, illness, more individually
疾病预防：Disease prevention
疫：Epidemic, communicable disease, more population-based (瘟疫 plague)
防疫：Epidemic prevention
免疫：Immunity
免疫学：Immunology
疫苗：Vaccine
预防接种 Vaccination （Inoculation）

4. How did we win the battles
Identify the pathogens - Germ Theory 病原理论
Effective therapy – Vaccine and Antibiotics 疫苗和抗菌素
Prevention and control - Public Health System 公共卫生

5. 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

6. Antonie van Leeuwenhoek 1632-1723
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

7. 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.
巴斯德
Louis Pasteur

8. Germ Theory vs Spontaneous Generation Theory
"Do not put forward anything that you cannot prove by experimentation"
broth
broth
swan-neck flask experiment

9. 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

10. Establishment of Germ Theory
Heinrich Hermann Robert Koch ( ）
German physician
Isolating  Bacillus anthracis (1877), Mycobacterium tuberculosis   (1882) and Vibrio cholera (1883)
Invented pure culture of bacteria
Development of Koch’s postulates

11. Pure culture of bacteria

12. Koch’s postulates

13. Koch’s postulates

14. Koch’s postulates

15. 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 J. Robin Warren
b b. 1937

16. 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）

17. March 年 Barry Marshall was awarded as Honorary Professor of Zhejiang University, and delivered a speech: An usual disease and unusual discovery.

18. Discovery of Plasmodium malariae
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.

19. 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

20. 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, discovered）
Ronald Ross

21. Plasmodium vivax Lifecycle
Anopheles sinensis
疟原虫生活史
Plasmodium vivax Lifecycle

22. 1812 Napoleon’s Invasion of Russia
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?

23. Who defeated Napoleon? Endemic Typhus
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

24. 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

25. Discovery of pathogen of typhus
The Nobel Prize in Physiology or Medicine 1928 was awarded to Danish scientist Charles Nicolle “for his work on typhus“， he discovered the disease is transmitted by biting of flea or louse.
（Pasteur Institute）
Charles Nicolle －1936

26. Discovery of Viruses 病毒的发现
tobacco mosaic virus
tulips breaking virus
1619 (a morbid beauty)

27. 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.
Ивановсқий
( ),

28. Martinus Beijernick (1851-1931)
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 ( )

29. Dimensions of viruses
about 20 nm to about 250nm in diameter

30. … just for comparison
Leukocyte
10 µm

31. Leukocyte Bacillus subtitlis
… just for comparison
Leukocyte Bacillus subtitlis 1 m
10 µm

32. Leukocyte Bacillus subtitlis Herpesvirus
… just for comparison
Leukocyte Bacillus subtitlis Herpesvirus 1 m
10 µm

33. 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
, Twort and d’Herelle discovered bacteriophage
1932 Ernst Ruska invented the first electron microscople
TMV（Tobacco mosaic virus)
phage

34. Shapes of Viruses Spherical Rod-shaped Brick-shaped Tadpole-shaped
Bullet-shaped
Filament

35. Bacteriophage 1 3 2 4

36. Bacteriophage
(Replication
of DNA virus ）

37. （Replication of RNA virus ）
Influenza Virus
（Replication of RNA virus ）

38. （Replication of retrovirus)
HIV
（Replication of retrovirus)

39. virology Blumberg discovered antigen of hepatitis B virus (HBsAg）
The Nobel Prize in Physiology or Medicine 1976
"for their discoveries concerning new mechanisms for the origin and dissemination of infectious diseases“
Blumberg discovered antigen of hepatitis B virus (HBsAg）
Gajdusek discovered the causation of Kuru disease
Baruch S. Blumberg ( )
D. Carleton Gajdusek
( )

40. Kuru Disease
Prevalent in Native Fore people from Fore Islands of New Guinea in 2050s. Among local inhabitants 80% had the disease particularly in women and children.
Symptoms: tremble, ataxia, dementia, disability of moving, died in 3-6 months.
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.

41. Discovery of Prions The Nobel Prize in Physiology or Medicine 1997
"for his discovery of Prions - a new biological principle of infection“
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

42. Cellular prion PrPc Viral prion PrPsc

43. Prion Diseases Human disease associated with Prion as a cause：
Kuru Disease，Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker (GSS) disease and Fatal familial insomnia (FFI)
Animal diseases：
scrapie （sheep） Spongiform Encephalopathy （mad cow disease)

44. The Nobel Prize in Physiology or Medicine 2008
"for his discovery of human papilloma viruses causing cervical cancer"
"for their discovery of human immunodeficiency virus"
Harald zur Hausen Francoise Barre-Sinoussi Luc Montagnier
Regulation Retroviral Infections Unit, Virology Department, Institut Pasteur, b 1947
World Foundation for AIDS Research and Prevention, b 1932
Germany Cancer Research Center , Heidelberg, b 1936

45. October 13 Zu Housen was awarded the honorary professorship of Zhejiang University and dilivaryed a speech.

46. Invention of Vaccine
In the 10th Century Chinese invented variolation (blow the scab of smallpox skin lesion)
In English doctor Edward Jenner invented cowpox vaccine against human smallpox

47. Invention of vaccines Chicken cholera bacteria 鸡霍乱
Attenuated
1880,Pasteur first invented chicken cholera live attenuated vaccine

48. 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

49. Invention of rabies vaccine 狂犬病
Negri body
Rabies virus
545

50. Rabies vaccine was first used on 9-year old Joseph Meister, on July 6, 1885

51. Invention of vaccines

52. 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

53. Diphtheria antitoxin 北里柴三郎 Kitasato Shibasaburo 1852-1931
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
北里柴三郎 Kitasato Shibasaburo
Emil Adolf von Behring 1854－1917

54. Tetanus antitoxin 破伤风
With the same principle Von Behring and Kitasato developed tetanus antitoxin
serum therapy against 
diphtheria and tetanus
opisthotonus角弓反张
dojingrsal， ventral

55. Invention of serum therapy
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

56. Poliomyelitis (infantile paralysis) ＆ Poliovirus 脊髓灰质炎 （小儿麻痹症）
18th Dynasty ( BC)
Equinus clubfoot

57. Jonas Salk invented live polio vaccine in 1954
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)

58. 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

59. Chemotherapy for Syphilis
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

60. 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

61. Discovery of antibiotics and the therapeutic revolution
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

62. Discovery of antibiotics and the therapeutic revolution
 Flaming discovered the antibiotic penicillin 青霉素 from the fungus Penicillium notatum in 1928, and published in 1928
Alexander Flaming
staphylococci

63. Sir Alexander Fleming Twice Saved Churchill's Life
(A false story)

64. Discovery of antibiotics and the therapeutic revolution
1939, biochemist Ernst Chain ( ）and pathologist Howard Florey ( ） 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)

65. 抗菌素的发现－治疗学的革命

66. 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链霉素was the first
antibiotic that could be used to cure
the disease tuberculosis
(1943)
Selman Waksman

68. 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

69. 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.。

70. Public Health System 公共卫生系统
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)

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

72. 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

73. 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."

74. 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 as well as law and regulation
Improving environment including living environment and occupational environment
Reproduction health
Epidemilogical survey, disease surveillance, statistics, research and education

75. Changing the Leading Causes of Death
Leading causes of death in US: comparison of 1990 and 年和1997年美国主要死因比较

76. Public Health System
婴幼儿死亡率 平均期望寿命

77. 再见
The End