医学史简论（ 8 ） A Brief History of Medicine

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 • 病：disease, illness, more individually • 疾病预防：Disease prevention • 疫：Epidemic, communicable disease, more population-based (瘟疫 plague) • 防疫：Epidemicprevention • 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 • 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 • 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 270diameters First to see and describe bacteria asanimalcules 小动物， Leeuwenhoek became the pioneer of microbiology Antonie van Leeuwenhoek 1632-1723

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

Pure culture of bacteria

Koch’s postulates

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

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. Ивановсқий (1864-1920),

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)

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 Herpesvirus 1 m 10 µm

Discovery of Viruses TYMV (Tomato yellow mosaic virus) • 1898 German scientist Loefflerand Froschdiscovered Foot-and-mouth disease virus • 1911,Rousdiscovered Rous sarcoma virus • 1915-1917,Twortand d’Herellediscovered bacteriophage TMV（Tobacco mosaic virus) 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 （Replicationof retrovirus)

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 placed 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 vaccinewas 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 diphtheriaevery year. 1891Von 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 andYersini discovered diphtheria toxin which is responsible for the symptoms of the disease • Von Behringand his co-worker Kitasato discovered the diphtheria antitoxin which lay foundation of serum therapy 北里柴三郎Kitasato Shibasaburo1852-1931 Emil Adolf von Behring1854－1917

Tetanus antitoxin 破伤风 • With the same principle Von Behringand 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角弓反张 dorsal， ventral

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 Salkinvented 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 Sabininvented oral live-attenuated vaccine (pills)

Chemotherapy for Syphilis 梅毒 Beforechemotherapyintroduced,mercuryusedbetheonlycureforsyphilis,buttheharmofmercurypoisoningismoreseriousthanthediseaseitself A night in the arms of Venus leads to a lifetime on Mercury 风流一夜情水银伴终生 Treponemapallidum

Chemotherapy for Syphilis • PaulEhrich intendedtofindthemagicbulletagainstmicroorganismfromchemicaldyes • In 1909 he and his student Hata Sahachiro(秦佐八郎）developeda 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)andHataSahachiro

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

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

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 1881-1955 staphylococci

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

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)

抗菌素的发现－治疗学的革命

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 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 • 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 • 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 • 1848passed British Public Health Act • 1946 CDCwas founded in US (Communicable Disease Center-1980 Centers of Disease Control)

医学史简论（ 8 ） A Brief History of Medicine