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医学史简论(2) A Brief History of Medicine Yu Hai Zhejiang University School of Medicine [email protected] 疾病改变历史,疾病改变人类 The history of mankind is the history of its diseases – Folke Henschen (1881-1977) Disease changes the human civilization and human history Disease changes human itself genetically 疾病对人类社会的影响 Impact of disease on the human society Fear, anxiety and panic results in social instability Population dramatically decreased, including the elite groups of society Political turmoil, economic recession and social development stagnated or went down Impact on the outcome of wars Enhance the development of public health and medical sciences The impact on population of disease 疾病对人类社会的影响 From Zhou and Qin (1046-256 BC) to Ming and Qing Dynasty (1368-1644) the Chinese population fluctuated from 10 to 60 million, it did not reach 100 million till Qianlong Reign (1735-1795)of Qing Dynasty Apart from war and famine the most influential factors for population is the disease epidemics 2011.10. 31 7 billion Trends of World Population 疾病 对文明进程的影响 Impact of disease on progress of civilization The golden ages of Greece ended by plaques in 430 BC Spartans (斯巴达人) ravaged the surrounding countryside of Athens, an epidemic (smallpox?)struck the crowded urban populace , killed thousands, including General Pericles (伯里克 利 429 BC). Ended the Greek golden age (338 BC Philip II of Macedonia, 146 BC fell in Roman) Pericles (495?-429) BC 疾病 对文明进程的影响 Impact of disease on progress of civilization The decline and fall of Rome Empire – impact of plagues 瘟疫导致罗马帝国的衰落 166-180 AD “Plaque of Galen” (smallpox?) two Roman emperors — Lucius Verus (169BC) and Marcus Aurelius (180BC) died from the epidemic, total death toll reached to 4-5 million 211-266 AD second epidemics contributed to final fall of Roman Empire in 476 AD Marcus Aurelius 121-180 (Falciparum malaria) Meditation 疾病 对文明进程的影响 Impact of disease on progress of civilization Since 16 century western colonists started entering the Africa, but the fatal infectious disease stopped them (white people’s tomb”) The discovery of quinine let Europeans managed to colonize Africa “Tropical disease” Voyage of Columbus Since 1492 Columbus discovered the new continent, European colonists brought disasters to native Americans Columbus voyage 1492 疾病 对文明进程的影响-美洲文明 Ancient American civilization Three civilizations Maya (2500BC-8th century) Aztec Inca Impact of Disease on civilization Spanish General Cortes conquered Aztec in 15191521 (300+ smallpox vs 15 million), The capital Tenochtitlan fell, population of Aztec dropped to 1million Spanish conquest Pizarro colonized Inca in 1553 resulting dramatically reduced Incan population (200 vs 50,000) Impact of Disease on Human Civilization 1518 slave trade started,brought infectious diseases previously not existing in America (malaria, yellow fever) and insects, resulting further decrease of native population Impact of Disease on Human Civilization 16th century epidemics in America 1518-1529 smallpox 1530-1531 measles 1546 typhus 1558-1559 influenza By the end of 16th century the number of native Americans reduced by 90-95% Disease changed human itself-Evolution of immune system 先天性免疫 Innate Immunity Toll样受体 Toll-like Receptor, TLR 获得性免疫 Adaptive Immunity 树突状细胞 Dendritic Cell, DC Disease changed human itself - Impact on human genes A T Gl Val Change of configuration HbAHbA HbAHbS HbSHbS A A AS SS 镰状红细胞贫血 Sickle cell anemia Homozygote Heterozygote Disease changed human itself - Impact on human genes Distribution of Falciparum malaria Distribution of sickle cell gene carrier Disease changed human itself - Impact on human genes In sub-Saharan Africa the incidence of sickle cell anamia as high as 1/400, Heterozygote--carriers of a single sickle cell allele are 810% The sickle cells have protection from malaria (plasmodium can not parasite), it may be the results of evolution (mutant events back to 70-150,000 years ago) AIDS virus And CD4 T-cells Two receptors are necessary for HIV to enter the CD4 T cell : CD4 and CCR5 CCR5 and HIV infection In 2008, German doctors reported that an HIVinfected leukemia patient had received a bone marrow transplant from a donor who is homozygous for the CCR5Δ32 trait. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues 疾病改变人类-CCR5Δ32 T-cell membrane receptor CCR5 variant CCR5-Δ32 was found in people with natural immune to HIV Frequency of CCR5-Δ32 varies: Not in African or Asian origin North European 14% Mediterraneans 2% Average 10% Europeans with one allele, 1% with two alleles Origin of CCR5 mutation? Eyam- the Plague village in England September 1665 Black death outbreak in the village, the villagers decided self-isolated from others 260 out of 350 villagers dies in 1 year From death records since 1630, the descendants of survivors were traced, 14% of them carry the gene mutation ofCCR5-Δ32 Origin of CCR5 mutation? Which disease facilitated the natural selection? Plague? Smallpox? Scott and Duncan: mathematical modeling study reveals the CCR5-Δ32 may appear 2500-3000 ago It may be related to a feverish viral disease similar to Ebola hemorrhagic fever Disease and the outcome of war (For want of a nail – rhyme) For want of a nail the shoe was lost. For want of a shoe the horse was lost. For want of a horse the rider was lost. For want of a rider the battle was lost. For want of a battle the kingdom was lost. And all for the want of a horseshoe nail. -Benjamin Franklin (1706-1790) 因缺少一颗钉子而损失一匹战马 Napoleon’s hemorrhoids and defeat at Waterloo Napoleon Bonaparte (1769-1821), was finally defeated by Duke of Wellington at Waterloo on June 18 1815, because painful thrombosis hemorrhoids prevented him personally surveying the battle fields on the horse back. (anecdotage) Exiled to Saint Helena 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? 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 Russian Revolution and Fall of Romanov Reign February 1917 Revolution (Julian calendar March in the Gregorian calendar) the Tzar Nicola II was deposed and replaced with the Provisional government October Revolution (November 7) the Provisional Government was removed and replaced with a Bolshevik (Communist) government, finally let to the establishment of Soviet Union Fate of Romanovs The Romanov family under house arrested in the Yekaterinburg were executed by Bolsheviks without any trial at early morning of April 17,1918 July 17, 1998 the remains of Royal family were reburied in a state ceremony Who overthrew the Romanov Regime? Vladimir Lenin 1870-1924 Queen Victoria 1817-1901 血友病 Hemophilia Hemophilia is a rare, inherited bleeding disorder in which the blood doesn’t clot normally Type A: 80-85%, deficiency of clotting factor VIII Type B: 15-20%, deficiency of clotting factor IX Sex chromosome-linked inheritance (recessive allele) A pedigree European Royal Family Victoria and Royal Family Tsar Nicholas II married Alexandra,gave birth of Alexis,the misfortune of Romanovs started: Tsar and Tsarina were preoccupied with the health of their son, the affairs of state deteriorated, culminating in the Russian revolution. But Alexis did not die from hemophilia, at the age of fourteen he was executed with the rest of the family. Starets Rasputin - the last straw The End