1. 医学史简论(2) A Brief History of Medicine
Yu Hai
Zhejiang University School of Medicine

2. 疾病改变历史，疾病改变人类
The history of mankind is the history of its diseases – Folke Henschen ( )
Disease changes the human civilization and
human history
Disease changes human itself genetically

3. 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

4. The impact on population of disease 疾病对人类社会的影响
From Zhou and Qin ( BC) to Ming and Qing Dynasty ( ) the Chinese population fluctuated from 10 to 60 million, it did not reach 100 million till Qianlong Reign ( )of Qing Dynasty
Apart from war and famine the most influential factors for population is the disease epidemics

5. Trends of World Population
billion

6. 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

7. 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
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
AD second epidemics contributed to final fall of Roman Empire in 476 AD (Falciparum malaria)
Marcus Aurelius
Meditation

8. 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”

9. Voyage of Columbus
Since 1492 Columbus discovered the new continent, European colonists brought disasters to native Americans
Columbus voyage 1492

10. 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

11. Impact of Disease on civilization
Spanish General Cortes conquered Aztec in (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)

12. 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

13. Impact of Disease on Human Civilization
16th century epidemics in America
smallpox
measles
typhus
influenza
By the end of 16th century the number of native Americans reduced by 90-95%

14. Disease changed human itself－Evolution of immune system

15. 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

16. Disease changed human itself － Impact on human genes
A T Gl Val
Change of configuration
镰状红细胞贫血
Sickle cell anemia
HbAHbA HbAHbS HbSHbS
 A A  AS SS
Homozygote Heterozygote

17. Disease changed human itself － Impact on human genes
Distribution of Falciparum malaria
Distribution of sickle cell gene carrier

18. 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 8-10%
The sickle cells have protection from malaria (plasmodium can not parasite), it may be the results of evolution (mutant events back to ,000 years ago)

19. AIDS virus
And
CD4 T-cells

20. Two receptors are necessary for HIV to enter the CD4 T cell ：CD4 and CCR5

21. CCR5 and HIV infection
In 2008, German doctors reported that an HIV-infected leukemia patient had received a bone marrow transplant from a donor who is homozygous for the CCR5-Δ32 trait. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues

22. 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　　

23. 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
Eyam- the Plague village in England

24. Origin of CCR5 mutation?
Which disease facilitated the natural selection?
Plague?
Smallpox?
Scott and Duncan: mathematical modeling study reveals the CCR5-Δ32 may appear ago
It may be related to a feverish viral disease similar to Ebola hemorrhagic fever

25. 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 （ ）
因缺少一颗钉子而损失一匹战马

26. Napoleon’s hemorrhoids and defeat at Waterloo
Napoleon Bonaparte ( )，was finally defeated by Duke of Wellington at Waterloo on June , because painful thrombosis hemorrhoids prevented him personally
surveying
the battle
fields on the
horse back.
（anecdotage)
Exiled to Saint Helena

27. 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?

28. 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

29. Russian Revolution and Fall of Romanov Reign
February 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

30. 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

31. Who overthrew the Romanov Regime?
Vladimir Lenin
Queen Victoria

32. 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

33. Sex chromosome-linked inheritance (recessive allele)

34. A pedigree European Royal Family

35. Victoria and Royal Family

36. 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

37. The End