(2) A Brief History of Medicine

Yu Hai Zhejiang University School of Medicineyuhai@zju.edu.cn

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

Impact of disease on the human societyFear, anxiety and panic results in social instabilityPopulation dramatically decreased, including the elite groups of society Political turmoil, economic recession and social development stagnated or went downImpact on the outcome of warsEnhance the development of public health and medical sciences

The impact on population of diseaseFrom 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 DynastyApart from war and famine the most influential factors for population is the disease epidemics

Trends of World Population 2011.10. 31 7 billion

Impact of disease on progress of civilizationThe golden ages of Greece ended by plaques in 430BC Spartans ravaged the surrounding countryside of Athens, an epidemic smallpoxstruck the crowded urban populace , killed thousands, including General Pericles ( 429 BC). Ended the Greek golden age (338 BC Philip II of Macedonia, 146 BC fell in Roman)Pericles (495?-429) BC

Impact of disease on progress of civilization The decline and fall of Rome Empire impact of plagues 166-180 AD Plaque of Galen (smallpox?) twoRoman emperorsLucius Verus (169BC) and Marcus Aurelius (180BC) died from the epidemic, total death toll reached to 4-5 million211-266 AD second epidemics contributed to final fall of Roman Empire in 476 AD (Falciparum malaria)Marcus Aurelius 121-180Meditation

Impact of disease on progress of civilizationSince 16 century western colonists started entering the Africa, but the fatal infectious disease stopped them (white peoples tomb)The discovery of quinine let Europeans managed to colonize AfricaTropical disease

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

-Ancient American civilizationThree civilizations Maya 2500BC-8th centuryAztecInca

Impact of Disease on civilizationSpanish General Cortes conquered Aztec in 1519-1521 (300+ smallpox vs 15 million, The capital Tenochtitlan fell, population of Aztec dropped to 1millionSpanish conquest Pizarro colonized Inca in 1553 resulting dramatically reduced Incan population (200 vs 50,000)

Impact of Disease on Human Civilization1518 slave trade startedbrought 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 America1518-1529 smallpox1530-1531 measles typhus1558-1559 influenzaBy the end of 16th century the number of native Americans reduced by 90-95%

Disease changed human itselfEvolution of immune system

Innate ImmunityTollToll-like Receptor, TLRAdaptive ImmunityDendritic Cell, DC

Disease changed human itself Impact on human genes

Sickle cell anemia

HbAHbA HbAHbS HbSHbS

A T Gl ValChange of configuration A A AS SSHomozygote 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 genesIn 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 70-150,000 years ago)

AIDS virusAndCD4 T-cells

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

CCR5 and HIV infectionIn 2008, German doctors reported that an HIV-infectedleukemiapatient had received a bone marrow transplant from a donor who is homozygous for the CCR5-32 trait. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues

CCR532T-cell membrane receptor CCR5 variant CCR5-32 was found in people with natural immune to HIVFrequency of CCR5-32 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?September 1665 Black death outbreak in the village, the villagers decided self-isolated from others260 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 ofCCR5-32Eyam- the Plague village in England

Origin of CCR5 mutation?Which disease facilitated the natural selection?Plague?Smallpox?Scott and Duncan: mathematical modeling study reveals the CCR5-32 may appear 2500-3000 agoIt may be related to a feverish viral disease similar to Ebola hemorrhagic fever

Benjamin Franklin 1706-1790

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.

Napoleons hemorrhoids and defeat at WaterlooNapoleon 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 Napoleons Invasion of RussiaJune 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 TyphusFatal epidemics of typhus outbroke among French soldiers, resulting severe depletion of troopers, when Napoleon entered Moscow only 90,000 men left.

Typhus (Trench Fever or Jail Fever)Caused by Rickettsia transmitted by louse or flea.Rickettsia Prowazekii

Russian Revolution and Fall of Romanov ReignFebruary 1917 Revolution (Julian calendar March in theGregorian calendar) the Tzar Nicola II was deposed and replaced with the Provisional governmentOctober 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 RomanovsThe Romanov family under house arrested in the Yekaterinburg were executed by Bolsheviks without any trial at early morning of April 17,1918July 17, 1998 the remains of Royal family were reburied in a state ceremony

Who overthrew the Romanov Regime?Vladimir Lenin 1870-1924Queen Victoria 1817-1901

HemophiliaHemophilia is a rare, inherited bleeding disorder in which the blood doesnt clot normallyType A: 80-85%, deficiency of clotting factor VIIIType 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 Alexandragave birth of Alexisthe 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

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