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The first European epidemic of the bubonic plague dates back to the mid 6th century and is called the Plague of Justinian. The largest plague epidemic was the Black Death in Europe in the 14th century. In medieval times, the large loss of people (due to the bubonic plague) in a town created an economic disaster. Community plague doctors were quite valuable and were given special privileges; for example, plague doctors were freely allowed to perform autopsies, which were otherwise generally forbidden in Medieval Europe, to research a cure for the plague.

In some cases, plague doctors were so valuable that when Barcelona dispatched two to Tortosa in 1650, outlaws captured them en route and demanded a ransom. The city of Barcelona paid for their release. The city of Orvieto hired Matteo fu Angelo in 1348 for four times the normal rate of a doctor of 50-florin per year. Pope Clement VI hired several extra plague doctors during the Black Death plague. They were to attend to the sick people of Avignon. Of 18 doctors in Venice, only one was left by 1348: five had died of the plague, and 12 were missing and may have fled.