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Viruses such as rabies are known as early as 3000-2000 BC, where texts describe this and related disease that affected both animals and humans. Early evidence from Mari, a city in modern Syria, indicates by about 4000 year BP, people who had symptoms of the cold or flue were isolated from other individuals. There is no indication that anyone understood what caused such sicknesses, but it is clear that they understood that viral infections could spread, leading to the creation of a type of quarantine system with isolated rooms built for sick individuals. In Pharaonic Egypt, measles were considered a normal occurrence in childhood. In the Roman Period, we also have detailed accounts of what can be described as small pox. Galen Pergamum, who worked as Marcus Aurelius' personal physician, describes a sickness with fever that caused vomiting and diarrhoea. Boils in the skin were also observed, with the Romans realizing that these disease probably occurred in crowded places. However, there is no evidence of large-scale attempts at prevention, except perhaps isolating infected individuals. Like many cultures, the Roman interpreted outbreaks as punishment from the gods for events or offenses they may have committed.

The first clear evidence Increasingly, more texts and descriptions of describing a virus on other biological viruses are found that described what they did to plant and animal life outside of humans might comes from the Roman period, where Roman authors described riderpest, a type of cattle virus, discussed as an affliction affecting herds. A disease in Japan in In the 8th century a plant virus was described by Empress Kōken, where she noticed a yellowing of leaves caused in plants that we can today attribute to tomato yellow leaf curl virus common in some plants. Throughout the Medieval period, many waves of measles and small pox plaques occurred. In the 16th century, a mysterious virus was described in Tutor England, which my have arrived in England during the conquest of the country by the Tudor dynasty. This disease may have been a type of hantavirus, a pulmonary virus, that seemed to kill victims within a day. It had devastating consequences in England and Europe, but it disappeared sometime in the mid-16th century. Isolation and herbal medicines were used to treat this virus. Perhaps the best know impacts of viruses in human history were the various viruses brought to the New World after the 15th century and spread throughout subsequent centuries. This included measles, influenza, and smallpox, which arguably aided the conquest of North and South America as very large numbers of native populations died. Today we know that native populations were vulnerable because these diseases had their origins from domesticated animals that were not native to the Americas. This meant populations there had not developed immunity over centuries as Old World populations had. By the 17th century, at least in the Ottoman Empire, there is evidence that there was an understanding that if you injected someone who did not have a sickness with a small amount of infected material, that person could develop an immunity. The use of variolation was practiced, which included injecting puss from an infected smallpox victim to a person who was not infected. This discovery saved many lives and Lady Mary Wortley Montagu, an English aristocrat, witnessed this form of treatment, which she brought back with her to England. This represents one of the first active attempts to immunize people to a virus.