Smallpox decimated the Native American population
Due to Europeans bringing the disease to America, an estimated 90% of the Native American population was killed by smallpox.
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When European people first came to modern-day North America, they bought smallpox with them. While the disease had been around for centuries in Europe and Asia, the indigenous peoples of North America had no immunity at all. This destroyed the indigenous populations, killing people in their tens of millions. Over a century, 90 to 95% of the indigenous population were killed. The indigenous population of Mexico went from 11 million to one million people, playing a significant part in the fall of the Aztec Empire. The Smallpox pandemic is notable not only because of the amount of people it killed (roughly 56 million, the second largest in history) but because of the way it symbolises the utter destruction colonialism inflicted on indigenous populations.
[P1] The smallpox pandemic killed huge numbers of indigenous people in modern day North America, due to Europeans bringing the disease with them. [P2] The smallpox pandemic is the worst in history because it also symbolises the wider destruction of colonialism.