What are some initial and subsequent motives that drove Columbus to oppress indingenous peoples?

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It is always difficult to assess the motives of historical people; we have never met them and we can't talk to them and ask them why they do things. All we know about the character and motivations of Christopher Columbus comes from historical records of what he did, many of them written by himself or people under his command.

Most of the deaths of indigenous people were not actually due to oppression but disease; contact with Europeans spread diseases such as smallpox rapidly through indigenous populations and killed millions.

That said, we do have reason to believe that one of his primary motives was quite simple: Money.

His original goal was to find a more efficient trade route to India. Why? Because trade with India was extremely profitable, and would become more so if there were a more efficient route. Columbus secured funding for his expedition on these grounds; investors gave him money up front, expecting higher profits from the improved trade route later.

Far from being "the first to realize the Earth is round" as the myth goes, Columbus was convinced that the Earth was considerably smaller than it actually is. The people he was contradicting were actually mostly basing their assessments of the Earth's size and shape on Greek geometers, who had estimated the Earth's radius to within about 5% of its actual size. Columbus did not sail because he knew the shape of the Earth and others didn't; Columbus sailed because he didn't know the shape of the Earth and others did. What others did not know was that there were other continents besides Europe, Africa and Asia; Columbus didn't know that either, and simply got lucky.

When Columbus and his expedition arrived at North America, they saw a huge money-making opportunity. There were plentiful valuable natural resources for the taking, especially gold, tobacco, and spices; moreover, the indigenous populations could be easily conquered and enslaved because they were disorganized and technologically far less advanced.

It's also quite likely that Columbus and his people were motivated by racism, which has been a part of human psychology since time immemorial. He may have believed that the local populations were not simply technologically inferior, but indeed physically and mentally inferior, worthy only to work at the command of White people that he believed were superior beings. Some of the greatest cruelty committed by Columbus and his men is most easily explained in this way; it's hard to see why they would commit mass rapes and beheadings if profit were their sole motive.

But even in the absence of racism, it's quite likely that Columbus would have sought to exploit the lands and peoples of the New World in the name of profit---just as modern corporations often do to poor countries today.

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