I'm currently reading 1491, a book which tries to piece together what the Americas were like pre-columbus. One of the main points of the book is that estimates that the Americas had several million people at the point of European arrival are ridiculously small, due to the fact that European diseases spread throughout the Americas much faster than European conquerers did. So the conquerers of the Aztecs, Incas etc. all encountered populations that had been dramatically reduced by the spread of European disease, possibly by 90-95%. There were many European diseases that the Native Americans had no natural defenses to, and they were all introduced within a very short time frame, meaning that the indigenous people didn't have anywhere near the time as populations to adjust to these new diseases, and were easily conquered by Europeans. My question is, was this inevitable? There is no way the Americas could have stayed isolated from the old world, at some point contact was inevitable, and with that contact, the spread of diseases. Is there any reasonable alternative path history might have taken that would have allowed the Native Americans to adjust to these diseases? Does anyone know about Native American immunology today? For instance, in Peru or Bolivia, do indigenous populations STILL have greater susceptibility to old-world diseases? Obviously many people in the Americas have mixed ancestry, which helps boost immunity, but have ''pure'' indigenous populations developed resistances that their ancestors lacked in 1491?