European settlement and expansion in North America negatively impacted Native Americans in several ways: 1) Unintentional disease transmission from Europeans devastated Native American populations. Smallpox epidemics in the 17th-18th centuries killed up to 90% of some tribes. 2) White political leaders justified removing Native Americans to lands west of the Mississippi River by citing treaties signed to acquire tribal lands for settlement and resources. 3) The Indian Removal Act of 1830 led to the forced relocation of many eastern tribes like the Cherokee to Oklahoma on the infamous Trail of Tears, during which over 1/4 of the Cherokee died along the route.