Variolation shortly after variolation began to outweigh the benefits of the procedure. From the 1760s, a number of individuals, including John Fewster, Peter Plett, Benjamin Jesty, and particularly Edward Jenner, were interested in the use of material from cowpox, an animal infection, to protect against smallpox. In 1796, Jenner vaccinated James Phipps, did more vaccinations in 1798, and was the first to publish evidence that cowpox protected against smallpox, was safer than variolation, and that his vaccine could be maintained by arm-to-arm transfer. The use of variolation soon began to decline as the smallpox vaccine became widely used and its benefits
1837 Great Plains smallpox epidemic experienced a major smallpox epidemic in 1780-81 which severely reduced their numbers down to less than a few thousand. Many other bands along the Missouri river suffered smallpox epidemics during 1801-02 and 1831. Sporadic efforts were made to promote vaccination among the Indigenous peoples since the turn of the nineteenth century. Later, the Indian Removal Act the U.S. Congress took its first step in 1832 to generate public support for vaccination of the Native Americans. But shortly after passage of this congressional act to extend vaccinations to Indians, Secretary Cass stated that no effort would be made "under any circumstances"