<P> After Edward Jenner's 1796 demonstration that the smallpox vaccination worked, the technique became better known and smallpox became less deadly in the United States and elsewhere . Many colonists and natives were vaccinated, although, in some cases, officials tried to vaccinate natives only to discover that the disease was too widespread to stop . At other times, trade demands led to broken quarantines . In other cases, natives refused vaccination because of suspicion of whites . The first international healthcare expedition in history was the Balmis expedition which had the aim of vaccinating indigenous peoples against smallpox all along the Spanish Empire in 1803 . In 1831, government officials vaccinated the Yankton Sioux at Sioux Agency . The Santee Sioux refused vaccination and many died . </P> <P> While epidemic disease was a leading factor of the population decline of the American indigenous peoples after 1492, there were other contributing factors, all of them related to European contact and colonization . One of these factors was warfare . According to demographer Russell Thornton, although many lives were lost in wars over the centuries, and war sometimes contributed to the near extinction of certain tribes, warfare and death by other violent means was a comparatively minor cause of overall native population decline . </P> <P> From the U.S. Bureau of the Census in 1894: "The Indian wars under the government of the United States have been more than 40 in number . They have cost the lives of about 19,000 white men, women and children, including those killed in individual combats, and the lives of about 30,000 Indians . The actual number of killed and wounded Indians must be very much higher than the given...Fifty percent additional would be a safe estimate ..." </P> <P> There is some disagreement among scholars about how widespread warfare was in pre-Columbian America, but there is general agreement that war became deadlier after the arrival of the Europeans and their firearms . The South or Central American infrastructure allowed for thousands of European conquistadors and tens of thousands of their Indian auxiliaries to attack the dominant indigenous civilization . Empires such as the Incas depended on a highly centralized administration for the distribution of resources . Disruption caused by the war and the colonization hampered the traditional economy, and possibly led to shortages of food and materials . The Arauco War, Chichimeca War, Red Cloud's War, Seminole Wars, War of 1812, Pontiac's Rebellion, Beaver Wars, French - Indian War, American Civil War, American Revolution, Modoc War, Oka Crisis, Battle of Cut Knife, all represented either pyrrhic victories by colonial forces, outright defeat, military stalemates, or further alliance - politics . Across the western hemisphere, war with various Native American civilizations constituted alliances based out of both necessity or economic prosperity and, resulted in mass - scale intertribal warfare . European colonization in the North American continent also contributed to a number of wars between Native Americans, who fought over which of them should have first access to new technology and weaponry--like in the Beaver Wars . </P>

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