From the very discovery of America the spiritual welfare of the native tribes was a subject of concern to the various colonizing nations, particularly Spain and France, with whom the Christianization and civilization of the Indians were made a regular part of the governmental scheme, and the missionary was frequently the pioneer explorer and diplomatic ambassador. In the English colonization, on the other hand, the work was usually left to the zeal of the individual philanthropist or of voluntary organizations.

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First in chronological order, historic importance, number of establishments, and population come the Catholic missions, conducted in the earlier period chiefly by Jesuits among the French and by Franciscans among the Spanish colonies. The earliest mission establishments within the present United States were those begun by the Spanish Franciscan Fathers, Padilla, Juan de In Cruz, and Descalona of the Coronado expedition, among the Quivira (Wichita), Pecos, and Tigua in 1542. Three years later the work was begun among the Texas tribes by Father Olmos. A century thereafter the first Protestant mission (Congregational) were founded by Mayhew and Eliot in Massachusetts. From that period the work was carried on both North and South until almost every denomination was represented, including Orthodox Russian in Alaska and the Mormons in Utah.

In the four centuries of American history there is no more inspiring chapter of heroism, self-sacrifice, and devotion to high ideals than that afforded by the Indian missions. Some of the missionaries were of noble blood and had renounced titles and estates to engage in the work; most of them were of finished scholarship and refined habit, and nearly all were of such exceptional ability as to have commanded attention in any community and to have possessed themselves of wealth and reputation, had they so chosen; yet they deliberately faced poverty and sufferings, exile and oblivion, ingratitude, torture, and death itself in the hope that some portion of a darkened world might be made better through their effort. To the student who knows what infinite forms of cruelty, brutishness, and filthiness belonged to savagery, from Florida to Alaska, it is beyond question that, in spite of sectarian limitations and the shortcomings of individuals, the missionaries have fought a good fight. Where they have failed to accomplish large results the reason lies in the irrepressible selfishness of the white man or in the innate incompetence and unworthiness of the people for whom they labored.