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He was a preeminent theologian and a proponent of hesychasm; he is venerated as a Saint in the Eastern Orthodox Church. He was initially asked by his fellow monks on Mount Athos to defend them from the charges of Barlaam of Calabria. Barlaam believed that philosophers had better knowledge of God than did the prophets, and valued education and learning more than contemplative prayer. As such, he believed the monks on Mount Athos were wasting their time in contemplative prayer when they should be studying. Gregory said that the prophets in fact had greater knowledge of God, because they had actually seen or heard God Himself. Addressing the question of how it is possible for humans to have knowledge of a transcendent and unknowable God, he drew a distinction between knowing God in his essence (Greek ousia) and knowing God in his energies (Greek energeiai), although workings or activities is probably a more appropriate English translation, since it avoids the esoteric connotations the word energies has acquired today. He maintained the orthodox doctrine that it remains impossible to know God in His essence (to know who God is in and of Himself), but possible to know God in His energies (to know what God does, and who He is in relation to the creation and to man), as God reveals himself to humanity. In doing so, he made reference to the Cappadocian fathers and other earlier Christian writers.
Gregory further asserted that when Peter, James and John witnessed the transfiguration of Jesus on Mount Tabor, that they were in fact seeing the uncreated light of God; and that it is possible for others to be granted to see that same uncreated light of God with the help of certain spiritual disciplines and contemplative prayer, although not in any automatic or mechanistic fashion.
Some of his writings are collected in the Philokalia.
The second Sunday of the Great Lent is called the Sunday of Gregory Palamas in the Eastern Orthodox Church for his commemoration.
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