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| 1491 |
| | Savonarola, the new prior of San Marco, is a stern critic of both the pope in Rome and the Medici in Florence | |
| | Savonarola Fotofile CG
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| 1492 |
| | Rodrigo Borgia, elected pope as Alexander VI, already has four illegitimate children and possibly sires three more while pope | |
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| 1493 |
| | Pope Alexander VI draws a line through the Atlantic, dividing new discoveries between Spain (west) and Portugal (east) | |
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| 1505 |
| | Pope Julius II summons Michelangelo to Rome to create the pope's own elaborately sculpted tomb | |
| | One of the 'slaves' for the tomb of Julius II Fotofile CG
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| 1509 |
| | Raphael begins work on the frescoes in the pope's apartment in the Vatican, known as the Stanze ('Rooms') | |
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| 1520 |
| | Luther's writings are burnt in Rome by order of the pope | |
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| 1521 |
| | Pope Leo X excommunicates Martin Luther after he has refused to recant | |
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| 1527 |
| | Pope Clement VII hides in Castel Sant'Angelo while Rome is sacked by German mercenaries | |
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| 1540 |
| | Pope Paul III establishes Ignatius Loyola and his followers as the Society of Jesus, or the Jesuits | |
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| 1542 |
| | Pope Paul III establishes the Roman Inquisition, with the specific task of fighting against the Protestant heresy | |
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