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| | 1502 | Columbus sails on his fourth and last voyage to the New World (Honduras and Panama) | |
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| | 1502 | Spanish explorer Rodrigo de Bastidas visits Panama, which was home to Cuna, Choco, Guaymi and other indigenous peoples | |
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| | 1509 | Beginnings of slave trade to New World | |
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| | 1513 | September 25: Vasco Nunez de Balboa, Spanish explorer, crossed the Isthmus of Panama and claimed the Pacific Ocean for Spain He was named governor of Panama and the Pacific by King Ferdinand | |
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| | 1514 | 1,500 Spanish settlers go to Panama | |
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| | 1519 - | Panama becomes Spanish Vice-royalty of New Andalucia (later New Granada) | |
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| | 1522 | First slave revolt in America occurs in Hispaniola | |
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| | 1566 | Two million Indians die in South America of typhoid fever | |
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| | 1810 | Overthrow of the king of Spain by Napoleon | |
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| | 1821 | Panama becomes independent of Spain Panama joins the confederacy of Gran Colombia which consists of Colombia, Venezuela, Ecuador, Peru and Bolivia | |
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| | 1830 | Panama becomes part of Colombia following the collapse of Gran Colombia | |
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| | 1850's | The building of the Panama Railway which is the first Transcontinental railway of the New World crossing the isthmus from Colon to Panama City | |
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| | 1880s | France makes a failed attempt to build a Canal to link the Atlantic and Pacific | |
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| | 1903 | November 3 - Panama splits from Colombia and becomes fully independent US buys rights to build Panama Canal and controls the waterway for nearly a century | |
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| | 1915 | 15 August Official opening of the Panama Canal a massive achievement - the Panama Canal is 65 km ( 40 miles ) in length | |
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| | 1939 - | Panama ceases to be a US protectorate | |
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| | 2000: | 1 January Control of the canal passes from USA to Panama by the Torrijos-Carter treaty | |
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