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Venice was threatened by land and sea, but struggled to stay independent, although it had frequent famines with people begging and often dying in the public square. The entire population was also temporarily incapacitated in 1588 by what was later called "grippe". Even the Grand Council was completely empty. The disease then spread to Milan, France, Spain and even the Americas. (Ref. 260 ) The famine, felt throughout the Mediterranean, was partially relieved in 1591 when wealthy merchants organized a spectacular diversion of northern ships, loaded with wheat and rye, into the Mediterranean. Portuguese merchants of Antwerp were among those making allegedly 300% profit on these ships, but that did not matter to starving Italians. (Ref. 292 )

Naples was one of the largest cities of Europe and an extravagant place, with the Neapolitan nobles striving to keep favor at the court of the Spanish viceroy. (Ref. 292 ) In general, southern Italy was Spain's and northwest Italy belonged to France. The other great powers, England and Germany, by remote measures changed sides from year to year and there was much confusion. In the end, Italy was devastated and financially exhausted. To add insult to injury, both syphilis

McNeill makes the interesting suggestion that syphilis may have been a transition from the old, endemic disease, yaws. (Ref. 140 )
and typhus appeared in Europe during the long series of Italian wars, lasting from 1494 to 1559. In Italy syphilis was called the "French Disease"; the Spanish called it "Naples Disease". Gonorrhea was also rampant. Typhus swept the peninsula in 1505 and again in 1528 while the first great influenza epidemic struck in 1510 and plague was in Rome in 1522. (Ref. 8 , 140 , 125 )

The papacy had its own history in this century. Caesar Borgia, son of Pope Alexander VI and a former cardinal, attempting to save Italy for the papacy in 1502 in his capacity as the Duke of the Romagna, joined the French in an attack on Naples to free it from the Spanish. The new pope, Julius II (1503-1513), frustrated his schemes, however, and he then turned to the Spanish side. Julius II, one of the greater popes, was a warrior and somewhat morose. He was followed by happy Leo X, who believed that joy should be unconfined, but who failed to realize the seriousness of the developing theological situation. Rome reached new heights of liberty and sexuality. Martin Luther came, saw Rome, was shocked and went home to Germany to initiate the reformation. (Ref. 51 )

In contrast to the turmoil on the political and religious scenes, however, the first half of this century also marked the apogee of the Renaissance, with intellectual and artistic supremacy. Michelangelo and Raphael continued their works and Titian added his classical art. Leonardo da Vinci lived well into this century, now residing chiefly in Milan and supported by the French King Louis XII, who controlled Milan most of this period. Subsequently he was subsidized by Francis I. It was also the time of Aretino, Santi, Cellini and last but not least Machiavelli, the amoral, political philosopher, who undoubtedly influenced the monarchies of the world for years to come. Wealth and urban development was concentrated chiefly in the Mediterranean and in Italy in particular, with the only cities of more than 100,000 in the western world being Naples, with 300,000, Venice, Milan, Constantinople and Paris. Rice was now grown throughout the peninsula, actually as an emergency foodstuff and the hard work involved began to make a sharp demarcation between the proletariat laborers and the capitalist owner. (Ref. 260 ) Communications were difficult, as evidenced by the fact that a message took 27 days to go from Venice to London, 46 days to Lisbon, 37 days to Constantinople, 80 days to Damascus, 65 days to Alexandria and even some 22 days just to go to Palermo, Sicily. Even so, Tuscany, Venice and Genoa moved tens of thousands of tons of grain from the Baltic and the Black Sea, through international merchants and letter of exchange in Nurenberg and Antwerp. (Ref. 260 ) Venice had commerce with the Hanseatic League through Flanders and Genoese merchants had similar connections as well as contact all over the Mediterranean and particularly at Seville, as we have seen. Florence bankers of the Medici family still controlled the capital in most northern European capitals. However, when Cosimo de Medici created a guard of 2,000 horsemen in Florence in 1531, the cost of the horses ruined him. (Ref. 260 , 121 , 8 )

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Source:  OpenStax, A comprehensive outline of world history. OpenStax CNX. Nov 30, 2009 Download for free at http://cnx.org/content/col10595/1.3
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