Initially, Leonardo may have planned to return to Milan. Conventional wisdom of the time held that Sforza would regain power, but these hopes were dashed when the duke was betrayed by his Swiss mercenaries. Even if he was planning to return, Leonardo does not appear to have been overly loyal to the duke. After all, the Ottomans were attacking Venice at Sforza's bidding. Sforza wanted to distract Venice, an ally of France, while he tried to retake Lombardy. Nonetheless, Leonardo was eager to devise scientific methods to defeat the Turks and quickly win the war for Venice. He was careful not to let his designs fall into the hands of criminals, but he did not seem to care which side of the war used them. Similarly, Leonardo did not seem to mind working for Cesare Borgia, who was renowned as an incestuous, impious man who had liaisons with his sister, had his brother murdered, and held as much responsibility for the corruption of the church as anyone else. It seems Leonardo's prime loyalty was to science.

When Leonardo returned to Florence, he was 48 years old. He had achieved great fame, but very few of his goals. He was no more likely to finish a commission than the last time he was in Florence, as seen in the case of the Virgin and Child with Saint Anne and a Lamb. His father was still alive. The city had changed a great deal. The Medici family had temporarily lost power, and the religious zealot Fra Savonarola took power, impugning the Church for impiety and ordering the burning of all books he found sinful. Though Savonarola had been burned at the stake by the time Leonardo reached Florence, some still appreciated his thoughts. One wonders whether Leonardo felt more or less comfortable in the Florence of 1500 than in the Florence of 1482.

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