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As the novel opens, Mateo Colombo, the most famous physician in Renaissance Italy, finds himself behind bars at the behest of Church authorities. He has been charged with heresy, but not for organizing a clumsy team of body snatchers to feed his anatomical research, nor for his obsessive pursuit of Mona Sofia, Venice's most beautiful prostitute. His crime is even more heinous, not only heretical in the Church's eyes, but equally subversive of the whole secular order of Renaissance society. Like his namesake Christopher Columbus, he has made a discovery of enormous significance for mankind.