Lyra is an orphan who lives in a parallel universe in which science, theology and magic are entwined. Lyra's search for a kidnapped friend uncovers a sinister plot involving stolen children, and turns into a quest to understand a mysterious phenomenon called Dust. She is later joined on her journey by Will, a boy who possesses a knife that can cut windows between worlds. As Lyra learns the truth about her parents and her prophesied destiny, the two young people are caught up in a war against celestial powers that ranges across many worlds.

In the fifteenth century, Pope Alexander VI tries to control all power in Italy with the help of his several sons, through murder, intrigue, war, and marriage alliances.