The English Patient tells the stories of four individuals whose lives come together at the end of World War II in an abandoned Italian villa: Hana, a 20-year-old nurse from Canada who seeks refuge from the proliferation of wartime death; Kirpal (Kip) Singh, a 25-year-old "sapper," or bomb dismantler, from India who is a member of the British Army; David Caravaggio, a friend of Hana's father who worked as a spy during the war and was severely disfigured while a captive of the Germans; and Hana's patient, a severely burned man whose identity is the mystery at the heart of this novel. Each of these characters finds him or herself far away from home, displaced by the war, and each of them finds a quiet refuge in the abandoned Italian villa to reconstruct their lives. While Hana and Kip eventually develop a romantic relationship, Caravaggio becomes more and more obsessed with the patient's true identity: Caravaggio believes that the patient may not be English, as everyone assumed, but a Hungarian who worked as a spy for the Germans. Interspersed into the story of the lives of these characters together in Italy are each character's clear recollections of the past, including the patient's hallucinatory memories of a torrid love affair, of desert exploration, and of friendship and betrayal. The novel becomes a collage of memories that explores themes of war, nationality, identity, loss, and love.

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