Born in 1868 in Nancy, to a Jewish family of the middle bourgeoisie, long established in Lorraine, Spire studied literature, then law. He attended the École libre des sciences politiques, now called the Paris Institute of Political Studies (Institut d'études politiques), or Sciences-Po, and later, in 1894, was appointed to the Conseil d'État on successfully passing the competitive entrance examination. A few months later, the Dreyfus Affair broke when a Jewish military officer was wrongly accused of treason, revealing how widespread antisemetism was at the time in France. Spire provoked a duel with a columnist from the Libre Parole (a nationalist and anti-semitic newspaper run by Edouard Drumont) for alleging that the Jews appointed to the Conseil d'Etat won their positions not on merit but through illicit influence. Spire was wounded in the arm.

In 1896, he and a Catholic colleague founded the Société des Visiteurs, dedicated to helping workers suffering from unemployment, illness, or injury. Shortly thereafter, he took part in the Cooperation des Idées, where he met Daniel Halévy. The two men founded an Université populaire. Spire left the Conseil d'Etat for the ministry of Labor, then joined the staff of Jean Dupuy, Minister of Agriculture in the government of Waldeck-Rousseau. He became friends with Charles Péguy who published his Et vous riez ! in Les Cahiers de la quinzaine (1905), poems which reflect a certain disappointment with the worker's movement.

In 1902, he was commissioned by the Office du Travail (Labor Office) to conduct an inquiry into the labor conditions of English workers and discovered the East European Jewish immigrant neighbourhood of Whitechapel in the East End of London. In 1904, he was deeply moved by a short story by Israel Zangwill in the Cahiers de la quinzaine entitled Chad Gadya. It relates the tale of a young Venetian Jew from a traditional family attracted by the external non-Jewish world. Not able to find his place in either world he ends by committing suicide.

Spire engaged in the Zionist cause, joining Zangwill's Jewish Territorial Organisation (ITO) and campaigned, publishing numerous articles.

During the First World War, Spire, not able to be mobilised, ran the family factory. He was also charged by the Ministry of Agriculture with work on the reconstruction of war-damaged regions. In 1920, Dr. Chaim Weizmann invited Spire to accompany him to Palestine.

Following the defeat of France in 1940, Spire was forced into exile in the United States of America where he was invited to teach French Literature at the New School for Social Research and the École libre des Hautes études in New York. Very active, Spire also participated in numerous conferences and completed his classic study of poetics Plaisir poétique et plaisir musculaire, essai sur l'évolution des techniques poétiques (José Corti 1949 ; new edition 1986).

After the war he returned to France. Spire died in Paris at the age of 98. His funeral was led by Rabbi David Feuerwerker.

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