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Helen Hayes was born in Washington D.C. on October 10, 1900. Her mother, Catherine Estelle (née Hayes), or Essie, was an aspiring actress who worked in touring companies. Her father, Francis van Arnum Brown, worked at a number of jobs, including as a clerk at the Washington Patent Office and as a manager and salesman for a wholesale butcher. Hayes' Irish Catholic maternal grandparents immigrated from Ireland during the Irish Potato Famine; her mother was a great-niece of Irish singer Catherine Hayes.

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Hayes began a stage career at an early age. She said her stage debut was as a 5-year-old singer at Washington's Belasco Theatre (on Lafayette Square, across from the White House.) By the age of ten, she had made a short film called Jean and the Calico Doll, but moved to Hollywood only when her husband, playwright Charles MacArthur, signed a Hollywood deal. She attended the Academy of the Sacred Heart Convent in Washington and graduated in 1917.

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Her sound film debut was The Sin of Madelon Claudet, for which she won the Academy Award for Best Actress. She followed that with starring roles in Arrowsmith (with Myrna Loy), A Farewell to Arms (with actor Gary Cooper, whom Hayes admitted to finding extremely attractive), The White Sister, What Every Woman Knows (a reprise from her Broadway hit) and Vanessa: Her Love Story. However, she never became a fan favorite and Hayes did not prefer the medium to the stage.