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Spiegelman attended the High School of Art and Design in New York City and SUNY Binghamton and received an honorary doctorate of letters from SUNY Binghamton in 1995. He began working for the Topps Gum Company in 1966, as association that lasted over twenty years. There he created novelty cards, stickers and candy products, including Garbage Candy, Wacky Packages and Garbage Pail Kids. He began producing underground comix in 1966, and in 1971 moved to San Francisco, where he lived until 1975.
His work began appearing in such publications as East Village Other, Bijou and Young Lust Comix. In 1975-76, he, along with Bill Griffith, founded Arcade, The Comic Revue. His book, Breakdowns, an anthology of his comics, was published in 1977.
Spiegelman moved back to New York City in 1975, and began doing drawing and comix for The New York Times, Village Voice and others. He became an instructor at The School of Visiual Arts from 1979-1987. In 1980, Spiegelman and his wife, Francoise Mouly, started the magazine RAW, which has over the years changed the public's perception of comics as an art form. It was in RAW that Maus was first serialized. In 1986, Pantheon Books published the first half of Maus and followed with Maus II in 1991. In 1994 he designed and illustrated the lost Prohibition Era classic by Joseph Moncure March, The Wild Party. In 1997, Spiegelman's first book for children, Open Me ... I'm a Dog was published by HarperCollins.
Art Spiegelman has received The National Book Critics Circle nomination in both 1986 and 1991, the Guggenheim fellowship in 1990, and a special Pulitzer Prize in 1992. His art has been shown in museums and gallery shows in the United States and abroad, including a 1991 show at the Museum of Modern Art in New York City.
He and his wife, Francoise Mouly, live in lower Manhattan with their two children, Nadja and Dashiell.