Herbert began researching Dune in 1959. He was able to devote himself wholeheartedly to his writing career because his wife returned to work full-time as an advertising writer for department stores, becoming the breadwinner during the 1960s. The novel Dune was published in 1965, which spearheaded the Dune franchise. He later told Willis E. McNelly that the novel originated when he was assigned to write a magazine article about sand dunes in the Oregon Dunes near Florence, Oregon. He got overinvolved and ended up with far more raw material than needed for an article. The article was never written, but it planted the seed that led to Dune. Another significant source of inspiration for Dune was Herbert's experiences with psilocybin and his hobby of cultivating mushrooms, according to mycologist Paul Stamets's account.

Dune took six years of research and writing to complete and was much longer than other commercial science fiction of the time. Analog (the renamed Astounding, still edited by John W. Campbell) published it in two parts comprising eight installments, "Dune World" from December 1963 and "Prophet of Dune" in 1965. It was then rejected by nearly twenty book publishers. One editor prophetically wrote, "I might be making the mistake of the decade, but..."

1984 was a tumultuous year in Herbert's life. During this same year of his wife's death, his career took off with the release of David Lynch's film version of Dune. Despite high expectations, a big-budget production design and an A-list cast, the movie drew mostly poor reviews in the United States. However, despite a disappointing response in the US, the film was a critical and commercial success in Europe and Japan.

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