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Born in Waverly, Iowa in 1937, Sladek was in England in the 1960s for the New Wave movement. His first novel, published in London by Gollancz as The Reproductive System and in the United States as Mechasm, dealt with a project to build machines that build copies of themselves, a process that gets out of hand and threatens to destroy humanity. In The Müller-Fokker Effect, an attempt to preserve human personality on tape likewise goes awry, giving the author a chance to satirize big business, big religion, superpatriotism, and men's magazines, among other things. Roderick and Roderick at Random offer the traditional satirical approach of looking at the world through the eyes of an innocent, in this case a robot. Sladek revisited robots from a darker point of view in Tik-Tok, featuring a sociopathic robot who lacks any moral "asimov circuits", and Bugs, a wide-ranging satire in which a hapless technical writer (a job Sladek held for many years) helps to create a robot who quickly goes insane.
Sladek was also known for his parodies of other science fiction writers, such as Isaac Asimov, Arthur C. Clarke, and Cordwainer Smith.
A strict materialist, Sladek subjected dubious science and the occult to merciless scrutiny in The New Apocrypha. Under the name of James Vogh, Sladek wrote Arachne Rising, which purports to be a nonfiction account of a thirteenth sign of the zodiac suppressed by the scientific establishment, in an attempt to demonstrate that people will believe anything. He also co-wrote two pseudonymous novels with his friend Thomas M. Disch, the Gothic The House that Fear Built (as Cassandra Knye) and the satirical thriller Black Alice (as Thom Demijohn).
Another of Sladek's notable parodies is of the anti-Stratfordian citation of the hapax legomenon in Love's Labour's Lost "honorificabilitudinitatibus" as an anagram of hi ludi, F. Baconis nati, tuiti orbi, Latin for "these plays, F. Bacon's offspring, are preserved for the world, "proving" that Francis Bacon wrote the play. Sladek noted that "honorificabilitudinitatibus" was also an anagram for I, B. Ionsonii, uurit <writ> a lift'd batch, thus "proving" that Shakespeare's works were written by Ben Jonson.
Sladek returned from England to Minnesota in 1986, where he lived until his death in 2000 from pulmonary fibrosis.