Destroy All Humans takes place in 1959. Cryptosporidium 137 along with his handler Pox venture to Earth to save Cryptosporidium 136 who has been captured by the human race. 136 was sent to extract pure Furon DNA from humans due to the Furon empire being on the brink of extinction. Since Furons cannot reproduce excessive cloning was used to continue the Furon race and has decayed their DNA. Humans have pure Furon DNA hidden within their DNA which can save the Furons.

Not only must Cryptosporidium 137 save 136 but prepare the planet for Furon conquest. The fate of the Furon's depends on this.

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