The principal link between Oryx and Crake and Frankenstein is the theme of scientific arrogance and overreach. Both Crake and Victor Frankenstein can plausibly claim, at the beginning of their scientific endeavors, that their motives are good. Both create havoc through their determination to play God and manipulate life.

Crake and Frankenstein are both obsessive in their devotion to pursuing knowledge and creating new beings. The exhilaration they both feel as they approach their goals quickly changes to a messianic zeal and an inability to admit that they have gone too far. Crucially, both believe that they can control their creations, and both turn out to be disastrously wrong.

Crake creates the Crakers (who bear his name as the monster has come to bear Frankenstein's) as an inferior race to be exploited like animals. This parallels Frankenstein's condescending and unimaginative attitude to his creation. The life's work of Crake, like that of Frankenstein, ends up with abject failure and destruction for the creator.