There is ample evidence that humans (and other primates) possess a knowledge instinct—a biologically driven impulse to make coherent sense of the world at the highest level possible. Yet behavioral decision-making data suggest a contrary biological drive to minimize cognitive effort by solving problems using simplifying heuristics. Individuals differ, and the same person varies over time, in the strength of the knowledge instinct. Neuroimaging studies suggest which brain regions might mediate the balance between knowledge expansion and heuristic simplification. One region implicated in primary emotional experience is more activated in individuals who use primitive heuristics, whereas two areas of the cortex are more activated in individuals with a strong knowledge drive: one region implicated in detecting risk or conflict and another implicated in generating creative ideas. Knowledge maximization and effort minimization are both evolutionary adaptations, and both are valuable in different contexts. Effort minimization helps us make minor and routine decisions efficiently, whereas knowledge maximization connects us to the beautiful, to the sublime, and to our highest aspirations. We relate the opposition between the knowledge instinct and heuristics to the biblical story of the fall, and argue that the causal scientific worldview is mathematically equivalent to teleological arguments from final causes. Elements of a scientific program are formulated to address unresolved issues.