ultra-large scales, with variable values of the moduli. Then the principle would emerge as a sort of converse to natural selection, selecting out the environments to which intelligence might successfully adapt.

-   [*Misanthropic Principle*]{}: Are the values of some or all of the moduli determined by historical accident? This could arise in the same circumstances. It is the analogue of genetic drift.

If we could make a strong case that small variations in $m_u$ and $m_d$, to be specific, would destroy the possibility of intelligent observers, then that would be [*prima facie*]{} evidence for the relevance of the anthropic principle, since these quantities appear to be very remotely conditioned by central principles of unified field theories, string theory, or anything else.

Fortunately, this subject has an empirical side. We can search for variation in the physical “constants" as a function of location or of time. For theorists, there is the challenge to quantify what we learn about possible changes in the fundamental constants from cosmic nucleosynthesis and from measurements of hyperfine splittings at different times, for example. One of the most powerful constraints on variation of constants comes from the Oklo natural reactor, which would have left a different residue 