setattr and similar dynamic features do make Python harder to optimize, but they're not that different from what you see in JavaScript. JavaScript has had an incredible amount of work spent optimizing it, but the result is a bunch of pretty damn fast language JITs that implement the full language, usually only slowing down in cases where actual use of those features requires it. Is it really that hard to come up with something like that for Python?

(Threading is a separate issue, though.)