This interview with Rudolf Peierls (of the Frisch-Peierls Memorandum) contains these comments on fissile material production:

I think the vital step was this, that to separate isotopes on a practical, on a macroscopic scale, seems a crazy idea. It seems like science fiction because nobody had separated isotopes except in microscopic quantities, or perhaps milligram quantities of very light elements where the mass ratio was much bigger and the difference was much bigger between the isotopes and so it was a much easier problem. So to do that with large amounts seemed quite crazy, and therefore, one didn’t practically think about what would happen if we separated 235. Although Heisenberg obviously had that picture, then he thought of that as an academic thing, not something , not as something we practically have.