In discussing wither mutations were “random with respect to fitness,” some interesting back and forth took place.
This brings us to an important classic experiment, the Luria-Delbruck Experiment. There were two possible outcomes A and B. They observed B, which showed that in this experiment that beneficial mutations arose before selection, not in direct response to it. To a first approximation, this is usually the case. However…
Even spontaneous mutations are biased towards beneficial (or at least away from detrimental)
There are well known cases where this general rule is violated.
As is the case for many things in biology, there is a rule, but there are exceptions, and the exceptions are important. Also, I’d add, that biologists do not always speak with mathematical precision.
We could also ask what biologists would consider non-random mutations in this context, to give some contrast. At least for me, a non-random mutation would be a system where a specific mutation is produced in a specific gene in response to a specific environmental cue. The closest example I can think of would be the CRISPR/Cas9 system that specifically inserts phage DNA into specific regions of the bacterial genome.
The Luria and Delbruck experiment was excellent work. However, for illustration purposes, the Lederbergs’ replica plating experiment really drives the point home and needs no mathematical derivation.
