> The use of out-of-band characters like NULLs to separate pieces of text does help, but I don't think there is a complete solution.

NULL is actually in-band, not out-of-band, and in fact it illustrates the issues with in-band communication you mention. That's what, presumably, ESC was for: a way to signal that the following character was raw and did not hold its normal meaning.

You can still devise a pretty good protocol with straight ASCII over a wire, using SYN to synchronise the signal, the separator characters to separate data values and ESC to escape the following character (like '\' is used in many programming languages).