There was a neat version of the "soulless" in a book called
The Flicker Men. A protagonist found some people who could not collapse the waveform by observing the photons passing through a slit in the
double-slit experiment. Apparently, according to the universe the soulless
didn't count as observers...
That's incredibly deep when you think about it. You could use it to build more of a cosmic science rather than religious atmosphere.
The soulless in the book were sort of running on autopilot, mimicking humanity. Stimulus-response on a very complex algorithm, but they didn't have real free will. They were the mooks in reality. Animals, not humans. Space-fillers for the souls around them. Maybe sociopaths. Anyway, eventually the protagonists developed a detector based upon the double-slit experiment. Then the book sort of goes off the rails, frankly. The first half is the most interesting.
Also, at some point some smartguy gets the idea to insert the detector into pregnant wombs to figure out when souls "attach" to a fetus, but the book doesn't explore this (deeply disturbing) aspect of the plot.