1000xresist is still a damn good game. Here's another small thing I'm Thinking about still.
From 'generation' to 'generation', there is constantly a leap of progress. It took the 50 forever to progress on a hypothetical cure - after they were gone, Iris did it by herself, presumably lacking the education outside of learning from the 50. Her first creations implicitly mimic the dynamic of the 50's main 5.
Iris never could put together a functional family dynamic for herself. The information is opaque to us, but we know that Principal made an entire society that mostly functioned. It was not just, nor was it great, but it was a step further than Iris.
By her own admission, Principal's plan took more than a century to work, if not the full 1000 years since her banishment. Learning to change her memories and manipulate the communion, finding the right person to take the role she sought, manipulating every last detail. Knower, meanwhile, condensed that into three years. If you want to look at the watcher-specific side of the plan, it took her one day.
The resistance keeps on cycling, stronger and stronger, passing on lessons even if it did not mean to. I don't know what to make of it exactly, but it's interesting.