Here's an imponderable about Enterprise episode "Observer Effect:
The Organians are inhabiting the crew of the Enterprise to observe the way that they respond to a contagious disease from a particular planet with a silicon based virus. In effect, the Organians are the observers and using a form of the Prime Directive, far before Starfleet adopts that principle.
I hadn't even heard of this episode, and the premise sounded great so I ran to watch it on Netflix...
...in the words of that little kid neighbor of The Incredibles Family...."That was awesome!!!" That was the best PD episode I've ever seen.