I didn't know the characters when i played. However, references to an older world should give a good hint as to where they are from at least. Also i won't ruin their grand entrance by spoiling it, that entrance gets ruined quite thoroughly by the actual characters in the game anyway.

I will say that they are awesome in this game, though.

Also that cutscene with Medicine and Yuuka is so adorable and heartwarming. I really like that the people making this game took that kind of effort to develop a character as rarely seen as Medicine.