Shifting Towards Death-lehem
As if the changing-of-seasons = marching toward death imagery wasn't grim enough, the act of shapeshifting is along these same lines. Except with shapeshifting, there's the added benefit of it being a terminal illness. Bonus! Cancer has nothing on lycanthropy. Take that, Fault in Our Stars!
Sam and Grace try to cope with Sam's inevitable demise, which is approaching a lot faster than he expected. When Grace asks him, “Tell me what happens, at the end,” (27.42) she's talking about his final transformation, but in many ways it feels like her trying to understand what it might be like to die.
Thinking about it this way, their search for a cure feels like a search for eternal life. Sam even says, “I'd rather risk [...] death than watch all this slip away” (52.11, 52.13). We humans have been comparing lycanthropy to death quite a bit, but for Sam, who actually has to live with it, it's a fate worse than death.