Of Mice and Men Theme of Isolation

No man is an island… unless he's an itinerant worker during the Great Depression, and then he's about as lonely as you can get. But for all the talk about loneliness in Of Mice and Men, these guys sure do hang out together a lot. (They even go to the whorehouse together. We bet they visit the bathroom at the same time, too.) Does this mean they're not isolated? Or do they meet, make new friends, new enemies, and then head out to their next job, all the while failing to make any real, human connections?

1. Why does everyone seem to feel so isolated all the time? Is this a function of the ranch, the era, the world, human nature, or something else?
2. Crooks's isolation is also his protection, especially witnessed by that awful scene where Curley's wife threatens him. Is this isolation worth it? Is it ever worth it? Would Lennie have been safer if he'd been isolated?
3. Why do those who are isolated "get mean," as George says, even if they're surrounded by people all the time?
4. Are George or Lennie ever isolated?

In Of Mice and Men, isolation is safer than togetherness.

Because they are together, George and Lennie are never truly isolated, no matter how different they may be.