Taken from the poem of animal-lover Robert Burns, the title of Steinbeck's novella evokes the power of an uncaring universe upon the fates of men:
The best laid schemes of mice and men
Go often awry,
And leave us nothing but grief and pain,
For promised joy!
Set during the desperate time of the Great Depression in which men and women lost their fortunes, their homes, and their ways of life, the characters of Of Mice and Men are figuratively much like the little mouse in the field that the speaker of Burns' poem mowed, in which the machine destroyed the winter nest of the mouse and the mouse itself. Metaphorically, the "machine" of government victimized and marginalized many in the 1930s.
Alienated from the social system and their homes, the bindle stiffs of Steinbeck's narrative wander in search of jobs that can, at least, sustain their lives, if only temporarily. In such an unsettling time of massive unemployment, these alienated men are naturally mistrustful of others as they fear losing their jobs, This Naturalistic world of survival pits the ranchworkers against one another, and they eye others suspiciously. When, for instance, Curley's wife first appears in the doorway, standing seductively with the light behind her, the cautious George warns Lennie not to look at her in the way he has,
"Listen to me...I don't care what she says and what she does. I seen 'em poison before, but I never seen no piece of jail bait worse than her. You leave her be."
Likewise, George is wary of the pugnacious Curley himself, the son of the boss:
"You know,Lennie, I'm scared I'm gonna tangle with that bastard myself. I hate his guts...."
This hatred, of course, is generated from fear. In much the same way, old and crippled Candy allows the stronger Carlson to take his old, useless dog out and shoot it. Moreover, he later tells George that he fears that a similar fate will occur with him when he is no longer useful on the ranch. In Chapter 5, for instance, he admits to Curley's wife how minimalized he and the other ranchhands are, "No,...."he agreed. "Nobody'd listen to us."
Indeed, the world of the bindle stiffs is one in which only the strong survive. Lennie, who is physically strong, but mentally weakened, is therefore, vulnerable in this naturalistic world and ultimately doomed to fail. Even though George makes every effort to protect him, Lennie cannot fully assess situations in which he can cause harm or be harmed. For, lacking any true fraternity of men and isolated in their struggles to survive and find happiness, like the little mouse of Burns' poem, the men fall victim to fate.