In the novel, George and Lennie are migrant workers who travel from place to place in search of work. They are lonely and isolated, with no family or friends to rely on. This is reflected in the experiences of people during the Great Depression, as many people were forced to leave their homes and families in search of work, leading to a sense of isolation and disconnection from their communities.

The characters in the novel also struggle to form meaningful connections with others, further highlighting the impact of isolation and loneliness. For example, Curley's wife is isolated due to her gender and the expectations placed on her, leading to her seeking attention from the male workers on the ranch. This underscores the difficulties faced by women during the Great Depression, as they often had limited opportunities for employment and faced discrimination and isolation in male-dominated spaces.

The economic conditions of the Great Depression also contributed to feelings of isolation and loneliness. The characters in the novel are forced to compete with each other for work, leading to a sense of mistrust and competition. This reflects the experiences of people during the Great Depression, as economic hardship often led to a breakdown in social cohesion and a rise in individualism.

Overall, the themes of isolation and loneliness in "Of Mice and Men" highlight the social and economic conditions of the Great Depression and reflect the experiences of people living through that time. The novel provides a powerful commentary on the impact of economic hardship on human relationships and the struggle for connection in a time of isolation and despair.
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