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I think that the significance of the Salinas River in the beginning and at the end represents how the natural world continues on in the midst of the world of human beings. It also serves to be a point of reference as to how much things have changed. At the opening of the novel, when Lennie and George are approaching the Salinas, the pristine nature of it is one where the lizard skittering across would make a sound. Steinbeck's description helps to bring out how the natural world still endures and perseveres, despite the mammoth of attempts of men to make themselves the center of all. The end description of the river in the last chapter helps to bring this out. The Salinas has not changed, for it is still intact. Yet, the snake's head acting like a periscope is the only difference. While the lizard skitters about to presumably find a home in the opening, Lennie and George are similar as they search for some place to find home. In the end, the snake's head popping out of the water acting like a periscope might also represent how everyone is on the search for Lennie. The natural world is shown to be a realm that continues and marches on, despite the ups and downs of the human world. There is a striking consistency and constancy in nature that is missing in the world of human beings.
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