From the introduction to "The Defendant" in the collection of essays In Defense of Sanity:
This is the great fall, the fall by which the fish forgets the sea, the ox forgets the meadow, the clerk forgets the city, every man forgets his environment and, in the fullest and most literal sense, forgets himself. This is the real fall of Adam, and it is a spiritual fall.
The rest of the animal kingdom has an advantage on us: They are what they are and can be nothing else. A bear cannot fail to be bearlike, or a worm wormlike. But man can fail to be human. Chesterton's wonderful description of Original Sin, imagining what it might be like should an animal suffer it, illuminates what it means for us. Imagine a fish that forgets the sea; meaning, I think, a fish who forgets how to live in the sea as a fish. Such a fish is never home, for the only home it could possibly know, the sea, is foreign to it. It must live its entire existence as a stranger in its own home.
Even better is the ox who forgets the meadow. Unlike the fish, for whom the entire sea is all home to it, or should be, the meadow is peculiarly the home for an ox. An ox in the city or on a mountain is not home. But the ox who forgets the meadow is still not home in the city or on the mountain; like the unfallen ox that finds itself in the city, it would search for home. But while the unfallen ox would recognize the meadow as home should it find it, the fallen ox may find the meadow but would, tragically, not recognize it as home... it would wander right through home and continue to pine for the home it already found.
The great fall for man means that he has lost the knowledge of how to live as man in the world; he feels that he is not at home, or that he should be home but somehow isn't. So what does he do? What can he do? A man at home lives naturally; he doesn't have to figure out how to live. Since we are not at home - or at least we have forgotten how to live at home - we must construct ways of living. And these ways are at some level false simply because they are constructed - they can never replace the natural way of living of unfallen man.
Rousseau noticed this artificiality but rejected Original Sin; for him, the social constructions of man are the fall rather than a consequence of the fall. This has the convenient consequence that the fall lies outside us rather than in us, and in dealing with it we don't have to change.
But the truth is that there is no state of nature that is our true home, and in which we would be at peace could we find it. We are already in our true home. We just don't know how to live here.