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The Screw.
One Good Turn: A History of the Screw
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Ohhh... good suggestion, but the nail & hammer is pretty good too.
I made the post originally because I thought about the line from Donnie Darko where they talk about sanitation and antibiotics being the greatest invention, and I felt that the lock and key was more ingenious. However, when I went to post I had a hard tiem not picking the light bulb, too many uses, television and the combuter wouldn't be up there without the light bulb.
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I think what makes an invention great is one that you realize you really need it before hand. For example, anti-biotics are great, because we all get to live longer. But, if we didn't know about anti-biotics and living longer we would accept our max average of X years. But, the screw is a good one. That was something that somebody said, we really need to hold this Y up or whatever. I don't know if that makes sense. Another example would be the wheel. How long did it take before they realized they needed something like that? And the obvious choice, the Pot Head Clapper. Essential stuff.