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An extended view and definition of E=MC2 can address each of these issues. This extended view has been around since the early 1960's.
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Five Great Foundational Problems of Theoretical Physics
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by:
Lee Smolin
Problem 1: Combine general relativity and quantum theory into a single theory that can claim to be the complete theory of nature. This is called the problem of quantum gravity.
Problem 2: Resolve the problems in the foundations of quantum mechanics, either by making sense of the theory as it stands or by inventing a new theory that does make sense. There are several different ways one might do this.
1. Provide a sensible language for the theory, one that resolves all puzzles like the ones just mentioned and incorporates the division of the world into system and observer as an essential feature of the theory.
2. Find a new interpretation of the theory — a new way of reading the equations — that is realist, so that measurement and observation play no role in the description of fundamental reality.
3. Invent a new theory, one that gives a deeper understanding of nature than quantum mechanics does.
Problem 3: Determine whether or not the various particles and forces can be unified in a theory that explains them all as manifestations of a single, fundamental entity. Let us call this problem the unification of the particles and forces, to distinguish it from the unification of laws, the unification we discussed earlier.
Problem 4: Explain how the values of the free constants in the standard model of particle physics are chosen in nature. It is devoutly hoped that a true unified theory of the particles and forces will give a unique answer to this question.
Problem 5: Explain dark matter and dark energy. Or, if they don’t exist, determine how and why gravity is modified on large scales. More generally, explain why the constants of the standard model of cosmology, including the dark energy, have the values they do. These five problems represent the boundaries to present knowledge.