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1, a third party candidate who is so charismatic, so smart, and so effective that he or she would steal 30% of all registered Democrats, 30% of all registered Republicans, and about 65% of all Independants.
2, America chnges it's entire Government system into a Parliament, meaning that enough Democrats AND Republicans would have to abandon their own party's interest to do it.
I suppose anything is possible, but until then the 2-party system is what we are stuck with.