Very little connects Louisville, KY and Clemson, SC in the historical record. Clemson's own John C. Calhoun (of Fort Hill Plantation) once tried to remedy that fact, quite literally, when in 1836 he proposed the construction of a rail line to connect Charleston's port to emerging trans-Appalachian settlements in the Ohio River Valley.
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The idea remained just that for the better part of two decades until 1852 when a group of investors initially culled together by Calhoun (who died in 1850) chartered the "Blue Ridge Railroad.