Throughout the first half of the 19th century, East Tennessee struggled to overcome the economic isolation created by its natural barriers, namely the Blue Ridge Mountains on the south and east and the Cumberland Plateau on the north and west. Shortly after the advent of railroads in the 1820s, the region's business leaders began discussing railroad construction as a way to relieve this isolation. In the mid-1830s, several businessmen, among them Knoxville physician J. G. M. Ramsey, planned and promoted a line connecting Cincinnati and Charleston (which would have passed through East Tennessee), but the Panic of 1837 doomed this initiative.