 It is sometimes argued that the cyclol hypothesis should never have been advanced, because of its "a priori" flaws, e.g., its steric clashes, its inability to accommodate proline, and the high free energy disfavoring the cyclol reaction itself.Although such flaws rendered the cyclol hypothesis "implausible", they did not make it "impossible".The cyclol model was the first well-defined structure proposed for globular proteins, and too little was then known of intramolecular forces and protein structure to reject it immediately.