Charles S. Peirce, polymath, philosopher, logician, lived a life of often wild extremes and, when he died in 1914, had earned a vile reputation as a debauched genius. Yet he created a unified, profound and brilliant work, both published and unpublished, a fact difficult to explain. In my 1993 biography, I proposed three hypotheses to account for his “Jekyll-Hyde” character: his obsession with the puzzle of meaning, two neurological pathologies, trigeminal neuralgia and left-handedness, and the powerful influence of his father. After publication, further research has led me to propose two additional hypotheses to explain his extraordinary life: manic-depressive illness and mystical experience, the last greatly influencing the development of his doctrine of semeiotic, of which his logic of science is a part.