The origin of hormesis: historical background and driving forces.

Copious historical reviews of Calabrese and Baldwin (Hum Exp Toxicol 2000; 19: 2-31; 32-40) attribute the description of the reversal of cellular activities from stimulation at low doses to inhibition at high doses by Schulz (Pflüg Arch 1988; 42: 517-41) as the prioritizing contribution to the phenomenon which was later called hormesis. However, an extended search of the older literature uncovers Virchow (Virch Arch 1854; 6: 133-34) as the first descriptor, three and a half decades in advance of Schulz. Virchow observed an increase of the beating activity of the ciliae of tracheal epithelia of postmortem mucosa by sodium and potassium hydroxide at low concentrations, and a concentration-dependent decrease to arrest at higher concentrations. This observation constituted a cornerstone in Virchow's 'cellular pathology', which was based on the theory of cellular 'irritation and irritability'. Schulz's experiment was essentially triggered by the psychiatrist Rudolf Arndt, an ardent protagonist of homeopathy. Schulz's pre-occupation with homeopathic principles, which dominates his scientific oeuvre over his lifetime, may be seen as one of the reasons for the marginalization of hormesis.