The Clark plot: a semi-historical case study.

A study has been made of the origins of the quantitative theory of simple competitive antagonism as manifest in the papers of Gaddum and of Clark. The classical data of Clark on the antagonism of acetylcholine by atropine were reanalysed by recently developed computer-based methods. It was seen how close Clark came to initiating a method having the following significant advantages over the Schild plot: (i) symmetrical treatment with respect to the control (zero antagonist) data; (ii) absence of difficulty with the cases where an estimated dose-ratio is less than unity; (iii) straightforward calculation of approximate standard errors for departure from overall simple competitivity at each antagonist level including control.