Brown and Fraser were the first to investigate the relationship between the chemical constitution of substances and their action upon the body.

"Although Crum Brown apparently never contemplated the practice of medicine, his training as a medical student gave him an interest in physiology and pharmacology which led him to collaborate during 1867–8 with T. R. Fraser, a distinguished medical graduate a few years younger than himself, in a pioneering investigation of fundamental importance on the connection between chemical constitution and physiological action. Their method "consists in performing upon a substance a chemical operation which shall introduce a known change into its constitution, and then examining and comparing the physiological action of the substance before and after the change." The change considered was the addition of ethyl iodide to various alkaloids and comparison of the iodides (and the corresponding sulfates) thus obtained with the hydrochlorides of the original alkaloids. Striking regularities were observed, amongst others "that when a nitrile [tertiary] base possesses a strychnialike action, the salts of the corresponding ammonium [quaternary] bases have an action identical with curare [poison]."^[6] (Wikipedia article on Alexander Crum Brown, accessed 4-2020).