Caught Between the Old and the New--Walther Straub (1874-1944), the Question of Drug Receptors, and the Rise of Modern Pharmacology

Abstract

This paper deals with an important development of scientific pharmacology, focusing on the reaction of the German pharmacologist Walther Straub to the receptor concept, which was a new approach to explain the binding of drugs to cells in the young discipline of pharmacology after 1900. The article analyzes how Straub as an important representative of his field between 1900 and 1944 was influenced by nineteenth-century thinking, and how he developed a rival physical theory to combat the receptor concept. Straub is seen as a man of transition, who on the one side tackled a core question of drug research with modern experimental methods, but on the other side was hardly able to accept new results in chemistry.

Drug - Receptor Interactions

“…He changed his mind only in 1907, partly due to results of his own further research, but in particular also because of a different kind of receptor theory that had been proposed by the Cambridge physiologist John Newport Langley (1852-1925). 2,3 Langley's concept is particularly interesting because it placed special importance on the notion of substance and of substance binding.…”

“…The great competitor to the receptor concepts of Ehrlich and Langley was the so-called 'potential-poison' theory of the German pharmacologist Walther Straub (1874-1944). 3 His research at the Stazione Zoologica in Naples involved the antagonism between atropine and the poison of the fly agaric, muscarine, on the heart of the sea snail (Aplysia) and the torpedo fish. He argued that a poison acted as long as there was a concentration difference or 'potential' between the outside and the inside of the cell.…”

A binding question: the evolution of the receptor concept

“…The effect was due to a deformation or other physical disturbance of the cell membrane when the poison molecules penetrated it. Like Langley, Straub was quick to generalize, suggesting that his physical theory of drug action applied also to other alkaloids, such as pilocarpine, physostigmine and nicotine, and to the hormone adrenalin [17]. Straub's theory found significant supporters in Britain, in particular Henry Dale (1875–1968) and George Barger (1878–1939) of the Wellcome Physiological Research Laboratories and Arthur Cushny (1866–1926), who held the chair in pharmacology at University College London [18].…”