Part of a Scientific Master Plan? Paul Ehrlich and the Origins of his Receptor Concept

Abstract

One of the basic theories oftwentieth-century scientific medicine is the receptor concept. It deals with the question of how information can be submitted to the cell. Receptors can be described as "small, discrete area(s) on the cell membrane or within the cell with which molecules or molecular complexes (for example, hormones, drugs, and other chemical messengers) interact" .1 The receptor concept became increasingly important, especially for pharmacology, as it explained the binding of drugs to cells and drug-effects on specific tissues and organs. The origins of the receptor concept stem from the last third of the nineteenth century and are chiefly connected with two names: Paul Ehrlich (1854-1915) and John Newport Langley (1852-1925). Remarkably, these two scientists approached the receptor idea on significantly different routes and from different backgrounds: John Newport Langley, professor ofphysiology in Cambridge, was predominantly concerned with the investigation of the functions of the autonomic nervous system, i.e. of those nerves which regulate, without our conscious influence, the vegetative functions of the body, such as blood-pressure and respiration. Paul Ehrlich, the Berlin bacteriologist and immunologist, was keen to examine the relations between bacterial toxins and antitoxins and to support contemporary efforts to combat infectious diseases. Both mentioned the idea first in 1878, and both returned to their former approaches only several years later-at the turn of the nineteenth to the twentieth century. According to our current knowledge about the history of the receptor concept, the two scientists developed their initial ideas on receptors independently.2

A binding question: the evolution of the receptor concept

“…A surplus of side-chains was released into the blood stream where they bound as anti-toxins or antibodies to the bacterial toxins—forming thus the basis of immunity (Figure 3). In 1900 Ehrlich replaced the term side-chain (or Seitenkette ) with the term Receptor [11].…”

Locating Therapeutic Vaccines in Nineteenth-Century History

“…5 In the late 1870s, Carl Weigert, soon to be followed by his nephew Paul Ehrlich, started to use aniline dyes and other chemical substances for histological staining andinspired by the specific affinity of such molecules to bacterial cells -later on tested some of these, such as methylene blue, as possible therapeutics against infectious diseases (Parascandola 1981;Prüll 2003). His understanding of the antitoxic properties of blood serum was closely related to the basic assumptions about infections purported by the Berlin group and the application of these assumptions to immunology.…”

Molecular decoys: antidotes, therapeutics and immunomodulators

“…A case in point is Clostridium difficile Toxin A, a major cause of antibiotic associated diarrhoea and colitis [7]. The toxin is a large protein (308 kDa) that binds to the trisaccharide sequence Gala [1][2][3] Galb [1][2][3][4] GlcNAc displayed on the luminal surface of the apical plasma membrane of the intestinal epithelium. Therefore, a sugarbased decoy was produced and tested by the Canadian Biotech company, Synsorb Biotech, who conjugated the trisaccharide onto an inert silicon-based support.…”

“…An elegant treatment of STEC infections has been proposed by Paton et al who have constructed a recombinant probiotic E. coli strain that displays Stx receptor mimics on its surface. Stx binds the glycolipid receptor, globtriaosyl ceramide (Gb3) that has the structure Gala [1][2][3][4] Galb [1][2][3][4] Glc ceramide. The glycosyl transferase genes IgtC and IgtE derived from Neisseria were introduced into E coli R1 rendering it able to produce a chimeric lipopolysaccharide (LPS) core terminating in Gala [1][2][3][4] Galb [1][2][3][4] Glc.…”

“…One hundred years have past since Ehrlich [1,2] and Langley [3,4] proposed the existence of 'receptors' as the responsive cellular components targeted by toxins. The interplay of ligands binding to their cognate receptors as a means to regulate cell function, induce proliferation or trigger apoptosis has since become fundamental to our understanding of cell biology, immunology and neurobiology, as well as to the rational design of innovative therapeutic drugs, laying the foundations of modern pharmacology.…”