Chapter I 

 THE DISCOVERY OF THE MAST CELLS 



ON the 17th January 1879 the Physiological Society of Berlin heard 

 a remarkable paper by a remarkable young man. The speaker was 

 Paul Ehrlich; his subject a granular cell of the loose connective tissues 

 which he had discovered as a medical student some two years previously 

 (Ehrlich, 1877) and for which he had proposed the name ' Mastzellen 7 (well-fed 

 cells) since the cells are more numerous in connective tissue whose nutrition is 

 enhanced (Ehrlich, 1878). Ehrlich pointed out that not only do the granules 

 of mammalian mast cells display great avidity for basic dyes, but that they also 

 tend to alter the shade of the dye ('metachromasia , ). Later, with his own 

 pupil, Westphal (1891), he stressed a second characteristic feature of the mast- 

 cell granules in many species, their solubility in water. As Michels (1938, p. 262) 

 remarks, ' Uncounted pages of useless and misleading research have been the 

 result of the failure on the part of many investigators to heed the admonition 

 originally given by Ehrlich and Westphal, that the mast granules are soluble 

 in water and that to preserve them tissues must be fixed in 50 per cent alcohol 

 and stained in alcoholic thionine'. 



From what we know of Ehrlich's enthusiastic temperament (Marquardt, 

 1949) it is not difficult to picture him giving this, his first public dissertation. 

 But the occasion was more than that. In discovering the mast cells Ehrlich 

 had discovered a principle which was to guide him through his working life and 

 inspire his later studies in chemotherapy. That the biological action of a drug 

 is a direct consequence of its molecular architecture is now a pharmacological 

 axiom so firmly established as to pass without comment: in Ehrlicrfs day when 

 medical treatment was still empirical and symptomatic, the idea of 'specific 

 affinity ' between drug and protoplasm was a novel conception. It is said 

 (Plesch, 1947) that the idea of specific affinities first germinated in Ehrlich's 

 mind when he was working in the laboratory of his cousin, Karl Weigert, who 

 had begun to use the new technique of staining histological sections. While 

 examining one of Weigert's slides under the microscope Ehrlich began to 

 speculate why one part of the cell should stain selectively with a particular dye 

 leaving the rest of the cell unstained. It was not long before he was seeking 

 the answer. 



Success came early. Ehrlich obtained samples of the latest commercial 

 dyes from German manufacturers who were then turning to such profitable 

 account Perkin's original discovery in Manchester of the first synthetic aniline 

 dye, mauve. On applying some of the new dyes to connective tissue Ehrlich 



