6 INTRODUCTION 



physiological investigations on the adrenals which followed the 

 appearance of his classic paper. 



Addison's publication prompted Brown-Sequard 96 in 1856 

 to extirpate the adrenals from a number of laboratory animals. 

 The rapidly fatal consequences of these operations led him to 

 the correct conclusion as to their indispensability for life. 

 Some subsequent workers failed to confirm Brown-Sequard's 

 conclusions. This controversy, regarding the period of sur- 

 vival of animals following adrenalectomy has continued to the 

 present day. 



During the latter half of the nineteenth and early part of 

 the twentieth century, the comparative anatomy of the adre- 

 nals was fully investigated. The earlier work of Stannius, 594 

 Gray, 239 Leydig, 396 Remak, Kolliker, His, and Braun 81 culmi- 

 nated in the researches of Balfour, 28 Soulie, 581 Poll, 508 Vin- 

 cent, 648 Kohn, 357 and others. 



The observations of Oliver and Schaefer 480 in 1894 of the 

 remarkable pressor effects of extracts of the adrenal medulla 

 turned attention to epinephrine, the existence of which had 

 been noted in 1856 by Vulpian 652 who described the green 

 coloration occurring when the medulla was moistened with 

 ferric chloride. The high concentration of epinephrine in the 

 gland (as compared to the relatively low concentrations in 

 which other hormones occur) led to its isolation and identifica- 

 tion in the course of a decade following Oliver and Schaefer's 

 publication. It was thus the first hormone to be crystallized, 

 identified, and synthesized. 



The remarkable pharmacological effects of epinephrine soon 

 found for it a permanent place in therapy. Physiologists 

 looked upon its production as the obvious function of the 

 adrenal glands and numerous studies appeared describing its 

 actions under various conditions. Bitter controversies raged 

 regarding the functional importance of epinephrine to the 

 organism. 



The adrenal cortex, in the meantime, was for the most part 



