16 Applied Biophysics 



eralizations is beyond the scope of the present article, and many 

 comprehensive reviews on the subject are already in existence. 

 But the central problem is to elucidate the mechanism by means 

 of which we can relate narcosis with the depression of the oxi- 

 dative events of the living cell and also with the association of 

 the drugs with the structural fabric of the cell. We can demon- 

 strate the inhibition of enzymic activity in isolated enzyme sys- 

 tems. We can also detect changes in the molecular orientations 

 of the structural fabrics which form the natural environment of 

 these enzyme systems, but we have been quite unable so far to 

 link these changes in the living system. 



Reconciliation of "Rival" Theories 



In view of the uncertainty which exists as to the nature of the 

 drug receptors, it may be more constructive at this stage to 

 assume that the "rival" theories which have been proposed from 

 time to time are not necessarily divergent, but are rather expres- 

 sions of experimentally observed regularities in the relationships 

 of drugs with particular systems. The justification for this as- 

 sumption will become apparent when we search for common 

 physicochemical factors in some of the diverse structural arrange- 

 ments in membrane organization which are consistent with 

 pharmacological action, and it will be of interest to notice that 

 the anomalous systems often provide more information than those 

 which show more regular coincidence with simple model systems. 



The early work of Overton stressed the importance of the 

 lipids in cell organization and membrane permeability, and the 

 parallelism between the uptake of substances by cells and differ- 

 ential oil-water solubility indicated the preponderance of fatty 

 material in the cell membrane. More recently Osterhout and 

 coworkers -^ have studied the permeability of homogeneous arti- 

 ficial membranes consisting of organic solvents, such as guaiacol, 

 and have related the passage of substances through such oil 

 films with the permeability of the protoplasmic surfaces of large 

 multinucleate plant cells, such as Valonia, Halicystis, and Nitella. 

 In these systems the cell membrane appears to behave as an 



