PROTOPLASM AND COLLOIDS 



195 



serious disappointniout. Finally, however, 

 it occurred to me that Avhereas sea water 

 is rich in calcium, when calcium is released 

 to the cell interior tliere may be only a 

 very low concentration of the ion present. 

 Hence it was necessary to test the effect 

 of dilute ether solutions on surface pre- 

 cipitation reactions occurring in the pres- 

 ence of traces of calcium. Under such 

 conditions, it is a simple matter to show 

 that the surface precipitation reaction of 

 the sea-urchin egg is prevented by two per 

 cent ether solutions (Heilbrunn 1934). 

 Similar results can also be obtained with 

 the fresh-water protozoan Stentor, which 

 lives in solutions normally much lower in 

 calcium concentration than sea water. 

 Stentor shows a beautiful surface precipi- 

 tation reaction, but tliis is completely pre- 

 vented by dilute solutions of ether.- Our 

 explanation of fat solvent anesthesia offers 

 a clue to the interpretation of one of the 

 strangest puzzles in physiology and phar- 

 macology. For over 100 years it has been 

 known that weak concentrations of fat sol- 

 vents may increase rather than suppress 

 irritability. In subanesthetic concentra- 

 tion, the very substances which suppress 

 and inhibit response tend to arouse and 

 excite the protoplasm. How to explain 

 this parodox has always been a mystery. 

 The only explanations offered have assumed 

 participation of the central nervous system. 

 Thus, when a eat exposed to ether strug- 

 gles violently as the ether begins to enter 

 its blood, it is assumed that inhibitory cen- 

 ters of the brain have been anesthetized by 

 the ether. Such explanation might be valid 

 for an entire animal, but it is of course 

 powerless to explain the stimulating effect 

 of dilute fat solvents on muscles cut free 

 from their connection with the central ner- 

 vous s^ystem. For this puzzling phenome- 

 non, the theory I have suggested offers a 

 simple interpretation. Fat solvents favor 

 the first stage of stimulation (calcium re- 

 lease) and tend to suppress the second 

 (clotting). A weak solution of ether may 

 be strong enough to prevent the clotting 

 reaction produced by the calcium. Actu- 

 ally, in the case of the interior protoplasm 



Of ameba, Daugherty has been able to show 

 that one per cent ether acts as a stimulant 

 in causing increase in protoplasmic vis- 

 cosity. On the other hand, with 2 per cent 

 ether, the anti-clotting effect of the fat 

 solvent prevails and viscosity decreases 

 (Daugherty 1937). Whether correct or 

 not, this explanation of the stimulating 

 effect of dilute fat solvents on isolated 

 tissues is as far as I know the only theory 

 that has ever been seriously proposed. 



Until now, I have spoken only of the cells 

 of invertebrates. As a biologist, alive to the 

 advances made in cytology, genetics, etc., 

 by studying favorable material such as 

 Ascaris and Drosophila, I have in the past 

 always sought out the most favorable cells 

 for my work, no matter what i)hylum they 

 came from. But whereas biologists are 

 readily impressed b.y evidence gotten any- 

 where in the animal or plant kingdom, 

 physiologists are often trained in the medi- 

 cal profession, and are somewhat dubious 

 concerning iiiformation obtained from 

 lower organisms, or from such unfamiliar 

 material as sea-urchin eggs or protozoa. 

 Accordingly, I have tried to do something 

 with vertebrate material, in the hope that 

 the general type of theory that I have been 

 expounding might be of some use in inter- 

 preting the activity of a conventional cell 

 like the vertebrate muscle cell. After all, 

 there are advantages in studying muscle 

 cells. An ameba can act in a variety of 

 ways following stimulation. In muscle 

 cells, the primary response is always some 

 form of shortening. The age-old prob- 

 lem of why a muscle shortens is still with 

 us. For although it may be true that 

 the myosin molecules fold or superfold 

 to produce a decrease in length, we know 

 practically nothing of the mechanism of 

 such a process or of the incentive for it. 



Within the last year, I have been busy 

 with experiments on isolated single muscle 

 fibers, and I should like to conclude this 

 lecture by discussing them. What I have 

 talked about thus far is work already pub- 

 lished, by now a little old and stale. But 

 until the last day or two before I left Phila- 

 delphia, I was enjoying some work with 



