164 L. J. MULLINS 



that DDT largely loses its effectiveness as the temperature is raised which sug- 

 gests that the expansion in the site size suffices to inhibit the phase change sug- 

 gested as the mechanism of action of the DDT at 20°. 



In answer to the question about the substances and whether they prefer to 

 be in their own pure liquid or in the membrane, these solids that we have been 

 talking about, such as the insecticides, all have to be melted in order to be used, 

 and, of course, the parameter is the latent heat of vaporization per unit volume 

 of the molecule that determines whether it would like to go into its own liquid 

 or whether it would like to go into the membrane. This is a physical-chemical 

 kind of a concept which is not too applicable to this situation, because if the 

 membrane were a homogeneous molecular lipid layer such as Dr. Davies was 

 suggesting then you have to do work to separate the molecules of the lipid so as 

 to insert this particular molecule we are talking about. Whether it would get in- 

 serted or not would depend upon the amount of work that you would have to 

 do to separate the molecules at this new phase that it is going into versus the 

 amount of work that would have to be done to get it back into its own liquid 

 assuming that it is outside. But a membrane pore already exists by virtue of 

 the structure of the membrane and no work has to be done to introduce a mole- 

 cule of the appropriate size, so that the situation is a little bit different. 



Chairman Gerard: I think we might move off in a somewhat different di- 

 rection. 



Dr. Orr Reynolds (Chief, Biological Sciences Division, ONR) : I would like 

 to ask two questions — one is whether Dr. Mullins has considered the rare gases, 

 which seem to be narcotic directly, as related to molecular weight and pressure, 

 and how they would fit into this in view of the fact that the molecular size pre- 

 sumably is smaller than the molecules presented here? 



The other question is whether or not this experiment has been done? If sites 

 of crystallization are formed and therefore the spaces around them become 

 larger, would you expect the larger molecules to become anesthetic before crys- 

 tallization? 



Dr. Ling: The point I want to raise is this: some time ago we proposed a 

 hypothesis which has been called the fixed charge hypothesis and one aspect of 

 that concerns permeability. 



The fixed charge hypothesis deals mostly with charged particles or ions, and 

 I think since it is probably generally agreed that ions play an important part 

 in nerve excitation and electrical potentials, this might be an appropriate oc- 

 casion to discuss it a little, and in relation to Dr. Mullins' presentation. 



I think in Dr. Mullins' picture one striking feature was the presence of holes. 

 If one goes back to the time when earlier theories were proposed for the mech- 

 anism of differential permeability and, for that matter, ionic accumulation and 

 generation of electrical potential, one always could not escape the repeated 

 observation and postulation that there were such holes. For instance, in one 



