460 J. van Overheek 



Dr. Wain: My third point is in relation to the naphthoic acids. 

 The 1 -naphthoic acid has only weak activity; if you reduce the sec- 

 ond ring then the 3,4-dihydro-derivative still has only weak activity. 

 On the other hand, the 1,4-dihydro- is highly active; the 1,2-dihydro- 

 is highly active, and so is 1,2,3,4-tetrahyclro-l-naphthoic acid. The ex- 

 perimental evidence is not in question, but there are other possibili- 

 ties in addition to those put forward by Dr. van Overbeek which ex- 

 plain the activity of these molecules. It will be noted that in all the 

 active compounds there is a hydrogen atom attached to the carbon 

 atom adjacent to the carboxyl group. As you all kno^v, we. at AVye, 

 have repeatedly stressed the importance of the a/p/ia-hydrogen atoms 

 in relation to activity, for I think this is the key to all considera- 

 tions of this kind. I refer to the fact that in those growth substances 

 in which the carbon atom adjacent to the carboxyl group is asym- 

 metric, there is usually activity with one enantiomorph and not the 

 other. To my mind this is one of the most important things of all, 

 and I'm rather surprised that steric considerations of this kind have 

 not been mentioned throughout the whole of this conference, for 

 here, surely, is an important clue to mode of action. AVe have very 

 definite ideas about this, but they are only ideas, and other views, of 

 course, are possible and will be put forward. But, I do think that any 

 proposed theory — and I do congratulate you, Dr. van Overbeek, on 

 the thought you have put into your theory — must take steric con- 

 siderations into account. I come back to what I said this morning, and 

 that is that so complex is the growth response — your molecule must 

 get in, must have the right physical properties to penetrate, to move 

 in the tissues, it must have adequate stability, then it must have the 

 structural requirements for activity at the site of action — that no 

 simple theory on mode of action is likely to be satisfactory. But. let's 

 not overlook this rather interesting clue to the whole situation — 

 this specificity of stereoisomers which, incidentally, was first discov- 

 ered by Dr. Smith and has been developed very considerably by the 

 Swedish school since that time. 



Dr. Bitancourt: I believe that the site of action of lAA is at the 

 interface between the cytoplasm and the cell wall, and Dr. van Over- 

 beek's theory seems to fit very well into this scheme. But if the hole 

 in the cytoskeleton is so small that only the dichlorophenoxyacetic acid 

 fits in there, how does the indole nucleus fit into this hole? 



Dr. van Overbeek: Indeed, the indole nucleus does fit. One has to 

 make the stereo models (Figure 3 D) in order to appreciate the 3- 

 dimensional aspects. 



Dr. Bitancourt: AVell, this can be understood, but then once all 

 the holes are occupied nothing ought to happen, and so you can't 



