Discussion 249 



extracts from dependent cells to see if we could get any effect on the 

 sensitive cells, but we found nothing. 



Lederberg: Dr. Eagle has the complete case. These were added resis- 

 tant cells which were in fact killed by being in the same environment 

 where the sensitive cells were killed, and that is to some extent a model 

 of some real situation. 



Eagle: This is an extremely strain-specific phenomenon. A mass of 

 sensitive organisms, e.g. staphylococci, will not kill a few resistant 

 streptococci or pneumococci. As I have mentioned, DNAse had no effect, 

 and we concluded that DNA was not passing from sensitive to resistant 

 organisms. Is it possible, however, that this has not been wholly excluded 

 by this experiment — that the mean distance between the sensitive and 

 the resistant organism in a crowded plate is so small, and the amount of 

 the DNAse added also so small, that there may not have been time for 

 the complete destruction of the DNA en route, so to speak? This is still 

 perhaps an open possibility. 



Pollock: It does not necessarily have to be DNA. There are a number 

 of other possibilities to explain this effect. 



Lederberg: It seems unlikely that this is a genetic effect at all, just 

 from the empirical fact that you get segregation of markers that have 

 been transduced. In other words, if you put a genetic fragment, i.e. a 

 sensitive gene, into a resistant cell, you don't necessarily get out a 

 sensitive clone. You get a mixture of sensitives and resistants. On the 

 other hand, the simplest assumption would be that you have had a 

 transfer of an essential component of the "phenome" as Prof. Davis 

 calls it, and this could be equally sensitive, and might even be RNA. 

 There are a few experiments that are analogous to this, i.e. transfer of 

 enzyme-forming ability from one genotj^De to another by means of RNA, 

 or by means of a metabolite of some protein. 



Knox: We have made several attempts to see whether heat-killed 

 sensitive organisms have any effect on the development of resistance, 

 but we have found nothing so far. 



Stocker: With regard to Prof. Knox's hypothesis on isoniazid resistance 

 resulting from a spontaneous mutation causing a block in the synthesis 

 of a peroxidase system, it is not clear to me whj^ such a block should 

 confer resistance. If the mutants which owe their resistance to this ty^Q 

 of mutation can survive only in media with catalase, or anaerobically, 

 then would one not expect sensitive organisms also to survive isoniazid 

 under such conditions ? If the system concerned were dispensable under 

 those conditions, then even if the system were blocked by the action of 

 isoniazid the sensitive organism would be unaffected. 



Knox: This question is tied up with the whole question of haemin and 

 the destruction of isoniazid. Catalase may be a different matter. With 

 regard to haemin, that is exactly what happens. If you inoculate sensitive 

 organisms into quite high concentrations of isoniazid in the presence of 

 haemin, they grow quite happily. That was originally thought by Fisher 

 to be a case of competitive antagonism. But it was later sho^NTi by 

 various people that haemin oxidizes isoniazid. In the presence of oxygen, 

 haemin catalyses the oxidation of isoniazid to a double compound 



