l60 DISCUSSION 



Mitchison: Once one accepts your conclusion that newborn mice can 

 be immunized, doesn't this imply that a comparison between paralysis 

 and tolerance cannot be drawn from your experiments ? The question 

 is, if you put antigen in before the animal can react, will the dosage 

 which is needed then be very much less? So in a sense your own 

 experiments have forced you into injecting the mice /// utero if you 

 really wish to answer the question. 



Michie: This gets us into terminological troubles, as to precisely how 

 the terms of paralysis and tolerance should be used : whether to erect a 

 distinction by definition or to regard the distinction as a distinction in 

 principle between two forms of central inhibition. 



Mitchison: There is a distinction in principle: but if you want the 

 antigen there from the beginning, before reactivity develops, you may 

 have to inject the antigens into the cytoplasm of the ovum ! There 

 must be a point before reactivity is present. And the question is, if 

 antigen is present from before that stage, will less be needed for 

 inhibition ? 



Hildemann: We were not especially surprised to find that preparations 

 of small lymphocytes from C57 mice failed to induce any runting 

 symptoms whatsoever in A-line mice older than 24 hours of age. Neither 

 were we surprised on injection of such preparations at dosage levels of 2 

 million cells from C57 to Fj hybrids to find that we got runting symp- 

 toms only in hybrids less than 48 hours of age. But when we increased 

 the lymphocyte dosage, as Simonsen and others have done, we still 

 failed to get runt disease in ¥^ animals injected after 2 days of age. What 

 the basis for this is I don't know, although I have a suspicion that F^ 

 hybrid vigour might be involved — since these F^ animals gain weight 

 at a much more rapid rate than do the parental-line animals. 



With respect to your experiments, I wonder if the so-called neutral 

 or null period really exists. It seems strange that a mouse which can 

 readily be made tolerant up to 24 hours of age should then enter a 

 period when it will become neither immune nor tolerant, and then at 

 about a week of age it may become immune. Surely there must be a 

 transitional stage between tolerance responsiveness and immune 

 responsiveness. 



Michie: Our own point of view on that is that the original null 

 period in fact corresponds to a null zone in dosage level. There is a 



