DISCUSSION 157 



the work of one or the other population, or both populations. In fact, 

 what evidence have we got of the work of the individual populations in 

 the primary host ? If you take them out and transfer them, you may 

 show that population A works, but was it working in its initial 

 environment ? 



Michie: If the initial environment is wrong, then the initial animal 

 will not be able to reject the skin graft — or not in the ordinary brisk 

 fashion. This is a very pertinent suggestion. 



Medawar: I should like to bring up a point which I don't think was 

 fully met in Dr. Michie's experiments. As I remember, in one of your 

 systems, a certain number, optimally 200,000, of adult CB Ax A hybrid 

 lymphoid cells are injected into a newborn A-line mouse. Two days 

 later, into this same A-line mouse, are injected adult CBA lymphoid 

 cells, and the consequence of that is that there is decidedly less splenic 

 enlargement in this mouse than there would have been if the CBA cells 

 had been injected without the prior injection of hybrid cells. Now, 

 forgetting about this prior injection and considering mice that have 

 been injected for the first time at two days with adult CBA cells, we 

 know from Simonsen's work that these CBA cells estabhshed in the 

 A-Hne mouse soon lose their competence to react against A-line anti- 

 gens (in the extreme case, in one of Simonsen's strain combinations, in 

 24 hours, though we know from some of RusseU's evidence that they 

 may continue to be reactive for perhaps four or five days). Anyhow, 

 they fairly soon lose their reactivity. Therefore, whatever effect this 

 prior injection has upon the CBA cells must take place pretty rapidly — 

 in two days plus whatever time it takes for the CBA cells to become 

 unreactive. So the first point to consider here is not merely the im- 

 munizabihty, if such it is, of the newborn mouse, but the great rate at 

 which it occurs. 



The second and more important point is this. If, as Simonsen's 

 experiment shows, these CBA cells are fairly rapidly inactivated by ex- 

 posure to A-line antigen, then why are they not paralysed or rendered 

 partially tolerant by the prior inoculation of what I should regard as 

 an extremely massive dose of cells containing A-Hne antigen — namely, 

 200,000 CBA X A hybrid cells. An alternative interpretation would be 

 that this prior inoculation, far from sensitizing the A-line mouse, acts 

 upon these CBA cells in such a way as to diminish their reactivity, and 



