344 General Discussion 



less remote than for our alternative approach — the control of 

 genotype. 



Until then, we can evade the problem by using more and different 

 antibiotics, alone and in combination. However, without funda- 

 mental knowledge, we may have to run twice as fast to stand in 

 place, at least for those afflictions, like tuberculosis, where inter- 

 current development of resistance is a serious problem. 



This analysis is premissed on the development of inherited 

 resistance by a process of mutation and selection, whose role in 

 at least some instances is no longer controverted. It has been 

 suggested that this is a counsel of despair. But it is not obvious to 

 me that our tactics would be greatly altered if we had to cope with 

 alternative mechanisms of direct adaptation. In either event, we 

 should need to learn a great deal more about the biology of bacteria 

 before we could put basic principles to practical use. In past years, 

 the inaccessibility of the genetic material to experimental modifi- 

 cation may have been overstated. We are just beginning to learn 

 something of its chemical make-up, and this does give us a glimpse 

 of future possibilities of controlled mutagenesis and synthetic 

 genes. But it would be a worse error now to oversimplify the prob- 

 lem, to overlook the very large extent to which bacteria mutate 

 indeterminately, when and as they please, rather than as an 

 accommodation to our own too crude techniques. 



Harington: This brings us to the end of our deliberations, and 

 there is little useful that I can add in my final remarks. I would 

 like particularly to thank Prof. Lederberg for his final contribu- 

 tion to the discussion, which seems to me to be an admirable 

 crystallization of the more practical issues. 



At the outset of the meeting I referred to the background of 

 disquiet about chemotherapy that was in the minds of some of us, 

 because of the continued empiricism of the subject on the chemical 

 side and because of preoccupation with the practical obstacles 

 raised by drug resistance. 



Obviously we have not in the last three days made any apparent 

 progress towards the solution of these practical problems ; equally 

 obviously we could not and did not expect to do so. On the other 

 hand there are directions in which we can, I think, claim to have 

 advanced. 



We chose for ourselves a subject that is essentially controversial 

 because of the clear distinction between the theoretical biological 

 approaches that can be made to it; these two approaches have 



