27 



" Lister Institute, recovered from the urine of a case of pyelitis a 

 " coliform strain which behaves in culture as if it were a mixture 

 " of bacilli and ' bacteriophage.' " 



I do not think there is any need to quote further instances. 

 If spontaneous production of lytic substance directly by the 

 bacteria had only been observed in rare instances, the true explana- 

 tion might have been that this substance was not produced de 

 novo but was present, though unnoticed, along with the strain 

 used as the starting point of the observations. But this objec- 

 tion will not hold, because these results have been observed 

 repeatedly by different investigators, who have started with pure 

 cultures showing no evidence whatever of the action of a " lytic 

 principle " when growth was allowed to take place under normal 

 conditions. 



Experiments with Agents capable of producing 

 Variants. 



I take as my starting point the production of pneumococcal 

 variants by growth in immune serum, which is described by 

 F. Griffith in the preceding report. Here the influence which 

 produces the variant can be identified at once; it is the action 

 of the specific " type " antibodies on the growth of the homologous 

 strain. The variant is viable in vitro but not in vivo ; and its 

 incapacity to thrive in the animal body is shown to be due to loss 

 of those elements in bacterial structure which are associated 

 with capsule formation and production of " specific soluble 

 substance." Hence the action of the serum in protection tests 

 is readily explained; the serum produces a variant which, owing 

 to these defects, is not viable in the animal body. Possibly 

 the therapeutic action which has been demonstrated for Type I 

 antipneumococcal serum is also to be explained, or partially 

 explained, on the same principle. 



At the same time it must be recognised that this principle is 

 only applicable under special circumstances and does not go 

 very far as a general explanation -of the more important facts 

 about immunity reactions and the production of variants. For 

 example, it is impossible to maintain that recovery from pneu- 

 monia, without serum treatment, is due to manufacture, by the 

 patient, of those antibodies which are demonstrable in artificially 

 prepared immune sera. And similar difficulties arise in attempting 

 to show that resistance to infections with other species of parasitic 

 bacteria is due to demonstrable antibodies. 



Hence, if the results cannot be explained as due to known and 

 demonstrable antibodies, one is led to consider whether there 

 may not be some other specific factor which operates in the living 

 body and converts the invading organism into a non-viable 

 variant. Antibodies, it should be remembered, are not the only 

 influences which are specific for bacteria. Bacterial attributes, 

 though they may be antigenic {i.e., capable, as foreign protein, of 

 giving rise to antibodies) may also act selectively, and even 



