JOSHUA LEDERBERG 



struction of fixed cells, and in this form autogamy is a blind alley without the 

 possibility of genetic novelty, and therefore not amenable to genetic test, (74). 



The genetic significance of another cycle, the "L-forms," is equally obscure. 

 It is expected that this problem will be clarified in the very near future to an 

 extent that makes a detailed discussion of its present status here premature. The 

 reader is referred to provocative discussions published elsewhere (50, 51, 52, 

 75, 76, 132, 123) These studies reopen the possibility of the existence of 

 diminutive forms of many bacteria which may be capable of passing through 

 ordinary bacterial filters. These forms may also be highly resistant (like the 

 endospores) to heat and antiseptics. Since they also may have special nutritional 

 requirements, they may remain dormant in ordinary bacteriological media 

 which support the normal bacterial form. If these observations are confirmed, 

 the filtrable L-forms might well play a role in some of the transformation 

 experiments cited earlier. However, the transforming agent would consist not 

 of a single genetic factor transferred from one cell to another, but of a diminutive 

 form of one cell which germinates under the influence of another. The analogy 

 between the diminutive forms and the gametes of other plants and animals 

 is obvious on a physical plane; the possibility that they may play a similar 

 function in bacterial biology is a provocative one which will require careful 

 study. 



One of the reasons for including papers on viruses and bacteria in the 

 same volume is the necessity for considering both the host and the "parasite" 

 in any physiological studies of their association. Furthermore, it is becoming 

 apparent that a great many bacterial cultures carry bacteriophages in a symbio- 

 tic relationship ( "lysogenicity" ) so that what are taken to be bacteriological 

 investigations have an unavoidable virological component. A second reason is 

 that the phage-bacterium complex may be profitably regarded as a unit for 

 comparison with other cellular systems which carry extranuclear hereditary 

 components (57, 119). Burnet's paper illustrates this very clearly (17). 



It might be worth pointing out also the formal analogy between the transfer 

 of a latent virus from a lysogenic to a sensitive bacterium and the transfer 

 of the capsular attributes from smooth to rough bacteria in the pneumococcus 

 transformation. Whether this analogy is more than superficial only time will 

 tell. It is becoming clear, however, that there is a continuous gradation of pro- 

 perties between systems of cytoplasmic heredity such as the chloroplasts of green 

 plants, and the metabolic granules of yeast, and infective associations such as 

 the "killer" factors in Paramecium, rickettsia in the Arthropoda, and viruses in 

 plants and mammals. In many instances at both extremes, "disinfection" or cure 

 is possible by the use of appropriate drugs (streptomycin for chloroplasts, acri- 

 flavine for yeast granules) (47, 57). 



Burnet's paper also illustrates one of the earliest and clearest cases of muta- 

 tion in a bacteriophage. In a later study, Luria described host range mutations 

 in phages which restore the virus' ability to attack bacteria which had mutated 

 to resistance to the previous form of the virus ( 18) . This process of compensatory 



