Discussion 75 



cent mortality or higher or lower than that. In the case of the "family 

 trees", about 80 per cent died. 



Ledcrberg: In regard to this matter of considering a genotype as a 

 norm of reaction, all geneticists have been worried about what is called 

 residual variation in supposedly pure lines. We never know if we can 

 ascribe this type of statistical variability to uncontrollable variation in 

 the environment, with maternal carry-over effects that have no genetic 

 significance, or very minor minimal changes in the genetic material 

 itself. Most genetic work is purposely concerned with changes so large 

 that they can easil}^ be scored, and in the case of bacteria, usually with 

 changes large enough and persistent enough to be scored in clones. We 

 have here quite a different dimension of analj^sis from that to which we 

 were accustomed, although it does recall the work of Dr. Jennings with 

 isolated rhizopods (Jennings, H. S. (1929). Bibliogr. genet., 5, 105). We 

 must seriously consider the possibility that there is another dimension 

 in genetic change besides the one to which we are accustomed. Here I 

 agree with Dr. Hughes that there may be, together with the fixed 

 continuity of polynucleotides which give the essential structure, other 

 chemical variations in the chromosome which could control the level of 

 activity of genetic material. Dr. Stocker has already alluded to phase 

 variation; here it was possible to show that the difference in antigenic 

 expression is due to oscillations in state between the expressivity and the 

 non-expressivity of a given specific antigenic determinant (Ledcrberg J., 

 and lino, T., (1956), Genetics, 41, 743) ; and this was a major change. We 

 would certainly not want to exclude the possibility that this is going on 

 all the time, and onty if you have the most refined methods of analysis 

 are you going to be able to pick up the changes in local activity of the 

 genetic material. We must, therefore, try to translate this type of ob- 

 servation into the possibility of conventional genetic analysis by recom- 

 binational methods, and see whether we can localize that sort of change 

 that you have described. Secondly, we should see whether we can control 

 these changes environmentally from the outside. There is no indication 

 as to the inherent nature of these changes, whether they are purely 

 metabolic accidents, or whether the type of medium they are in may have 

 something to do with them. 



Pontecorvo: If instead of studying bacterial cells, which seem to be 

 locked into a tough membrane, you looked at mammalian cells in tissue 

 culture, you would find there is an enormous amount of variation in 

 shape, size, etc. Each cell has an individualitj?^, so to speak. 



Eagle: There are large differences with respect to resistance to drugs. 



Lederberg: You might also find a very wide variation in chromosome 

 number from one cell to another. But is that residual variation wholly 

 genetic in the sense that Dr. Gj^orffy was using the term, or are there 

 other methods of variation? 



Hayes: Cells oiEsch. coH in young culture as a rule contain four nuclear 

 analogues. This means that two generations are required for segregation 

 of a cell which is under the sole control of one of the four nuclei of the 

 initial cell. There is good evidence to suggest that one normal nucleus 

 within a cell is able to support normal growth. If Dr. Hughes" non- viable 



