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multiple transduction. Apparently they are hard to find. This again should not 

 disturb us. One of the first things that happens as a result of active phage infec- 

 tion or induction of an active phage synthesis is fragmentation of the nuclear ap- 

 paratus. 



A very simple picture of what transduction is all about is that accident- 

 ally during the formation of mature phage, one of these fragments gets incorpor- 

 ated into the phage particle. When it gets into the cell, then this phenomenon 

 occurs. The chances of getting Z characters transduced will then depend upon 

 how close they are together on the chromosome. We have few characters which 

 are very close together; our map, thus far, is sparsely dotted with loci. As we 

 add more loci we should increase the frequency of multiple transduction. 



KAMEN: That has very little to do with irradiation. 



KAPLAN: There is one possible analogy here to the material from 

 bone marrow and spleen that seems to exert some effects on X irradiated mice 

 and possibly other species. There is now fairly good evidence that the activity 

 resides in the nucleus of the cell. 



There is a little evidence, which Cole has put forth, which would indi- 

 cate that the activity is destroyed by DNA-ase and by trypsin but not by RNA- 

 ase. This material, if injected in the form of differentially centrifuged nuclei 

 (but thus far not extractable from the nuclei) acts remotely on radiation-dam- 

 aged cells that have been blocked from going through mitosis. Very shortly 

 after it is administered, there is a release from this mitotic block and the cells 

 start to proliferate in the thymus, the spleen, and in lots of other places where 

 they have been unable to recover. Concurrently with this, a whole host of at- 

 tributes of the animal that have been knocked out, suddenly come back. Its 

 ability to combat infection, for example, is restored almost overnight. 



This material nnay be analogous to the transfornning principle, as Cole 

 has pointed out, although the analogy is a rather remote one at this time. 



MAZIA: Must the nuclei be of the same genetic strain as the animal 

 into which they are injected in order to be effective? 



KAPLAN: Well, we are not completely certain of that. There is a 

 little evidence that Lorenz published, that would suggest that there may be a 

 small heterologous effect but in order to demonstrate such an effect one needs 

 a much larger amount of material. 



It is interesting that this material is found only in bone marrow and in 

 the spleen of the mouse and not in any other tissue. 



It appears in rat marrow and it is probably going to work in marrow of 

 all species. If you look at it biologically, the spleen of the mouse is unique in 

 the sense that it functions very actively as extra-skeletal bone marrow and this 

 is not true of other species; therefore, if you talk about the spleen of the mouse 

 you are really talking about bone marrow and to beconne too narrowly concerned 

 with spleen as spleen is not important. 



DUBOIS: How much protection has been obtained in the rat? 



KAPLAN: About 50 percent. The difficulty is that in the rat, there is 

 another unique event, namely the sensitivity of the intestines, which is apparent- 

 ly not related to the marrow factor. The hematopoietic injury can be, in a large 



