GENETIC CONTROL OF CELL INTEGRATION 351 



systems under investigation are from the operating molecules in whose 

 name the interpretations are drawn. It should also be evident, however, 

 that the direction of modern biology is towards systems which will give 

 answers to biological questions, and yet be interpretable at the molecular 

 level. This goal is not often reached, and in some lines of research 

 hardly attempted. Of course, a hazard of the analytical approach is that 

 by focusing upon elements of a system, one may altogether miss the over- 

 all view. An example of a line of research which appears to be very 

 promising in terms of over-all view rather than analytical detail is that 

 of nuclear transfer. 



NUCLEAR TRANSFER 



Within recent years, the technique has been developed of trans- 

 planting intact nuclei from one cell to another in amphibian oocytes and 

 early embryos. Owing primarily to the pioneering efforts of Briggs and 

 King, it has become possible to explore the changes, if any, occurring 

 in nuclei during embryonic development. 



The method consists essentially of enucleating an oocyte (they used 

 the frog Rana pipiens) and transferring into it a nucleus from some 

 particular cell of a developing embryo. In the initial experiments, the 

 transferred nucleus was derived from an early blastula stage only a few 

 divisions removed from the original diploid nucleus of the fertilized egg. 

 Techniques were developed to such a remarkable state that 40-80 per 

 cent of the resulting oocytes underwent normal development, giving rise 

 finally to tadpoles. 



Using these results as a control, Briggs and King compared the be- 

 havior of these nuclei from early blastulae with nuclei obtained from a 

 number of specified regions of embryonic development during succeeding 

 stages. In brief, they found that nuclei from increasingly differentiated 

 cells lost their capacity to determine normal development after transfer. 

 The problem then arose how to interpret these results. Are the nuclei 

 becoming altered in situ before transfer, or are they merely more sus- 

 ceptible to injury? 



The experimental approach to this question was derived from micro- 

 biological methodology: to determine whether or not the alterations ob- 

 served were stable upon subculture. With microorganisms one follows 

 the stability of a phenotype by observing the descendants of a particular 

 cell, i.e., a clone, through many generations. A kind of cloning was 

 developed with nuclear transfer experiments. First, nuclei from some 

 chosen stage of development were transferred to oocytes, which were 

 allowed to develop to early blastula, that is, for some 12-14 divisions. 



