The Origin of Specific Proteins 109 



Nuclear dUSvrvntiution 



Chemically induced chromosomal changes also seem to provide an 

 explanation for the results ohtained by Moore (1960) in his trans- 

 plantation of nuclei between two species of fiog, Rana sylvatica and 

 R. pipiens. Rana sylvatica eggs were fertilized by R. pipiens sperm 

 and then the egg nucleus removed before fusion with the sperm 

 nucleus could occur. Such R. sylvatica eggs equipped with haploid 

 R. pipiens sperm developed into blastulas, but then development 

 stopped. By the time of developmental arrest, the original sperm 

 nucleus would have divided about 12 to 14 times and the arrested 

 blastula would be composed of approximately 25,000 cells. Nuclei from 

 such arrested blastulas may be transferred again to eggs of the foreign 

 species. The same pattern of cell division and arrest of development 

 at blastula will again occur. Since hybrid amphibian embryos com- 

 monly cease development as blastulas, this result is not surprising but 

 it does demonstrate a nucleo-cytoplasmic interdependence. Most sug- 

 gestive, however, is the discovery that nuclei after a period of resi- 

 dence in foreign cytoplasm were not immediately able to support 

 normal development even when retransplanted to their species- specific 

 cytoplasm. Serial transplantation of these nuclei for six generations 

 produced only arrested blastulas just like those produced by the 

 original hybrid combination. Multiplication of the nuclei in foreign 

 cytoplasm had evidently produced a persistent change, probably in 

 the chromosomes. 



An attractive interpretation of these results is that replication of 

 chromosomes in foreign cytoplasm leads to the attachment of foreign 

 substances to the chromosomes, thus pi - eventing their normal differen- 

 tiation and inhibiting their heterosynthetic functions. It is important 

 to remember that chromosome replication during nuclear division 

 involves more than just the DNA. Many replications might be neces- 

 sary, therefore, in order for a chromosome to lose a component ac- 

 quired during its residence in a chemically foreign environment. 



These observations on the failure of chromosomes to promote nor- 

 mal development after they had multiplied in foreign cytoplasm 

 prompted us to test the hypothesis that cellular differentiation reflects 

 an antecedent chemical differentiation of the chromosomes. Our ex- 

 perimental design was simple to the point of being naive. Various 

 macromolecular fractions were prepared from the nuclei of adult 

 frog-liver cells. These fractions were dialyzed against a physiological 

 saline solution and then injected into fertilized eggs of the same 



