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to today's co-enzymes and prosthetic groups? What was the relation- 

 ship, the transition, between pregenetic "metabolism" and what 

 would later be the true cellular metabolism? It has been customary 

 to think that the first cells were heterotrophs and so had very little 

 metabolism of their own (they took all amino acids, nucleotides, 

 etc., from their rich growth medium). Is this a correct view? Is the 

 Horowitz hypothesis for the origin of metabolic pathways (i.e., 

 by backward evolution, one enzymatic step at a time) a correct view? 



Also, we must be concerned with the problem of primitive 

 energy sources. What mechanism generated chemical energy for pre- 

 biotic, pregenetic systems? Was there a pregenetic photosynthesis 

 (visible-infrared range)? To what extent were chemical reactions, 

 such as C0 2 + 2H 2 -+ CH 4 + 2H 2 0, present and utilized? Did 

 membrane-associated energy production occur, such as through sys- 

 tems that automatically generated transmembrane H + (or other) 

 gradients? 



We should, in addition, elucidate the nature of the development 

 of a genetic (informational) system. What is the molecular mecha- 

 nism of translation? How do various versions (eucaryotic, archea- 

 bacterial, eubacterial) of the ribosome differ from one another, 

 and what does this tell us about the origin of that structure? What is 

 the most primitive form of the translation apparatus? How did the 

 genetic code evolve? What is the relationship between its evolution 

 and the various stages in the evolution of the translation mechanism? 

 What is the relationship between nucleic-acid replication (or its 

 transcriptions) and translation? What is the significance of the fact 

 that bacterial RNA viral replicase has four subunits, three of which 

 are associated with the translation process in the host cell? What was 

 the nature of the aboriginal genome? Was it RNA or DNA? How was 

 it organized? What were the aboriginal genes (what functions were 

 encoded)? What was the relationship between the aboriginal genes 

 and their gene products? 



Finally, we must investigate the nature of the eucaryotic cell. 

 How did it evolve? To what extent and in what ways are endosym- 

 bioses responsible for the uniqueness of the eucaryotic cell? Was the 

 eucaryotic cell basically formed by the fusion of various procary- 

 otes? Or, did most of the important characteristics that are specifi- 

 cally eucaryotic stem from a pre-procaryotic stage in evolution? To 



