The nature of the first genetic material and the prebiotic chemistry that permitted its emergence are central themes in discussions of the origins of life. The discovery of ribozymes and the consequent rather general acceptance of the RNA world hypothesis (1) pose an inescapable question: How were ribonucleotides first formed on the primitive earth? This is a very difficult problem. Stanley Miller's synthesis of the amino acids by sparking a reducing atmosphere (2) was the paradigm for prebiotic synthesis for many years, so at first, it was natural to suppose that similar methods would meet with equal success in the nucleotide field. However, nucleotides are intrinsically more complicated than amino acids, and it is by no means obvious that they can be obtained in a few simple steps under prebiotic conditions. A remarkable synthesis of adenine (3) and more or less plausible syntheses of the pyrimidine nucleoside bases (4) have been reported, but the synthesis of ribose and the regiospecific combination of the bases, ribose, and phosphate to give 
-nucleotides remain problematical. The recent work of Eschenmoser and his co-workers (5) has led to a specific synthesis of ribose 2,4-bisphosphate, but prebiotically plausible sequences of steps to the precursors of this ribose derivative and from it to the standard nucleotides are not obvious.
What are the alternatives if we tentatively agree that the direct prebiotic synthesis of standard nucleotides is implausible? Clearly, some complex chemistry must have "self-organized" on the primitive earth (or wherever else terrestrial life originated, if the panspermia hypothesis is correct) and facilitated the appearance of the RNA world. But what was it like? A popular hypothesis supposes that there was an earlier "genetic system," based on monomers that are more easily formed under prebiotic conditions than nucleotides, and that this primary genetic system "learned" to synthesize the nucleotides (1). This is the simplest form of the hypothesis, but the route to the RNA world could have passed through more than one transitional "genetic system." Possible transitional systems might have been based, for example, on pRNA, an isomer of RNA involving the pyranose form of ribose (6), or PNA, a molecule like RNA but with a peptide backbone (7).
The basis of the above hypothesis is the belief that there is a suite of monomers simple enough to form directly under primitive-earth conditions, but still able to form the self-replicating polymers of a primary genetic system. This belief has, with good reason, been challenged repeatedly. It is claimed that some other form of self-organization was needed to supply the components of the first self-replicating molecules and perhaps to catalyze their polymerization. The exact nature of the prior form of self-organization that is postulated differs from one scenario to the next, but all scenarios have one feature in common: a self-organized cycle or network of chemical reactions that does not depend directly or indirectly on a genetic polymer (8-11). In this paper, I will discuss chemical cycles with particular reference to one of the best developed of these theories, that of Wächtershäuser (9, 12).
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