ends. Others would have grown in fits and starts to- 

 ward the earliest living entities. It is also likely that 

 Danvinian-style natural selection winnowed entire 

 populations of molecules and chemical systems. From 

 that perspective, the first entities that could replicate, 

 catalyze, and multiply would have truly marked the 

 origin of life and its evolution. 



Surely, RNA meets all those requirements. But 

 RNA is also highly unstable. A self-catalyzing, selt- 

 replicatmg RNA molecule is unlikely to have arisen 

 spontaneously. So where did it come from? 



The answer is not so clear. This difficulty has led 

 to the suggesdon that a pre-RNA world of pri- 

 mordial living systems predated and gave rise to the 

 RNA world. Such a pre-RNA world would have 

 spawned the first "genetic polymers" captable ot en- 

 coding and perhaps transmitting information. If that 

 view is correct, the denizens of a pre-RNA world 

 may actually have initiated what is now called hered- 

 ity. They, in turn, would have subsequently evolved 

 through natural selection toward RNA. 



To explore the possibilities of such reactions, Al- 

 bert Eschenmoser, an organic chemist at the Eid- 

 genossiche Technische Hochschule in Zurich, and 

 his colleagues have modified nucleic acids to include 

 various versions of ribose and other simple sugars. 

 Still other investigators have synthesized similar 



reasonable to assume that protein synthesis and the 

 encapsulation of machinery to replicate informa- 

 tion did not originate until the RNA world 

 emerged. As the molecular biologists Gerald Joyce 

 of the Scripps Institute, Jack W. Szostak of the 

 Howard Hughes Research Institute, and David Bar- 

 tel of the Whitehead Institute for Biomedical Re- 

 search in Cambridge, Massachusetts, among others, 

 have shown, ribozymes alone can perform the re- 

 actions needed to construct key chemical bonds. 



Taking into account the latest experimental evi- 

 dence, it seems likely that abiotic synthesis gener- 

 ated the raw materials needed to assemble the first 

 self-maintaining molecular systems capable of repli- 

 cating. Even if the first living systems had little ca- 

 pacity to synthesize their own compounds, their pri- 

 mary sources of raw materials would have been or- 

 ganic molecules synthesized in the prebiotic soup. 

 Perhaps the energy needed to enable these primi- 

 tive systems to grow and reproduce came from 

 cyanamide or other high-energy compounds. 



Yet by the time RNA-based life appeared on 

 Earth, the supply of raw materials needed to sustain 

 life had probably become exhausted. This famine, 

 so to speak, would have favored the natural selec- 

 tion of simple metabolic-like pathways that could 

 supply materials needed to sustain simple living be- 

 ings. Ribozymes may have helped maintain some 



Extraterrestrial molecules may 



polymers without ribose or phosphate. Did systems 

 of such polymers predate the RNA world? The an- 

 swer to that question remains unknown. 



Precisely how the first genetic machinery evolved 

 also persists as an unresolved issue. The hypothesis 

 of a pre-RNA world does not presume that genet- 

 ic polymers could evolve only from simpler genet- 

 ic polymers, in a never-ending succession of mole- 

 cular takeovers. But it cioes point toward a need to 

 simulate, under plausible prebiotic conditit:)ns, the 

 pathways that simple monomers and genetic poly- 

 mers might have taken to become evolutionary pre- 

 cursors of RNA. Perhaps the best way to compre- 

 hend life's emergence is through the molecular dy- 

 namics, and evolution, of systems with "replicating 

 entities," endowed with polymers that can store ge- 

 netic information and replicate differentially. 



Whether or not membranes enclosed such enti- 

 ties is also not yet clear. But as I mentioned earlier, 

 lipids and other fatty acids were almost certainly pre- 

 sent in the prebiotic soup. Thus cell-like enclosures 

 may have been present as well. Nevertheless, it is 



have spiced the prebiotic soup. 



metabolic pathways, until they eventually gave way 

 to protein-based catalysts — that is, enzymes. 



In spite of all of the scientific debates, the hy- 

 pothesis that a prebiotic soup fostered an RNA 

 world that then spawned life still offers the most 

 coherent framework to explain life's evolution. The 

 exact pathway tor life's origin may never be known. 

 Many gaps in understanding persist. 



Yet, however imperfect it may be, today's evolu- 

 tionary framework is rich enough not to require any 

 appeal to the supernatural or to religious accounts 

 such as those based on "intelligent design." Evidence 

 of scientific incompleteness is not evidence for cre- 

 ationism. Although healthy disagreements on this 

 subject will continue, scientists see such debates as 

 challenges, not as reasons to abandon reason or data. 

 The fact that people can reconstruct life's emergence 

 at all, albeit with imperfect precision, should be 

 cause for celebration: an intellectual achievement of 

 the first rank in shedding so much light on one of 

 the fundamental questions of existence. □ 



February 2006 NATCR Al iiistc)R\- 



41 



