In Dr. Ferris's concept, the RNA, vesicles, and proteins—not enclosed by a cell membrane—would bind to mineral surfaces. Their shape and dimensions would be determined by the features of the substrate and rates of formation of RNA. These organisms could be as small as some purported nanobacteria, or about twice the size of the Q-beta virus, which contains three genes consisting of about 1,500 bases each. Dr. Ferris concluded that the fossil signature of such RNA-based life-forms would be difficult to identify.

Dr. Szostak proposed that a simple ancestral cell with the capability to evolve into a more complex cell may have started with polynucleotides, which can have catalytic activity, and vesicles, which are spontaneously assembling systems. Once a replicase and vesicle are brought together, a synergistic evolution could build up to produce a megabase of information that leads to a free-living organism. This process sets the stage for peptide synthesis and large-scale structural and regulatory components.

Dr. Szostak observed that evolution is inhibited by the free interaction of replicases in solution. The only way to achieve interesting Darwinian evolution is to have a compartmentalized system that can grow and divide, thus providing a selective advantage for mutations. But how can there be a cell cycle without any internal encoded machinery? Small vesicles, 30 to 100 nm in size, could interact and fuse to generate larger ones that combined different internal molecules. In the laboratory an artificial system can be created in which cells divide, fuse, divide, and fuse. Much larger vesicles can be fragmented with mild shear forces.

Dr. Benner proposed that the minimum cell size would be determined by the robustness of a single-biopolymer system in making the chemical compromise between genetics and catalysis, which pose competing and contradictory demands (e.g., in terms of the biopolymer's complexity, ease of folding, and capability to change physical properties). The problem is that nucleic acids are generally not good catalysts: one must sort through 2 × 1013 random RNA sequences to find one that modestly increases the rate of a templated ligation. Adding functional groups does improve catalytic power and versatility, but it is not clear whether functionalized RNA can sustain Darwinian evolution.

Dr. Benner said that chemical studies attempting to resolve these contradictions will help define life's origins on Earth and how best to find life elsewhere. In the meantime, short of historical context, information content is the only reliable signature of a Darwinian chemical system. A single-biopolymer system must be able not only to replicate but also to evolve. There is evidence that life before proteins had functionalized RNA, so this chemistry should be sought in samples from Mars. He also proposed that a genetic molecule needs a polycharged backbone to exhibit the behavior needed to support Darwinian evolution. Such a chemical structure would be fairly easy to detect on Mars, perhaps robotically.

The First Biopolymer System

A question was raised concerning how the first biopolymer was formed, given that even modern cells must work hard to make highly activated molecules. In fact, as Dr. Orgel noted, this is a matter of dispute within the prebiotic research community. Dr. Ferris said that a primitive process for forming such molecules is plausible, because polymeric phosphates can be made by heating phosphates.

Dr. Fraenkel asked whether prebiotic evolution would have been assisted by high temperatures. Dr. Benner noted that high temperature speeds all reactions, whether desirable or not, and it destroys the secondary structure of nucleic acids. Dr. de Duve noted that some scientists believe that life originated at cold temperatures—below zero degrees centigrade.

Dr. Ferris said that scientists have been looking for a polymer system other than RNA that could have driven early life-forms, but they have failed so far, so RNA remains the best model. Dr. Orgel



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