For many scientists in the origin-of-life field, those shadows had lifted two decades earlier with the discovery of ribozymes, enzyme-like substances made of RNA. A simple solution to the chicken-and-egg riddle now appeared to fall into place: Life began with the appearance of the first RNA molecule. In a germinal 1986 article, Nobel Laureate Walter Gilbert of Harvard University wrote in the journal Nature: "One can contemplate an RNA world, containing only RNA molecules that serve to catalyze the synthesis of themselves. & The first step of evolution proceeds then by RNA molecules performing the catalytic activities necessary to assemble themselves from a nucleotide soup." In this vision, the first self-replicating RNA that emerged from non-living matter carried out the functions now executed by RNA, DNA and proteins.

A number of additional clues seemed to support the idea that RNA appeared before proteins and DNA in the evolution of life. Many small molecules, called cofactors, play a necessary role in enzyme-catalyzed reactions. These cofactors often carry an attached RNA nucleotide with no obvious function. These structures have been considered "molecular fossils," relics descended from the time when RNA alone, without DNA or proteins, ruled the biochemical world. In addition, chemists have been able to synthesize new ribozymes that display a variety of enzyme-like activities. Many scientists found the idea of an organism that relied on ribozymes, rather than protein enzymes, very attractive.

The hypothesis that life began with RNA was presented as a likely reality, rather than a speculation, in journals, textbooks and the media. Yet the clues I have cited only support the weaker conclusion that RNA preceded DNA and proteins; they provide no information about the origin of life, which may have involved stages prior to the RNA world in which other living entities ruled supreme. Just the same, and despite the difficulties that I will discuss in the next section, perhaps two-thirds of scientists publishing in the origin-of life field (as judged by a count of papers published in 2006 in the journal Origins of Life and Evolution of the Biosphere) still support the idea that life began with the spontaneous formation of RNA or a related self-copying molecule. Confusingly, researchers use the term "RNA World" to refer to both the strong and the weak claims about RNA's role prior to DNA and proteins. Here, I will use the term "RNA first" for the strong claim that RNA was involved in the origin of life.

The Soup Kettle is Empty

The attractive features of RNA World prompted Gerald Joyce of the Scripps Research Institute and Leslie Orgel of the Salk Institute to picture it as "the molecular biologist's dream" within a volume devoted to that topic. They also used the term "the prebiotic chemist's nightmare" to describe another part of the picture: How did that first self-replicating RNA arise? Enormous obstacles block Gilbert's picture of the origin of life, sufficient to provoke another Nobelist, Christian De Duve of Rockefeller University, to ask rhetorically, "Did God make RNA?"

RNA's building blocks, nucleotides, are complex substances as organic molecules go. They each contain a sugar, a phosphate and one of four nitrogen-containing bases as sub-subunits. Thus, each RNA nucleotide contains 9 or 10 carbon atoms, numerous nitrogen and oxygen atoms and the phosphate group, all connected in a precise three-dimensional pattern. Many alternative ways exist for making those connections, yielding thousands of plausible nucleotides that could readily join in place of the standard ones but that are not represented in RNA. That number is itself dwarfed by the hundreds of thousands to millions of stable organic molecules of similar size that are not nucleotides.

The RNA nucleotides are familiar to chemists because of their abundance in life and their resulting commercial availability. In a form of molecular vitalism, some scientists have presumed that nature has an innate tendency to produce life's building blocks preferentially, rather than the hordes of other molecules that can also be derived from the rules of organic chemistry. This idea drew inspiration from a well known experiment published in 1953 by Stanley Miller. He applied a spark discharge to a mixture of simple gases that were then thought to represent the atmosphere of the early Earth. Two amino acids of the set of 20 used to construct proteins were formed in significant quantities, with others from that set present in small amounts. (A description of the Miller experiment and the chemical structures of an amino acid and a nucleotide can be found in "The Origin of Life on the Earth," by L. E. Orgel; Scientific American, October 1994.) In addition, more than 80 different amino acids, some present and others absent from living systems, have been identified as components of the Murchison meteorite, which fell in Australia in 1969. Nature has apparently been generous in providing a supply of these particular building blocks. By extrapolation of these results, some writers have presumed that all of life's building could be formed with ease in Miller-type experiments and were present in meteorites and other extraterrestrial bodies. This is not the case.