Fig. 22. RNA world hypothesis on the origin of life. The RNA world hypothesis is based on self-replication of RNA, which has been proposed to explain the development of life on the earth. The unanticipated discovery of RNA catalysts or ribozymes initiated extensive discussion of the role of RNA in the origin of life. But, we think that there are many problems in the RNA world hypothesis to be impossible to solve, as followings. (1) Nucleotides, substrates of RNA synthesis, are too structurally complex to synthesize from simple organic compounds without effective catalysts, such as enzymes. (2) Self-replication of RNA would be principally impossible, because it requires RNA templates without tertiary structure, whereas catalytic action requires RNA catalysts with a stable tertiary structure. (3) Probability that self-replicated RNA encodes the amino acid sequence, which can be folded into appropriate three-dimensional structure, must be quite small, since there is not any relationship between the self-replicated RNA and the informational RNA encoding a globular protein.