In 1986, American physicist, biochemist, and molecular biology pioneer Walter Gilbert was the first to propose the term “RNA world hypothesis” for the origin of life since the possibility of Darwin’s “proteine” arrival in the “warm little pond” was beyod any realm of possibility. Gilbert suggested that because RNA can synthesize itself in the absence of proteins, RNA may have originated on the early Earth before proteins or DNA; this is known as the RNA world. According to the RNA world hypothesis, the RNA molecule later evolved into DNA and protein molecules. While the DNA molecule evolved into a data storage role, the protein molecules evolved into a catalytic role.

In 1959, Spanish Catalan biochemist Joan Oró began to synthesize adenine, a key component of RNA and DNA, from hydrogen cyanide, similar to a Miller–Urey experiment. 

Like the Miller–Urey experiment though, the lack of geological evidence for hydrogen cyanide in the fossil record is missing. Another problem with hydrogen cyanide is that at room temperature, it becomes a gas toxic to cellular metabolism. During the German Nazi regime in the mid-twentieth century, hydrogen cyanide was used as an agent for mass murder.  

To date, not one laboratory experiment with realistic early Earth elements and conditions has produced a single nucleic acid. Scripps Research Institute biochemist Gerald Joyce states that the “most reasonable interpretation is that life did not start with RNA.” The origin of life is so difficult a problem that German researcher Kaus Dose stated in 1988 that the RNA theory is “a scheme of ignorance. Without fundamentally new insights in evolutionary processes … this ignorance is likely to persist.” 

In 1998, Leslie Orgel, senior research fellow and research professor at the Salk Institute for Biological Studies, where he directed the Chemical Evolution Laboratory, acknowledged that “we are very far from knowing whodunit” or what were the early environmental conditions on the Earth. 

Nearly twenty years later, the role of RNA in the origin of life remains elusive, if not improbable. In 2007, commenting in Proceedings of the National Academy of Sciences of the United States of America on a paper by Phillipp Baaske and Eugene V. Koonin, senior investigator, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, stated that while more is known about RNA, the evolutionary role of RNA has severe difficulties and “still is a hypothetical entity; … the evolutionary path to the translation systems remains essentially uncharted.”