The RNA world hypothesis, to be true, has to overcome major hurdles:
1. Life uses only right-handed RNA and DNA. The homochirality problem is unsolved. This is an “intractable problem” for chemical evolution
2. RNA has been called a “prebiotic chemist’s nightmare” because of its combination of large size, carbohydrate building blocks, bonds that are thermodynamically unstable in water, and overall intrinsic instability. Many bonds in RNA are thermodynamically unstable with respect to hydrolysis in water, creating a “water problem”. Finally, some bonds in RNA appear to be “impossible” to form under any conditions considered plausible for early Earth. In chemistry, when free energy is applied to organic matter without Darwinian evolution, the matter devolves to become more and more “asphaltic”, as the atoms in the mixture are rearranged to give ever more molecular species. In the resulting “asphaltization”, what was life comes to display fewer and fewer characteristics of life.
3. Systems of interconnected software and hardware like in the cell are irreducibly complex and interdependent. There is no reason for information processing machinery to exist without the software and vice versa.
4. A certain minimum level of complexity is required to make self-replication possible at all; high-fidelity replication requires additional functionalities that need even more information to be encoded
5. RNA catalysts would have had to copy multiple sets of RNA blueprints nearly as accurately as do modern-day enzymes
6. In order a molecule to be a self-replicator, it has to be a homopolymer, of which the backbone must have the same repetitive units; they must be identical. In the prebiotic world, the generation of a homopolymer was however impossible.
7. Not one self-replicating RNA has emerged to date from quadrillions (10^24) of artificially synthesized, random RNA sequences.
8. Over time, organic molecules break apart as fast as they form
9. How could and would random events attach a phosphate group to the right position of a ribose molecule to provide the necessary chemical activity? And how would non-guided random events be able to attach the nucleic bases to the ribose? The coupling of ribose with a nucleotide is the first step to form RNA, and even those engrossed in prebiotic research have difficulty envisioning that process, especially for purines and pyrimidines.”
10. L. E. Orgel: The myth of a self-replicating RNA molecule that arose de novo from a soup of random polynucleotides. Not only is such a notion unrealistic in light of our current understanding of prebiotic chemistry, but it should strain the credulity of even an optimist’s view of RNA’s catalytic potential.
11. Macromolecules do not spontaneously combine to form macromolecules
125. The transition from RNA to DNA is an unsolved problem.
13. To go from a self-replicating RNA molecule to a self-replicating cell is like to go from a house building block to a fully built house.
14. Arguably one of the most outstanding problems in understanding the progress of early life is the transition from the RNA world to the modern protein-based world. 31
15. It is thought that the boron minerals needed to form RNA from pre-biotic soups were not available on early Earth in sufficient quantity, and the molybdenum minerals were not available in the correct chemical form. 33
16. Given the apparent limitation of double-stranded RNA (dsRNA) genomes to about 30 kb, together with the complexity of DNA synthesis, it appears dif¢cult for a dsRNA genome to encode all the information required before the transition from an RNA to a DNA genome. Ribonucleotide reductase itself, which synthesizes deoxyribonucleotides from ribonucleotides, requires complex protein radical chemistry, and RNA world genomes may have reached their limits of coding capacity well before such complex enzymes had evolved.