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Molecular Infertility: New Long Story Short on RNA Replication and Life’s Origin

Rob Stadler
Image source: Discovery Institute.

According to biologist Richard Dawkins, “Darwin made it possible to be an intellectually satisfied atheist.”1 Dawkins was satisfied naïvely, because his materialistic worldview lacks a naturalistic explanation for the origin of life.

One universally accepted requirement for the origin of life is replication. Materialists envision a world of molecular replication, long before cellular replication, where information-containing molecules like RNA were copied, with occasional errors, and filtered by natural selection to accumulate information and advance toward life. The latest video from the cheeky Long Story Short series addresses the lack of scientific support for this vision of molecular replication and chemical evolution.

Still the Best Candidate

RNA remains the best candidate for this envisioned chemical evolution because it can provide information storage and catalytic functions, while providing a convenient templating mechanism for replication. Early enthusiasm for this concept converged upon the “RNA World” hypothesis. Some have suggested that RNA had some assistance, such as in the “RNA-Peptide World” hypothesis, but replication of RNA remains foundational.

Although scientists and science popularizers have made many strong claims about RNA replication, a detailed review of the literature provides a sober perspective. The concept of prebiotic RNA replication runs counter to known chemistry and physics, yet remains at the forefront of origin-of-life research because the materialistic worldview lies at stake.

The concept starts by assuming prebiotic RNA formation, which has never been demonstrated. Claims that RNA can form prebiotically are plagued by unnaturally pure starting materials, relay synthesis, the water paradox, the mass transfer problem, the vastly predominant accumulation of “tar,” absence of homochirality, lack of consistent polymer formation, and rapid natural degradation of RNA. For details, see these earlier two Long Story Short episodes:

And see my previous posts at Evolution News:

Not to Be Discouraged

You might think that such severe impediments to prebiotic RNA formation would be enough to discourage fanciful proposals of RNA replication. But you would be wrong.

Starting with a prebiotically formed RNA molecule, we next need an RNA molecule with a sequence of nucleotides that perform a useful function, such as the ability to join nucleotide monomers to make a copy of itself. Origin-of-Life researcher Tomonori Totani has suggested that such an RNA would require at least 40 to 100 nucleotides in a specified order, which is unlikely to arise by random processes even if we consider the volume of the entire observable universe.2

A Host of Challenges 

Even if such a molecule could have formed, science has uncovered a host of challenges in replicating it by natural processes.

First, RNA needs to exist in a folded form (with portions bonded to itself) to function as a catalyst (a ribozyme) but in an unfolded form to function as a template, allowing for replication. Temperature increases can unfold an RNA, but those same temperature increases remove the function of a ribozyme, increase natural degradation rates, and decrease the likelihood that loose nucleotides will match up to the RNA template to form a complementary RNA. It is also well known that individual nucleotides in water don’t spontaneously match up to complementary bases on RNA — this only occurs with oligonucleotides containing at least four bases.3

Second, if a complementary RNA could form according to the template, the two would remain bonded together, with the strength of the bond being proportional to the length of the RNA. RNA with greater than 20 to 30 matches between template and complementary strand cannot be separated even by boiling water.4 Thus, an effort to duplicate an RNA of reasonable size would come to a halt after a duplex is formed. Living organisms take advantage of this process to block unwanted RNA activity by producing antisense RNA.5 Even if some physical conditions could separate the two complementary strands, they would naturally join together again before further copying could occur.

Third, chemical evolution requires some differences (i.e., “mutations”) to occur during the replication process, but too many differences would rapidly lead to error catastrophe.6 Experiments to simulate a prebiotic world have not demonstrated sufficient accuracy to meet these needs.

Fourth, the rate of template copying needs to exceed the natural degradation rate of RNA.7

Fifth, the available nucleotides (that are intended to link up with the template RNA to form a complementary RNA) must be activated (i.e., placed into a high energy state to facilitate reactions), but this high energy state naturally degrades and brings the reactions to a halt.8

Sixth, divalent metal cations are very prevalent in prebiotic conditions. For example, magnesium is the eighth most common element in the Earth’s crust and the third most common element dissolved in seawater.9 Magnesium breaks RNA into pieces. Living organisms intentionally use magnesium to degrade and recycle RNA (in a controlled manner, as part of complex enzymes like RNAse E).10

Seventh, if RNA could form naturally, such an uncontrolled ligation of nucleotides to produce random RNA arrangements would use up all resources, producing a spaghetti of useless RNA.

Finally, an RNA replication process would naturally favor parasitic, short RNAs that replicate the fastest but provide no function. These would be like cancer, using up all resources and contributing nothing of value. Spiegelman’s Monster taught this lesson.11

An Extensive Family Tree

Even if prebiotic, self-replicating RNA can be convincingly demonstrated someday, advancing toward life would require an extensive family tree of millions of incrementally improved self-replicators, each growing in complexity, outcompeting rivals, accumulating information faster than natural process degrade, and advancing toward cooperative chemical reactions worthy of the term “metabolism.” 

Science has thus provided a clear response regarding the prospects of an RNA World or a more complex RNA-Peptide World. Efforts to demonstrate a true self-replicating molecule will remain unsuccessful.


  1. Richard Dawkins, The Blind Watchmaker. 1996, London, W. W Norton & Company.
  2. Totani, T. Emergence of life in an inflationary universe. Scientific Reports. 2020; 10:1-7.
  3. Sawada T, Fujita M. A single Watson-Crick GC base pair in water: Aqueous hydrogen bonds in hydrophobic cavities. JACS 2010: 132; 7194-7201.
  4. Engelhart, A., Powner, M. & Szostak, J. Functional RNAs exhibit tolerance for non-heritable 2′–5′ versus 3′–5′ backbone heterogeneity. Nature Chem 2013; 5: 390–394. https://doi.org/10.1038/nchem.1623
  5. Pelechano V, Steinmetz LM. Gene regulation by antisense transcription. Nature Reviews. Genetics. 2013; 14: 880–893. doi:10.1038/nrg3594
  6. Eigen, M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften. 1971; 58: 465-523. 
  7. Prywes N, et al. Nonenzymatic copying of RNA templates containing all four letters is catalyzed by activated oligonucleotides. eLife. 2016; 5: e17756.
  8. Szostak JW. The eightfold path to non-enzymatic RNA replication. Journal of Systems Chemistry. 2012; 3: https://doi.org/10.1186/1759-2208-3-2
  9. https://www.usgs.gov/centers/national-minerals-information-center/magnesium-statistics-and-information, accessed February 4, 2023.
  10. Mackie GA. RNase E: at the interface of bacterial RNA processing and decay. Nature Reviews Microbiology. 2013: 11; 45-57. 
  11. Mills DR et al. An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. PNAS 1967: 58; 217-224.