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Origin of the First Self-Replicating Molecules

Image: RNA, via Illustra Media’s documentary Origin.

Editor’s note: We are delighted to present a series by Walter Bradley and Casey Luskin on the question, “Did Life First Arise by Purely Natural Means?” This is the sixth entry in the series, a modified excerpt from the recent book The Comprehensive Guide to Science and Faith: Exploring the Ultimate Questions About Life and the CosmosFind the full series so far here.

In an undergraduate seminar taught by Stanley Miller that I (Casey Luskin) took as a student at the University of California, San Diego, Dr. Miller taught us that “making compounds and making life are two different things.”1 Many variants of Stanley Miller’s experimental setup have been used in attempting to demonstrate the conversion of energy-rich, gaseous-phase chemicals into amino acids and other biomolecular monomers. But this is not nearly sufficient to generate life. Any origin-of-life explanation must include plausible biochemical paths from individual bio-building blocks like amino acids or nucleic acids to functional polymers such as proteins and DNA. The origin-of-life explanation must also include ways to speed up chemical reactions that are naturally slow. In living cells, long chains of amino acids fold up into 3-D structures that allow them to function as enzymes that greatly accelerate chemical reactions, as seen in the figure below. How could these arise before life existed? More importantly, any origin-of-life model must account for the very particular sequencing of the molecules — i.e., the ordering of amino acids in proteins and nucleotide bases in RNA and DNA that allows them to function properly. This means explaining a crucial aspect of life: the origin of its information, or what proponents of intelligent design (ID) call the “information sequence problem.” 

Figure 4. Proteins have multiple levels of structure, where a chain of amino acids can fold up into a three-dimensional shape with a surface topography that can attract and hold atoms or molecules in place to facilitate their chemical reaction and release. Credit: Valerie Gower, © Discovery Institute. Used with permission. 

The Most Popular Proposal 

For some theorists, the origin of life is defined as the natural origin of a self-replicating system capable of undergoing Darwinian evolution.2 The most popular proposal for the first self-replicating molecule is RNA — where life was first based upon RNA carrying both genetic information (akin to modern DNA) and performing catalytic functions (akin to modern enyzmes), in what is termed the RNA world. Before we delve deeply into that, it is instructive to use the proceedings of a conference organized by the International Society for the Study of the Origin of Life (ISSOL) at the University of California, Berkeley, in 1986 to measure the progress that has been made in origin-of-life research from 1952-1986. 

I (Walter Bradley) attended this conference and watched one of the plenary sessions devoted to a spirited debate between scientists who believed that the first life was made of DNA (“DNA-first”) and those who believed that the first biomolecules were proteins (“protein-first”). Neither group had yet been able to synthesize under plausible conditions either protein or DNA. Proteins can act as a chemical catalyst. DNA is the repository of information that is used to make functional protein. One of the outcomes from the conference was the sense that neither protein-first nor DNA-first were promising pathways to explaining the origin of life. But the difficulty demonstrating a plausible biochemical pathway for the origin of life that went through DNA-first or protein-first created an openness to new alternative possibilities. In 1986, the RNA world was just emerging as a popular alternative to protein-first or DNA-first models.

At the concluding plenary session, leading origin-of-life researcher Robert Shapiro addressed the RNA world and traced citations in the biochemical literature of the synthesis of RNA molecules under conditions thought to represent the early Earth conditions. The results were shocking. He cited a 1986 paper indicating RNA synthesis under prebiotic conditions had been demonstrated repeatedly, citing a 1985 paper and alluding to others. But that 1985 paper did not present original work — rather, it cited a 1984 paper and went all the way back to 1968 without any original work cited. A close reading of the 1968 paper indicated that the authors thought that they might have synthesized RNA molecules under prebiotic conditions but had not actually found any. 

Five Huge Barriers

Shapiro’s talk subsequently presented five huge barriers to this biochemical pathway from prebiotic chemistry to the first living systems. At the end of his dramatic presentation, the room of most of the world’s most active origin-of-life researchers fell silent. The chair of the session, who was also the editor of the premiere journal Origins of Life and Evolution of Biospheres, repeatedly invited questions from the stunned audience. It was the only time in my (Walter Bradley) professional lifetime that I attended a plenary session of scientists and engineers where there were no questions. The chair closed the session without any questions offered, and he closed with the comment, “Robert, do you have to be so pessimistic?” Robert did not reply, but might have said he was letting the data do the talking, and the data told a very pessimistic story. 

History has confirmed Shapiro’s pessimism. Despite these difficulties, to this day, the RNA world remains the most popular model for the origin of life. But there are major problems with the RNA world hypothesis and claims that a self-replicating RNA molecule appeared by pure chance. 

First, RNA has not been shown to assemble in a laboratory without the help of a skilled chemist intelligently guiding the process. Origin-of-life theorist Steven Benner explained that a major obstacle to the natural production of RNA is that “RNA requires water to function, but RNA cannot emerge in water, and does not persist in water without repair” due to water’s “rapid and irreversible” corrosive effects upon RNA.3 In this “water paradox,” Benner explains that “life seems to need a substance (water) that is inherently toxic to polymers (e.g., RNA) necessary for life.”4

To overcome such difficulties, Benner and other chemists carefully designed experimental conditions that are favorable to the production of RNA. But Robert Shapiro explains that these experiments do not simulate natural conditions: “The flaw is in the logic — that this experimental control by researchers in a modern laboratory could have been available on the early Earth.”5 Reviewing attempts to construct RNA in the lab, James Tour likewise found that “[t]he conditions they used were cleverly selected,” but in the natural world, “the controlled conditions required to generate” RNA are “painfully improbable.”6 Origin-of-life theorists Michael Robertson and Gerald Joyce even called the natural origin of RNA a “Prebiotic Chemist’s Nightmare” because of “the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth.”7 In the end, these experiments demonstrate one thing: RNA can only form by intelligent design. 

A Second Problem

Today, RNA is capable of carrying genetic information, but RNA world advocates claim that in the past, it also fulfilled the kinds of catalytic roles that enzymes perform today. A second problem with the RNA world is that RNA molecules do not exhibit many of the properties that allow proteins to serve as worker molecules in the cell. While RNA has been shown to perform a few roles, there is no evidence that it could perform all necessary cellular functions.8 As one paper put it, proteins are “one million times fitter than RNA as catalysts” and “[t]he catalytic repertoire of RNA is too limited.”9

The Origin of Information

The most fundamental problem with the RNA world hypothesis is its inability to explain the origin of information in the first self-replicating RNA molecule — which experts suggest would have had to be at least 100 nucleotides long, if not between 200 and 300 nucleotides in length.10 How did the nucleotide bases in RNA become properly ordered to produce life? There are no known chemical or physical laws that can do this. To explain the ordering of nucleotides in the first self-replicating RNA molecule, origin-of-life theorists have no explanation other than blind chance. As noted, ID theorists call this obstacle the information sequence problem, but multiple mainstream theorists have also observed the great unlikelihood of naturally producing a precise RNA sequence required for replication. Shapiro puts the problem this way:

A profound difficulty exists, however, with the idea of RNA, or any other replicator, at the start of life. Existing replicators can serve as templates for the synthesis of additional copies of themselves, but this device cannot be used for the preparation of the very first such molecule, which must arise spontaneously from an unorganized mixture. The formation of an information-bearing homo-polymer through undirected chemical synthesis appears very improbable.11

Elsewhere, Shapiro notes, “The sudden appearance of a large self-copying molecule such as RNA was exceedingly improbable” with a probability that “is so vanishingly small that its happening even once anywhere in the visible universe would count as a piece of exceptional good luck.”12 A 2020 paper in Scientific Reports similarly notes, “Abiotic emergence of ordered information stored in the form of RNA is an important unresolved problem concerning the origin of life” because “the formation of such a long polymer having a correct nucleotide sequence by random reactions seems statistically unlikely.”13 Steven Benner refers to the “Information-Need Paradox,” where self-replicating RNA molecules would be “too long to have arisen spontaneously” from available building blocks.14 Benner raises an additional logical difficulty in that generating an RNA molecule capable of catalyzing its own replication is much less likely than generating RNA molecules that catalyze the destruction of RNA. This suggest a grave theoretical difficulty where RNA world theorists are faced with a “chemical theory that makes destruction, not biology, the natural outcome.”15

An Intractable Problem

The paper in Scientific Reports proposed a solution to these quandaries that showed just how intractable this problem is: It concluded that because the formation of a single self-replicating RNA molecule is prohibitively unlikely in the observable universe, and therefore the universe must be far larger than we observe — an “inflationary universe” that increases the probabilistic resources until such an unlikely event becomes likely. This is just like the materialist response to the fine-tuning of physics: When the observed specificity of nature appears to indicate design, they invent multiverses to overcome probabilistic difficulties. When RNA world theorists are appealing to the origin-of-life’s version of the multiverse to avoid falsification, it’s clear that their project has fatal problems. 

Next, “Still Unexplained: The First Living Cell.”


  1. Statements made by Stanley Miller at a talk given by him for a UCSD Origins of Life seminar class on January 19, 1999 (the talk was attended and notated by the author of this article).
  2. Steven A. Benner, “Paradoxes in the Origin of Life,” Origins of Life and Evolution of Biospheres 44 (2014), 339-343.
  3. Benner, “Paradoxes in the Origin of Life.”
  4. Benner, “Paradoxes in the Origin of Life.”
  5. Robert Shapiro, quoted in Richard Van Noorden, “RNA world easier to make,” Nature News (May 13, 2009), http://www.nature.com/news/2009/090513/full/news.2009.471.html (accessed November 18, 2020).
  6. James Tour, “Are Present Proposals on Chemical Evolutionary Mechanisms Accurately Pointing Toward First Life?,” Theistic Evolution: A Scientific, Philosophical, and Theological Critique, eds. Edited by J.P. Moreland, Stephen C. Meyer, Christopher Shaw, Ann K. Gauger, and Wayne Grudem (Wheaton, IL: Crossway, 2017), 165-191.
  7. Michael P. Robertson and Gerald F. Joyce, “The Origins of the RNA World,” Cold Spring Harbor Perspectives in Biology 4 (May 2012), a003608.
  8. See Stephen C. Meyer, Signature in the Cell: DNA and the Evidence for Intelligent Design (New York: HarperOne, 2009), 304.
  9. Harold S Bernhardt, “The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others),” Biology Direct 7 (2012), 23.
  10. Jack W. Szostak, David P. Bartel, and P. Luigi Luisi, “Synthesizing Life,” Nature, 409 (January 18, 2001), 387-390; Tomonori Totani, “Emergence of life in an inflationary universe,” Scientific Reports 10 (2020), 1671.
  11. Robert Shapiro, “A Replicator Was Not Involved in the Origin of Life,” IUBMB Life 49 (2000), 173-176.
  12. Robert Shapiro, “A Simpler Origin for Life,” Scientific American (June 2007), 46-53.
  13. Totani, “Emergence of life in an inflationary universe.”
  14. Benner, “Paradoxes in the Origin of Life.”
  15. Benner, “Paradoxes in the Origin of Life.”

Walter Bradley

Fellow, Center for Science and Culture
Walter L. Bradley received his B.S. degree in Engineering Science (Physics) in 1965 and his Ph.D. in Materials Science and Engineering in 1968, both from the University of Texas (Austin).  He subsequently taught at the Colorado School of Mines, Texas A&M University as Full Professor of Mechanical Engineering, and for 10 years at Baylor University as a Distinguished Professor. His research area has been Materials Science and Engineering, with a focus on the mechanical properties of plastics and polymeric (plastic) composite materials, fracture and life prediction. He has received more than $7 million in research funding and published more than 150 refereed technical papers and book chapters.  He has been honored by the American Society for Materials and the Society of Plastics Engineers as Educator of the Year. His most recent work has focused on converting agricultural waste into functional fillers for engineering plastics to provide new economic opportunities for poor farmers in developing countries.

Casey Luskin

Associate Director, Center for Science and Culture
Casey Luskin is a geologist and an attorney with graduate degrees in science and law, giving him expertise in both the scientific and legal dimensions of the debate over evolution. He earned his PhD in Geology from the University of Johannesburg, and BS and MS degrees in Earth Sciences from the University of California, San Diego, where he studied evolution extensively at both the graduate and undergraduate levels. His law degree is from the University of San Diego, where he focused his studies on First Amendment law, education law, and environmental law.



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