The Origin of Life

Benner, Steven A.  “Paradoxes in the Origin of Life.”  Origins of Life and Evolution of Biospheres 44:339–343.  2014.  Page 339:  “Discussed here is an alternative approach to guide research into the origins of life, one that focuses on 'paradoxes', pairs of statements, both grounded in theory and observation, that (taken together) suggest that the 'origins problem' cannot be solved.”  A short commentary by a prebiotic chemist, presented at the Open Questions on the Origin of Life conference in Kizugawa, Kyoto, on 12–13 July 2014.  It proposes guiding origin-of-life research with paradoxes, pairs of statements that are each grounded in theory and observation and that together suggest the origins problem cannot be solved.  The article cites it for the author's own verdict on six decades of work, and for his expectation that most paradoxes will be resolved.  The paper was received on 21 September 2014 and published online on 22 January 2015.  It is frequently miscited as Astrobiology 2014; it is not. ↩

1. 1a.

   Page 340:  “We are now 60 years into the modern era of prebiotic chemistry.  That era has produced tens of thousands of papers attempting to define processes by which 'molecules that look like biology' might arise from 'molecules that do not look like biology', find conditions where oligomers might form spontaneously from those molecules, identify constraints on pre-metabolic cycles that might deliver those molecules without leaking material into the complexity sometimes characterized as 'asphalt', or assemble ways to create chiral compounds largely free from their enantiomers.  For the most part, these papers report 'success' in the sense that those papers define the term.  ¶  And yet, the problem remains unsolved.” ↩ ↩

2. 1b.

   Page 343:  The paper's final paragraph.  “The prescription that experimentalists focus on paradoxes in origins rather than puzzles in origins (Cleland and Chyba 2002) offers important constraints to researchers who must live in a world where financial resources are limited.  However, the concept of 'paradox' should not be daunting.  We expect that (hope that?) most of these paradoxes will be resolved by experiments that show that the theories that generate them are incorrect, incomplete, or inapplicable to particular molecular systems that just happen to have been present on early Earth.  Others may be resolved because, like most exercises that apply logic to the real world, their reasoning is imperfect.  However, they must be resolved as a condition for the community to conclude that the origins problem has been 'solved'.” ↩ ↩

Koonin, Eugene V.  “The cosmological model of eternal inflation and the transition from chance to biological evolution in the history of life.”  Biology Direct 2:15.  2007.  “even in this toy model that assumes a deliberately inflated rate of RNA production, the probability that a coupled translation-replication emerges by chance in a single O-region is P < 10^-1018.”  “The model considered here is not supposed to be realistic by any account.”  A 2007 hypothesis article by Eugene Koonin of the National Center for Biotechnology Information.  It proposes that in an infinite multiverse, a coupled translation and replication system could arise by chance, so an RNA world need never have existed.  The article cites its probability figure, which apologists quote most often, and Koonin's rejection of the design reading in the same paper. ↩

1. 2a.

   Page 14:  Koonin's published reply to referee Eric Bapteste, who had written that the argument "might open too broad an avenue to the supporters of intelligent design."  The reply is printed with its typographical error.  “The main text of this paper contains a clear statement on Intelligent Deisgn (ID) but, since this is a serious concern for Bapteste (and I agree that ID is an important, even if meta-scientific, issue), I will reiterate and further reinforce my position that directly follows from the reasoning explicated in this paper.  The above discussion of the anthropic principle implies an unequivocal sentence for Intelligent Design;  let us spell it out.  As indicated above, in an infinite multiverse, anthropic selection guarantees the emergence of systems of whatever complexity that are required for the biological evolution to take off (see Fig. 3).  This scenario is watertight:  first, chance/anthropic selection, then biological evolution.  There is no gap here where the ID wedge could fit.  Properly interpreted, the anthropic principle is a death knell to ID.”  Page 8:  The body of the paper says the same more briefly.  “sidesteps the issue of irreducibility and leaves no room whatsoever for any form of intelligent design.” ↩ ↩

Joyce, Gerald F., and Leslie E. Orgel.  “Prospects for Understanding the Origin of the RNA World.”  The RNA World.  Cold Spring Harbor Laboratory Press.  Edited by Gesteland and Atkins.  1993.  Page 19:  The 1993 text, quoted in full.  “The second group of scientists are much more pessimistic.  They believe that the de novo appearance of oligonucleotides on the primitive earth would have been a near miracle.  (The authors subscribe to this latter view.)  Time will tell which is correct.”  Page 68:  The same passage in the 1999 second edition.  A chapter by Gerald Joyce and Leslie Orgel in the 1993 first edition of The RNA World, with the same passage in the 1999 second edition, where it is chapter 2, pages 49–77.  The authors place themselves in the camp that thinks the spontaneous appearance of oligonucleotides on the primitive Earth would have been a near miracle.  The article cites it for the sentence that follows the "near miracle" line, and the parenthesis in which the authors say they hold the view.  The parenthetical is real and stood in both the 1993 and 1999 editions, so it is Joyce and Orgel's own view.  Robertson and Joyce's 2012 version silently deletes the parenthesis while rewriting the surrounding sentences.  The sentence cannot be detached from "Time will tell which is correct."  The line is not Orgel's alone, and it does not come from the 2004 paper it is usually credited to. ↩ ↩

Johnson, Adam P. et al.  “The Miller Volcanic Spark Discharge Experiment.”  Science 322:404.  2008.  Page 404:  “We were interested in the second apparatus because it possibly simulates the spark discharge synthesis by lightning in a steam-rich volcanic eruption (6) (Fig. 1A).”  “We reanalyzed 11 vials in order to characterize the diversity of products synthesized in this apparatus.”  “We identified 22 amino acids and five amines in the volcanic experiment (Fig. 1C), several of which had not been previously identified in Miller's experiments.”  “The yield of amino acids synthesized in the volcanic experiment is comparable to, and in some cases exceeds, those found in the experiments Miller conducted (1, 3, 5).”  Miller built three configurations in 1953–54, not one, and only the first was published in 1953.  Section Supporting Online Material:  “Amino acids with chiral centers were racemic within the precision of the measurements.”  A 2008 report by six researchers who re-analysed vials of residue from Stanley Miller's 1953–54 spark-discharge experiments, which were found in boxes after his death in 2007.  The volcanic apparatus, which injected steam and gas into the spark, produced 22 amino acids and five amines in the eleven vials they re-analysed, several of them not previously reported in Miller's experiments.  The article uses it to show that a neutral-atmosphere spark experiment still produced amino acids. ↩ ↩

Bergman, Jerry.  “Why the Miller–Urey research argues against abiogenesis.”  Journal of Creation 18(2):28–36.  Aug 2004.  Section Was there a methane-ammonia atmosphere?:  “The problem was stated as follows:  '… the accepted picture of the earth's early atmosphere has changed:  It was probably O₂-rich with some nitrogen, a less reactive mixture than Miller's, or it might have been composed largely of carbon dioxide, which would greatly deter the development of organic compounds.'”  A 2004 creationist article by Jerry Bergman, first published in the Journal of Creation and reprinted by Answers in Genesis.  It argues that the Miller–Urey experiment does not show that life can arise from non-living molecules.  The article cites it as the most-cited creationist treatment of the atmosphere question, and as the worst single item in its own audit.  The sentence inside the quotation is adopted, not composed, by Bergman; reconstructing his footnote numbering against his reference list traces it to Flowers, Charles, A Science Odyssey: 100 Years of Discovery (William Morrow, 1998), p. 173, a companion book to a PBS television series.  Bergman's own internal cross-references are inconsistent, so the numbering is not fully reliable, but every candidate source in that stretch of his list is popular-level and none is a geochemistry paper. ↩ ↩ ↩

Powner, Matthew W. et al.  “Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions.”  Nature 459:239–242.  May 14, 2009.  Five years earlier Orgel had written the sentence this paper falsified, in Critical Reviews in Biochemistry and Molecular Biology 39 (2004): 99-123:  “The synthesis of nucleosides from ribose and the nucleoside bases is the weakest link in the chain of prebiotic reactions leading to oligonucleotides”.  Section Abstract:  “Here we show that activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates.  The starting materials for the synthesis—cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and inorganic phosphate—are plausible prebiotic feedstock molecules, and the conditions of the synthesis are consistent with potential early-Earth geochemical models.”  A synthesis paper that made activated pyrimidine ribonucleotides from cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and phosphate, by a route that never passes through free ribose, going through arabinose amino-oxazoline and anhydronucleoside intermediates.  All the experimental conditions used in this article come from the Supplementary Information.  The authors call those starting materials plausible prebiotic feedstock, but guanine remains awkward across the literature: Sutherland's later route gives inosine-type purines only as deoxyribonucleosides (Xu, Jianfeng, et al., Nature 582 (2020): 60–66), and no published route makes all four canonical ribonucleotides from one-carbon feedstocks in one environment.  The article uses it to show that 'nobody has ever made a nucleotide' is false, while noting that the route is a bypass rather than a solution. ↩ ↩

Noorduin, Wim L. et al.  “Emergence of a Single Solid Chiral State from a Nearly Racemic Amino Acid Derivative.”  Journal of the American Chemical Society 130:1158–1159.  2008.  The chiral additive phenylglycine also set the handedness, at concentrations of.  “as low as 0.1 mol %”.  A laboratory experiment that stirred a nearly equal mix of left- and right-handed crystals of an amino acid derivative with glass beads, to see whether the mix settles into one handedness.  The conditions, from the methods, were magnetic stirring at 1,250 rpm with 2.5 mm glass beads, in methanol or acetonitrile, with DBU as the base; a starting imbalance of 2-3% was driven to a single chiral solid that stayed stable.  The authors present it as a proof of concept and claim no prebiotic scenario, and the article cites it as an example of attrition turning a small bias into one handedness. ↩

Breslow, Ronald, and Mindy S. Levine.  “Amplification of enantiomeric concentrations under credible prebiotic conditions.”  Proceedings of the National Academy of Sciences 103:12979–12980.  2006.  A 2006 short report in which two chemists show that a small handedness imbalance can be raised by simple evaporation.  Solutions of phenylalanine with 1% extra of one mirror-image form were taken to 90% by two evaporations that precipitate the 50/50 mixture.  The article cites it as one of the mechanisms that amplify a small imbalance.  The mechanism was characterised the same year by Klussmann et al., Nature 441 (2006): 621–623: the racemic crystalline solid is less soluble than the pure enantiomer, so partially dissolving a near-racemic solid leaves a strongly enriched solution. ↩ ↩

Weber, Arthur L., and Sandra Pizzarello.  “The peptide-catalyzed stereospecific synthesis of tetroses: a possible model for prebiotic molecular evolution.”  Proceedings of the National Academy of Sciences 103:12713–12717.  2006.  A 2006 laboratory paper on a stereospecific synthesis, one that makes a single handed form of the molecule, of tetroses (four-carbon sugars), in which short peptide chains help the reaction.  The title calls it a possible model for prebiotic molecular evolution.  The article uses it for the step where L-dipeptides, short chains of two amino acids with one handedness, hand their handedness to sugars in water. ↩

Hein, Jason E. et al.  “A route to enantiopure RNA precursors from nearly racemic starting materials.”  Nature Chemistry 3:704–706.  2011.  The paper also supplies the honest cost of the rival photochemical route to a first handedness bias, and the RNA precursor it makes is on Sutherland's route, not a model compound.  “enantiomeric yields of 20% e.e. may be realized only at the expense of 99% photodestruction of both enantiomers.”  A 2011 laboratory study from the Scripps Research Institute in which amino acids with only a small handedness bias steered a racemic sugar-and-amino-oxazole mixture into single-handed RNA precursors.  Proline gave the most selective result, and its additive table gives it at 55-58% e.e., far ahead of the next best amino acid; enantiopure crystals formed from mixtures containing as many as 14 amino acids.  The article uses it as the mechanism that answers the claim that homochirality cannot arise naturally. ↩ ↩

Pasek, Matthew A.  “Rethinking early Earth phosphorus geochemistry.”  Proceedings of the National Academy of Sciences 105:853–858.  2008.  Section Abstract:  Pasek's route is extraterrestrial: reduced-oxidation-state phosphorus.  “originated from extraterrestrial material that fell during the heavy bombardment period or was produced during impacts.”  A paper in PNAS that proposes the early Earth's phosphorus was controlled by reduced compounds such as phosphite, which the paper says are more soluble and reactive than orthophosphate.  The reduced phosphorus came from extraterrestrial material that fell during the heavy bombardment or was made during impacts, and the author suggests meteorite schreibersite as its source.  The article uses it for the concession that meteorites may have supplied reactive phosphorus, and notes that this route depends on a bombardment flux, which is a live question elsewhere in the article. ↩

Boehnke, Patrick, and T. Mark Harrison.  “Illusory Late Heavy Bombardments.”  Proceedings of the National Academy of Sciences 113:10802–10806.  2016.  Section Abstract:  “Our results show that plateau histograms tend to yield age peaks, even in those cases where the input impact curve did not contain such a spike, in part due to the episodic nature of lunar crust or parent body formation.  Restated, monotonically declining impact histories yield apparent age peaks that could be misinterpreted as LHB-type events.”  Section Significance:  “Thus, impacts may have played a minimal role in terrestrial habitability, early Earth dynamics, and the formation of Hadean zircons.”  The authors state their own limit:  “while the most widely used evidence to support the LHB hypothesis yields unreliable impact histories, it does not preclude the existence of such events.”  A 2016 PNAS paper that models how argon dating of the Apollo samples can produce age clusters that look like a bombardment spike.  Its physical model of argon loss shows that plateau-age histograms tend to produce peaks even when the impact rate declined steadily.  The article cites it for the claim that the Late Heavy Bombardment is probably an artefact of argon loss in the Apollo samples. ↩ ↩

Zellner, Nicolle E. B.  “Cataclysm No More: New Views on the Timing and Delivery of Lunar Impactors.”  Origins of Life and Evolution of Biospheres 47:261–280.  2017.  Its abstract says:  “Importantly, it is demonstrated that most evidence supports a prolonged lunar (and thus, terrestrial) bombardment from ~4.2 to 3.4 Ga and not a cataclysmic spike at ~3.9 Ga.”  Its conclusion, with the clause the article quotes:  “The long-held idea of a 'lunar cataclysm' at ~3.9 Ga is being replaced by the idea of an extended lunar bombardment from ~4.2 Ga to 3.5 Ga.  While the effects of this prolonged bombardment on the evolution and development of life on Earth have yet to be closely investigated, the timeline for the assembly of the first biomolecules has been lengthened.”  From the implications section:  “Thus, impact frustration and/or sterilization are unlikely, and a cool Earth, hospitable to the development of biomolecules via endogenous and exogenous processes, may have provided the necessary temperature conditions required for biomolecules to be stable.”  A 2017 review of the lunar impact record by Nicolle Zellner of Albion College, which tests the idea of a "lunar cataclysm", a short spike of impacts about 3.9 billion years ago, against the rock samples, orbital images and dynamical models.  It finds that the evidence supports a longer bombardment from about 4.2 to 3.4 billion years ago, and it asks what that means for the conditions for the origin of life.  The article uses it for the claim that the timeline for the first biomolecules has been lengthened. ↩ ↩

Yue, Z. et al.  “Lunar chronology model with the Chang'e-6 farside samples and implications for the early impact history.”  Science Advances 12:eady9265.  2026.  Their framing of why the farside mattered is the important part:  “previous samples were from the lunar nearside and the radiometric ages of those samples that can be associated with particular surfaces are <4.0 billion years.”  A 2026 paper that uses rock samples brought back from the far side of the Moon by China's Chang'e-6 mission in June 2024 to refine the lunar chronology function, the formula that turns crater counts into ages.  The farside norites, dated to 4247 ± 5 Ma (million years ago), likely date the South Pole–Aitken basin, and the article uses the paper as the decisive test of the bombardment argument, because every Apollo sample came from the nearside. ↩ ↩

Pearce, Ben K. D. et al.  “Constraining the Time Interval for the Origin of Life on Earth.”  Astrobiology 18:343–364.  2018.  Section Abstract:  “The habitability boundary could be as early as 4.5 Ga, the earliest possible estimate of the time at which Earth had a stable crust and hydrosphere, or as late as 3.9 Ga, the end of the period of heavy meteorite bombardment.  The lack of consensus on whether there was a late heavy meteorite bombardment that was significant enough to prevent life is the largest uncertainty in estimating the time of the habitability boundary.  The biosignature boundary is more closely constrained.  Evidence from carbon isotope ratios and stromatolite fossils both point to a time close to 3.7 Ga.  Life must have emerged in the interval between these two boundaries.  The time taken for life to appear could, therefore, be within 200 Myr or as long as 800 Myr.”  A review of astronomical, geological and biological evidence for when life first appeared, which sets two boundaries: a habitability boundary, between 4.5 and 3.9 Ga, and a biosignature boundary near 3.7 Ga.  Life must have emerged between them, within 200 Myr or as long as 800 Myr.  The 3.7 Ga boundary partly rests on the Nutman 2016 Isua stromatolites, which Allwood et al. rebutted in Nature on 16 October 2018, after the arXiv preprint of 28 August 2018, so the authors did not have that rebuttal; the boundary still rests on Rosing 1999 and Ohtomo 2014, which the authors also cite, though half its support has since been contested.  The article uses it for the 200 to 800 million year window that unaided chemistry had.  Mirror:  arXiv ↩ ↩

Mojzsis, S. J. et al.  “Evidence for life on Earth before 3,800 million years ago.”  Nature 384:55–59.  1996.  The rebuttal is van Zuilen, Lepland and Arrhenius, Nature 418 (2002): 627–630, named here to identify it.  The authors' own framing of the choice of isotopes over fossils, for rocks older than 3,500 Myr:  “have experienced intense metamorphism, which would have obliterated any fragile microfossils contained therein.”  A Nature paper that looked for evidence of life in isotopes, not fossils, in rocks older than 3,800 million years.  The article uses it as the founding 3.8-billion-year Isua isotope claim, which it says is largely abandoned. ↩ ↩

Brasier, Martin D. et al.  “Questioning the evidence for Earth's oldest fossils.”  Nature 416:76–81.  2002.  “are nearly a billion years older than putative cyanobacterial biomarkers, genomic arguments for cyanobacteria, an oxygenic atmosphere and any comparably diverse suite of microfossils.”  That last point is the strongest part of their case, and it is not an isotope argument at all.  A 2002 Nature paper that questions whether the oldest claimed fossils on Earth are fossils at all.  Its alternative account is Fischer-Tropsch-type synthesis of amorphous graphite in a hydrothermal setting.  The article cites it as the start of the dispute over the oldest morphological fossils, which is unresolved.  The quotation is from the abstract.  The authors note that the structures. ↩ ↩

Jenewein, Christian et al.  “Concomitant formation of protocells and prebiotic compounds under a plausible early Earth atmosphere.”  Proceedings of the National Academy of Sciences 122(2):e2413816122.  2025.  A 2025 laboratory study in which a plausible early-Earth gas mixture, meeting water and silica, produced a solid organic film of hydrogen cyanide polymers containing nano- to micron-sized "protocells."  The structures are polymers of hydrogen cyanide precipitated at a water-gas interface, not lipid compartments.  The article uses it to show that inorganic chemistry can make cell-shaped objects with organic walls. ↩

Gianni, Edoardo et al.  “A small polymerase ribozyme that can synthesize itself and its complementary strand.”  Science 391(6789):1022–1028.  Mar 5, 2026.  Section Abstract:  “RNA polymerase ribozymes can replicate RNA, but their large size and structural complexity impede self-replication and preclude their spontaneous emergence.  Here we describe QT45:  a 45-nucleotide polymerase ribozyme, discovered from random sequence pools, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate (triplet) substrates in mildly alkaline eutectic ice.  QT45 can synthesize both its complementary strand using a random triplet pool at 94.1% per-nucleotide fidelity, and a copy of itself using defined substrates, both with yields of ~0.2% in 72 days.”  A 2026 Science paper from Philipp Holliger's group in Cambridge that reports QT45, a 45-nucleotide polymerase ribozyme (an RNA enzyme) that copies RNA and copies itself, in mildly alkaline eutectic ice, a partly frozen solution.  The article cites it as the point at which a molecule was first shown to copy itself, and it states the narrower version of that claim. ↩ ↩ ↩

1. 19a.

   The two yields are 0.24% for the complementary strand (from a random 64-triplet pool) and 0.17% for the copy of itself (from defined substrates plus one pre-made hexamer), each over 72 days.  On fidelity, the authors say:  “This analysis suggests that at the fidelities observed for QT45 products (92.6% and 94.1%) the population of active variants (quasispecies) would be minimal (<0.5%), but an increase in fidelity to levels observed in other polymerase ribozymes (e.g. 97.4%), would enable maintenance of a sizeable population of active variants of QT45 length in the current mutational landscape (~12% of the total population).”  On the separation of the two reactions, the authors say:  “These results show that the two key synthetic reactions required for a self-replication cycle:  (−) and (+) strand self-synthesis, can both be carried out by the QT45 ribozyme in separate reactions under identical buffer, salt, and RNA concentrations.” ↩ ↩

2. 19b.

   “We conjecture that, at higher concentrations, the (+) strand outcompetes triplet substrates for binding to the (−) strand template, driving increasing formation of the unproductive (+)(−) strand duplex.  Indeed, in the absence of the QT45 (+) strand, we observed efficient full-length synthesis by 5TU.  This suggests that the strand-inhibition problem, caused by the formation of the dead end (+)(−) strand duplex, is a key obstacle to closing the self-replication cycle.” ↩

Lincoln, Tracey A., and Gerald F. Joyce.  “Self-sustained replication of an RNA enzyme.”  Science 323:1229–1232.  2009.  A 2009 Science paper by Tracey Lincoln and Gerald Joyce on the self-sustained replication of an RNA enzyme.  The article cites it for the point that cross-catalytic RNA enzymes have replicated exponentially since 2009.  The limitation the article states is not this paper's own framing; it is Joyce and Szostak's later assessment in their 2018 review, where they describe this class of cross-replicating ligases as joining pre-formed oligonucleotide substrates rather than copying a sequence.  Anyone relying on this paper against the article's argument should read that qualification. ↩ ↩

Lee, Jessica et al.  “Hybrid Protocells Based on Coacervate-Templated Fatty Acid Vesicles Combine Improved Membrane Stability with Functional Interior Protocytoplasm.”  Small 20:e2406671.  2024.  A laboratory study that wrapped fatty-acid membranes around droplets of a polymer and adenosine diphosphate, then tested them with added magnesium.  Fatty-acid vesicles alone were disrupted by Mg2+, while the coacervate-supported membranes stayed intact and impermeable at 25 and 50 mM added Mg2+.  The paper's own methods give the cost: the coacervate is poly(allylamine hydrochloride) with adenosine diphosphate, and poly(allylamine hydrochloride) is a laboratory polymer, not a prebiotic one.  The article uses it as the single strongest published answer to the magnesium argument, and it belongs in any honest treatment of that argument. ↩ ↩

Robertson, Michael P., and Gerald F. Joyce.  “The Origins of the RNA World.”  Cold Spring Harbor Perspectives in Biology 4:a003608.  2012.  The phrase 'a near miracle' does not appear anywhere in Orgel 2004, Critical Reviews in Biochemistry and Molecular Biology 39: 99–123.  A separate, genuine Orgel 'near miracle' is about the reductive citric acid cycle, not RNA: 'I have argued that the self-organization of the reductive citric acid cycle without the help of 'informational' catalysts would be a near miracle' (PNAS 97 (2000): 12503–12507, p. 12506).  The parenthetical '(The authors subscribe to this latter view.)' is not in the 2012 text, but it is in the book, so this republication is not a faithful reprint of the passage and should not be used to check what Joyce and Orgel meant.  See the 1993 Joyce and Orgel chapter.  The acknowledgments establish the lineage:  Section Acknowledgments:  “Previous versions of this article, which were published in the First (1993), Second (1999), and Third (2006) Editions of The RNA World, were coauthored by Leslie Orgel, who died on October 27, 2007.  Many portions of the text have not been changed in the current edition because they remain an accurate reflection of current scientific understanding.”  A review article, the open-access descendant of Joyce and Leslie Orgel's chapter in The RNA World (Cold Spring Harbor Laboratory Press), first edition 1993, carried through the 1999 and 2006 editions.  It finds strong evidence that an RNA world existed, but says that whether life itself began with RNA is far from solved.  The article uses it to trace the 'near miracle' line to Joyce and Orgel's chapter, not to Orgel's 2004 paper, and to show that the two camps on RNA-first chemistry are both real. ↩

1. 22a.

   Section 3.1:  The section, quoted in full:  “Scientists interested in the origins of life seem to divide neatly into two classes.  The first, usually but not always molecular biologists, believe that RNA must have been the first replicating molecule and that chemists are exaggerating the difficulties of nucleotide synthesis.  They believe that a few more striking chemical 'surprises' will establish that a pool of racemic mononucleotides could have formed on the primitive Earth, and that further experiments with different activating groups, minerals, and chiral amplification processes will solve the enantiomeric cross-inhibition problem.  The second group of scientists are much more pessimistic.  They believe that the de novo appearance of oligonucleotides on the abiotic Earth would have been a near miracle.  Time will tell which is correct.”  The 2012 text reads 'on the abiotic Earth'; renderings in circulation say 'on the primitive earth'.  The earlier book editions may have used the earlier wording, and this cannot be checked without opening them. ↩

Morowitz, Harold J.  “Testimony for the plaintiffs.”  McLean v. Arkansas Board of Education, 494–513.  Dec 1981.  Pages 500–501:  “Q:  Now, you have been explaining why the creation science dual model approach to the teaching of origins of life on this planet is unscientific.  Is there any other aspect of the creation science treatment of the origins of life on this planet that is similarly unscientific?  A:  Well, I find the use of probabilistic arguments to be somewhat deceptive. …  To do the probabilistic calculations, we would have to know all the kinetic and mechanistic details by which the processes have come about…  We are simply lacking the information to do the calculations now, so to present them on the basis of the random model is somewhat deceptive.  Q:  Is it also in your view unscientific?  A:  Since deception is unscientific, the answer to that is yes.”  Morowitz spent his career arguing the opposite of what his number is used for.  His own preface reads:  Section Preface to Energy Flow in Biology (Academic Press, 1968), page vii:  “I have rejected the prebiological notion of 'historical accident' as a kind of know-nothingness which renders further study impossible.”  Sworn testimony given for the plaintiffs in McLean v. Arkansas Board of Education, in December 1981.  Asked whether the probabilistic arguments of creation science are unscientific, he said they are "somewhat deceptive" because the calculations need kinetic and mechanistic details that are not known, and that deception is unscientific.  The article uses it for his sworn view that creationist probability arguments are somewhat deceptive. ↩ ↩

Axe, Douglas D.  “Estimating the prevalence of protein sequences adopting functional enzyme folds.”  Journal of Molecular Biology 341(5):1295–1315.  2004.  Page 1310:  The decomposition of the headline number is Axe's own: his measured 10⁷⁷, times a foldability factor of 10⁷⁷ taken from Lau and Dill's theoretical lattice model at.  “their least stringent folding criterion”.  , times 10⁷⁷for the proportion of folds suited to a given task, which Axe introduces with the words.  “A reasonable estimate of the average proportion suited to a particular task is 0.1%.”  Axe states the range himself in the same paragraph:  “the proportion of all sequences of large-domain length that perform the specified function by means of any tertiary fold… is estimated to be in the range of one in 10⁷⁷ to one in 10⁵³.”  Page 1300:  His rationale for the destabilised construct, in his own words:  “The objective here, however, is to introduce a large number of mildly disruptive changes so as to render many side-chains suboptimal throughout the fold.  This is best achieved by introducing many changes together, without intervening selection.”  A 2004 laboratory paper that estimates how rare a working enzyme sequence is.  Axe randomly changed clusters of ten side-chains in the fold of a beta-lactamase enzyme (TEM-1) and tested which versions still worked.  Roughly one in 10^64 signature-consistent sequences formed a working domain, and he combines that with two theoretical and estimated factors to reach his headline figure.  The article cites it because the famous 1-in-10^77 protein figure is a range, 10^77 to 10^53, and the figure is one measurement times one theoretical number times one stated guess.  Note also that 10^64, 10^77 and 10^97 are three different quantities in the same paper, and they are routinely swapped for one another downstream.  The Lau and Dill foldability figure is the single most load-bearing unexamined input in the argument. ↩ ↩

Thaxton, Charles B. et al.  The Mystery of Life's Origin: Reassessing Current Theories.  Philosophical Library.  1984.  Chapter 8:  Chapter 8 opens by conceding the physics, verbatim:  “In Chapter 7 it has been shown that energy and/or mass flow through a system can constrain it far from equilibrium, resulting in an increase in order.  Thus, it is thermodynamically possible to develop complex living forms, assuming the energy flow through the system can somehow be effective in organizing the simple chemicals into the complex arrangements associated with life.”  “Without a doubt, the atoms and molecules which comprise living cells individually obey the laws of chemistry and physics, including the laws of thermodynamics.  The enigma is the origin of so unlikely an organization of these atoms and molecules.”  The thermodynamic concession is in this chapter, and so is the passage with the words.  “atoms and molecules… individually obey the laws”.  The chapter also contains both Morowitz work terms, the chemical work and the thermal entropy decrease.  Chapter 9:  Their summary of the whole three-chapter treatment:  “We found it to be a reasonable explanation for doing the chemical and thermal entropy work, but clearly inadequate to account for the configurational entropy work of coding (not to mention the sorting and selecting work).  We have noted the need for some sort of coupling mechanism.”  A 1984 book by Charles Thaxton, Walter Bradley and Roger Olsen, and the founding book of the design movement on this subject, the origin of life.  Chapters 7 to 9 ask whether the second law of thermodynamics, which says that disorder tends to grow, rules out the rise of living complexity; they find that the physics of chemistry and heat flow allows it, but that the second law is inadequate to account for the information needed for coding.  The book rejects the second-law argument in print, and its real claim is about coupling, not about entropy bookkeeping, so it should be argued in the language of chemistry.  This is the 1984 text only; the 2020 revised edition (Discovery Institute Press), which carries new material by Stephen Meyer, James Tour, Guillermo Gonzalez, Brian Miller and Jonathan Wells, is not discussed.  The article cites it because the founding book concedes the thermodynamics in its own text. ↩ ↩

Larralde, Rosa et al.  “Rates of decomposition of ribose and other sugars: implications for chemical evolution.”  Proceedings of the National Academy of Sciences 92:8158–8160.  1995.  Page 8158:  “The ribose half-lives are very short (73 min at pH 7.0 and 100°C and 44 years at pH 7.0 and 0°C).”  Page 8159:  “The half-life at pD 7.4 extrapolates to 300 days at 25°C and to 44 years at 0°C.  Even with correction for the buffer concentration, this is a very short period of geological time, and it is difficult to see how ribose could have been available for prebiotic use, even at low temperatures.”  The authors leave a door open.  “it is possible that stable prebiotic derivatives of ribose were present in the primitive ocean that could have been converted to ribose by one or two enzymatic steps.”  A 1995 paper by Rosa Larralde, Michael Robertson and Stanley Miller of the University of California at San Diego, who measured how fast ribose and other sugars break down at neutral pH and between 40 and 120 °C.  The article uses it for the instability of ribose, which the authors say made it very hard to have been available for prebiotic use.  The measurements used deuterated buffer, so the body reports pD and converts pH to pD with pD = pH + 0.4, meaning pD 7.4 is pH 7.0; the abstract and body describe the same experiment, measured by 1H NMR.  The paper says ribose cannot accumulate, not that it cannot form.  The authors checked the isotope effect directly and found none (kH2O/kD2O = 1.0 ± 0.2). ↩ ↩

Joyce, and Szostak.  “Protocells and RNA Self-Replication.”  Cold Spring Harbor Perspectives in Biology 10(9):a034801.  2018.  A 2018 review by Joyce and Szostak on protocells and the self-replication of RNA.  The article cites it for the magnesium that RNA copying needs, which is incompatible with fatty-acid membranes, and for the summary that no laboratory has built a compartment whose contents are copied and inherited across generations.

1. 27a.

   “However, nonenzymatic copying of RNA templates requires very high concentrations of divalent cations, typically Mg²⁺, and most ribozymes require high concentrations of Mg²⁺ for optimal activity.  In contrast, fatty acid–based membranes become unstable in ≥4 mM Mg²⁺, indicating an apparent incompatibility between the two systems.” ↩ ↩

2. 27b.

   “It also is not clear how to achieve multiple generations of nucleic acid replication within the context of a protocell.  If and only if all of these challenges can be met will it be possible to synthesize an evolving protocell.” ↩

Lynch, Michael, and Andrew Ellington.  “A symbiotic origin of the ribosome?”  PNAS Nexus 5:pgag019.  2026.  A 2026 perspective by Michael Lynch and Andrew Ellington, which proposes that the earliest ribosome began as a parasite that coevolved with its host.  The authors say the hypothesis is offered as testable rather than established.  The article cites it for its statement of the problem and its numbers, not as a solution. ↩

1. 28a.

   “the earliest stages of life likely relied upon nonenzymatic templated replication, which has in vitro error rates of 0.01 to 0.1 per nucleotide site.”  Set that beside the fidelity figures in the RNA-world section above: the best polymerase ribozymes run at 89-98% per nucleotide, which is an error rate of 0.02-0.11, the same range Lynch and Ellington describe as the starting problem. ↩

Rimmer, Paul B. et al.  “Timescales for Prebiotic Photochemistry Under Realistic Surface Ultraviolet Conditions.”  Astrobiology 21:1099–1120.  2021.  The authors put the period at.  “several years”.  as a lower limit.  A laboratory study of how long prebiotic photochemical steps take under realistic surface ultraviolet light.  The apparatus is StarLab, a solar simulator built for the faint young Sun rather than the mercury lamps used in most of this literature.  The one clear failure is worth stating plainly because almost nothing else in this field publishes its failures: a step that works under a laboratory lamp did not work under simulated sunlight.  The article uses it for that one clear failure. ↩

Orgel, Leslie E.  “The Implausibility of Metabolic Cycles on the Prebiotic Earth.”  PLoS Biology 6(1):e18.  Jan 2008.  The paper ends constructively:  “The demonstration of the existence of a complex, nonenzymatic metabolic cycle, such as the reverse citric acid, would be a major step in research on the origin of life, while demonstration of an evolving family of such cycles would transform the subject.”  Page 5:  The paper states the submission history on this page, including that Joyce edited the final version.  Page 11:  Discussing Ghadiri's peptide experiments, Orgel says they.  “illustrate 'intelligent design' of input peptides, not spontaneous self-organization of polymerizing amino acids.”  The phrase is easy to misuse, because the scare quotes are Orgel's own and mean the chemist's design of the starting materials.  Page 12:  Two further sentences belong with any use of this paper.  On the geneticists as well as the metabolists:  “However, solutions offered by supporters of geneticist or metabolist scenarios that are dependent on 'if pigs could fly' hypothetical chemistry are unlikely to help.”  And, against his own side's use of the argument:  “Theories of the origin of life based on metabolic cycles cannot be justified by the inadequacy of competing theories:  they must stand on their own.”  An essay by Leslie Orgel, submitted to PLoS Biology after his death on 27 October 2007, by Gerald Joyce.  It argues that metabolic cycles such as the reverse citric acid cycle are implausible on the prebiotic Earth, because a nonenzymatic cycle would need catalysts that are far too specific, and that the total turnover of a cycle matters more than its rate.  The article uses it as an attack on metabolism-first models from inside the field, to show that the leading figures attack each other's models rather than naturalism itself. ↩ ↩

Shapiro, Robert.  “A Simpler Origin for Life.”  Scientific American 296(6):46–53.  Jun 2007.  His attack on RNA-first is real:  “No physical law need be broken for spontaneous RNA formation to happen, but the chances against it are so immense, that the suggestion implies that the non-living world had an innate desire to generate RNA.”  But the piece argues that life is more probable, not less, so quoting it against naturalism inverts its thesis.  His own alternative:  “These requirements are general in nature, however, and are immensely more probable than the elaborate multi-step pathways needed to form a molecule that can function as a replicator.”  And his closing paragraph:  “A highly implausible start for life, as in the RNA-first scenario, implies a universe in which we are alone…  The small-molecule alternative, however, is in harmony with the views of biologist Stuart Kauffman:  'If this is all true, life is vastly more probable than we have supposed.'”  A Scientific American essay by Robert Shapiro, professor emeritus of chemistry at New York University, a specialist in DNA damage, who died in 2011.  It argues that the RNA-first origin of life is too improbable, and that a simpler small-molecule start is far more probable.  The article uses it as a leading figure's attack on RNA-first models, which shows that the leading figures attack each other's models rather than the naturalistic project. ↩

Whitesides, George M.  “Revolutions In Chemistry: Priestley Medalist George M. Whitesides' address.”  Chemical & Engineering News 85(13):12–17.  Mar 26, 2007.  A 2007 cover-story address by George Whitesides, a Priestley Medallist, in which the argument is that chemistry is on the verge of revolutions and that understanding the cell is ultimately a question of chemistry.  The Priestley Medal is a lifetime achievement award, and this is the medal address.  The article cites it because the sharpest doubt about the origin of life comes from a Priestley Medallist, in the medal address itself. ↩

1. 32a.

   The sentences immediately following, with one textual caution.  The captured text reads.  “The idea of an RNA world is good hint,”.  with no article before "good", which is either a typo in C&EN's own HTML or a dropped character in the print, so it is reproduced here rather than silently repaired, and anyone quoting further should re-read the printed issue.  The closing line on the passage:  “That idea would, of course, start us down the path toward systems that evolve autonomously — revolution indeed.” ↩

Trail, Dustin et al.  “The oxidation state of Hadean magmas and implications for early Earth's atmosphere.”  Nature 480:79–82.  2011.  A 2011 study of the oxidation state of magmas from the Hadean, the earliest part of Earth's history.  Its method, a calibration that uses cerium in zircon crystals to estimate oxygen levels, has a critical literature.  The article uses it as evidence that outgassing from these magmas would not have produced a reducing atmosphere like the one in Miller's experiment. ↩

Cleaves, H. James et al.  “A Reassessment of Prebiotic Organic Synthesis in Neutral Planetary Atmospheres.”  Origins of Life and Evolution of Biospheres 38:105–115.  2008.  Section Abstract:  “We show here that contrary to previous reports, significant amounts of amino acids are produced from neutral gas mixtures.  The low yields previously reported appear to be the outcome of oxidation of the organic compounds during hydrolytic workup by nitrite and nitrate produced in the reactions.  The yield of amino acids is greatly increased when oxidation inhibitors, such as ferrous iron, are added prior to hydrolysis.”  A 2008 laboratory paper that reruns spark-discharge experiments on a neutral atmosphere, 0.13 bar each of carbon dioxide and nitrogen over 100 ml of water for 48 hours, and finds significant amounts of amino acids.  The low yields reported earlier are attributed to the products being oxidised during the workup.  The yield was 2.5% of amino acids on input nitrogen, against the ₄^-2% that had been the field's figure since Schlesinger and Miller in 1983.  The authors' own caveat is real: ascorbate is not prebiotic, and of six candidate prebiotic antioxidants tested, four did nothing, FeSO₄ gave 2× and pyrites 10×, against ascorbate's 100×.  The article cites it for the finding that spark experiments have worked in neutral gas since 2008.  Stanley Miller is a posthumous co-author. ↩

Wollrab, Eva et al.  “Chemical Analysis of a "Miller-Type" Complex Prebiotic Broth.”  Origins of Life and Evolution of Biospheres 46:149–169.  2016.  “Contrary to expectations, we cannot identify any preferred reaction product.”  From the discussion:  “As far as we can say from our global approach, these species are not mere side products of a few preferred products.  Rather many different species appear with equally important concentrations.”  The paper's own gloss is:  “The experiment produced thousands of molecules from a broad mass range.”  A 2016 chemical analysis of the products of a Miller-type experiment, in which sparks run through a gas mixture over water, examined without choosing compounds in advance, by mass spectrometry and NMR (nuclear magnetic resonance) spectroscopy.  The 668 distinct compounds were identified by FT-ICR mass spectrometry in one narrow window, with the instrument tuned to m/z 150–300.  The article uses it because it found no single preferred product. ↩

Becker, S. et al.  “Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides.”  Science 366:76–82.  2019.  A 2019 Science paper by Carell and colleagues that makes both the purine and the pyrimidine RNA building blocks by one route.  The article uses it because the route feeds ribose in as a reagent, and the paper itself says it is unclear how ribose could have formed selectively.

1. 36a.

   “It remains unclear, however, how ribose or any other carbohydrate, such as glycerol or threose, needed to form the backbone of RNA or pre-RNA could have formed selectively.  Sugars such as ribose can be produced non-selectively in a formose-like reaction, which is possible in a variety of different physico-chemical environments.” ↩

Richert, Clemens.  “Prebiotic chemistry and human intervention.”  Nature Communications 9:5177.  2018.  Page 1:  The 'Hand of God' framing is his own:  “When Diego Maradona was asked about having used his hand to score a goal in the quarter-finals of the 1986 soccer World Cup, he initially claimed that there had been divine intervention, and the term 'Hand of God Goal' was coined.—There had been manual intervention, and there had been an understandable interest of the player not to admit it.—Organic chemists, if not all experimentalists in the field of prebiotic chemistry, are faced with a similar dilemma.  We do our best to perform experiments that we believe re-enact possible steps of prebiotic evolution, but we know that we need to intervene manually to obtain meaningful results.”  One parenthetical of his, which belongs with any use of him:  “(And yes, most of us are not comfortable with the idea of divine intervention in this context.)”  He also rejects the naive alternative:  “Simply mixing chemicals and watching for a living system to appear from the broth seems unreasonable to me.  This approach has never worked, and it is not expected to work.”  Page 2:  His proposal:  “When it becomes unavoidable to intervene as experimentalist, just state the number of discontinuities in the experimental conditions or human interventions!”  A comment piece of about a page and a half, which does not tabulate the interventions in anyone's synthesis.  Its author is professor of organic chemistry at Stuttgart and publishes prebiotic RNA chemistry himself, and he argues that chemists should state how many manual interventions an experiment needed and what prebiotic scenario it is meant to address.  The article uses it for the 'Hand of God' dilemma, the name Richert gives to the problem that every route needs a fixed sequence of environments, and no field site has been shown to run one. ↩

Tour.  “Two Experiments in Abiogenesis.”  Inference: International Review of Science 2(3).  Sep 2016.  A 2016 review in which James Tour, a synthetic organic chemist, criticises two 2016 papers that made nucleosides (the sugar-and-base units that RNA is built from) under conditions meant to be prebiotic, one by Becker and colleagues in Science and one by Cafferty and colleagues in Nature Communications.  The article uses it for Tour's point that each study starts from products that an earlier study made under messy conditions.

1. 38a.

   The bookkeeping objection is a criticism of inference across papers, not of any one experiment, which is why it survives results that answer the individual steps.  Set it beside Richert's "Hand of God" comment: two chemists, independently, asking the field to report what it supplied. ↩

Tour, James M.  “An Open Letter to My Colleagues.”  Inference: International Review of Science 3(2).  Aug 2017.  A 2017 open letter by the synthetic chemist James Tour, arguing that a chemist could not build a cell even if every needed molecule were supplied, because the lipid membranes and the sugar coat of a cell are too complex to make.  Footnote 2 for the genome numbers reads, in its entirety, "See Wikipedia, 'Minimal Genome.'" and footnote 3 gives "David Dearner" for David Deamer and dates a 2005 paper to 2008, while supplying the correct DOI.  The article uses it for his figure of 256 protein-coding genes for the first cell, a number he sourced to Wikipedia and which was seventeen months out of date when he wrote it. ↩

Hirakawa, Y. et al.  “Interstep compatibility of a model for the prebiotic synthesis of RNA consistent with Hadean natural environments.”  Proceedings of the National Academy of Sciences 122:e2516418122.  2025.  A 2025 study from Benner's group, which models the prebiotic synthesis of RNA under conditions consistent with Hadean natural environments.  The article uses it for the field's strongest reply to the chemist's-hand objection, a 6-mer RNA chain made without a chemist.

1. 40a.

   Section Discussion:  “Thus, the DSM is continuous to form 6-mer RNA, predominately 3′,5′-linked, except at points marked with *.  These points are also points where decisions about chirality might be made.” ↩

Viedma, Cristóbal.  “Chiral symmetry breaking during crystallization: complete chiral purity induced by nonlinear autocatalysis and recycling.”  Physical Review Letters 94:065504.  2005.  “complete chiral purity”.  An earlier version of the paper, which peer review revised, says that the population.  “moves into complete chiral purity disappearing one of the enantiomers,”.  and it carries a different title,  “Total chiral symmetry breaking by bifurcation from racemic systems: when 'left' and 'right' cannot coexist.”  A 2005 Physical Review Letters report by Cristóbal Viedma of a crystallisation experiment in which abrasion-grinding with glass balls, in a saturated solution, drives the crystals of sodium chlorate to one handedness.  Sodium chlorate is achiral in solution, so its handedness exists only in the crystal and is erased on dissolution; that is why Noorduin et al. 2008 was necessary, and why this paper alone does not settle anything about biological molecules.  The article uses it as evidence that a natural mechanism can give complete handedness. ↩

Glavin, Daniel P. et al.  “Abundant ammonia and nitrogen-rich soluble organic matter in samples from asteroid (101955) Bennu.”  Nature Astronomy 9:199–210.  2025.  Section Abstract:  “We detected amino acids (including 14 of the 20 used in terrestrial biology), amines, formaldehyde, carboxylic acids, polycyclic aromatic hydrocarbons and N-heterocycles (including all five nucleobases found in DNA and RNA), along with ~10,000 N-bearing chemical species.  All chiral non-protein amino acids were racemic or nearly so, implying that terrestrial life's left-handed chirality may not be due to bias in prebiotic molecules delivered by impacts.”  Section Results:  “A total of 33 amino acids were identified in the Bennu aggregates…  These included 14 of the 20 standard protein amino acids used in terrestrial biology…  Glycine was the most abundant amino acid (44 nmol g^-1), with the majority in a free form.”  The argument that the molecules are genuinely extraterrestrial.  “The violation of Chargaff's rules… and diversity of N-heterocycles, including biologically uncommon molecules… also indicate a non-terrestrial origin.”  A 2025 analysis of carbon-rich material from the asteroid Bennu, returned to Earth by NASA's OSIRIS-REx mission without uncontrolled exposure to Earth's biosphere.  The team found more carbon, nitrogen and ammonia than in Ryugu samples or most meteorites, and detected amino acids, all five nucleobases and ~10,000 other nitrogen-bearing compounds.  The article uses it for the 33 amino acids and five nucleobases in a sample that never touched the ground, and for the finding that the amino acids are racemic. ↩

1. 42a.

   Section Results:  “All chiral non-protein amino acids that could be enantiomerically resolved, including isovaline, norvaline, β-amino-n-butyric acid, β-aminoisobutyric acid and 3-aminopentanoic acid, were present as racemic or near racemic mixtures (equal abundances of d- and l-enantiomers) within analytical uncertainties.”  Section Discussion:  “The source of the meteoritic l-amino acid enrichments remains a mystery.  At least for now, the lack of any amino acid enantiomeric excesses of confirmed extraterrestrial origin in the Bennu material analysed here, as well as in samples from Ryugu and some lithologies of Tagish Lake and Tarda, challenges the hypothesis that the emergence of left-handed protein-based life on Earth was influenced by an early Solar System bias toward l-amino acids.”  The companion pristine-sample results are Parker, Eric T., et al., Geochimica et Cosmochimica Acta 347 (2023): 42-57 (Ryugu, β-AIB D/L = 0.95 ± 0.08 and 0.98 ± 0.12), and Chan, Queenie H. S., Jonathan S. Watson, and Mark A. Sephton, LPSC 54, abstract 1474 (2023) (Winchcombe).  A caveat from Baczynski, Allison A., et al., PNAS 123 (2026): e2517723123.  “Even when bulk products are racemic, at the smallest scales, D- and L-enantiomers are not necessarily in equal proportions.” ↩

Brazil, Rachel.  “Are we closer to understanding the origins of biological homochirality?”  Chemical & Engineering News 104(7).  May 21, 2026.  Blackmond is speaking about her own laboratory's result in Deng, Min; Yu, Jinhua; Blackmond, Donna G., "Symmetry breaking and chiral amplification in prebiotic ligation reactions," Nature 626 (2024): 1019–1024.  “You still have to have a chiral source to get any kind of differentiation.”  This quotation is frequently attributed to her 2010 review, which does not contain it.  A 2026 magazine news feature on the origin of homochirality, the one-handedness of life's molecules, in which Donna G. Blackmond is quoted about her own laboratory's work.  The article cites it for Blackmond's 2026 view that a chiral source is still needed to get any differentiation. ↩

Attwater, James et al.  “Trinucleotide substrates under pH-freeze-thaw cycles enable open-ended exponential RNA replication by a polymerase ribozyme.”  Nature Chemistry 17:1129–1137.  2025.  The authors put the word in their own scare quotes:  “'fragmentary' self-replication”.  A laboratory study from Philipp Holliger's group at the MRC Laboratory of Molecular Biology in Cambridge.  Short three-letter RNA pieces, called trinucleotides, let a polymerase ribozyme copy RNA, and cycles of pH and freezing and thawing made the copying exponential.  The copied RNA included a fragment of the ribozyme itself, so the article cites it for part of a ribozyme being replicated, not the whole ribozyme.  Read the word part carefully: what replicates exponentially is a segment of the ribozyme, not the whole of it. ↩

Joyce, Gerald F. et al.  “Chiral selection in poly(C)-directed synthesis of oligo(G).”  Nature 310:602–604.  1984.  Section Abstract:  “We report here that poly(C)-directed oligomerization of activated guanosine mononucleotides proceeds readily if the monomers are of the same optical handedness as the template, and is indeed far less efficient if the monomers are of the opposite handedness.  However, in template-directed reactions with a racemic mixture, monomers of the opposite handedness to the template are incorporated as chain terminators at the 2′(3′) end of the products.  This inhibition raises an important problem for many theories of the origin of life.”  A 1984 Nature paper by Gerald Joyce, Leslie Orgel and colleagues on copying RNA-like chains from guanosine building blocks.  The article cites it for the finding that a building block of the wrong handedness stops a growing chain.  The mechanism matters: the wrong-handed monomer does not fail to add; it adds, and then the chain cannot be extended past it.  Joyce restated the problem thirty years later in Sczepanski, Jonathan T., and Gerald F. Joyce, Nature 515 (2014): 440–442, calling it "a severe challenge for the spontaneous emergence of RNA-based life." ↩

Attwater, James et al.  “Ribozyme-catalysed RNA synthesis using triplet building blocks.”  eLife 7:e35255.  2018.  Section Triphosphorylated triplet synthesis:  “pppNNN was generated by combination of equal amounts of each of the 64 triplet stocks.”  A laboratory study from Philipp Holliger's group in Cambridge.  The authors built a ribozyme that copies RNA three letters at a time, using triplets, and found that triplets can copy RNA templates that fold into structures which block ordinary copying.  Triplets are made with T7 RNA polymerase, a modern enzyme, from synthetic DNA templates, and then purified on a 30% acrylamide gel with 3 M urea.  That feedstock step is one the whole polymerase-ribozyme literature inherits, and it is not prebiotic.  The article cites it for the feedstock step, in which the triplets are made by a modern protein enzyme from synthetic DNA templates. ↩

Le Vay, Kristian, and Hannes Mutschler.  “The difficult case of an RNA-only origin of life.”  Emerging Topics in Life Sciences 3:469–475.  2019.  A 2019 perspective by Kristian Le Vay and Hannes Mutschler of the Max Planck Institute of Biochemistry, which says the RNA world is probably the most studied model for the origin of life but has seemingly insurmountable weaknesses.  The article cites it for the feedstock problem, which the authors say has not been solved.  The QT45 authors themselves cite this objection as reference 22 of Gianni et al. 2026. ↩

Wächtershäuser, Günter.  “Before Enzymes and Templates: Theory of Surface Metabolism.”  Microbiological Reviews 52(4):452–484.  Dec 1988.  Page 452:  The central thesis is stated on this page.  A 1988 review that proposes a theory of the first life: acellular organisms with no enzymes, no templates and no cell, whose chemistry runs on the surfaces of minerals such as pyrite (an iron sulfide), and that later give rise to membranes and then to true cells.  The article cites it as the theory that puts chemistry before genes, on mineral surfaces. ↩

Vasas, Vera et al.  “Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life.”  Proceedings of the National Academy of Sciences 107:1470–1475.  2010.  “In sharp contrast with template-dependent replication dynamics, we demonstrate here that replication of compositional information is so inaccurate that fitter compositional genomes cannot be maintained by selection and, therefore, the system lacks evolvability (i.e., it cannot substantially depart from the asymptotic steady-state solution already built-in in the dynamical equations).  We conclude that this fundamental limitation of ensemble replicators cautions against metabolism-first theories of the origin of life, although ancient metabolic systems could have provided a stable habitat within which polymer replicators later evolved.”  The last clause is not a rejection of metabolism-first chemistry, only of its heredity.  A 2010 mathematical study that tests metabolism-first theories, which say that chemical cycles came before genes.  It finds that the replicating networks in its model cannot be kept improving by selection, so they lack evolvability.  The authors include Eörs Szathmáry, who co-wrote The Major Transitions in Evolution with John Maynard Smith, so this is a result from the centre of mainstream evolutionary theory.  The article uses it as the sharpest objection to metabolism-first chemistry, and it comes from inside evolutionary biology. ↩

Jackson, J. Baz.  “Natural pH Gradients in Hydrothermal Alkali Vents Were Unlikely to Have Played a Role in the Origin of Life.”  Journal of Molecular Evolution 83:1–11.  2016.  A 2016 open-access review by J. Baz Jackson, a bioenergeticist at the University of Birmingham, who argues that natural pH gradients across inorganic membranes in alkaline vents are unlikely to have powered the origin of life.  He is not one of the origin-of-life camps, and he thanks Lane and Martin in his acknowledgments.  The article uses it as a better-placed critique than any creationist treatment of the same model. ↩

Jackson, J. Baz.  “Ancient Living Organisms Escaping from, or Imprisoned in, the Vents?”  Life 7(3):36.  2017.  “Our arguments apply to three of the four concurrent models employed by the proponents of the natural pH gradient hypothesis.  A fourth model is exempt from these arguments but has other intrinsic difficulties.”  A 2017 open-access paper by J. Baz Jackson, the same author as the 2016 review, which argues against the natural pH gradient model for vents.  He is explicit about scope, and the article uses it for that scope. ↩

Jordan, Sean F. et al.  “Promotion of protocell self-assembly from mixed amphiphiles at the origin of life.”  Nature Ecology & Evolution 3:1705–1714.  2019.  The mixtures were made of twelve fatty acids and alkanols, at 600 mM NaCl, 50 mM Mg2+ and 10 mM Ca2+, at pH 11–12.  The critical bilayer concentration fell thirtyfold, from 39 mM for pure decanoic acid to 1.3 mM for the mixture.  Neither camp stresses this catch: the alkaline hydroxide complexation that removes the divalent cations and the RNA-hostile pH are the same fact.  Jordan et al. report "very few" vesicles below pH 9, and RNA does not survive pH 11–12.  A 2019 laboratory study from University College London's Nick Lane group, which found that mixtures of C10 to C15 fatty acids and alcohols, the kind alkaline hydrothermal chemistry can make, form vesicles at modern seawater ionic strength and at about 70 °C.  The article uses it to answer the objection that vents cannot make membranes.  Damer and Deamer cite the result and do not dispute it, but their answer is that a plausible prebiotic source of such mixtures "remains uncertain" (Damer, Bruce, and David Deamer, "The Hot Spring Hypothesis for an Origin of Life," Astrobiology 20 (2020): 429–452). ↩

Mulkidjanian, Armen Y. et al.  “Origin of first cells at terrestrial, anoxic geothermal fields.”  Proceedings of the National Academy of Sciences 109:E821–E830.  2012.  A study that combined geochemical analysis with a comparison of the genomes of modern cells, to ask which ions the first cells would have needed in their surroundings.  It concludes that the ion mix needed for the origin of cells could not have existed in marine settings, but fits the vapor-dominated zones of inland geothermal systems.  The weakness is methodological: the argument runs from the composition of modern cells back to their setting, so it inherits whatever is wrong with treating universal components as primordial, the same methodological limit Gogarten states for LUCA reconstructions elsewhere in this article.  The article uses it for the claim that no marine setting supplies the potassium and phosphate every cell is built on. ↩

Deamer, David W. et al.  “The first cell membranes.”  Astrobiology 2(4):371–381.  2002.  A 2002 review in Astrobiology on how membranes could have formed from organic molecules that reached the early Earth from space.  Amphiphilic molecules, which have a water-loving end and a water-repelling end, self-assemble into membrane layers, and the abstract says laboratory simulations show that such vesicles readily encapsulate functional macromolecules, including nucleic acids and polymerases.  The article cites it for the first step: fatty acids form vesicles by themselves. ↩

Hanczyc, Martin M. et al.  “Experimental Models of Primitive Cellular Compartments: Encapsulation, Growth, and Division.”  Science 302:618–622.  2003.  Szostak's own laboratory later supplied the limit, in Zhu and Szostak's 2009 paper, which says that this division mechanism.  “results in significant loss of protocell contents during each division cycle.”  A 2003 laboratory study by Martin Hanczyc, Shelly Fujikawa and Jack Szostak on how fatty acids form vesicles, the membrane bubbles that may have enclosed the first cells.  Adding the clay montmorillonite increased the initial rate of vesicle formation by a factor of 100 in the experiment shown in its Figure 1A, clay particles often became encapsulated in the vesicles, and the vesicles grew and divided through small pores without diluting their contents.  The article cites it as the genuinely impressive laboratory work in the field, because clay speeds up the process and carries RNA into the vesicles. ↩

Adamala, Katarzyna, and Jack W. Szostak.  “Nonenzymatic Template-Directed RNA Synthesis Inside Model Protocells.”  Science 342:1098–1100.  2013.  “However, the conditions required for RNA replication chemistry and fatty acid vesicle integrity have appeared to be fundamentally incompatible (5) (Fig S1).  Both ribozyme catalyzed and non-enzymatic RNA copying reactions require high (50–200 mM) concentrations of Mg²⁺ (or other divalent) ions (6), but Mg²⁺ at such concentrations destroys vesicles by causing fatty acid precipitation.”  A laboratory study of model protocells, artificial cells made of fatty-acid vesicles, that screened chemicals for ones that protect the vesicles from magnesium.  Citrate protected them and still let RNA copying proceed inside, the authors report.  The article cites it as the sharpest objection to protocell chemistry, and the objection comes from Szostak's own laboratory.  Mirror:  PMC ↩

Freeland, Stephen J., and Laurence D. Hurst.  “The Genetic Code Is One in a Million.”  Journal of Molecular Evolution 47:238–248.  1998.  “In addition, if we employ weightings to allow for biases in translation, then only 1 in every million random alternative codes generated is more efficient than the natural code.”  The stronger optimality claim quoted in this article is from Freeland, Stephen J., Robin D. Knight, Laura F. Landweber, and Laurence D. Hurst, "Early Fixation of an Optimal Genetic Code," Molecular Biology and Evolution 17 (2000): 511–518.  That paper says the code is.  “at or very close to a global optimum”.  The 2000 abstract makes that conditional, saying:  “if theoretically possible code structures are limited to reflect plausible biological constraints.”  A 1998 study that compares the standard genetic code with random alternative codes.  The load-bearing and almost never stated detail is the sampled set.  The random alternatives are not arbitrary mappings of 64 codons onto 21 meanings; they are built by shuffling the twenty amino acids among the standard code's own synonymous codon blocks, keeping the block structure and degeneracy fixed; that is a space of 20! ≈ 2.4 × 10^18 codes.  A hit rate of 10^-6 therefore implies roughly 2.4 × 10^12 codes that beat the standard code.  The article cites it for the one-in-a-million result, which is real and is misreported by both sides.  The quotation is from the abstract. ↩

Koonin, Eugene V.  “Frozen Accident Pushing 50: Stereochemistry, Expansion, and Chance in the Evolution of the Genetic Code.”  Life 7(2):22.  2017.  “Extensive quantitative analyses that employed cost functions differently derived from physico-chemical properties of amino acids have shown that the code is indeed highly resilient, with the probability to pick an equally robust random code being on the order of 10^-7–10^-8 [14,15,61–68].  Obviously, however, among the ~10⁸⁴ possible random codes, there is a huge number with a higher degree of error minimization than the SGC.  Furthermore, the SGC is not a local peak on the code fitness landscape because certain local rearrangements can increase the level of error minimization;  a quantitatively, the SGC is positioned roughly halfway from an average random code to the summit of the corresponding local peak [15] (Figure 1).”  A 2017 concept paper in the open-access journal Life by Eugene Koonin, which reviews Crick's frozen-accident theory of the genetic code and proposes a testable scenario in which amino acids are recognised by sites on proto-tRNAs and the code grows by duplication.  The article uses it to show that the code is robust to error, while the origin of its specific codon assignments remains unexplained. ↩

1. 58a.

   “The subsequent 49 years of code studies have elucidated notable features of the standard code, such as high robustness to errors, but failed to develop a compelling explanation for codon assignments.” ↩

Shulgina, Yekaterina, and Sean R. Eddy.  “A computational screen for alternative genetic codes in over 250,000 genomes.”  eLife 10:e71402.  2021.  A computational study that introduced Codetta, a program that predicts which amino acid each codon codes for from sequence data, and used it to screen 251,571 assembled genomes for alternative codes.  It found five new reassignments of arginine codons in bacteria, the first sense-codon changes found in bacteria, and the CGA and CGG reassignments were found in genomes with low GC content.  The article uses it for the point that the genetic code is not universal. ↩

Miyachi.  TODO: full citation not in packet.  Jul 2026.  A laboratory study that tested the error-minimisation theory of the genetic code by translating individual reporter proteins in a reconstituted in vitro system, using non-standard codes and mutagenized libraries.  It found that the effects of mutations on protein function were similar across all the genetic codes tested, which the article uses as the first laboratory test of the theory.

1. 60a.

   Section Discussion:  “The error minimization theory predicts that the deleterious effect of mutations on protein function becomes more severe when using genetic codes with higher mutational cost (Freeland et al., 2003;  Freeland and Hurst, 1998;  Haig and Hurst, 1991;  Massey, 2008).  In contrast to this prediction, translation experiments using the non-SGCs and mutagenized libraries revealed that the effects of mutations on protein functions were similar across all genetic codes and reporter genes examined here, suggesting that the mutational robustness of protein activity remained largely unchanged within at least the ranges of mutational cost tested in this study.”  The authors' own limits:  “It should be noted that this conclusion is limited to the activity of individual reporter proteins translated in a reconstituted in vitro system.  Therefore, whether similar trends would be observed at the level of cellular fitness or long-term evolution remains an open question.”  And:  “only three amino acids (Ala, Ser, and Leu) can be reassigned to different codons.” ↩

2. 60b.

   “In both integrated indices, the near-SGC showed the lowest overall cost when compared with all 19,683 candidate non-SGCs (Figure 5—figure supplement 7), indicating that no candidate non-SGC exhibited a lower combined cost than the near-SGC when the three physicochemical properties were considered jointly.” ↩

Bokov, Konstantin, and Sergey V. Steinberg.  “A hierarchical model for evolution of 23S ribosomal RNA.”  Nature 457:977–980.  2009.  “Surprisingly, a detailed analysis of the structure of the modern ribosome reveals a concerted and modular scheme of its early evolution.”  Petrov, Anton S., et al., "History of the ribosome and the origin of translation," PNAS 112 (2015): 15396–15401, states the logic:  “Bokov and Steinberg (2) reasoned that the donating adenosine in an A-minor interaction is dependent on the accepting double helix, whereas the accepting helix is less dependent on the adenosine.  If the conformation and structure of the rRNA was maintained throughout its evolution, the donating adenosine is the more recent addition.”  Fox, George E., "Origin and Evolution of the Ribosome," Cold Spring Harbor Perspectives in Biology 2 (2010): a003483, names two limits of the model.  The first is that the peptidyl transferase centre's primacy is an input, not an output:  “The core areas of the structure are again the PTC by assumption”.  The second is that the small subunit, which holds the decoding centre where the code is actually read, is treated as late:  “Bokov and Steinberg argue that the acquisition of the GTPase center and L1 protuberance and even the addition of the 30S subunit are relatively late additions to the ribosome.”  The root is also contested in print.  Caetano-Anollés, Gustavo, "Ancestral Insertions and Expansions of rRNA do not Support an Origin of the Ribosome in Its Peptidyl Transferase Center," Journal of Molecular Evolution 80 (2015): 162–165, disputes the root of the model, and says:  “Unwarranted assumptions, dismissals of conflicting data, structural insertion ambiguities, and lack of phylogenetic information compromise the construction of an unequivocal insertion-based model of macromolecular accretion.”  That is a dispute about which end the ribosome grew from, between two groups who both accept that it grew by accretion and that the history is recoverable.  A 2009 Nature paper that models how the RNA of the large ribosome subunit (23S) built up over time, deriving it from a small proto-ribosome by nested insertions.  The article cites it for the ribosome having a derivable history.  The abstract says: ↩

Xiao, Hong et al.  “Structural basis of specific tRNA aminoacylation by a small in vitro selected ribozyme.”  Nature 454:358–361.  2008.  “Flexizyme is a 45-nucleotide ribozyme capable of charging tRNA in trans with various activated l-phenylalanine derivatives.  In addition to a more than 10(5) rate enhancement and more than 10(4)-fold discrimination against some non-cognate amino acids, this ribozyme achieves good regioselectivity:  of all the hydroxyl groups of a tRNA, it exclusively aminoacylates the terminal 3′-OH.”  Miyachi and Ichihashi, writing in 2026, summarised the state of the art, verbatim:  “although protein synthesis using ribozyme-based aminoacylation is still a challenge (Chen et al., 2021).”  The flexizyme system was introduced in Murakami, Hiroshi, Atsushi Ohta, Hikaru Ashigai, and Hiroaki Suga, Nature Methods 3 (2006): 357–359, titled.  “A highly flexible tRNA acylation method for non-natural polypeptide synthesis”.  Its precedent was Illangasekare, Mali, Gregory Sanchez, Timothy Nickles, and Michael Yarus, Science 267 (1995): 643–647, titled.  “Aminoacyl-RNA synthesis catalyzed by an RNA”.  A 2008 paper on the flexizyme, a short RNA enzyme (a ribozyme) selected in the test tube that attaches an amino acid to transfer RNA, the molecule that carries amino acids to the ribosome, with no protein involved.  Flexizymes are promiscuous by design: their value in synthetic biology is that they charge almost any tRNA with almost any activated acyl donor, which is the opposite of what a genetic code requires.  A flexizyme is a charging catalyst, not a coding catalyst, because its specificity is for the leaving group on the amino acid, not for the pairing of a side chain with an anticodon.  The article cites it for Suga's flexizyme, which charges tRNA with an amino acid using no protein at all. ↩

Koonin, Eugene V.  “The origins of cellular life.”  Antonie van Leeuwenhoek 106:27–41.  2014.  Section Introduction:  Two sentences earlier he quotes Carl Woese: the origin of cells is "the greatest of evolutionary problems," and "all of biological evolution that occurred after the origin of cells … is routine compared to that momentous breakthrough."  A 2014 review by Eugene Koonin of the National Center for Biotechnology Information on how cells came to exist, comparing protocellular scenarios with non-cellular ones.  The article cites it because Koonin borrows an apologists' phrase to describe how the parts of the translation system depend on one another. ↩

Keefe, Anthony D., and Jack W. Szostak.  “Functional proteins from a random-sequence library.”  Nature 410:715–718.  2001.  A 2001 Nature paper by Anthony Keefe and Jack Szostak.  A DNA library of about 4 × 10¹⁴ independently generated random sequences was converted by mRNA display into about 6 × 10¹² purified, non-redundant proteins, each carrying 80 contiguous random amino acids, then passed over an ATP-agarose column.  Four unrelated protein families came out.  The article uses the count to measure how rare a working protein is.  The arithmetic is a straight count of 4 hits in 6 × 10¹² proteins, about 6.7 × 10^-13, multiplied by ten to correct for roughly 10% folding efficiency. ↩

Dryden, David T. F. et al.  “How much of protein sequence space has been explored by life on Earth?”  Journal of the Royal Society Interface 5:953–956.  2008.  “4×10²¹ different protein sequences tested since the origin of life”.  A 2008 short paper that estimates how much of the space of possible protein sequences life could have explored since the origin of life.  The authors argue that most of that space may have been explored, and they put a lower bound on the sequences tested since the origin of life.  Their 10^34 is a generous estimate of all genes that have ever existed.  The article cites it to set the number that every probability claim has to beat. ↩

Hazen, Robert M. et al.  “Functional information and the emergence of biocomplexity.”  Proceedings of the National Academy of Sciences 104(Suppl 1):8574–8581.  2007.  A 2007 colloquium paper on origin of life and complexity by four researchers, one of them Jack Szostak.  It defines functional information as the negative base-2 logarithm of the fraction of all possible configurations of a system that reach at least a given degree of function, and tests the measure on letter sequences, the Avida artificial-life platform and RNA aptamers.  The paper credits the formalism to Szostak, writing "In the formalism of Szostak", so it is a development of his 2003 Nature proposal rather than a new coinage, and the article uses the definition as the mainstream one. ↩

Matlock, and Swamidass.  “Evolution and Functional Information.”  bioRxiv.  2017.  A 2017 preprint by Matlock and Swamidass that tests the MISA estimate of functional information on simulated sequences.  The article uses it because it shows that the Durston measure scores a simulated family under zero constraint the same as real proteins.

1. 67a.

   Section 2:  From the Matlock and Swamidass preprint, immediately after its uniform-evolution simulation.  The setup, in their words, follows.  “This simulation samples several extant sequences a fixed number of mutational events away from a single ancestral sequence.  There are no functional constraints, so the FI by definition equals zero.  If MISA is a good estimate of FI, it should converge to zero bits too.  We find that MISA does not converge to zero, even as more extant sequences are sampled.” ↩

Nature.  Nature volume 294, issue 5837.  Nov 12, 1981.  The news story on page 105 is Rich, Vera.  "Albanian development:  Hoxha looks ahead."  Nature 294 (1981): 105, at https://www.nature.com/articles/294105a0.  The page itself states.  “Nature volume 294, page 105 (1981).”  The table of contents of volume 294, issue 5837, of 12 November 1981, read item by item.  The issue has no article by Hoyle, and none titled 'Hoyle on evolution', and the article that occupies page 105 is a news story about Albania.  The article uses it to show that its citation for Hoyle's 747 count goes to a news page. ↩

Hoyle, Fred.  “The Universe: Past and Present Reflections.”  Engineering and Science 45(2):8–12.  1981.  Pages 10–11:  “If amino acids were linked at random, there would be a vast number of arrangements that would be useless in serving the purposes of a living cell.  When you consider that a typical enzyme has a chain of perhaps 200 links and that there are 20 possibilities for each link, it's easy to see that the number of useless arrangements is enormous, more than the number of atoms in all the galaxies visible in the largest telescopes.  This is for one enzyme, and there are upwards of 2000 of them, mainly serving very different purposes.  So how did the situation get to where we find it to be?  This is, as I see it, the biological problem — the information problem.”  Page 11:  “So try as I would, I couldn't convince myself that even the whole universe would be sufficient to find life by random processes — by what are called the blind forces of nature. …  Rather than accept the fantastically small probability of life having arisen through the blind forces of nature, it seemed better to suppose that the origin of life was a deliberate intellectual act.  By 'better' I mean less likely to be wrong.”  A November 1981 essay in the Caltech magazine Engineering and Science, in which the astronomer Fred Hoyle explains why he concluded that life could not arise by blind chance.  The article cites it for his enzyme arithmetic: a typical enzyme has about 200 links, each with 20 possibilities, and there are upwards of 2000 enzymes. ↩

Yockey, Hubert P.  Dr. Hubert Yockey's answer to FTE amicus brief.  Nov 16, 2005.  A letter of 16 November 2005 in which the information theorist Hubert Yockey answers the amicus brief that the Foundation for Thought and Ethics filed in Kitzmiller v. Dover Area School District.  The foundation published The Mystery of Life's Origin, which is why Yockey was answering it.  Yockey says the missing ingredient for the origin of living matter is the genome, not Intelligent Design, and that the origin of life is unknowable by scientific methods.  The article uses it because Yockey, writing as an information theorist, rejects creationism and intelligent design in print. ↩

Bunn, Emory F.  “Evolution and the second law of thermodynamics.”  American Journal of Physics 77:922–925.  2009.  “We conclude that the entropy reduction required for life on Earth is far less than |ΔS_life| ∼ 10⁴⁴ k.”  “If we compare this value with the rate of entropy production due to sunlight in Eq. (3), we find that the second law, in the form of Eq. (1), is satisfied as long as the time required for life to evolve on Earth is at least Δt = … ∼ 10⁷ s, or less than a year.  Life on Earth took four billion years to evolve, so the second law of thermodynamics is safe.”  Bunn says that Styer's paper rests on.  “an unjustified and probably incorrect assumption.”  A 2009 physics paper by Emory Bunn that answers the claim that evolution breaks the second law of thermodynamics.  It estimates the entropy that sunlight brings to Earth and compares it with the entropy decrease that life would need, and finds that the decrease is far smaller.  The article cites it for the sum that sunlight pays for the entropy bill.  Bunn corrects a 2008 paper by Daniel Styer, and the two physicists differ over how to do the sum, but both conclude there is no conflict.  Styer's paper is cited as American Journal of Physics 76 (2008): 1031–1033.  Mirror:  arXiv ↩

Sarfati, Jonathan.  Thermodynamics and evolution.  Creation Ministries International.  2011.  “I have yet to see the calculations involving either heat transfer or Boltzmann microstates involved for natural selection.  Until creationists can do that, they should refrain from claiming that organic evolution contradicts the Second Law;  a trite appeal to 'things become more disordered according to the Second Law' is inadequate.”  And, in the same answer:  “I tend not to use entropy arguments at all for biological systems.”  “I must admit that I hardly ever refer to the second law, although as a Ph.D. physical chemist I am well qualified to do so.  Without meaning to brag, if I don't use it, then few people should;  instead, concentrate on the information argument.”  The answer carves out the origin of life as a different case:  “Origin of first life is different, since natural selection can't occur without two or more self-reproducing entities”.  That carve-out is no longer a second-law argument; it is the information argument, and the answer says so in the same breath.  This is a different page from the 2006 "Answers to Critics" article, also by Sarfati, which does defend thermodynamic arguments "when done properly."  Both are live; the two are five years apart and the later one is the concession.  A 2011 web answer by Jonathan Sarfati, who holds a PhD in physical chemistry and is Creation Ministries International's house scientist, which is what gives the concession its force.  The article uses it because a creationist physical chemist stops relying on the second law of thermodynamics and moves the argument to information. ↩

Carter, Robert W.  “Can mutations create new information?”  Journal of Creation 25(2):92–98.  Aug 2011.  Section standfirst:  “It depends on what you mean by 'new' and 'information'.”  Section second body paragraph:  It is not the article's opening sentence; it begins the second body paragraph, after the standfirst.  “In the same way that species are not static, neither are genomes…”  An article by a creationist scientist, first printed in the Journal of Creation in 2011 and posted online by Creation Ministries International (CMI) on 28 October 2011, updated 21 February 2025.  It argues that mutations can create new information, depending on what 'information' is taken to mean.  The author holds a doctorate in marine biology, and CMI describes him as a senior scientist and speaker for CMI-USA whose current research for them is human genetics, so the article does not call him a geneticist, because inflating the description would be the same credential-stretching that the article audits in others.  The article uses the piece for its concession that mutations can create new information, which carries weight because he writes for the creationist movement, not because of his degree. ↩

Hutchison, Clyde A. III et al.  “Design and synthesis of a minimal bacterial genome.”  Science 351:aad6253.  2016.  Section Abstract:  “Three cycles of design, synthesis, and testing, with retention of quasi-essential genes, produced JCVI-syn3.0 (531 kilobase pairs, 473 genes), which has a genome smaller than that of any autonomously replicating cell found in nature.  JCVI-syn3.0 retains almost all genes involved in the synthesis and processing of macromolecules.  Unexpectedly, it also contains 149 genes with unknown biological functions.”  Section Conclusion:  “Unexpectedly, it also contains 149 genes with unknown biological functions, suggesting the presence of undiscovered functions that are essential for life.”  Section Discussion:  A stricter figure in the discussion is arguably more striking.  “there are 79 genes (17%) that we have been unable to assign to a functional category…  13 of the 19 functionally unassigned e-genes are of completely unknown function.”  The authors' own caveat about the minimal genome.  “This definition is incomplete, because the genetic requirements for survival, and therefore the minimal genome size, depend on the environment in which the cell is grown.  The work described here has been conducted in medium that supplies virtually all the small molecules required for life.”  The 2019 follow-up on the improved strain syn3A counts 91 genes of unclear function, of which 30 are essential, in Breuer, Marian, et al., eLife 8 (2019): e36842.  A 2016 report from the J. Craig Venter Institute team that designed and built JCVI-syn3.0, a bacterial cell run by a 531-kilobase synthetic genome with 473 genes, which grows in laboratory medium that supplies almost every small molecule it needs.  The article uses it as the simplest living cell that has been built, and for the 149 genes of unknown function that its builders report.  The paper says the 149 unknown-function genes are the sum of two confidence classes: 84 generic and 65 unknown. ↩ ↩

Kilinc, Mesih et al.  “Improving the annotations of JCVI-Syn3a proteins.”  Methods in Molecular Biology 2867:153–168.  2025.  Section Abstract:  “While the ancestor has 863 genes, the synthetic progeny has only 473, with 434 of these coding for proteins.  Despite initial efforts to understand all functions of the organism, a significant number of these protein-coding genes still have unknown functions, and subsequent studies have been only partially successful in elucidating their roles.  In this study, we employ our innovative method PROST to identify homologs…  PROST successfully finds functionally annotated homologs for 93% of the minimal genome with a high level of accuracy, both confirming previously identified functions, as well as proposing new functions for others.”  A 2025 book chapter by Mesih Kilinc, Kejue Jia and Robert Jernigan, which uses their PROST method to find annotated homologs for the proteins of JCVI-Syn3a, the minimal cell.  The article cites it for the claim that the unknown-function count has moved since 2016.  A protein-language-model homology hit at as low as 16% identity is a hypothesis about function, not an experiment, and the point stands only against the claim that the 2016 number is frozen.  The chapter reports 15 protein sequences with no homologs of significant structural similarity. ↩

Moger-Reischer, R. Z. et al.  “Evolution of a minimal cell.”  Nature 620:122–127.  2023.  Section Abstract:  Two further details from the abstract, both relevant to the article: mutation rates in the minimal cell.  “were the highest among all reported bacteria, but were not affected by genome minimization”.  A laboratory evolution experiment that compared a synthetic minimal cell, a stripped-down Mycoplasma mycoides with only the genes it needs, with the non-minimal cell it was derived from, over 2,000 generations.  Streamlining cut the minimal cell's fitness by more than half, and evolution regained it, but cell size did not recover, which the abstract ties to epistatic effects of mutations in ftsZ.  The article uses it to show that the minimal cell is not on a knife-edge. ↩

Nakabachi, Atsushi et al.  “The 160-Kilobase Genome of the Bacterial Endosymbiont Carsonella.”  Science 314:267.  2006.  A short report that sequenced the genome of Carsonella ruddii, a bacterium that lives inside a psyllid insect, and found 159,662 base pairs with only 182 open reading frames.  The authors say its gene inventory seems insufficient for most processes essential to bacteria, and that the host cell may make up for it.  The article uses it as an example of the smallest natural genomes, which it says are worse models of a first cell still. ↩

Weiss, Madeline C. et al.  “The physiology and habitat of the last universal common ancestor.”  Nature Microbiology 1:16116.  2016.  “Among 286,514 protein clusters, we identified 355 protein families (∼0.1%) that trace to LUCA by phylogenetic criteria.”  The methodological attack comes from inside the field: Berkemer and McGlynn, in Molecular Biology and Evolution 37 (2020): 2332–2340, report that adding more sequence homologs.  “rejects a simple LUCA hypothesis based on phylogenetic separation of the bacterial and archaeal domains for a majority of the previously identified LUCA proteins (∼82%).”  A 2016 genome study of the last universal common ancestor, or LUCA, the population that all living cells descend from.  The authors compared 6.1 million protein-coding genes from sequenced prokaryotic genomes, and the 355 protein families that trace back to LUCA by their evolutionary trees describe it as an anaerobic, hydrogen-dependent microbe living in a hydrothermal setting.  The article uses it for the count of 355 gene families, one end of a disagreement between reconstructions that differ by an order of magnitude. ↩

Moody, Edmund R. R. et al.  “The nature of the last universal common ancestor and its impact on the early Earth system.”  Nature Ecology & Evolution 8:1654–1666.  2024.  The authors' own caveat is that their composite age estimate for LUCA runs.  “from 3.94 Ga to 4.52 Ga”.  That is a spread of 580 Myr, wider than the window the age is used to constrain.  The paper also reconstructs a Wood–Ljungdahl carbon-fixation pathway, and says:  “support for the presence of 19 class 1 CRISPR–Cas effector protein families in the genome of LUCA…  This is consistent with the idea that cellular life was already involved in an arms race with viruses at the time of LUCA.”  A recent survey, Bell, Elizabeth A., and Gregory P. Fournier, Astrobiology 26 (2026): 633–643, calls the method:  “challenging and highly uncertain”.  A molecular-clock study that dates the last universal common ancestor (LUCA), the common ancestor of all living cells, to about 4.2 Ga (4.09–4.33 Ga), and reconstructs its genome at 2.75 Mb (2.49–2.99 Mb), encoding 2,657 proteins (2,451–2,855).  The article uses it for the early LUCA date, which is reachable only because the team set aside the late heavy bombardment window.  The 4.09–4.33 Ga figure is the range from the preferred relaxed-clock models, not the total uncertainty. ↩

1. 79a.

   Section Methods:  “Some previous studies have placed a younger maximum constraint on the age of LUCA based on the assumption that life could not have survived Late Heavy Bombardment (LHB) (~3.7–3.9 billion years ago (Ga)).  However, the LHB hypothesis is extrapolated and scaled from the Moon's impact record, the interpretation of which has been questioned in terms of the intensity, duration and even the veracity of an LHB episode.  Thus, the LHB hypothesis should not be considered a credible maximum constraint on the age of LUCA.  We used soft-uniform bounds, with the maximum-age bound based on the time of the Moon-forming impact (4,510 million years ago (Ma) ± 10 Myr), which would have effectively sterilized Earth's precursors…”  Their reference for the questioned interpretation is Boehnke and Harrison 2016. ↩

Crapitto, Andrew J. et al.  “A consensus view of the proteome of the last universal common ancestor.”  Ecology and Evolution 12:e8930.  2022.  “while some studies performed well on the inter-rater tests… none of them showed a high or even moderate level of similarity with any other individual study.”  A 2022 study that compares eight published reconstructions of the last universal common ancestor (LUCA), the population from which all living cells descend, and builds a consensus from them.  The raw prediction counts run from 80 to 571, and the consensus contains 366 protein families, which the paper calls eggNOG clusters.  The article cites it for the finding that the reconstructions disagree with one another.  Mirror:  PMC ↩

Gogarten, Johann Peter.  “The progenote, LUCA, and the root of the cellular tree of life.”  Handbook of Astrobiology.  CRC Press.  Edited by Vera M. Kolb.  2019.  Woese and Fox's 1977 definition of a progenote is a stage.  “before a strict coupling between geno- and phenotype had emerged.”  Figure 8.1.1:  The caption has panel B contrasted with panel A, whose sketch is.  “the view popularized through the work of Carl Woese and Otto Kandler”.  in which the three domains evolve independently from the progenote.  Chapter 8.1 of the Handbook of Astrobiology, edited by Vera M. Kolb, on the progenote, a stage in the evolution of cells that came before a strict coupling between genotype and phenotype, and on where the root of the tree of life lies.  The article cites it because the author does not argue that LUCA, the last universal common ancestor, was a progenote; he argues the reverse. ↩

Goldman, Aaron D., and Arturo Becerra.  “A new view of the last universal common ancestor.”  Journal of Molecular Evolution 92:659–661.  2024.  “This depiction of a physiologically and ecologically complex LUCA provides strong evidence that this stage of evolutionary history was far removed from the origin of life.”  Page 659:  “the 4.2 Ga dating, if correct, suggests that early evolution, from the origin of life to the LUCA, may have occurred within only 100–200 million years.”  “despite this general consensus, the specific predictions of individual studies often diverge, rendering them somewhat unreliable (Crapitto et al. 2022).”  A two-page commentary by two evolutionary biologists on a 2024 study by Moody et al., which used tree reconciliation on 9,365 protein families to estimate what the last universal common ancestor, or LUCA, had, and dated LUCA to about 4.2 billion years ago (4.09–4.32 Ga).  The article quotes one sentence from it, for the authors' reading that the LUCA described by that study was far removed from the origin of life.  The commentary supplies the strongest version of the window argument, and it is not a creationist one.  On the reconstructions themselves, the authors say the specific predictions of individual studies often diverge. ↩

Allwood, Abigail C. et al.  “Reassessing evidence of life in 3,700-million-year-old rocks of Greenland.”  Nature 563:241–244.  2018.  “Here we report new research that shows a non-biological, post-depositional origin for the structures…  the 'stromatolites' are more plausibly interpreted as part of an assemblage of deformation structures formed in carbonate-altered metasediments long after burial.”  A 2018 Nature paper that re-examines the 2016 claim of microbial structures 3.7 billion years old at Isua in Greenland, and argues that the structures have a non-biological origin, formed in altered rock long after burial.  The article cites it as the rebuttal of the Isua stromatolites.  The paper rebuts Nutman, Allen P., et al., "Rapid emergence of life shown by discovery of 3,700-million-year-old microbial structures," Nature 537 (2016): 535–538.  Its second author, Minik Rosing, published the 1999 Isua carbon-isotope evidence for life, and its first author, Abigail Allwood, established the 3.43-billion-year Strelley Pool stromatolite reef in 2006, so neither is a sceptic of early life.  Zawaski, Michael J., et al. reinforce the rebuttal in "Reappraisal of purported ca. 3.7 Ga stromatolites from the Isua Supracrustal Belt," Earth and Planetary Science Letters 545 (2020): 116409.  Nutman's group has not conceded; see Precambrian Research 331 (2019): 105347, and Earth-Science Reviews 262 (2025): 105034.  The quotation is from the abstract. ↩

Westall, Frances.  “What the earliest evidence for life tells us about the early evolution of the biosphere.”  Philosophical Transactions of the Royal Society B 380:20240106.  2025.  “the abundance of biosignatures as of the Palaeoarchaean, and as early as 3.48 Ga, suggests a diverse community including chemotrophs and phototrophs.”  On Isua:  “the combined evidence of possible morphology, carbon and iron isotopes, and elemental composition… of remnant carbonaceous matter is suggestive of the presence of life, although not definitive because of the various possible alternative abiotic sources for each potential biosignature.”  On Nuvvuagittuq:  “Possibly dating from the Hadean (4.3 Ga), but most likely of Eoarchaean age (3.7 Ga)… which has a 2.5 Gyr hydrothermal overprint.”  The review also notes a hazard:  “Westall & Folk [79] noted the presence of recent and recently fossilised phototrophic endoliths in these sediments that could confuse measurements.”  The papers behind the 3.48 Ga floor are Djokic, Tara, et al., Nature Communications 8 (2017): 15263 (Dresser Formation hot springs), and Baumgartner, Raphael J., et al., Geology 47 (2019): 1039–1043 (sulfidized organic matter in drill core below the weathering profile, δ¹³C_OM = −29.6‰ ± 0.3‰), with the accepted 3.43 Ga reef in Allwood, Abigail C., et al., Nature 441 (2006): 714–718.  A 2025 review by Frances Westall of the Centre de Biophysique Moléculaire in Orléans, on the geological and fossil evidence for early life and on the ways that non-living chemistry can imitate it.  The article uses it for the robust floor of evidence, about 3.48 billion years old, and for its cautions about each older claim. ↩

Bottke, William F., and Marc D. Norman.  “The Late Heavy Bombardment.”  Annual Review of Earth and Planetary Sciences 45:619–647.  2017.  “the excellent agreement obtained by multiple techniques provides confidence that the ages are meaningful.”  A 2017 review article that summarises the evidence for the Late Heavy Bombardment, a spike of impacts on the early Earth and Moon.  The review argues that rock and meteorite shock ages point toward a discrete episode of impacts between about 3.5 and 4.0–4.2 billion years ago.  The article cites it for the defence of that discrete episode.  The authors argue that the age clustering appears in Rb-Sr, Sm-Nd and U-Pb as well as in ⁴⁰Ar/³⁹Ar: ↩

Spiegel, David S., and Edwin L. Turner.  “Bayesian analysis of the astrobiological implications of life's early emergence on Earth.”  Proceedings of the National Academy of Sciences 109:395–400.  2012.  Their direct hit on Lineweaver and Davis, in the body:  “their conclusion that q cannot be too small and thus that life should not be too rare in the Universe is not a consequence of the evidence of the early emergence of life on the Earth but almost only of their particular parameterization of the problem.”  The selection effect, from the body:  “if evolution requires 3.5 Gyr for life to evolve from the simplest forms to intelligent, questioning beings, then we had to find ourselves on a planet where life arose relatively early, regardless of the value of λ.”  Note what this does and does not show: it establishes that the timing data are uninformative, not that abiogenesis is improbable.  Section Abstract:  “We find that, given only this very limited empirical information, the choice of Bayesian prior for the abiogenesis probability parameter has a dominant influence on the computed posterior probability.  Although terrestrial life's early emergence provides evidence that life might be common in the Universe if early-Earth-like conditions are, the evidence is inconclusive and indeed is consistent with an arbitrarily low intrinsic probability of abiogenesis for plausible uninformative priors.  Finding a single case of life arising independently of our lineage… would provide much stronger evidence that abiogenesis is not extremely rare in the Universe.”  A statistical study that uses Bayesian reasoning, which weighs what the data say against a starting assumption, to ask what the early emergence of life on Earth implies about how common abiogenesis is in the Universe.  The authors find that the timing data are consistent with an arbitrarily low chance of abiogenesis for plausible uninformative priors, so the early emergence does not show that life is common.  The article uses it in its discussion of how much time chemistry had on the early Earth, where the early emergence of life is at issue.  Mirror:  arXiv ↩

Martins, Zita et al.  “Extraterrestrial nucleobases in the Murchison meteorite.”  Earth and Planetary Science Letters 270:130–136.  2008.  A laboratory study of the Murchison meteorite, which measured the carbon isotope ratios of its purine and pyrimidine bases, the letters of RNA and DNA.  The ratios for uracil (+44.5 per mil) and xanthine (+37.7 per mil) show a non-Earth carbon signature, so the authors say these compounds were already in the meteorite.  The article uses it as the isotope evidence that some meteorite nucleobases did not come from Earth, and a caution that belongs with any use of meteoritic nucleobase data: cytosine degrades with a half-life of about 17,000 years and guanine converts to xanthine with a half-life of 1.3 Myr at 0 °C and pH 7, so what is measured in a meteorite reflects degradation as much as synthesis.  Mirror:  arXiv ↩

Kawaguchi, Yuko et al.  “DNA Damage and Survival Time Course of Deinococcal Cell Pellets During 3 Years of Exposure to Outer Space.”  Frontiers in Microbiology 11:2050.  2020.  A laboratory experiment that attached dried pellets of the radiation-resistant bacterium Deinococcus to the outside of the International Space Station for 1 to 3 years.  Pellets were still alive after 3 years in space and had repaired their DNA damage when cultured, and the authors estimate that 1 mm pellets could endure 2–8 years.  The extrapolation to 1 mm pellets is the authors' own, and the article uses the paper for one point: transport between planets is real. ↩ ↩

Crick, Francis H. C., and Leslie E. Orgel.  “Directed Panspermia.”  Icarus 19:341–346.  1973.  The passage the article engages, verbatim:  “It has also been argued that 'infective' theories of the origins of terrestrial life should be rejected because they do no more than transfer the problem of origins to another planet.  This view is mistaken;  the historical facts are important in their own right.  For all we know there may be other types of planet on which the origin of life ab initio is greatly more probable than on our own.  For example, such a planet may possess a mineral, or compound, of crucial catalytic importance, which is rare on Earth.”  Writing in the conclusion, they say:  “At the moment it seems that the experimental evidence is too feeble to make this discrimination.  It is difficult to avoid a personal prejudice, one way or the other, but such prejudices find no scientific support of any weight.”  A 1973 paper by Francis Crick and Leslie Orgel proposing that life on Earth may have been deliberately sent here by intelligent beings on another planet.  Two things cut against how this paper is normally used.  They proposed it because they thought the natural versions of panspermia, the idea that life travels between worlds, had failed, on Sagan's radiation and dynamical arguments.  They were candid about their own evidence, the molybdenum anomaly and the universality of the genetic code, and both pieces have since collapsed.  The widely repeated claim that Crick later recanted directed panspermia could not be verified and is not made here: he published a book defending it eight years later, and the Scientific American piece usually cited attributes the abandonment to Orgel, without a quotation.  The article cites it only for the difficulty it names, a rare catalytic mineral that has gone unnamed since 1973, and never for its conclusion. ↩

Behroozi, Peter S., and Molly Peeples.  “On the History and Future of Cosmic Planet Formation.”  Monthly Notices of the Royal Astronomical Society 454:1811–1817.  2015.  Section Abstract:  “In the Hubble Volume (10¹³ Mpc³), we expect there to be ∼10²⁰ Earth-like and ∼10²⁰ giant planets;  our own galaxy is expected to host ∼10⁹ and ∼10¹⁰ Earth-like and giant planets, respectively.”  “The Solar System formed at the median age for existing giant planets in the Milky Way, and consistent with past estimates, formed after 80% of Earth-like planets.”  A 2015 modelling paper that combines galaxy formation histories with planet formation models to estimate how many Earth-like and giant planets have formed, and when.  These are model estimates, not counts.  The article cites it for the scale of the planet lottery that panspermia would open.  The article's arithmetic on these numbers: restricting the origin of life to Earth gives one planet and a window of a few hundred million years; opening it to the observable universe gives about 10^20 Earth-like planets and roughly nine billion years before the Solar System formed, which is about twenty orders of magnitude in sites and about one in time.  Mirror:  arXiv ↩ ↩

Sandberg, Anders et al.  “Dissolving the Fermi Paradox.”  arXiv.  2018.  Section §3.1.1:  “Since our arguments are only strengthened by high uncertainties, we shall conservatively take LU[f_l] to be 200…  We represent the current scientific uncertainty over the rate of abiogenesis per lifetime of a habitable planet with a log-normal, whose standard deviation is 50 orders of magnitude.”  "LU" is their log-uncertainty, the number of orders of magnitude the honest uncertainty spans; they set it at 200 for the chance that life arises on a habitable planet and call that conservative.  Section §3.1:  “one could easily argue for much larger LU.”  Their methodological point is the general one:  “We show that this conflict arises from the use of Drake-like equations, which implicitly assume certainty regarding highly uncertain parameters.”  Their Fermi conclusion, which this article does not rely on, is.  “a substantial probability that we are alone in our galaxy, and perhaps even in our observable universe (53%–99.6% and 39%–85% respectively).”  A 2018 preprint from the Future of Humanity Institute at Oxford University, which argues that the Fermi paradox (the puzzle that a galaxy this large should already show signs of other civilisations) comes from using Drake-style equations with single best-guess values.  Treated honestly, the uncertainty about the origin of life spans many orders of magnitude, and the authors find a substantial chance that we are alone.  The article uses it for the size of that uncertainty, so the odds of abiogenesis are not known to any useful precision. ↩ ↩

Drummond, Henry.  The Ascent of Man (The Lowell Lectures).  James Pott & Co., New York.  3rd edition.  1894.  Pages 333–334:  “There are reverent minds who ceaselessly scan the fields of Nature and the books of Science in search of gaps—gaps which they will fill up with God.  As if God lived in gaps?  What view of Nature or of Truth is theirs whose interest in Science is not in what it can explain but in what it cannot, whose quest is ignorance not knowledge, whose daily dread is that the cloud may lift, and who, as darkness melts from this field or from that, begin to tremble for the place of His abode?  What needs altering in such finely jealous souls is at once their view of Nature and of God.  Nature is God's writing, and can only tell the truth;  God is light, and in Him is no darkness at all.”  A book of lectures by Henry Drummond, The Lowell Lectures.  Drummond coined the phrase, and he was an evangelist, a friend of D. L. Moody, and a professor at the Free Church College in Glasgow.  The article quotes it on the theological side of the argument from gaps in scientific knowledge. ↩

1. 92a.

   Page 334:  The next page, and the harder of the two objections, the theological one rather than the epistemic one.  “The reason why men grudge to Evolution each of its fresh claims to show how things have been made is the groundless fear that if we discover how they are made we minimize their divinity.  When things are known, that is to say, we conceive them as natural, on Man's level;  when they are unknown, we call them divine—as if our ignorance of a thing were the stamp of its divinity.  If God is only to be left to the gaps in our knowledge, where shall we be when these gaps are filled up?  And if they are never to be filled up, is God only to be found in the disorders of the world?  Those who yield to the temptation to reserve a point here and there for special divine interposition are apt to forget that this virtually excludes God from the rest of the process.  If God appears periodically, he disappears periodically.  If he comes upon the scene at special crises he is absent from the scene in the intervals.” ↩

Tyson, Neil deGrasse.  “The Perimeter of Ignorance.”  Natural History.  Nov 2005.  “Science is a philosophy of discovery.  Intelligent design is a philosophy of ignorance.  You cannot build a program of discovery on the assumption that nobody is smart enough to figure out the answer to a problem.”  The charge, stated in full:  “Another practice that isn't science is embracing ignorance.  Yet it's fundamental to the philosophy of intelligent design:  I don't know what this is.  I don't know how it works.  It's too complicated for me to figure out.  It's too complicated for any human being to figure out.  So it must be the product of a higher intelligence.”  Laplace's version of the Newton case:  “Rather than view the mysterious stability of the solar system as the unknowable work of God, Laplace declared it a scientific challenge.”  A November 2005 essay in Natural History magazine by Neil deGrasse Tyson, written against intelligent design.  Its worked example is Newton, who could not show that the Solar System was stable under mutual planetary perturbations and attributed its stability to God, and Laplace, who solved the problem a century later.  The article uses it for the modern secular version of its argument that ignorance is not a scientific explanation.  Mirror:  Naturalhistorymag.com ↩

1. 93a.

   “There may be a limit to what the human mind can figure out about our universe.  But how presumptuous it would be for me to claim that if I can't solve a problem, neither can any other person who has ever lived or who will ever be born.” ↩

Larmer, Robert.  “Is there anything wrong with 'God of the gaps' reasoning?”  International Journal for Philosophy of Religion 52:129–142.  2002.  His core distinction, in his words:  “It is clearly fallacious to argue that a statement must be false solely on the basis that it has not been proven true, or that a statement must be true solely on the basis that it has not been proven false.  Typically, however, people do not argue in such a manner.  Usually, we find them utilizing a premise, whether it be implicit or explicit, that if a proposition P were true (or not true) then we should reasonably expect to find evidence for it being true (or not true).  When we do not find such evidence we can take this as a kind of evidence that P is false (or true).”  The application:  “What is really at issue is not the logical structure of 'God of the gaps' arguments, but rather the legitimacy of the premise that enough can be known about the operation of natural causes to make it reasonable to conclude that at least some gaps in purely naturalistic explanations are evidence of supernatural intervention.”  That is a much harder standard than ignorance, and this article holds itself to it.  Larmer also quotes Del Ratzsch, Nature, Design and Science (SUNY Press, 2001), p. 48, for the point that impossibility claims are ordinary in science:  “there is nothing inherently unscientific in the idea of gaps in nature—of things that nature cannot do.  Science, in fact, is littered with impossibility claims.”  An article by Robert Larmer of the University of New Brunswick, asking whether arguing from gaps in naturalistic explanation is always fallacious.  It concludes that gap reasoning is not automatically fallacious, and that the real question is whether enough is known about natural causes to make a gap meaningful, which is a harder standard than ignorance.  The article uses it as the best philosophical answer to the charge of 'God of the gaps' reasoning, because gap arguments are not automatically fallacious.  Mirror:  Theistic.net ↩

1. 94a.

   The sentence that converts the philosophical stalemate into an empirical question.  “Equally, however, it must be acknowledged that this claim is strengthened if, as science progresses, the prospects of providing completely naturalistic explanations become increasingly remote.  Put a little differently, this line of argument must grant the possibility that the progress of science has strengthened, rather than weakened, 'God of the gaps' arguments.”  The corollary runs the other way too, and this article reports it that way: within origin-of-life chemistry, the gaps that have closed since 2008 are all monomer-synthesis gaps, and the gaps in polymerisation, information and replication have not closed. ↩

Schoenmakers, Ludo et al.  “Evolution at the Origins of Life?”  Life 14:175.  2024.  Their fuller point, in their words:  “is increasing;  however, the picture fed by a variety of theories of evolution and hypotheses on the formation of metabolic pathways and networks itself remains very diffuse.”  A review of whether evolutionary theory can be extended to the origin of life.  Its fuller point is that the building-block picture is growing, but the picture of how theories of evolution and metabolic networks fit together remains very diffuse.  They are arguing about the correct use of evolutionary vocabulary before a replicator exists, not about whether the problem can be solved.  The article uses the conclusion as a description of where the research programme stands, not a claim that the story is untellable. ↩

Meyer, Stephen C.  Signature in the Cell: DNA and the Evidence for Intelligent Design.  HarperOne.  2009.  Section Appendix A, "Some Predictions of Intelligent Design", pages 481–496.  The design movement's most detailed statement on the question, and it is specifically about the origin of life.  The article audits its Appendix A and finds one genuine unfalsified prediction, that ribozymes will prove insufficient to build a self-replicating system.  That prediction is shared with Orgel, Shapiro and Benner, so it discriminates between nothing; the remaining items either restate the conclusion (the 500-bit prediction), are structured so that no result can count against them (functional reasons or evidence of degenerative evolution), or are predicted in both directions by rival design sub-hypotheses, which Meyer concedes in print. ↩

1. 96a.

   The vera causa material, the rule that a proposed cause must be known from present experience to produce the effect in question, is at these pages.  Pages 154, 160, 171.  Page 330:  The design inference is described as.  “the only known cause”.  of specified information. ↩

2. 96b.

   Page 377:  The god-of-the-gaps objection is answered here.  Page 385:  The DNA-as-analogy form is disowned here.  Both matter for fairness here.  This article's audit table rates "DNA is a code so it needs a mind" as overstated, and Meyer agrees that the analogy alone will not carry the argument; the case rests on the elimination structure instead.  The definition of information is also closer to Hazen's than a reader of the secondary literature would expect; the substantive difference is that Hazen supplies a way to measure the quantity and Meyer does not. ↩

3. 96c.

   Zero occurrences of Powner, Sutherland, Benner, Deamer, Ferris, Wächtershäuser, "hydrothermal" or "iron-sulfur," and no citation of Keefe and Szostak 2001 or Hazen et al. 2007.  Powner, Gerland and Sutherland was published on 14 May 2009, and Signature in the Cell appeared in June.  The point is not that Meyer should have cited a five-week-old paper; it is that a book presented as the definitive treatment of this subject has not been revised in the seventeen years since, and the field it describes has moved. ↩

4. 96d.

   Pages 132–135:  The replication and translation interdependence is argued here.  Pages 318–323:  The ribozyme-engineering objection is made here.  Page 537:  In an endnote, Meyer makes a criticism of Lincoln and Joyce's cross-catalytic system: the system joins pre-made halves supplied by the experimenter, the same objection that this article reaches.  Recording where a critic is right is the point of an audit, and Meyer reached that objection in 2009.  Meyer does not use Hubert Yockey's probability figures, so two rows of the audit table are not aimed at him. ↩

Simons Foundation.  Simons Collaboration on the Origins of Life.  n.d.  Retrieved Aug 25, 2026.  The full list of twenty-two: Donna Blackmond, Tanja Bosak, Dieter Braun, David Catling, Irene Chen, Jason Dworkin, John Eiler, Woody Fischer, Greg Fournier, Wilhelm Huck, Joel Hurowitz, Gerald Joyce, Ram Krishnamurthy, Sheref Mansy, Karin Öberg, Matthew Powner, Didier Queloz, Sarah Stewart, Roger Summons, Alexis Templeton and George Whitesides, under directors Sasselov and Szostak (2013-2018) and Grotzinger and Sutherland (2018-2023).  A programme page of the Simons Foundation for a collaboration that ran from 2013 to 2023, with twenty-two named investigators, directed by Sasselov and Szostak and then by Grotzinger and Sutherland.  The page gives no dollar figure, and none is printed here.  The article uses it to check the claim of excellent funding, and it names the investigators it cites from the list. ↩