Openai/686aedb2-60b0-8003-98a8-e1766cf496a6: Difference between revisions

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{{DISPLAYTITLE:RNA World Criticism Analysis}}
{{DISPLAYTITLE:RNA World Criticism Analysis}}


''This conversation was exported from ChatGPT''<ref>{{cite web|title=RNA World Criticism Analysis|url=https://chatgpt.com/share/686aedb2-60b0-8003-98a8-e1766cf496a6|publisher=ChatGPT|access-date=2025-11-13}}</ref>
''This conversation was exported from ChatGPT''<ref>{{cite web|title=RNA World Criticism Analysis|url=https://chatgpt.com/share/686aedb2-60b0-8003-98a8-e1766cf496a6|publisher=ChatGPT|access-date=2025-11-15}}</ref>


== gpt-4o ==
== gpt-4o ==
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===== Support for his stance =====
===== Support for his stance =====
* Better pre-biotic syntheses. Sutherland’s team has now extended one-pot routes to both purine and pyrimidine ribonucleotides and to lipid–RNA co-synthesis, mitigating the “too complex” objection. pmc.ncbi.nlm.nih.gov<ref>{{cite web|title=pmc.ncbi.nlm.nih.gov|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10351881/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-11-13}}</ref>
* Better pre-biotic syntheses. Sutherland’s team has now extended one-pot routes to both purine and pyrimidine ribonucleotides and to lipid–RNA co-synthesis, mitigating the “too complex” objection. pmc.ncbi.nlm.nih.gov<ref>{{cite web|title=pmc.ncbi.nlm.nih.gov|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10351881/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-11-15}}</ref>
* Non-enzymatic replication strides. 2024 modelling and bench work from the Szostak and Georgia Tech groups show template copying of 4-base mixed sequences assisted by activated oligonucleotides and “NERPE” primer-extension platforms, directly attacking the fidelity problem Bernhardt flagged. biorxiv.org<ref>{{cite web|title=biorxiv.org|url=https://www.biorxiv.org/content/10.1101/2024.07.17.603910v1.full.pdf|publisher=biorxiv.org|access-date=2025-11-13}}</ref>ssdl.gatech.edu<ref>{{cite web|title=ssdl.gatech.edu|url=https://ssdl.gatech.edu/2024/01/31/nerpe-non-enzymatic-rna-primer-extension/|publisher=ssdl.gatech.edu|date=2024-01-31|access-date=2025-11-13}}</ref>
* Non-enzymatic replication strides. 2024 modelling and bench work from the Szostak and Georgia Tech groups show template copying of 4-base mixed sequences assisted by activated oligonucleotides and “NERPE” primer-extension platforms, directly attacking the fidelity problem Bernhardt flagged. biorxiv.org<ref>{{cite web|title=biorxiv.org|url=https://www.biorxiv.org/content/10.1101/2024.07.17.603910v1.full.pdf|publisher=biorxiv.org|access-date=2025-11-15}}</ref>ssdl.gatech.edu<ref>{{cite web|title=ssdl.gatech.edu|url=https://ssdl.gatech.edu/2024/01/31/nerpe-non-enzymatic-rna-primer-extension/|publisher=ssdl.gatech.edu|date=2024-01-31|access-date=2025-11-15}}</ref>
* Nucleotide-bias overcome. A 2025 NAR paper reports near-uniform copying yields for A- and U-rich templates by tweaking leaving groups – progress Bernhardt predicted was possible. academic.oup.com<ref>{{cite web|title=academic.oup.com|url=https://academic.oup.com/nar/article/52/22/13515/7893325|publisher=academic.oup.com|access-date=2025-11-13}}</ref>
* Nucleotide-bias overcome. A 2025 NAR paper reports near-uniform copying yields for A- and U-rich templates by tweaking leaving groups – progress Bernhardt predicted was possible. academic.oup.com<ref>{{cite web|title=academic.oup.com|url=https://academic.oup.com/nar/article/52/22/13515/7893325|publisher=academic.oup.com|access-date=2025-11-15}}</ref>


Challenges / new wrinkles
Challenges / new wrinkles
* RNA-peptide world. Experiments generating peptide-decorated RNA chimeras under plausible pre-biotic conditions suggest a hybrid stage, partly vindicating “co-evolution” advocates and softening Bernhardt’s dismissal of peptides-first. nature.com<ref>{{cite web|title=nature.com|url=https://www.nature.com/articles/s41586-022-04676-3|publisher=nature.com|access-date=2025-11-13}}</ref>
* RNA-peptide world. Experiments generating peptide-decorated RNA chimeras under plausible pre-biotic conditions suggest a hybrid stage, partly vindicating “co-evolution” advocates and softening Bernhardt’s dismissal of peptides-first. nature.com<ref>{{cite web|title=nature.com|url=https://www.nature.com/articles/s41586-022-04676-3|publisher=nature.com|access-date=2025-11-15}}</ref>
* Proteins-first phylogenetics continues. Caetano-Anollés’ camp keeps publishing protein-centric trees; they have not disproved RNA-first, but the debate has broadened rather than closed.
* Proteins-first phylogenetics continues. Caetano-Anollés’ camp keeps publishing protein-centric trees; they have not disproved RNA-first, but the debate has broadened rather than closed.


Overall, none of the post-2012 data decisively overturn Bernhardt’s critiques; most reinforce his view that RNA-world weaknesses are being eroded experimentally.
Overall, none of the post-2012 data decisively overturn Bernhardt’s critiques; most reinforce his view that RNA-world weaknesses are being eroded experimentally.


===== Yes. He has published on tRNA evolution (2016) and origin-of-life chemistry (2021 Maillard reaction), both consistent with an RNA-centric outlook, and in a 2019 interview reiterated that RNA world remains “the best hypothesis we’ve got right now.” mdpi.com<ref>{{cite web|title=mdpi.com|url=https://www.mdpi.com/2075-1729/6/1/10|publisher=mdpi.com|access-date=2025-11-13}}</ref>scholar.google.com<ref>{{cite web|title=scholar.google.com|url=https://scholar.google.com/citations?hl=en&user=HgBBirMAAAAJ|publisher=scholar.google.com|access-date=2025-11-13}}</ref>curioussciencewriters.org<ref>{{cite web|title=curioussciencewriters.org|url=https://curioussciencewriters.org/articles/2019/08/10/the-origin-of-life-did-ancient-rna-act-alone/|publisher=curioussciencewriters.org|date=2019-08-10|access-date=2025-11-13}}</ref> =====
===== Yes. He has published on tRNA evolution (2016) and origin-of-life chemistry (2021 Maillard reaction), both consistent with an RNA-centric outlook, and in a 2019 interview reiterated that RNA world remains “the best hypothesis we’ve got right now.” mdpi.com<ref>{{cite web|title=mdpi.com|url=https://www.mdpi.com/2075-1729/6/1/10|publisher=mdpi.com|access-date=2025-11-15}}</ref>scholar.google.com<ref>{{cite web|title=scholar.google.com|url=https://scholar.google.com/citations?hl=en&user=HgBBirMAAAAJ|publisher=scholar.google.com|access-date=2025-11-15}}</ref>curioussciencewriters.org<ref>{{cite web|title=curioussciencewriters.org|url=https://curioussciencewriters.org/articles/2019/08/10/the-origin-of-life-did-ancient-rna-act-alone/|publisher=curioussciencewriters.org|date=2019-08-10|access-date=2025-11-15}}</ref> =====


===== Bernhardt himself leaves the door open, expecting refinements (e.g., an acidic-ice setting or an RNA-peptide transitional stage) rather than a wholesale abandonment. The field today largely agrees: the centre of gravity is still “RNA first, possibly with helper peptides or XNAs,” not a radically different paradigm. Recent comprehensive syntheses still treat RNA world as the baseline to beat. pmc.ncbi.nlm.nih.gov<ref>{{cite web|title=pmc.ncbi.nlm.nih.gov|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10351881/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-11-13}}</ref> =====
===== Bernhardt himself leaves the door open, expecting refinements (e.g., an acidic-ice setting or an RNA-peptide transitional stage) rather than a wholesale abandonment. The field today largely agrees: the centre of gravity is still “RNA first, possibly with helper peptides or XNAs,” not a radically different paradigm. Recent comprehensive syntheses still treat RNA world as the baseline to beat. pmc.ncbi.nlm.nih.gov<ref>{{cite web|title=pmc.ncbi.nlm.nih.gov|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10351881/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-11-15}}</ref> =====


===== - It is one of the most-cited critical yet pro-RNA reviews; even detractors quote its “worst theory … except all the others” line. crev.info<ref>{{cite web|title=crev.info|url=https://crev.info/2024/11/rna-world-suffers-a-backhand-blow/|publisher=crev.info|access-date=2025-11-13}}</ref> =====
===== - It is one of the most-cited critical yet pro-RNA reviews; even detractors quote its “worst theory … except all the others” line. crev.info<ref>{{cite web|title=crev.info|url=https://crev.info/2024/11/rna-world-suffers-a-backhand-blow/|publisher=crev.info|access-date=2025-11-15}}</ref> =====
* Its balanced tone—acknowledging flaws while skewering rivals—makes it a common starting point for graduate seminars.
* Its balanced tone—acknowledging flaws while skewering rivals—makes it a common starting point for graduate seminars.
* Subsequent advances have tended to fill the specific gaps he catalogued, so the paper has aged well as a roadmap of outstanding problems rather than a dated polemic.
* Subsequent advances have tended to fill the specific gaps he catalogued, so the paper has aged well as a roadmap of outstanding problems rather than a dated polemic.
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===== - Peer-reviewed rebuttals specifically targeting their differential-equation analysis have not (yet) appeared in the literature up to mid-2025. Their follow-up papers in Molecular Biology & Evolution (2018) and IJMS (2020) extend, rather than retract, the framework and have met mostly with interest, not demolition. =====
===== - Peer-reviewed rebuttals specifically targeting their differential-equation analysis have not (yet) appeared in the literature up to mid-2025. Their follow-up papers in Molecular Biology & Evolution (2018) and IJMS (2020) extend, rather than retract, the framework and have met mostly with interest, not demolition. =====
* Skeptical commentary does exist. Journalistic pieces (e.g., Quanta Magazine) note that the PRCW evidence is “purely computational” and stress that the RNA world still enjoys far more experimental support; several origin-of-life researchers quoted there regard any claim of formal falsification as premature quantamagazine.org<ref>{{cite web|title=quantamagazine.org|url=https://www.quantamagazine.org/the-end-of-the-rna-world-is-near-biochemists-argue-20171219/|publisher=quantamagazine.org|access-date=2025-11-13}}</ref>.
* Skeptical commentary does exist. Journalistic pieces (e.g., Quanta Magazine) note that the PRCW evidence is “purely computational” and stress that the RNA world still enjoys far more experimental support; several origin-of-life researchers quoted there regard any claim of formal falsification as premature quantamagazine.org<ref>{{cite web|title=quantamagazine.org|url=https://www.quantamagazine.org/the-end-of-the-rna-world-is-near-biochemists-argue-20171219/|publisher=quantamagazine.org|access-date=2025-11-15}}</ref>.
* Mainstream origin-of-life reviews since 2018 (e.g., “The difficult case of an RNA-only origin of life”, 2019) cite Wills & Carter as part of a growing peptide-RNA camp but treat their verdict as one hypothesis among several, not a settled matter. None mounts a point-by-point mathematical refutation.
* Mainstream origin-of-life reviews since 2018 (e.g., “The difficult case of an RNA-only origin of life”, 2019) cite Wills & Carter as part of a growing peptide-RNA camp but treat their verdict as one hypothesis among several, not a settled matter. None mounts a point-by-point mathematical refutation.


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===== - Chemistry of the building blocks – ''closer''.  Powner’s network chemistry and follow-on work have reduced the “clutter” objection. Subsequent studies now give one-pot purine + pyrimidine ribonucleotides at useful scale pubs.acs.org<ref>{{cite web|title=pubs.acs.org|url=https://pubs.acs.org/doi/10.1021/jacs.1c07403|publisher=pubs.acs.org|access-date=2025-11-13}}</ref> and have shown that selective crystallisation or evaporation can enrich biologically relevant stereochemistry. =====
===== - Chemistry of the building blocks – ''closer''.  Powner’s network chemistry and follow-on work have reduced the “clutter” objection. Subsequent studies now give one-pot purine + pyrimidine ribonucleotides at useful scale pubs.acs.org<ref>{{cite web|title=pubs.acs.org|url=https://pubs.acs.org/doi/10.1021/jacs.1c07403|publisher=pubs.acs.org|access-date=2025-11-15}}</ref> and have shown that selective crystallisation or evaporation can enrich biologically relevant stereochemistry. =====
'' Information & coding – ''further away* (at least for a pure RNA scenario).  Wills & Carter’s modelling claims a fatal instability for an RNA-only coding world; no published rebuttal has dismantled their maths. Until someone demonstrates a ribozyme that replicates itself and its error-rate stays below the Eigen threshold, that critique stands.
'' Information & coding – ''further away* (at least for a pure RNA scenario).  Wills & Carter’s modelling claims a fatal instability for an RNA-only coding world; no published rebuttal has dismantled their maths. Until someone demonstrates a ribozyme that replicates itself and its error-rate stays below the Eigen threshold, that critique stands.
* Bridging chemistry to genetics – still unbridged.  No paper in this trio delivers a self-sustaining polymer system that copies sequence information with adequate fidelity, nor any encoder-code-decoder triad.
* Bridging chemistry to genetics – still unbridged.  No paper in this trio delivers a self-sustaining polymer system that copies sequence information with adequate fidelity, nor any encoder-code-decoder triad.
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==== 🔍 1. David L. Abel (2024): "Why Is Abiogenesis Such a Tough Nut to Crack?" ====
==== 🔍 1. David L. Abel (2024): "Why Is Abiogenesis Such a Tough Nut to Crack?" ====
'' '''Core criticism''': All mainstream hypotheses lack natural mechanisms to ''steer* reactions toward functional metabolic pathways.
'' '''Core criticism''': All mainstream hypotheses lack natural mechanisms to ''steer* reactions toward functional metabolic pathways.
* '''Key point''': There’s no scientific explanation for how chemical systems develop control or directionality; they rely on “could have been,” “may have been,” or “suggests,” but no causal mechanism is demonstrated arxiv.org<ref>{{cite web|title=arxiv.org|url=https://cdn.fortunejournals.com/articles/why-is-abiogenesis-such-a-tough-nut-to-crack.pdf|publisher=cdn.fortunejournals.com|access-date=2025-11-13}}</ref>.
* '''Key point''': There’s no scientific explanation for how chemical systems develop control or directionality; they rely on “could have been,” “may have been,” or “suggests,” but no causal mechanism is demonstrated arxiv.org<ref>{{cite web|title=arxiv.org|url=https://cdn.fortunejournals.com/articles/why-is-abiogenesis-such-a-tough-nut-to-crack.pdf|publisher=cdn.fortunejournals.com|access-date=2025-11-15}}</ref>.
* '''Conclusion''': Without cybernetic or computational structures, models offer only statistical plausibility—not mechanistic plausibility.
* '''Conclusion''': Without cybernetic or computational structures, models offer only statistical plausibility—not mechanistic plausibility.


==== 2. “Assembly Theory” critiques (2024) ====
==== 2. “Assembly Theory” critiques (2024) ====
* '''Critique''': Simplistic reductionist models can’t explain how assembly complexity arises.
* '''Critique''': Simplistic reductionist models can’t explain how assembly complexity arises.
'' '''Key point''': Proposals based solely on chemical kinetics or energetics ignore the requirement for ''system-level information control*, which remains unaddressed fortunejournals.com<ref>{{cite web|title=fortunejournals.com|url=https://www.fortunejournals.com/articles/why-is-abiogenesis-such-a-tough-nut-to-crack.html|publisher=fortunejournals.com|access-date=2025-11-13}}</ref>.
'' '''Key point''': Proposals based solely on chemical kinetics or energetics ignore the requirement for ''system-level information control*, which remains unaddressed fortunejournals.com<ref>{{cite web|title=fortunejournals.com|url=https://www.fortunejournals.com/articles/why-is-abiogenesis-such-a-tough-nut-to-crack.html|publisher=fortunejournals.com|access-date=2025-11-15}}</ref>.


==== 3. Integrated Review: "What It Takes to Solve the Origin(s) of Life" (2023) ====
==== 3. Integrated Review: "What It Takes to Solve the Origin(s) of Life" (2023) ====
* '''Coverage''': Multi-disciplinary assessment of chemistry, physics, math, and computation in OoL research.
* '''Coverage''': Multi-disciplinary assessment of chemistry, physics, math, and computation in OoL research.
* '''Critique''': Highlights a '''lack of shared standards''' and '''no unified framework''' for testing major hypotheses.
* '''Critique''': Highlights a '''lack of shared standards''' and '''no unified framework''' for testing major hypotheses.
'' '''Bottom line''': Even with diverse inputs, there is ''no experimental validation* of the core informational/control structures required for life en.wikipedia.org<ref>{{cite web|title=en.wikipedia.org|url=https://arxiv.org/abs/2308.11665|publisher=arxiv.org|access-date=2025-11-13}}</ref>researchgate.net<ref>{{cite web|title=researchgate.net|url=https://www.researchgate.net/publication/373333153_What_it_takes_to_solve_the_Origins_of_Life_An_integrated_review_of_techniques|publisher=researchgate.net|access-date=2025-11-13}}</ref>en.wikipedia.org<ref>{{cite web|title=en.wikipedia.org|url=https://creation.com/origin-of-life-questions|publisher=creation.com|access-date=2025-11-13}}</ref>.
'' '''Bottom line''': Even with diverse inputs, there is ''no experimental validation* of the core informational/control structures required for life en.wikipedia.org<ref>{{cite web|title=en.wikipedia.org|url=https://arxiv.org/abs/2308.11665|publisher=arxiv.org|access-date=2025-11-15}}</ref>researchgate.net<ref>{{cite web|title=researchgate.net|url=https://www.researchgate.net/publication/373333153_What_it_takes_to_solve_the_Origins_of_Life_An_integrated_review_of_techniques|publisher=researchgate.net|access-date=2025-11-15}}</ref>en.wikipedia.org<ref>{{cite web|title=en.wikipedia.org|url=https://creation.com/origin-of-life-questions|publisher=creation.com|access-date=2025-11-15}}</ref>.


==== 4. Autocatalytic and compartmentalization analyses ====
==== 4. Autocatalytic and compartmentalization analyses ====
* Discusses the '''iron–sulfur world''' and '''clay/vesicle''' models, acknowledging that although they promote reaction concentration, they still fail to: - Provide '''encoded information processing'''. - Show '''heritable functionality''' beyond mere catalysis or compartment formation en.wikipedia.org<ref>{{cite web|title=en.wikipedia.org|url=https://en.wikipedia.org/wiki/Iron%E2%80%93sulfur_world_hypothesis|publisher=en.wikipedia.org|access-date=2025-11-13}}</ref>creationresearch.org<ref>{{cite web|title=creationresearch.org|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8099592/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-11-13}}</ref>.
* Discusses the '''iron–sulfur world''' and '''clay/vesicle''' models, acknowledging that although they promote reaction concentration, they still fail to: - Provide '''encoded information processing'''. - Show '''heritable functionality''' beyond mere catalysis or compartment formation en.wikipedia.org<ref>{{cite web|title=en.wikipedia.org|url=https://en.wikipedia.org/wiki/Iron%E2%80%93sulfur_world_hypothesis|publisher=en.wikipedia.org|access-date=2025-11-15}}</ref>creationresearch.org<ref>{{cite web|title=creationresearch.org|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8099592/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-11-15}}</ref>.


===== 🧭 Summary Table =====
===== 🧭 Summary Table =====