Open research questions in Origins and Evolution of Life
51 unresolved questions extracted from the limitations and future-work sections of 279 Origins and Evolution of Life papers in our library. Each links back to the study that raised it.
What the literature leaves open
Understanding the emergence of proto-antibiotic and proto-resistance molecules in the prebiotic world is a significant challenge. The evolution of antibiotics and resistance is a complex process that requires further study. The development of new antibiotics is a pressing challenge in the face of rising antibiotic resistance.
The phosphate problem presents a challenge for prebiotic chemistry. The poor solubility and reactivity of phosphate-bearing minerals under early Earth conditions is a challenge. The need for alternative phosphorus sources to drive phosphorylation is a challenge.
The challenge of deriving various concepts such as the identity of infinity and infinitesimal, the boundary law, and the Ψ–Ξ anchoring ontological information mechanism. The challenge of putting forward three quantitatively distinguishable testable predictions and clear falsifiability conditions. The challenge of addressing the gap in our understanding of the universe and the nature of reality.
PFUSRC-INT-001 From Two Intersecting Lines to the Living Cosmos: A Geometrically Intuitive Ontological Reconstruction of the 11-Dimensional Triple Coaxial Biconical Topological Unified System (PFUSRC) · 2026 · DOIFurther development of the ordered-bundle ontology is needed. The application of the ordered-bundle account to specific biological systems is a direction for future research. The exploration of the implications of the support-reconstruction distinction for the classification of entities as living or non-living is a direction for future research.
The Living Entity as an Ordered Bundle: Composition, Persistence, and Biological Organisation · 2026 · DOIThe existing approaches to explaining the continuity of living entities are insufficient. The gap in the existing approaches is the failure to account for the organisation of living entities.
The Living Entity as an Ordered Bundle: Composition, Persistence, and Biological Organisation · 2026 · DOIExtreme-temperature planets lack liquid-phase media. Mainstream modern theories treat life as products of random complex chemical reactions.
The Ultimate Essential Nature of Chemical Reactions and the Origin of Life‑A Unified‑Field Mechanism Based on Dynamic Game of Primordial Positive‑Dark‑Energy and Primordial Negative‑Dark‑Energy · 2026 · DOIThe transition from chemistry to life remains a mystery - The origin of life from nonlife is not understood
In particular, the formose calculation below is explicitly an illustrative model calculation whose parameters remain to be measured.
Despite the fact that many data remain controversial and continue to be debated, over the past decades, there has been a remarkable advancement in our understanding of the processes that may have occurred on early Earth. The explosive influx of new geological, geophysical, and geochemical data allowed proposing terrestrial, atmospheric, and aquatic conditions, which favored the emergence of life. Investigating the history of our planet and the origin of life is the most fascinating scientific field. This research field allows us to understand who we are and how humans evolved from simple life forms. Redox reactions played significant roles in geological and biological evolution of Earth. The abiotically occurring redox reactions contributed to the formation of the Earth’s atmosphere and oceans, driving geochemical cycles of redox-active elements and the synthesis of organic molecules, leading to the origin and evolution of life. The dominant theories of the origin of life are based on redox reactions, which could have occurred in the Hadean atmosphere, deep-ocean, and shallow waters emphasizing the crucial roles of minerals and energy sources. allowing these reactions to proceed. The first life forms probably emerged as early as between 4.1 and 3.8 Ga, at the boundary between the Hadean and Archean eons. However, it was during the Hadean eon known as the early Earth, that atmospheric and aquatic conditions were favorable for the first organic synthesis. Based on recent advances in the field, some hallmarks of the origin of life on early Earth can be distinguished. The Hadean atmosphere was likely slightly oxidizing with dominance of CO2, H2O, and SO2; however, CH4, NH3, and HCN could have been delivered to Earth by meteorite impacts, and transient reducing atmosphere could have existed during the Hadean eon. Moreover, meteorite could have delivered transition metals such as iron and organic compounds from extraterrestrial sources. Atmospheric composition and reactions and oceanic processes influenced each other, and the Hadean environments could have created conditions that favored redox reactions. Geothermal gradient created in hydrothermal systems provided energy, fueling organic synthesis underlying both Oparin-Haldane heterotrophic theory and mineral by chemoautotrophic Wächtershäuser. surface-based proposed theory The first organic molecules necessary for the synthesis of the building blocks of life could have been formed in various environmental settings including the atmosphere, deep-ocean hydrothermal vents, and terrestrial shallow waters such as lakes, ponds, and hot springs. These environments utilized different energy sources such as UV radiation, volcanic activity, lightning, and geothermal heat. Depending on the availability of elements and energy sources, each environmental setting may favor the formation of specific organic molecules. However, these compounds could have been transported between different environmental settings for further processing. Therefore, life could have emerged in multiple interplayed environments, which allowed for diverse organic molecules to converge, eventually leading to self-replication and life. There are two contrasting principles: “metabolism-first” and “gene first”, each with its own controversy. The “metabolism-first” principle’s controversy is that an early network of metabolic chemical reactions could not be sustainable without programmed replication-based genetic instructions. The “gene-first” principle’s controversy is that, for the formation of genetic molecules such as RNA, thermodynamically stable and selfreplicating systems could not have emerged under severe conditions on early Earth. However, these two principles are not completely exclusive and can be reconciled because metabolic processes are necessary for the synthesis of nucleotides, which are the building blocks of RNA and DNA. It is probable that both metabolic pathways and the genetic system are evolved in an interdependent manner. Heterotrophs and autotrophs could have originated through synchronizing evolutionary paths, and therefore both heterotrophic and chemoautotrophic theories of the origin of life may complement each other. According to chemoautotrophic theory of the origin of life, carbon fixation from CO2 using mineral surfaces in early Earth’s hydrothermal environments relies on reactions of reduction by H2 produced with the involvement of Fe2+ or H2S. This includes exergonic and thermodynamically favorable reductive metabolic processes such as the WLP and rTCA, which could prebiotically produce precursors for building blocks of proteins and nucleic acids. These metabolic cycles are considered as self-sustaining chemical systems, and organic molecules produced in these processes could be consumed by first heterotrophic organisms.
Open questions and promising research directions Several open problems can now be read as designable experiments. One is continuity across steps, which boundary conditions allow activated substrate generation, oligomer assembly, and copying to co-occur without mutually exclusive requirements, and with net accumulation across repeated cycles (Pressman et al., 2015; Ding et al., 2023; Muñoz-Velasco et al., 2024; Vázquez-Salazar, 2026). A second is system-level selection, how compartment type, exchange rates, and spatial structure shift parasite control and effective error thresholds, even when copying fidelity remains modest (Higgs and Lehman, 2015; Vaidya et al., 2012; Papastavrou et al., 2024). A third is catalytic breadth.
The paper's axial transport framework and pure time formalism are applied to explain biological boundary formation and proto-cellular emergence, but no empirical datasets from origin-of-life chemistry experiments, clay surface chemistry, or lipid assembly kinetics are cited to validate whether the predicted cost minimization and gradient-driven boundary closure actually occur in measurable timeframes and concentration regimes.
Pure Time Theory - Application I - From Pure Time to Lived Time - Fundamental chemistry, the living and heritability under axial transport · 2026 · DOISection 7 begins to address the heritable support question but remains incomplete. The transition from active reconstruction at the individual level to transmission of validated organizational patterns across generations requires specification of which organizational features are heritable, by what molecular mechanism inheritance occurs in pre-genetic systems, and how fidelity of transmission scales with organization complexity.
Pure Time Theory - Application I - From Pure Time to Lived Time - Fundamental chemistry, the living and heritability under axial transport · 2026 · DOIThe object-based universe is no longer supported by modern science. Physics still describes patterns and behaviors as if they were objects, due to a linguistic and ontological lag.
THE GTii MANIFESTO: A NEW PARADIGM Redefinition for Physics, Ontology, and Generative Reality · 2026 · DOIThe proposal that the same Internal Exclusionary Entity (IEE) dynamics explain biological cancer, psychological dissociation, and ideological rigidity simultaneously is a formal analogy, not a derived result. The extension of Ξ* to Level 2 (symbolic-cognitive organisation) remains operationally underdetermined.
Proto-Selective Dynamics and the Emergence of Operational Closure: A Unified Dynamic Model of Mind Framework for the Origin of Biological Organization · 2026 · DOIThe gap between the FEP and autopoiesis theory. The lack of a thermodynamic framework for the dynamical genesis of operational closure.
Proto-Selective Dynamics and the Emergence of Operational Closure: A Unified Dynamic Model of Mind Framework for the Origin of Biological Organization · 2026 · DOIConceptual vagueness in the study of emergence. The need for a clear framework for describing and analyzing complex dynamical systems. The challenge of formalizing emergence without postulating additional metaphysical entities.
Towards a Structural Theory of Emergent Coherence: A Minimal Framework for Complex Dynamical Systems · 2026 · DOIExploratory implementations such as the Prompt Coherence Engine (PCE) suggest possible applications for studying and stabilizing long-horizon coherent dynamics in generative artificial systems.
Towards a Structural Theory of Emergent Coherence: A Minimal Framework for Complex Dynamical Systems · 2026 · DOIThe fundamental driving force behind material variations remains undiscovered. The theoretical gap of primordial-power-source research within modern science.
The Ultimate Essential Nature of Chemical Reactions and the Origin of Life‑A Unified‑Field Mechanism Based on Dynamic Game of Primordial Positive‑Dark‑Energy and Primordial Negative‑Dark‑Energy · 2026 · DOIThe paper identifies a gap in the current understanding of the emergence of physical structures. The theory proposes that certain observable physical structures may emerge from global constraints imposed on a compact phase dynamics.
The paper identifies a gap in our understanding of the nature of symmetry and asymmetry. The author argues that the current perspective on symmetry is flawed.
Superasymmetry (SASY): The Foundation — Asymmetry as Foundation, Change as the Only Constant, and the Observer at Zero Who Cannot Close the Read From Within · 2026 · DOIIndependent replication to elevate the framework to an unqualified law. Application of the framework across domains and across roughly twenty orders of magnitude.
Superasymmetry (SASY): A Single-Constant Coupling Framework, Its Dimensional Ladder, and a Candidate Law of Substrate Coupling · 2026 · DOIAlthough the "RNA World" hypothesis suggests that RNA played a crucial role in the origin of life [7], the functional framework of RNA in prebiotic protein synthesis and the mechanisms of genetic code formation during the prebiotic period remain poorly understood.
The Origin and Evolution of Protein Synthesis: A Co-Adaptation Flexible-Rigid Docking Model Based on First-Principles Reasoning · 2026 · DOIThe primary geochemical form of phosphorus is poorly soluble and unreactive under early Earth conditions, presenting the phosphate problem. Alternative phosphorus sources, such as reduced phosphorus compounds, are needed to drive phosphorylation.
Existing scientific definitions of structure do not provide a deeper generative layer that explains how structures arise, independent of their domain-specific interpretation. There is a need for a framework that can describe physics, mathematics, biology, social systems, culture, language, and intellect within one coherent generative ontology.
The paper identifies a gap in our understanding of the universe and the nature of reality. The paper addresses the gap by constructing the complete ontological backbone of the PFUSRC theoretical framework.
PFUSRC-INT-001 From Two Intersecting Lines to the Living Cosmos: A Geometrically Intuitive Ontological Reconstruction of the 11-Dimensional Triple Coaxial Biconical Topological Unified System (PFUSRC) · 2026 · DOI
Most-cited papers in Origins and Evolution of Life
- How Droplets Can Accelerate Reactions─Coacervate Protocells as Catalytic Microcompartments · Accounts of Chemical Research · 2024 · 127 citations
- A multi-perspective analysis of retractions in life sciences · Scientometrics · 2021 · 40 citations
- Quantum Mechanics predicts evolutionary biology · Progress in Biophysics and Molecular Biology · 2018 · 35 citations
- The role of purifying selection in the origin and maintenance of complex function · Studies in History and Philosophy of Science Part A · 2021 · 24 citations
- Biology transcends the limits of computation · Progress in Biophysics and Molecular Biology · 2021 · 23 citations
- Structure, scale and emergence · Studies in History and Philosophy of Science Part A · 2020 · 11 citations
- Metabolism Instead of Machine: Towards an Ontology of Hybrids · Philosophy & Technology · 2022 · 11 citations
- BION’S GRAPH OF “IN SEARCH OF EXISTENCE” · The American Journal of Psychoanalysis · 2021 · 10 citations
- The Force of the Pacemaker Concept in Theories of Aggregation in Cellular Slime Mold · Perspectives in biology and medicine · 1983 · 10 citations
- Prebiotic dimer and trimer peptide formation in gas-phase atmospheric nanoclusters of water · Physical Chemistry Chemical Physics · 2023 · 7 citations
Most recent work
- Superasymmetry (SASY): The Foundation — Asymmetry as Foundation, Change as the Only Constant, and the Observer at Zero Who Cannot Close the Read From Within · Zenodo (CERN European Organization for Nuclear Research) · 2026
- Superasymmetry (SASY): A Single-Constant Coupling Framework, Its Dimensional Ladder, and a Candidate Law of Substrate Coupling · Zenodo (CERN European Organization for Nuclear Research) · 2026
- H₂O · Seed of Life · Creation: McCaul's Law of Coherence Applied to the Origin of Life and the Role of Water as the SOL Center Node · Zenodo (CERN European Organization for Nuclear Research) · 2026
- A Modular 3D-Printed Design to Investigate Prebiotic Chemical Systems in Hot Spring Pools · Astrobiology · 2026
- Molecular Dissipative Structuring; The Fundamental Creative Force in Biology · 2026
- The Totality of Bonding Relationships - A Universal Principle from Quantum Vacuum to Cosmos · This paper is part of the SymbioMind Bonding Relationships Series (2026) · 2026
- On the Methodological Foundations of Biosemiotics · Biosemiotics · 2026
- Contact Before Separation: Membrane Ontology and the Conditions of Determinability · Zenodo (CERN European Organization for Nuclear Research) · 2026
- Redox chemistry of early Earth and the origin of life · Communications Chemistry · 2026
- Emergent Synthesis of Life’s Molecular Toolkit from Bare Atoms via Free-Market Agent-Based Modeling · ChemRxiv · 2026
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