📋 General Index

I. Foundations and Context

  • 1. Introduction
    • Journal of Molecular Biology context
    • Naturalistic paradigm vs. IDT
    • Central result: P(function) = (1.2 ± 0.6) × 10⁻¹⁵⁰
  • 2. Why This Debate Matters
    • Proteins as essential molecules
    • Challenge to neo-Darwinian model
    • Fundamental question of biological complexity

II. Methodology and Experimental Rigor

  • 3. Axe's 15 Experimental Controls
    • 3.1 Genetic and Expression Controls (4 controls)
    • 3.2 Structural and Physicochemical Controls (4 controls)
    • 3.3 Functional and Biochemical Controls (3 controls)
    • 3.4 Environmental and Viability Controls (4 controls)
  • 4. ÎČ-Lactamase Dependency Map
    • 4.1 Active site (His106–Ser130–Lys234)
    • 4.2 TIM barrel structure
    • 4.3 Thermodynamic stability (ΔG)
    • 4.4 Catalytic efficiency
    • 4.5 Causal dependency map
    • 4.6 Interdependency analysis

III. Probabilistic Analysis

  • 5. Probabilistic Update
    • 5.1 Probability of function
    • 5.2 Available resources in the universe
    • 5.3 Chance vs. capacity comparison
    • 5.4 Sequence space and number of functional sequences
    • 5.5 Calculation of minimal systems with multiple proteins
    • 5.6 Conclusion of probabilistic analysis

IV. Systematic Refutation of Criticisms

  • 6. Methodological Criticisms
    • 6.1 "Inadequate methodology"
    • 6.2 "Incorrect temperature"
    • 6.3 "Inadequate protein model"
  • 7. Evolutionary Criticisms
    • 7.1 "Evolution from existing proteins"
    • 7.2 "Outdated view of rigid proteins"
    • 7.3 "Cherry-picking problematic protein"
    • 7.4 "Generalization error"
  • 8. Credibility Criticisms
    • 8.1 "Discredited by broad review"
    • 8.2 "Axe ignored neutrality of mutations"
    • 8.3 "Experiment assumes evolution in a single step"
    • 8.4 "ÎČ-lactamase is overly complex protein"
  • 9. Interpretation Criticisms
    • 9.1 "Calculations ignore natural selection"
    • 9.2 "Results are laboratory artifacts"
    • 9.3 "Axe linearly extrapolated sequence space"

V. Meta-Scientific Analysis

  • 10. Confirmation Bias in Citations
    • Statistical data on critical citations
    • Analysis of absence of alternative methodologies
    • Interpretation for lay readers
  • 11. Unintentional Self-Criticisms
    • Lynch (2020): Population limits
    • Doolittle (2013): Unexplained origin of coagulation
    • Tokuriki (2009): Confirmation of evolutionary constraints

VI. Conclusion and Challenges

  • 12. Conclusion: What the Data Really Show
    • Methodological solidity after 20 years
    • Absence of empirical basis in criticisms
    • Continued validity of P < 10⁻¹⁵⁰
  • 13. Invitation to Critical Community
    • Proposal of alternative controls
    • Replication challenge with 10⁷⁷ variants
    • Mathematical models within universal limits

📊 Additional Resources

  • Detailed experimental controls
  • Physical resources of the universe
  • Methodology comparisons
  • Critical citation rates
  • Self-refuting priority sources (Îș > 0.9)
  • Layman analogies index