The RNA World Hypothesis (RWH) posits that self-replicating RNA molecules were the primary precursors to life, functioning as both genetic material and catalysts in Earth’s prebiotic environment. Supported by NASA’s Astrobiology Program, RWH experiments have simulated early Earth conditions, such as tidal pools (pH 6-6.5, 25-50°C, 0.5 M NaCl) and hydrothermal vents (60-100°C, 10-100 atm), as well as extraterrestrial environments like the icy moons Europa and Enceladus (0°C, 0.1-1 atm, pH 7-8). Despite decades of research, RWH faces significant challenges: RNA’s chemical instability in aqueous settings, high replication error rates leading to “error catastrophe,” unsustainable nucleotide synthesis, vesicle instability, non-prebiotic ribozyme designs, and energy-dependent hybrid systems. These limitations suggest that RNA alone may not suffice as the sole precursor to life, prompting a critical reevaluation of the model.The Matter World Hypothesis (MWH) offers a paradigm shift, envisioning life’s origin as a cooperative “matter soup” comprising RNA, DNA, peptides, lipids, carbohydrates, and catalysts, driven by molecular affinity, environmental gradients (e.g., temperature, pH, salinity), extended timescales (10⁶-10⁷ years), and natural selection. Unlike RWH’s RNA-centric focus, MWH emphasizes multi-molecular synergy, where each component enhances the system’s stability, replication, and catalytic efficiency, forming robust protocells. Supported by computational simulations (e.g., molecular dynamics [MD], dissipative particle dynamics [DPD], agent-based models [ABM]) and experimental data from global research spanning over 15 countries (e.g., Japan, China, Sweden, Australia, India, Brazil), MWH addresses RWH’s shortcomings and aligns with NASA’s shift toward non-RNA-centric models, such as peptide nucleic acids (PNA) and threose nucleic acids (TNA), as well as icy moon exploration (e.g., Europa Clipper mission, launched October 2024).This e-book provides an exhaustive critique of six NASA RWH projects, focusing on replication, stability, nucleotide synthesis, vesicle encapsulation, ribozyme catalysis, and metabolism-first hybrid systems. It integrates MWH perspectives and incorporates new studies to strengthen the analysis.