Patient-Zero: Scaling Synthetic Patient Agents to Real-World Distributions without Real Patient Data

Synthetic data generation with Large Language Models (LLMs) has emerged as a promising solution in the medical domain to mitigate data scarcity and privacy constraints. However, existing approaches remain constrained by their derivative nature, relying on real-world records, which pose privacy risks and distribution biases. Furthermore, current patient agents face the Stability-Plasticity Dilemma, struggling to maintain clinical consistency during dynamic inquiries. To address these challenges, we introduce Patient-Zero, a novel framework for ab initio patient simulation that requires no real medical records. Our Medically-Aligned Hierarchical Synthesis framework generates comprehensive and diverse patient records from abstract clinical guidelines via stratified attribute permutation. To support rigorous clinical interaction, we design a Dual-Track Cognitive Memory System to enable agents dynamically update memory while preserving logical consistency and persona adherence. Extensive evaluations show that Patient-Zero establishes a new state-of-the-art in both data quality and interaction fidelity. In human expert evaluations, senior licensed physicians judge our synthetic data to be statistically indistinguishable from real human-authored data and higher in clinical quality. Furthermore, downstream medical reasoning model trained on our synthetic dataset shows substantial performance gains (MedQA +24.0%; MMLU +14.5%), demonstrating the practical utility of our framework.