# MedZERO: Self-Evolving Agents for Open-Ended Medical Reasoning Through Controlled Knowledge Accumulation

arXiv: https://arxiv.org/abs/2610.08327 · HTML: https://mlsanity.com/paper/2610.08327/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 22 of its 42 references that are in the map.
- First posted on arXiv 6 Oct 2026.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)
- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)
- Synthetic data and self-improvement for LLMs / [Medical synthetic data and agents](https://mlsanity.com/synth/medical-synthetic-data-and-agents/)

## Builds on (most cited first, 22 of 22)

- [DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Models](https://mlsanity.com/paper/2402.03300/) (2024)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Search-R1: Training LLMs to Reason and Leverage Search Engines with Reinforcement Learning](https://mlsanity.com/paper/2503.09516/) (2025)
- [Does Reinforcement Learning Really Incentivize Reasoning Capacity in LLMs Beyond the Base Model?](https://mlsanity.com/paper/2504.13837/) (2025)
- [Self-Rewarding Language Models](https://mlsanity.com/paper/2401.10020/) (2024)
- [Absolute Zero: Reinforced Self-play Reasoning with Zero Data](https://mlsanity.com/paper/2505.03335/) (2025)
- [AgentClinic: a multimodal agent benchmark to evaluate AI in simulated clinical environments](https://mlsanity.com/paper/2405.07960/) (2024)
- [R-Zero: Self-Evolving Reasoning LLM from Zero Data](https://mlsanity.com/paper/2508.05004/) (2025)
- [MedXpertQA: Benchmarking Expert-Level Medical Reasoning and Understanding](https://mlsanity.com/paper/2501.18362/) (2025)
- [Agent Hospital: A Simulacrum of Hospital with Evolvable Medical Agents](https://mlsanity.com/paper/2405.02957/) (2024)
- [Online Difficulty Filtering for Reasoning Oriented Reinforcement Learning](https://mlsanity.com/paper/2504.03380/) (2025)
- [SPIRAL: Self-Play on Zero-Sum Games Incentivizes Reasoning via Multi-Agent Multi-Turn Reinforcement Learning](https://mlsanity.com/paper/2506.24119/) (2025)
- [VerlTool: Towards Holistic Agentic Reinforcement Learning with Tool Use](https://mlsanity.com/paper/2509.01055/) (2025)
- [Efficient Reinforcement Finetuning via Adaptive Curriculum Learning](https://mlsanity.com/paper/2504.05520/) (2025)
- [A Survey on Self-Evolution of Large Language Models](https://mlsanity.com/paper/2404.14387/) (2024)
- [Agent0: Unleashing Self-Evolving Agents from Zero Data via Tool-Integrated Reasoning](https://mlsanity.com/paper/2511.16043/) (2025)
- [Search Self-play: Pushing the Frontier of Agent Capability without Supervision](https://mlsanity.com/paper/2510.18821/) (2025)
- [MedBrowseComp: Benchmarking Medical Deep Research and Computer Use](https://mlsanity.com/paper/2505.14963/) (2025)
- [Socratic-Zero : Bootstrapping Reasoning via Data-Free Agent Co-evolution](https://mlsanity.com/paper/2509.24726/) (2025)
- [Position: The Hidden Costs and Measurement Gaps of Reinforcement Learning with Verifiable Rewards](https://mlsanity.com/paper/2509.21882/) (2025)
- [KnowGuard: Knowledge-Driven Abstention for Multi-Round Clinical Reasoning](https://mlsanity.com/paper/2509.24816/) (2025)

## Built on by (most cited first, 1 of 1)

- [ECG-RSI: Recursive Self-Improvement through Targeted Electrocardiogram Waveform Evolution](https://mlsanity.com/paper/2610.17718/) (2026)

## Abstract (arXiv)

Large language models (LLMs) have shown promise in medical question answering and clinical reasoning, yet their improvement remains constrained by static parametric knowledge and costly expert supervision. Self-evolving agents offer a promising alternative by enabling models to improve through iterative task generation and problem-solving. However, most existing self-evolving methods are designed for easily verifiable domains such as mathematics and coding, where solutions can be checked by exact answers or executable programs. Medical reasoning is fundamentally different: it is open-ended, knowledge-intensive, and often only partially verifiable. We present MedZERO, a self-evolving framework for open-ended medical reasoning. MedZERO couples an Examiner that generates frontier medical question-option pairs with a Reasoner that solves them through evidence-grounded multi-turn reasoning with external knowledge tools. To support reliable, continual improvement, MedZERO adopts controlled knowledge accumulation, which maintains temporary exploratory knowledge and curated persistent knowledge in reasoning. We evaluate MedZERO on five public medical reasoning benchmarks using 4B- and 8B-scale base models under open-ended evaluation. Across all settings, MedZERO consistently outperforms the underlying base models and prior self-evolving baselines, achieving up to 13.7 average accuracy-point gains over the next-best self-evolving baseline.