Feedback Descent: Open-Ended Text Optimization via Pairwise Comparison

We introduce \textit{Feedback Descent}, a framework that optimizes text artifacts -- prompts, code, and molecules -- through structured textual feedback, rather than relying solely on scalar rewards. By preserving detailed critiques instead of compressing them to binary preferences, Feedback Descent widens the information bottleneck in preference learning, enabling directed optimization in text space rather than weight space. We show that in-context learning can transform structured feedback into gradient-like directional information, enabling targeted edits. Unlike prior approaches that collapse judgments into single bits, our evaluators pair each comparison with textual feedback, which functions as high-bandwidth supervision. The iteration loop is done purely at inference time, without modifying any model weights, and is task-agnostic. We evaluate Feedback Descent on three diverse domains and find that it outperforms state-of-the-art prompt optimization (GEPA), reinforcement learning methods (GRPO, REINVENT), and even specialized graph-based molecular optimizers. In the DOCKSTRING molecule discovery benchmark, Feedback Descent identifies novel drug-like molecules surpassing the $99.9$th percentile of a database with more than $260{,}000$ compounds across six protein targets.

Disentangling Reasoning and Knowledge in Medical Large Language Models

Medical reasoning in large language models (LLMs) aims to emulate clinicians' diagnostic thinking, but current benchmarks such as MedQA-USMLE, MedMCQA, and PubMedQA often mix reasoning with factual recall. We address this by separating 11 biomedical QA benchmarks into reasoning- and knowledge-focused subsets using a PubMedBERT classifier that reaches 81 percent accuracy, comparable to human performance. Our analysis shows that only 32.8 percent of questions require complex reasoning. We evaluate biomedical models (HuatuoGPT-o1, MedReason, m1) and general-domain models (DeepSeek-R1, o4-mini, Qwen3), finding consistent gaps between knowledge and reasoning performance. For example, m1 scores 60.5 on knowledge but only 47.1 on reasoning. In adversarial tests where models are misled with incorrect initial reasoning, biomedical models degrade sharply, while larger or RL-trained general models show more robustness. To address this, we train BioMed-R1 using fine-tuning and reinforcement learning on reasoning-heavy examples. It achieves the strongest performance among similarly sized models. Further gains may come from incorporating clinical case reports and training with adversarial and backtracking scenarios.

TextGrad: Automatic "Differentiation" via Text

AI is undergoing a paradigm shift, with breakthroughs achieved by systems orchestrating multiple large language models (LLMs) and other complex components. As a result, developing principled and automated optimization methods for compound AI systems is one of the most important new challenges. Neural networks faced a similar challenge in its early days until backpropagation and automatic differentiation transformed the field by making optimization turn-key. Inspired by this, we introduce TextGrad, a powerful framework performing automatic ``differentiation'' via text. TextGrad backpropagates textual feedback provided by LLMs to improve individual components of a compound AI system. In our framework, LLMs provide rich, general, natural language suggestions to optimize variables in computation graphs, ranging from code snippets to molecular structures. TextGrad follows PyTorch's syntax and abstraction and is flexible and easy-to-use. It works out-of-the-box for a variety of tasks, where the users only provide the objective function without tuning components or prompts of the framework. We showcase TextGrad's effectiveness and generality across a diverse range of applications, from question answering and molecule optimization to radiotherapy treatment planning. Without modifying the framework, TextGrad improves the zero-shot accuracy of GPT-4o in Google-Proof Question Answering from $51\%$ to $55\%$, yields $20\%$ relative performance gain in optimizing LeetCode-Hard coding problem solutions, improves prompts for reasoning, designs new druglike small molecules with desirable in silico binding, and designs radiation oncology treatment plans with high specificity. TextGrad lays a foundation to accelerate the development of the next-generation of AI systems.