Scientific Hypothesis Generation

Large Language Models (LLMs) have demonstrated potential in automating scientific ideation, yet current approaches relying on iterative prompting or complex multi-agent architectures often suffer from hallucination or computational inefficiency. A critical bottleneck in applying Reinforcement Learning (RL) to this open-ended domain is reward hacking -- where models exploit imperfect evaluation proxies to maximize scores without producing genuine scientific innovation. To address these limitations, we propose an RL framework explicitly tailored for high-quality scientific idea generation. We propose the first multi-agent reward function designed to serve as a judge, decoupling methodological validation from implementation details while providing strict binary rewards that are robust to reward hacking. To effectively optimize against this sparse signal, we utilize an unbiased variant of Group Relative Policy Optimization to mitigate artificial length bias. We grounded our training in ICLR-320, a curated dataset of problem-solution pairs extracted from ICLR 2024 proceedings. Experiments demonstrate that our framework significantly outperforms state-of-the-art baselines across expert-evaluated metrics of novelty, feasibility, and effectiveness.

Identifying promising research directions in fast-moving subareas is one of the most cognitively expensive tasks in modern AI research. Existing LLM-driven scientific discovery systems are typically limited to one-shot prompting on static literature snapshots and are validated only against contemporary judges such as human reviewers, agent peer review, wet-lab assays, or self-evaluation, leaving open whether they can anticipate future trends. We present Continuous Knowledge Metabolism (CKM), an AI workflow for hypothesis generation with three key capabilities: (i) continuous literature metabolism via sliding windows that maintain an evolving knowledge state; (ii) predictive evaluation, which grades hypotheses against papers published after the generation window; and (iii) practitioner-grade failure detection that diagnoses workflow failure modes from its outputs. On a 50-topic machine learning benchmark, CKM-Lite produces at least one validated hypothesis on 72% of topics (36 out of 50), more than doubling a one-shot baseline (30%) at approximately 3 dollars per topic and achieving 91% lower token cost. Validated hypotheses precede their matched papers by an average of 404 days (55 hits across 36 topics; median 399 days, range 66-757 days). Broadly, predictive validation against future literature provides a falsifiable, low-cost alternative to contemporary-judge evaluation protocols and can be applied wherever a corpus has dated publication records.

Scientific discovery depends on expert judgement and foresight, which we call scientific taste: the ability to judge and propose research ideas with potential for long-term scientific impact. Whether AI can learn this ability remains an open question. Here we provide evidence that artificial intelligence can learn judgement and ideation. We introduce Reinforcement Learning from Community Feedback (RLCF), a training paradigm that uses large-scale signals from scientific community as supervision. We first train Scientific Judge on field- and time-matched pairs of high- vs. low-citation papers to judge ideas. We then train a Scientific Thinker, to propose research ideas with high potential impact. Experiments show that the 30B Scientific Judge variant outperforms strong LLM baselines (e.g., GPT-5.4 Thinking), while Scientific Judge generalizes across future-year papers, unseen fields, and other community metrics. Furthermore, Scientific Thinker proposes research ideas with higher potential impact than baselines. These results suggest that AI can learn scientific taste, marking an important step towards AI systems that could help accelerate scientific discovery.

The rapid growth of biomedical evidence makes it difficult to translate biomarker mechanisms into actionable drug combination hypotheses. We present CoDHy, an interactive AI co-scientist for biomarker-guided hypothesis generation in oncology. CoDHy constructs task-specific knowledge graphs from curated databases and biomedical literature, then combines graph embeddings with agent-based reasoning to generate, validate, and rank evidence-grounded drug combinations. Through a web interface, researchers specify the biomarker, cancer context, and literature scope; inspect supporting evidence and intermediate results; and iteratively refine the generated hypotheses. The demonstration presents CoDHy's end-to-end workflow and shows how researchers can interactively explore and compare mechanistically supported drug combinations while remaining in control of hypothesis prioritization.

Scientific discovery is driven by scientists generating novel hypotheses for complex problems that undergo rigorous experimental validation. To augment this process, we introduce Co-Scientist, a multi-agent AI system built on Gemini for structured scientific thinking and hypothesis generation. Co-Scientist aims to help scientists discover new original knowledge. Conditioned on their research objectives and prior scientific evidence, it formulates demonstrably novel research hypotheses for experimental verification. The system's design involves agents continuously generating, critiquing and refining hypotheses accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute scaling, improving hypothesis quality over time. While general purpose, we focus the validation in three biomedical applications: drug repurposing, novel target discovery, and explaining mechanisms of anti-microbial resistance. Specifically, Co-Scientist helped identify new drug repurposing candidates and synergistic combination therapies for acute myeloid leukemia, which were validated through in vitro experiments. These real-world validations demonstrate the potential of Co-Scientist to accelerate scientific discovery and usher in an era of AI empowered scientists.

The rapid growth of scientific literature makes it increasingly challenging for researchers to identify novel and impactful ideas, especially across disciplines. Modern artificial intelligence (AI) systems offer new opportunities for scientific ideation, but how compelling are AI-generated ideas, and how can their quality be improved? Here, we introduce SciMuse, which generates personalized research ideas using a knowledge graph of 58 million papers and a large language model (LLM). A central focus of this work is to understand how interesting these ideas are. Therefore, we conducted a large-scale evaluation in which more than 100 research group leaders -- spanning the natural sciences to the humanities -- rated over 4,400 personalized ideas according to their level of interest. Overall, expert ratings were modest (mean 2.40 on a 5-point scale, most common rating 1), while 24.9% of ideas were rated 4 or 5. We find that supplying concept pairs selected using the knowledge graph does not improve expert-rated interest over a titles-only GPT baseline. High-citation-predicted pairs even showed a weak tendency (1.94$σ$) toward lower interest than random pairs. Nevertheless, graph features can be used to control properties of ideas, and, using this unique evaluation dataset, we show that idea interest can be predicted with both a supervised neural network based on graph features and a zero-shot ranking approach based on an LLM. Our work provides an AI methodology for generating scientific ideas and a large-scale interdisciplinary expert evaluation, paving the way to study and improve difficult-to-measure metrics such as expert-perceived scientific interestingness.