Large Language Model-Guided Scientific Discovery

The Gilbert-Pollak Conjecture \citep{gilbert1968steiner}, also known as the Steiner Ratio Conjecture, states that for any finite point set in the Euclidean plane, the Steiner minimum tree has length at least $\sqrt{3}/2 \approx 0.866$ times that of the Euclidean minimum spanning tree (the Steiner ratio). A sequence of improvements through the 1980s culminated in a lower bound of $0.824$, with no substantial progress reported over the past three decades. Recent advances in LLMs have demonstrated strong performance on contest-level mathematical problems, yet their potential for addressing open, research-level questions remains largely unexplored. In this work, we present a novel AI system for obtaining tighter lower bounds on the Steiner ratio. Rather than directly prompting LLMs to solve the conjecture, we task them with generating rule-constrained geometric lemmas implemented as executable code. These lemmas are then used to construct a collection of specialized functions, which we call verification functions, that yield theoretically certified lower bounds of the Steiner ratio. Through progressive lemma refinement driven by reflection, the system establishes a new certified lower bound of 0.8559 for the Steiner ratio. The entire research effort involves only thousands of LLM calls, demonstrating the strong potential of LLM-based systems for advanced mathematical research.

AI-Scientist systems risk manufacturing spurious discoveries through uncontrolled multiple testing. We present a functional architecture that enforces statistical rigor at two levels: a Haskell embedded domain-specific language (the Research monad) that makes it impossible to test a hypothesis without updating the error budget, and a declarative scaffold, backed by an OS-level sandbox, that makes validation data physically absent from the environment in which LLM-generated code runs. We ground the design in a machine-checked Lean4 formalization of LORD++ online false-discovery-rate (FDR) control: we derive its error budget and prove both marginal and full FDR control, then close the gap to the implementation by verifying the budget's wealth invariant over IEEE754 arithmetic in SPARK/Ada. To our knowledge this is the first verified chain from theorem to floating-point implementation for an online FDR procedure. In simulation, the architecture holds the false discovery rate near 1% against a 5% target, where a naive approach reaches 41%. In end-to-end case studies, a valid test avoids the false discoveries a flawed one produces, yet still finds real effects when the data allow. An adversarial evaluation confirms that generated code cannot read the held-out data even when given its exact path.

The process of scientific discovery relies on an interplay of observations, analysis, and hypothesis generation. Machine learning is increasingly being adopted to address individual aspects of this process. However, it remains an open challenge to fully automate the heuristic, iterative loop required to discover the laws of an unknown system by exploring it through experiments and analysis, without tailoring the approach to the specifics of a given task. Here, we introduce SciExplorer, an agent that leverages large language model tool-use capabilities to enable exploration of systems without any domain-specific blueprints, and apply it to physical systems that are initially unknown to the agent. We test SciExplorer on a broad set of models spanning mechanical dynamical systems, wave evolution, and quantum many-body physics. Despite using a minimal set of tools, primarily based on code execution, we observe impressive performance on tasks such as recovering equations of motion from observed dynamics and inferring Hamiltonians from expectation values. The demonstrated effectiveness of this setup opens the door toward similar scientific exploration in other domains, without the need for fine-tuning or task-specific instructions.

Large language models (LLMs) are beginning to reshape how organic-synthesis workflows are represented, queried, planned, and connected to experimental automation. Assessing their contribution is not straightforward because reaction-specific transformers, chemistry-adapted LLMs, tool-using agents, optimizers, and autonomous laboratories are often discussed under the same broad terminology despite operating at different levels of the synthesis workflow. This Review traces the progression from reaction prediction and retrosynthetic planning to reaction development, literature-to-protocol translation, and robotic execution, with representative numerical claims verified against primary sources available through 4 September 2026. We examine where language models provide genuine added value, where established specialist methods remain the principal source of performance, and how retrieval, uncertainty-aware optimization, deterministic chemistry tools, robotics, sensing, and human oversight alter system behavior. The evidence shows a clear transition from isolated language-model demonstrations toward modular scientific systems that combine broad language priors with specialized computation and experimentally grounded feedback. Emerging work on multimodal reaction understanding, standardized tool interoperability, provenance-aware execution, and programmable laboratory infrastructure extends this transition further. Despite this progress, reliable deployment continues to depend on generalization beyond historical reaction corpora, calibrated uncertainty, transparent component attribution, safety controls, reproducible system state, and prospective experimental validation.

Innovation is a key driving force of human civilization. As the body of knowledge has grown considerably, bridging knowledge across different disciplines, where significant innovation often emerges, has become increasingly challenging. The recent advancements in machine learning models, particularly Large Language Models (LLMs), have provided effective access to extensive knowledge sources and shown impressive abilities in reasoning, rendering significant opportunities for interdisciplinary discovery. Our research aims to understand the capabilities of state-of-the-art LLMs in integrating knowledge from different fields for interdisciplinary research (IDR). To address this fundamental problem, we introduce IDRBench, a pioneering framework that includes both datasets and evaluation tasks: (1) IDR Paper Identification, (2) IDR Idea Integration, and (3) IDR Idea Recommendation. Our study on ten mainstream LLMs provides a comprehensive analysis of their behavior and establishes benchmarks and baselines for future research. To the best of our knowledge, IDRBench is the first to provide a comprehensive investigation of LLMs' IDR capability.

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.

Recent advancements in large language models (LLMs) have demonstrated their potential in automating the scientific research ideation. Existing approaches primarily focus on prompting techniques, often producing ideas misaligned with expert standards - novelty, feasibility, and effectiveness, which are widely recognized by the research community as the three key subdimensions of high-quality ideas. Also, balancing these dimensions remains challenging due to their inherent trade-offs. To address these limitations, we propose the first framework that employs a two-stage approach combining Supervised Fine-Tuning (SFT) and controllable Reinforcement Learning (RL) for the task. In the SFT stage, the model learns foundational patterns from pairs of research papers and their corresponding follow-up ideas. In the RL stage, multi-dimensional reward models guided by fine-grained feedback evaluate and optimize the model across key dimensions. During inference, dimensional controllers coordinated by a sentence-level decoder enable dynamic context-aware steering of the idea generation process. Our framework provides a balanced approach to research idea generation, achieving high-quality outcomes in the experiment by dynamically navigating the trade-offs among novelty, feasibility, and effectiveness.

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.