Daily Papers

As advancements in artificial intelligence (AI) propel progress in the life sciences, they may also enable the weaponisation and misuse of biological agents. This article differentiates two classes of AI tools that could pose such biosecurity risks: large language models (LLMs) and biological design tools (BDTs). LLMs, such as GPT-4 and its successors, might provide dual-use information and thus remove some barriers encountered by historical biological weapons efforts. As LLMs are turned into multi-modal lab assistants and autonomous science tools, this will increase their ability to support non-experts in performing laboratory work. Thus, LLMs may in particular lower barriers to biological misuse. In contrast, BDTs will expand the capabilities of sophisticated actors. Concretely, BDTs may enable the creation of pandemic pathogens substantially worse than anything seen to date and could enable forms of more predictable and targeted biological weapons. In combination, the convergence of LLMs and BDTs could raise the ceiling of harm from biological agents and could make them broadly accessible. A range of interventions would help to manage risks. Independent pre-release evaluations could help understand the capabilities of models and the effectiveness of safeguards. Options for differentiated access to such tools should be carefully weighed with the benefits of openly releasing systems. Lastly, essential for mitigating risks will be universal and enhanced screening of gene synthesis products.

Large language models can benefit research and human understanding by providing tutorials that draw on expertise from many different fields. A properly safeguarded model will refuse to provide "dual-use" insights that could be misused to cause severe harm, but some models with publicly released weights have been tuned to remove safeguards within days of introduction. Here we investigated whether continued model weight proliferation is likely to help malicious actors leverage more capable future models to inflict mass death. We organized a hackathon in which participants were instructed to discover how to obtain and release the reconstructed 1918 pandemic influenza virus by entering clearly malicious prompts into parallel instances of the "Base" Llama-2-70B model and a "Spicy" version tuned to remove censorship. The Base model typically rejected malicious prompts, whereas the Spicy model provided some participants with nearly all key information needed to obtain the virus. Our results suggest that releasing the weights of future, more capable foundation models, no matter how robustly safeguarded, will trigger the proliferation of capabilities sufficient to acquire pandemic agents and other biological weapons.

The White House Executive Order on Artificial Intelligence highlights the risks of large language models (LLMs) empowering malicious actors in developing biological, cyber, and chemical weapons. To measure these risks of malicious use, government institutions and major AI labs are developing evaluations for hazardous capabilities in LLMs. However, current evaluations are private, preventing further research into mitigating risk. Furthermore, they focus on only a few, highly specific pathways for malicious use. To fill these gaps, we publicly release the Weapons of Mass Destruction Proxy (WMDP) benchmark, a dataset of 4,157 multiple-choice questions that serve as a proxy measurement of hazardous knowledge in biosecurity, cybersecurity, and chemical security. WMDP was developed by a consortium of academics and technical consultants, and was stringently filtered to eliminate sensitive information prior to public release. WMDP serves two roles: first, as an evaluation for hazardous knowledge in LLMs, and second, as a benchmark for unlearning methods to remove such hazardous knowledge. To guide progress on unlearning, we develop CUT, a state-of-the-art unlearning method based on controlling model representations. CUT reduces model performance on WMDP while maintaining general capabilities in areas such as biology and computer science, suggesting that unlearning may be a concrete path towards reducing malicious use from LLMs. We release our benchmark and code publicly at https://wmdp.ai

Open-weight bio-foundation models present a dual-use dilemma. While holding great promise for accelerating scientific research and drug development, they could also enable bad actors to develop more deadly bioweapons. To mitigate the risk posed by these models, current approaches focus on filtering biohazardous data during pre-training. However, the effectiveness of such an approach remains unclear, particularly against determined actors who might fine-tune these models for malicious use. To address this gap, we propose BioRiskEval, a framework to evaluate the robustness of procedures that are intended to reduce the dual-use capabilities of bio-foundation models. BioRiskEval assesses models' virus understanding through three lenses, including sequence modeling, mutational effects prediction, and virulence prediction. Our results show that current filtering practices may not be particularly effective: Excluded knowledge can be rapidly recovered in some cases via fine-tuning, and exhibits broader generalizability in sequence modeling. Furthermore, dual-use signals may already reside in the pretrained representations, and can be elicited via simple linear probing. These findings highlight the challenges of data filtering as a standalone procedure, underscoring the need for further research into robust safety and security strategies for open-weight bio-foundation models.

Frontier large language models (LLMs) are increasingly integrated into scientific workflows, yet their growing biological capabilities may outpace current safeguards. To assess the biological risks of frontier models, we develop Intern-BioBreaker, a specialized bio-red-teaming model, together with an integrated computational-to-physical framework that couples model-level stress testing with wet-lab validation. Within this framework, Intern-BioBreaker generates targeted jailbreak prompts to test whether aligned models can be induced to provide operational guidance for safety-sensitive biological tasks or produce sequence-level outputs with potentially harmful properties. Selected sequence outputs are then carried forward for DNA synthesis, host expression, and orthogonal protein verification to assess whether model-generated designs can yield the intended biological products. Our evaluation reveals a concerning gap between text-level safeguards and the risks posed by capable scientific models: (i) Intern-BioBreaker outperforms baseline attack models and reveals widespread bio-risk jailbreak vulnerabilities across both open-weight and proprietary frontier LLMs, with several targets reaching near-saturated or 100% task-level attack success rate (ASR); (ii) in sequence-level case studies, GPT-5.5 can be induced to generate modified viral candidate sequences with pathogenic potential; the corresponding translated proteins may exhibit even stronger receptor-binding affinity and thus enhanced infection potential; and (iii) end-to-end verification shows that selected model-generated biological designs are not merely textual artifacts, but can be physically realized under controlled experimental settings. These findings underscore the need for stronger biological red-teaming, nucleic acid synthesis screening, and safety mechanisms that keep pace with model capabilities.

Machine learning-based antibody design is emerging as one of the most promising approaches to combat infectious diseases, due to significant advancements in the field of artificial intelligence and an exponential surge in experimental antibody data (in particular related to COVID-19). The ability of an antibody to bind to an antigens (called binding affinity) is one of the the most critical properties in designing neutralizing antibodies. In this study we introduce Ab-Affinity, a new large language model that can accurately predict the binding affinity of antibodies against a target peptide, e.g., the SARS-CoV-2 spike protein. Code and model are available at https://github.com/ucrbioinfo/AbAffinity.

We propose a novel type of Artificial Immune System (AIS): Symbiotic Artificial Immune Systems (SAIS), drawing inspiration from symbiotic relationships in biology. SAIS parallels the three key stages (i.e., mutualism, commensalism and parasitism) of population updating from the Symbiotic Organisms Search (SOS) algorithm. This parallel approach effectively addresses the challenges of large population size and enhances population diversity in AIS, which traditional AIS and SOS struggle to resolve efficiently. We conducted a series of experiments, which demonstrated that our SAIS achieved comparable performance to the state-of-the-art approach SOS and outperformed other popular AIS approaches and evolutionary algorithms across 26 benchmark problems. Furthermore, we investigated the problem of parameter selection and found that SAIS performs better in handling larger population sizes while requiring fewer generations. Finally, we believe SAIS, as a novel bio-inspired and immune-inspired algorithm, paves the way for innovation in bio-inspired computing with the symbiotic paradigm.

Large language models (LLMs) such as those embedded in 'chatbots' are accelerating and democratizing research by providing comprehensible information and expertise from many different fields. However, these models may also confer easy access to dual-use technologies capable of inflicting great harm. To evaluate this risk, the 'Safeguarding the Future' course at MIT tasked non-scientist students with investigating whether LLM chatbots could be prompted to assist non-experts in causing a pandemic. In one hour, the chatbots suggested four potential pandemic pathogens, explained how they can be generated from synthetic DNA using reverse genetics, supplied the names of DNA synthesis companies unlikely to screen orders, identified detailed protocols and how to troubleshoot them, and recommended that anyone lacking the skills to perform reverse genetics engage a core facility or contract research organization. Collectively, these results suggest that LLMs will make pandemic-class agents widely accessible as soon as they are credibly identified, even to people with little or no laboratory training. Promising nonproliferation measures include pre-release evaluations of LLMs by third parties, curating training datasets to remove harmful concepts, and verifiably screening all DNA generated by synthesis providers or used by contract research organizations and robotic cloud laboratories to engineer organisms or viruses.

Nucleotide sequences constitute the fundamental genetic basis of biological systems, rendering viral genomic analysis critical for biomedical advancement. Despite progress in biological foundation models, specifically nucleotide foundation models (NFMs), the field lacks a unified standard for viral genomics to facilitate community development and enforce biosecurity constraints. To address this, we introduce ViroBench, the first comprehensive and large-scale benchmark specifically designed for NFMs in viral settings. ViroBench evaluates models across two critical dimensions: biological understanding and latent biosecurity risk, covering 18 diverse scenarios within 4 task types. Extensive evaluation of 66 NFMs across diverse architectures yields three critical conclusions. Firstly, NFMs exhibit a performance degradation in biological understanding under phylogenetic and temporal shifts, indicating weak extrapolation capabilities. Secondly, generation tasks reveal a decoupling between statistical likelihood and biological functional validity, posing latent biosecurity risks. Thirdly, controlled ablation studies reveal that taxonomic diversity in pretraining data outweighs parameter scale. Specifically, a lightweight baseline trained on diverse data achieves a 67.5% performance gain over its original model. Overall, ViroBench provides interpretable, diagnostic evaluations and a reproducible measurement framework for future research on viral nucleotide foundation models. The datasets and code are publicly available at https://github.com/QIANJINYDX/ViroBench.

To build effective therapeutics, biologists iteratively mutate antibody sequences to improve binding and stability. Proposed mutations can be informed by previous measurements or by learning from large antibody databases to predict only typical antibodies. Unfortunately, the space of typical antibodies is enormous to search, and experiments often fail to find suitable antibodies on a budget. We introduce Clone-informed Bayesian Optimization (CloneBO), a Bayesian optimization procedure that efficiently optimizes antibodies in the lab by teaching a generative model how our immune system optimizes antibodies. Our immune system makes antibodies by iteratively evolving specific portions of their sequences to bind their target strongly and stably, resulting in a set of related, evolving sequences known as a clonal family. We train a large language model, CloneLM, on hundreds of thousands of clonal families and use it to design sequences with mutations that are most likely to optimize an antibody within the human immune system. We propose to guide our designs to fit previous measurements with a twisted sequential Monte Carlo procedure. We show that CloneBO optimizes antibodies substantially more efficiently than previous methods in realistic in silico experiments and designs stronger and more stable binders in in vitro wet lab experiments.

Public viral genome resources such as the National Center for Biotechnology Information (NCBI) Virus database are central to outbreak response, evolutionary analysis, vaccine design, and genomic surveillance. Yet many high-value retrieval workflows remain optimized for interactive use rather than deterministic, reproducible programmatic interfaces. This creates a challenge for Large Language Model (LLM)-based scientific agents, where errors in metadata interpretation, filtering logic, or retrieval can propagate into incorrect datasets. To evaluate agentic viral data retrieval, we built VirBench, a manually curated benchmark of 120 queries spanning diverse pathogens, taxonomic levels, and metadata filters. When autonomous AI systems, including Biomni, Claude, GPT, and Edison Analysis, were tasked with these queries without a dedicated retrieval layer, performance varied widely: mean accuracy ranged from 16.9% for Claude Sonnet 4 to 91.3% for GPT-5.5, with newer frontier models showing progress but residual errors remaining consequential. To address this, we built gget virus, a deterministic query framework that formalizes NCBI Virus-style filtering as a reproducible programmatic system. By staging retrieval, applying metadata constraints before sequence download, and retrieving structured GenBank records, gget virus reduces data transfer by more than 98% for high-volume queries while preserving exact-match semantics. Instructing autonomous AI systems to use gget virus increased accuracy to at least 90.0% across all evaluated systems and up to 99.7% for GPT-5.5, improved response stability to 0.92-1.00, reduced error magnitude, and generally decreased runtime and tool calls. Together, this work establishes deterministic data access as critical infrastructure for reliable agentic science and provides a reproducible retrieval layer for robust human- and AI-driven viral genomics workflows.

To understand and identify the unprecedented risks posed by rapidly advancing artificial intelligence (AI) models, this report presents a comprehensive assessment of their frontier risks. Drawing on the E-T-C analysis (deployment environment, threat source, enabling capability) from the Frontier AI Risk Management Framework (v1.0) (SafeWork-F1-Framework), we identify critical risks in seven areas: cyber offense, biological and chemical risks, persuasion and manipulation, uncontrolled autonomous AI R\&D, strategic deception and scheming, self-replication, and collusion. Guided by the "AI-45^circ Law," we evaluate these risks using "red lines" (intolerable thresholds) and "yellow lines" (early warning indicators) to define risk zones: green (manageable risk for routine deployment and continuous monitoring), yellow (requiring strengthened mitigations and controlled deployment), and red (necessitating suspension of development and/or deployment). Experimental results show that all recent frontier AI models reside in green and yellow zones, without crossing red lines. Specifically, no evaluated models cross the yellow line for cyber offense or uncontrolled AI R\&D risks. For self-replication, and strategic deception and scheming, most models remain in the green zone, except for certain reasoning models in the yellow zone. In persuasion and manipulation, most models are in the yellow zone due to their effective influence on humans. For biological and chemical risks, we are unable to rule out the possibility of most models residing in the yellow zone, although detailed threat modeling and in-depth assessment are required to make further claims. This work reflects our current understanding of AI frontier risks and urges collective action to mitigate these challenges.

We introduce ABLE, a benchmark for evaluating LLM agents' ability to use biological AI models (BAIMs), such as ProteinMPNN and AlphaFold3, in dual-use protein design workflows. ABLE assesses agent performance through a set of tasks spanning structure retrieval, sequence generation, and design validation. We evaluate 15 frontier models and find that seven refuse all tasks, while the remaining models exhibit substantial performance differences. Claude Sonnet 4 and Gemini 3 Pro achieve the highest scores across information retrieval, tool selection, and tool use. We further compare model performance on a subset of tasks against an expert human baseline. Our results suggest that current LLMs can substantially lower barriers to protein design, but remain inconsistent in planning, strategy generation, and integrating biological knowledge with tool use.