# A Blind Spot in Alignment: Quantifying Biosecurity Risks in Large Language Models

arXiv: https://arxiv.org/abs/2608.02684 · HTML: https://mlsanity.com/paper/2608.02684/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 42 of its 83 references that are in the map.
- First posted on arXiv 3 Aug 2026.

## Builds on (most cited first, 30 of 42)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [Llama 2: Open Foundation and Fine-Tuned Chat Models](https://mlsanity.com/paper/2307.09288/) (2023)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [Direct Preference Optimization: Your Language Model is Secretly a Reward Model](https://mlsanity.com/paper/2305.18290/) (2023)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Efficient Memory Management for Large Language Model Serving with PagedAttention](https://mlsanity.com/paper/2309.06180/) (2023)
- [Deep reinforcement learning from human preferences](https://mlsanity.com/paper/1706.03741/) (2017)
- [Universal and Transferable Adversarial Attacks on Aligned Language Models](https://mlsanity.com/paper/2307.15043/) (2023)
- [Constitutional AI: Harmlessness from AI Feedback](https://mlsanity.com/paper/2212.08073/) (2022)
- [MMLU-Pro: A More Robust and Challenging Multi-Task Language Understanding Benchmark](https://mlsanity.com/paper/2406.01574/) (2024)
- [Jailbroken: How Does LLM Safety Training Fail?](https://mlsanity.com/paper/2307.02483/) (2023)
- [HarmBench: A Standardized Evaluation Framework for Automated Red Teaming and Robust Refusal](https://mlsanity.com/paper/2402.04249/) (2024)
- [Fine-tuning Aligned Language Models Compromises Safety, Even When Users Do Not Intend To!](https://mlsanity.com/paper/2310.03693/) (2023)
- [ChatGLM: A Family of Large Language Models from GLM-130B to GLM-4 All Tools](https://mlsanity.com/paper/2406.12793/) (2024)
- [Red Teaming Language Models with Language Models](https://mlsanity.com/paper/2202.03286/) (2022)
- [DeepSeek-V3.2: Pushing the Frontier of Open Large Language Models](https://mlsanity.com/paper/2512.02556/) (2025)
- [Is BERT Really Robust? A Strong Baseline for Natural Language Attack on Text Classification and Entailment](https://mlsanity.com/paper/1907.11932/) (2019)
- [The WMDP Benchmark: Measuring and Reducing Malicious Use With Unlearning](https://mlsanity.com/paper/2403.03218/) (2024)
- [XSTest: A Test Suite for Identifying Exaggerated Safety Behaviours in Large Language Models](https://mlsanity.com/paper/2308.01263/) (2023)
- ["Do Anything Now": Characterizing and Evaluating In-The-Wild Jailbreak Prompts on Large Language Models](https://mlsanity.com/paper/2308.03825/) (2023)
- [Great, Now Write an Article About That: The Crescendo Multi-Turn LLM Jailbreak Attack](https://mlsanity.com/paper/2404.01833/) (2024)
- [A StrongREJECT for Empty Jailbreaks](https://mlsanity.com/paper/2402.10260/) (2024)
- [Deliberative Alignment: Reasoning Enables Safer Language Models](https://mlsanity.com/paper/2412.16339/) (2024)
- [ShieldGemma: Generative AI Content Moderation Based on Gemma](https://mlsanity.com/paper/2407.21772/) (2024)
- [SORRY-Bench: Systematically Evaluating Large Language Model Safety Refusal](https://mlsanity.com/paper/2406.14598/) (2024)
- [Scalable and Transferable Black-Box Jailbreaks for Language Models via Persona Modulation](https://mlsanity.com/paper/2311.03348/) (2023)
- [LinkBERT: Pretraining Language Models with Document Links](https://mlsanity.com/paper/2203.15827/) (2022)
- [Model evaluation for extreme risks](https://mlsanity.com/paper/2305.15324/) (2023)

## Built on by (most cited first, 2 of 2)

- [Dense Clinical Contrasts Enhance Medical Knowledge Updating in Large Language Models](https://mlsanity.com/paper/2608.30405/) (2026)
- [Artificial intelligence and biosecurity: capabilities, threat pathways, and defense-in-depth governance](https://mlsanity.com/paper/2609.16213/) (2026)

## Abstract (arXiv)

Large Language Models (LLMs) are accelerating biological research, yet this same capability poses a critical biosecurity threat: models that assist in protein engineering can equally be prompted to generate predicted toxin-like sequences, potentially lowering the barrier to biological misuse. Current safety evaluations, however, operate in natural language and cannot determine whether a model-generated amino acid sequence is biological gibberish or a computational risk signal. To address this evaluation blind spot, we introduce SPIKE-Bench, coupling 631 curated toxin-design prompts across seven functional categories with the SPIKE funnel, a three-stage protocol that filters output through compliance, biological plausibility, and predicted toxicity, producing stage-level diagnostics and an aggregate function-aware metric: the Functional Harmfulness Rate (FHR). An audit of 32 LLMs reveals that most models freely comply with toxin-design requests; FHR is driven primarily by biological generation capability rather than safety alignment, reaching 50.7%; and Refusal Rate fails to predict functional risk. As a first step toward mitigation, we provide BioSafe-Guard, a domain-specialized classifier that substantially reduces predicted functional risk while preserving benign utility. We release SPIKE-Bench and BioSafe-Guard at https://github.com/PKU-Alignment/SPIKE-Bench to support more rigorous biosecurity evaluation of LLMs.