DNA synthesis companies serve as a critical chokepoint in the biosecurity ecosystem. The argument is straightforward: to create a biological threat agent, an actor needs to obtain its genetic sequence in physical DNA form. DNA synthesis companies, which produce custom DNA sequences on demand for legitimate research, represent the last physical control point before that sequence enters the world. Screening orders against databases of dangerous sequences before synthesizing them should prevent acquisition of threat agents through commercial channels.
How Current Screening Works
The International Gene Synthesis Consortium, representing the major commercial DNA synthesis providers, has maintained a voluntary screening commitment since 2009. The screening approach uses sequence alignment algorithms to compare ordered sequences against databases of select agents and toxins listed under biosafety regulations. Orders matching dangerous sequences above a threshold similarity are flagged for manual review and potential rejection.
The AI Bypass Problem
The 2024 arXiv preprint from the Johns Hopkins Center for Health Security (arXiv 2406.08027) documented a specific vulnerability. AI protein design tools including ESM3 and RFdiffusion can generate novel sequences with similar three-dimensional structure and function to dangerous proteins but with low sequence similarity to any known protein in screening databases. A viral toxin redesigned by AI to be functionally equivalent but sequentially dissimilar could pass sequence-based screening while retaining biological activity. The IBBIS proposal for functional screening uses AI models that predict protein function from sequence to flag sequences likely to produce dangerous functional outputs, regardless of their similarity to known threat agents.
What Policy Has Done
The September 2023 Biden Executive Order on AI specifically addressed AI-enabled biosecurity risks and required NIST, NIAID, and other agencies to develop screening requirements for AI-designed genomic sequences. The IBBIS consortium published a technical framework for next-generation screening in 2024. As of early 2026, large commercial synthesis providers have begun piloting AI-augmented functional screening, but the transition from sequence-similarity to function-based screening is not yet complete across the industry.
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Primary sources: Tucker JB et al., “Governing Dangerous Pathogens: A Framework Based on Risk,” available at IBBIS; arXiv preprint on AI bypass of DNA synthesis screening, arXiv 2406.08027.