Abstract

Biological weapons have been used for thousands of years, but recent advances in synthesis technologies have made peptide and protein toxin production more accessible and pose a threat to biosecurity worldwide. Natural toxins such as conotoxins, certain hemolytic compounds, and enterotoxins are peptide agents that can be synthesized in an environment with weak biosecurity measures and rudimentarily weaponized for limited use against smaller targets for lethal or nonlethal effects. Technological advances are changing the threat landscape around biological weapons and potentially facilitating a shift from state sponsored to more micro-level threats stemming from terror cells, insider threats, and lone wolf attacks. Here, we present the reader with an overview of the threat of peptide and protein toxins, provide examples of potent peptide toxins, and introduce capabilities of a proposed biosecurity program utilizing artificial intelligence that unifies commercial nucleotide and peptide synthesis vendors.

Highlights

  • The use of biological agents and toxins as biological weapons (BW) have been documented throughout history, with some of the earliest uses involving Scythians dipping their arrows in decomposing cadavers of adders and human blood hypothesized to have contained Clostridium perfringens and Clostridium tetani (Barras and Greub, 2014)

  • A holistic, biosecurity approach using artificial intelligence that combines multiple layers of screening and prediction with user network analysis in the biosecurity AI network (BAIN) package outlined in this article will help provide a level of biological arms control and counterproliferation that is needed

  • BAIN cannot screen synthesized products created without the aid of commercial synthesis vendors such as with portable synthesizers or though extraction and purification from natural or bioengineered sources

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Summary

INTRODUCTION

The use of biological agents and toxins as biological weapons (BW) have been documented throughout history, with some of the earliest uses involving Scythians dipping their arrows in decomposing cadavers of adders and human blood hypothesized to have contained Clostridium perfringens and Clostridium tetani (Barras and Greub, 2014). BAIN would screen every commercial nucleic acid order (including gene blocks and oligonucleotides) and peptide order against a database containing genomic and proteomic data of known pathogens as well as toxic peptides and proteins This is similar to a United States Intelligence Advanced Research Projects Agency initiative launched in 2016 (Reardon, 2019). While the current focus for screening is on synthesis of longer nucleic acid sequences, short oligonucleotides could be used as primers to clone peptide toxins and other genes of concern from an organism (of both pathogens and non-pathogens). In this case, the oligonucleotides themselves are initially seen as harmless, but the sequence that a pair of these primers flank may be extracted and encode a toxin or other harmful product. BAIN serves as a conceptual framework for enhanced biosecurity among commercial synthesis vendors and users that is needed to counter biothreats before they are created and, at the least, serves as a deterrent

CONCLUSION
DATA AVAILABILITY STATEMENT
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