A Break-Glass Plan for Biological Security: Bibliometric Analysis of Methods for Building Virus-Length Recombinant DNA Constructions Identifies Advanced DNA Polymerases as Key Reagents and Suggests Additional Controls that Might Be Imposed in Response to Triggering Biological Incidents

Abstract

Today, in 2026, there is concern that existing or improved pandemic pathogens might be made in labs, and that construction of pathogens might be assisted by Artificial Intelligence (AI). In the near future, it seems possible that pathogen construction might be assisted by AI agents acting under human direction or even on their own initiative. Such pathogens would be made by some combination of construction of stretches of specified nucleotide sequence with directed evolution (by means such as passaging on different cell lines or through humanized transgenic animals) to select variant organisms with desired properties. Current safety policy to prevent lab-made catastrophic pandemics depends on control of commercially synthesized DNA. This regulatory approach supposes that it will be possible to identify dangerous DNA sequences, and that regulation and law can prevent commercial DNA synthesis vendors from filling orders for those dangerous sequences. Here, we surveyed methods used to make "virus sized" DNA constructs in papers published in seven important journals over the 50+ years since the advent of recombinant DNA methods. Our results show that most contemporary large DNA constructions depend on high fidelity, high processivity thermostable DNA polymerases, either to make the synthetic DNA used to generate segments that are later assembled into the construct, or to join those segments via polymerase-based methods such as Gibson Assembly. Our results suggest that imposition of controls on these advanced thermostable polymerases together with restrictions on other materiel and equipment could provide additional means to increase the safety of the biological enterprise in the wake of a triggering events such as the release of lab-made pathogens. We then describe and discuss a contingency regulatory regime that would license institutions, laboratory workers, and independently reviewed lines of R&D, that could be imposed after such a triggering event.