Project Summary
DNA synthesis is a powerfully enabling capability for engineering biology to address important challenges across sectors, but as these capabilities become more accessible, the biosecurity risks they pose rises. In 2024 and 2025, EBRC, with support from Sentinel Bio, will conduct end-to-end stress testing (E2EST) of nucleic acid synthesis providers. We will use customers with different attributes and sequences with different biorisk profiles to learn about provider customer, sequence, and follow-up screening practices.
To this end, EBRC will develop a framework for E2EST informed by engagement with stakeholders including providers themselves, U.S. and International law enforcement and national security agencies, biosecurity experts, and members of the engineering biology community. By including diverse stakeholders in the framework development, we will identify screening parameters that are most important to stress test and learn from providers what would be most useful to them.
With this framework in place, a stress test team will be assembled from members of the engineering biology and/or virology communities to generate sequences and customer profiles that will be submitted to companies via their typical order streams. EBRC will collect and analyze the results of these order submissions, culminating in an anonymized report that will be used to brief stakeholders on identified vulnerabilities.
As a result of these activities, EBRC aims to:
- provide insights into screening practices across the industry, including general adoption of sequence and customer screening, which may enable the measurement of progress in future years;
- enable targeted outreach to providers who may need support for adopting best screening practices;
- identify areas of substantial screening differences between providers, supporting the further development of industry best practices; and
- identify sequences that may be of significant concern but that are not flagged by screening systems.
Background
In the early 2000’s, the U.S. Government (USG) recognized that, as synthetic nucleic acid synthesis became more reliable and affordable, associated risks would increase. In 2010, USG issued the Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA to support providers as they worked to implement systems to screen sequences and customers. Industry also recognized the growing risk and established the International Gene Synthesis Consortium “to design and apply a common protocol to screen both the sequences of synthetic gene orders and the customers who place them.”
As technology advanced, the Guidance and the IGSC Harmonized Screening Protocol grew out-of-date. The IGSC released version 2.0 of its protocol in 2017, and in 2023, USG released a long-anticipated update to its Guidance, which reconsidered the definition of “sequence of concern”, benchtop nucleic acid synthesis equipment, screening windows, and more. Shortly thereafter, USG released an Executive Order (EO) on the Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence. This EO (among other things):
- recognized that there currently are no means by which to assess the performance of nucleic acid synthesis screening. It directed NIST to work toward the development of a set of sequences to use for conformity assessment and directed the Department of Homeland Security to establish a framework “to conduct structured evaluation and stress testing of nucleic acid synthesis procurement screening.” (EBRC’s E2EST effort is entirely independent of any work by DHS in fulfillment of the EO.); and
- directed the Office of Science and Technology Policy (OSTP) to establish a new Framework for nucleic acid sequence screening, requiring recipients of federal funds to only purchase synthetic nucleic acids from providers that attest to adhering to the OSTP Framework.
The resultant Framework for Nucleic Acid Synthesis Screening was released in April 2024 and effective October 2024. While many nucleic acid providers already implement robust customer and sequence screening practices, this policy creates an incentive for those providers that do not screen to do so. Still, providers may have vastly different approaches to screening, and it is likely that not all providers will choose to attest to adhering to the Framework. Independent testing of provider practices would therefore provide key insights on which providers have implemented the Framework and to what extent.