Testing v0.1 of the Common Mechanism

The Common Mechanism sequence screening package is open-source software under active development. It was initially proposed in 2020 by an international working group jointly convened by the Nuclear Threat Initiative (NTI) and the World Economic Forum (WEF). From 2020-2023, a Technical Consortium guided the design of the baseline Common Mechanism screening process, and software and databases were developed by a team of technical consultants led by Dr. Nicole Wheeler of the University of Birmingham. In late 2023, beta testing of the software by synthesis providers began. In 2024, IBBIS was launched as the long-term home of the Common Mechanism, and the software was publicly released.

Below, you will find a summary of test results from our beta testing by synthesis providers and internal testing of the software prior to the version 0.1 release.

Compliance with best industry practices

Twist Bioscience ran a series of real customer orders through the Common Mechanism, finding that the tool would allow users to screen their orders in compliance with industry best practices.

A number of other synthesis providers, including benchtop manufacturers, academic biofoundries, and smaller synthesis companies were engaged to install and test the tool during the beta testing process.

The Common Mechanism is designed to meet and exceed current screening guidance, such as the IGSC Harmonized Screening Protocol and U.S. Framework for Nucleic Acid Synthesis Screening. IBBIS is a member of the International Gene Synthesis Consortium and an active participant in efforts to standardize best practices for synthesis screening, such as through ongoing engagements with EBRC and NIST.

<2% false positive flags of real synthetic biology designs

The Common Mechanism was run against the iGEM Registry of Standard Biological Parts, a public database capturing over 20,000 biological parts used to build synthetic biology devices and systems. Teams participating in the international iGEM Competition submit the biological parts designed for their projects to the Registry every year.

In total, less than 2% of the parts were flagged (422/22809). Not all of these represent false positives; in fact, the search highlighted several sequences that we have reported to iGEM HQ as likely requiring safety flags.

Results of the Common Mechanism run against the iGEM Registry. 124 parts were flagged because of homology to a regulated toxin (“biorisk” in the Sankey diagram above), 9 due to homology to a regulated virus, and 315 for homology to non-viral regulated pathogens.

Performance on par with industry screening tools

IBBIS is among the screening tools providers participating in the development of a standard test set for benchmarking synthesis screening performance.

As reported in Progress and Prospects for a Nucleic Acid Screening Test Set, the Common Mechanism showed strong alignment with other screening tools: 100% agreement for Orbivirus sequences, 99.5% agreement for bacterial sequences from Coccidioides and 92.1% agreement for fungal sequences from Francisella tularensis. Other tools showed similar levels of agreement and disagreement.

The Common Mechanism is currently being tested against sequences from every pathogen on the U.S. Select Agent List and Australia Group Common Control Group List, paired with sequences from non-listed close relatives. Results for this testing will be reported once consensus flags have been established among the working group of RTX BBN, Aclid, and Battelle.

Resilience to AI-generated challenges

The Common Mechanism has been tested against various obfuscation challenges, including functional reformulation of toxins using AI protein design tools, camouflaging sequences with “decoy” non-hazard sequences that could be removed using standard laboratory methods, and splitting hazards for later reassembly. A paper showing these results is currently being prepared for publication.