@unpublished{GE20, author = { Dana Gretton and Brian Wang and Leonard Foner and Jens Berlips and Theia Vogel and Benjamin Weinstein-Raun and Martin Kysel and Walther Chen and Erika A. DeBenedictis and Andrew B. Liu and Emma Chory and Hongrui Cui and Xiang Li and Jiangbin Dong and Andres Fabrega and Christianne Dennison and Otilia Don and Tong Ye and Kaveri Uberoy and Ron Rivest and Mingyu Gao and Yu Yu and Carsten Baum and Ivan Damgard and Andrew C. Yao and Kevin M. Esvelt }, title = { Random adversarial threshold search enables specific, secure, and automated {DNA} synthesis screening }, url = { https://www.securedna.org/download/Random_Adversarial_Threshold_ Screening.pdf }, date = { 2020-01 }, urla = { SecureDNA }, abstract = { In 1992, members of the Aum Shinrikyo cult tried but failed to obtain Ebolavirus for use as a biological weapon. Today, many individuals can assemble viruses from synthetic DNA that is not screened for hazards. A major barrier to universal screening is the high rate of false alarms requiring expensive human curation. Here we develop, test, and implement “random adversarial threshold” (RAT) search, a highly specific approach that looks for exact matches to short peptide windows and predicted functional equivalents found in hazards but not in any unrelated genes. To determine whether bad actors could obtain replication-competent viruses by incorporating mutations to evade screening, we built databases to protect nine windows found in M13 bacteriophage virus and launched $~21,000$ attacks at each window by experimentally building and measuring the fitness of variants with up to six amino acid changes. Finding that defensible windows capable of reliably blocking attacks shared certain predictable features, we identified similar windows from the Australia Group list of pathogens, constructed databases of variants, and wrote software enabling cryptographically secure screening of synthesis orders. RAT search offers a way to safeguard biotechnology by automating DNA synthesis screening. }, }