Research
A system capable of verifiably and privately screening global DNA synthesis
Summary
A free DNA screening system based on multi-party oblivious hashing preserves customer privacy while verifiably checking gene and oligonucleotide synthesis orders at high speed with a negligible false alarm rate.
Abstract
Printing custom DNA sequences is essential to scientific and biomedical research, but the technology can be used to manufacture plagues as well as cures. Just as ink printers recognize and reject attempts to counterfeit money, DNA synthesizers and assemblers should deny unauthorized requests to make viral DNA that could be used to ignite a pandemic. There are three complications. First, we don't need to quickly update printers to deal with newly discovered currencies, whereas we regularly learn of new viruses and other biological threats. Second, anti-counterfeiting specifications on a local printer can’t be extracted and misused by malicious actors, unlike information on biological threats. Finally, any screening must keep the inspected DNA sequences private, as they may constitute valuable trade secrets. Here we describe SecureDNA, a free, privacy-preserving, and fully automated system capable of verifiably screening all DNA synthesis orders of 30+ base pairs against an up-to-date database of hazards, and its operational performance and specificity when applied to 67 million base pairs of DNA synthesized by providers in the United States, Europe, and China.
Random adversarial threshold search enables automated DNA screening
Summary
Searching for exact matches to pre-computed functional variants unique to hazardous genes enables sensitive, secure, and automated DNA synthesis screening.
Abstract
Custom DNA synthesis underpins modern biology, but hazardous genes in the wrong hands could threaten many lives and public trust in science. In 1992, a virology-trained mass murderer tried and failed to obtain physical samples of Ebola; today, viruses can be assembled from synthetic DNA fragments. Screening orders for hazards is unreliable and expensive because similarity search algorithms yield false alarms requiring expert human review. Here we develop “random adversarial threshold” (RAT) search, which looks for exact matches to short nucleic acid and peptide subsequence windows from hazards and predicted functional variants that aren’t found in any known innocuous genes. To experimentally assess sensitivity, we used RAT search to protect nine windows from the M13 bacteriophage virus, then invited a “red team” to launch up to 21,000 attacks at each window and measure the fitness of their designed mutants. We identified defensible windows from regulated pathogens, built a curated test database that our M13 experiments indicate will block 99.999% of functional attacks, and verified its sensitivity against orders designed to evade detection. RAT search offers a way to safeguard biotechnology by securely automating DNA synthesis screening.