{"id":741,"date":"2026-02-25T16:02:34","date_gmt":"2026-02-25T16:02:34","guid":{"rendered":"https:\/\/sentinelbio.org\/?p=741"},"modified":"2026-04-06T16:16:26","modified_gmt":"2026-04-06T16:16:26","slug":"why-were-doubling-down-on-synthesis-screening","status":"publish","type":"post","link":"https:\/\/sentinelbio.org\/why-were-doubling-down-on-synthesis-screening\/","title":{"rendered":"Why We’re Doubling Down on Synthesis Screening"},"content":{"rendered":"\n

Last year, we decided<\/a> to narrow Sentinel’s focus on biotech governance. Since then, we’ve stress-tested our strategy relentlessly \u2013 asking hard questions about where we might be wrong, while doubling down where the evidence gives us conviction.<\/p>\n\n\n\n

In 2025, we put this to the test with a research sprint organized around two questions:<\/p>\n\n\n\n

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  1. If we reach our victory condition, how much would synthesis screening reduce bioterrorism risks?<\/li>\n\n\n\n
  2. Are any other physical materials, equipment, or services even better chokepoints than synthetic DNA?<\/li>\n<\/ol>\n\n\n\n

    First and foremost, we examined this from an impartial perspective. Independent of any organizational constraints, what are the best chokepoints for risk reduction? (\u201cWhat would a billionaire with a 100 FTE team do?\u201d) Then we considered Sentinel\u2019s perspective: What should we do, given our available resources, constraints, and comparative advantage?<\/p>\n\n\n\n

    \"\"<\/figure>\n\n\n\n

    An ambitious victory condition for synthesis screening<\/strong><\/h3>\n\n\n\n

    To assess the biorisk reduction we can get from robust synthesis screening, we first defined what success looks like. <\/p>\n\n\n\n

    Using our metrics for tracking progress \u2013 the global prevalence and quality of synthesis screening \u2013 we stipulated what it\u2019d look like to achieve victory by 2030: more than 80% of mail-order providers and benchtop manufacturers globally are screening sequences >50 nucleotides, and more than 90% of companies that screen correctly identify a non-obvious sequence of concern in a realistic red-teaming scenario.<\/p>\n\n\n\n

    To be clear, this is incredibly ambitious. But we’re encouraged by recent policy developments in the US<\/a>, EU<\/a>, UK<\/a>, and elsewhere<\/a>, with several legislative proposals to ensure high-quality biosecurity screening across crucial biotechnology jurisdictions. This year, Lawmakers have concrete opportunities to deliver some of the biggest policy wins for biotech governance in a decade.<\/p>\n\n\n\n

    Beyond the policy developments, we have made significant progress in developing free<\/a> screening tools<\/a>, advancing the science<\/a> of biosecurity screening<\/a>, and building a growing community of dedicated colleagues working on this full-time. As we seize this momentum, it will soon be far harder for bad actors to obtain synthetic DNA.<\/p>\n\n\n\n

    What we learned about synthesis screening<\/strong><\/h3>\n\n\n\n

    Next, we worked with a team of biosecurity experts to model the probability that malicious non-state actors would acquire synthetic DNA under our stated victory condition. <\/p>\n\n\n\n

    The honest answer is that reaching our win condition won\u2019t make it impossible for bad actors to acquire synthetic DNA. But we can close the easiest and cheapest pathways for buying DNA that exist today, such as ordering gene-length DNA from providers that don\u2019t screen at all, making it meaningfully harder for anyone to weaponize biology.<\/p>\n\n\n\n

    The question we\u2019re asked the most (by far!) when presenting this work is why it\u2019s sufficient that only 80% of providers screen. A key insight from our modelling is that securing synthetic DNA isn’t just about denying orders outright. Screening can also deter bad actors from buying synthetic DNA in the first place, and it creates opportunities for law enforcement to detect and intercept attacks before they unfold. <\/p>\n\n\n\n

    The deterrent effect is especially powerful if bad actors can’t easily tell which providers screen and which don’t. When we achieve a system where illegitimately ordering hazardous DNA carries a real risk of law enforcement intervening, fewer malicious actors will try in the first place, reducing the number of illicit attempts our screening systems need to detect. At Sentinel, we\u2019ve historically invested less in deterrence and law enforcement, so we’re using this quarter to develop a strategy and explore grants in these areas.<\/p>\n\n\n\n

    At the same time, we’re tirelessly investigating key cruxes around the feasibility of reaching our victory condition by 2030. For example, we\u2019re conducting a study on the difficulty of assembling shorter DNA fragments, helping us understand the significance of securing access to short oligonucleotides. Given the decentralized nature of the oligo market and the proliferation of benchtop synthesizers, establishing access controls for short oligos would entail a substantial update to our strategy and the feasibility of achieving our victory condition.<\/p>\n\n\n\n

    Some of our strategic cruxes remain unresolved, and we’re working hard to make progress on them over the coming months. We may have to update our strategy along the way, but we’re committed to going where the evidence leads us.<\/p>\n\n\n\n

    Since there are many other interventions in biosecurity we could spend our finite time and resources on, we keep coming back to a simple gut check: would we be willing to commit many years of our lives to this one cause, given the opportunity cost? <\/p>\n\n\n\n

    Today, both of us can answer this with a clear yes.<\/p>\n\n\n\n

    What we learned about other physical chokepoints<\/strong><\/strong><\/h3>\n\n\n\n

    There are two reasons we explored physical chokepoints beyond synthesis screening. First, while synthesis screening will be critical for preventing bioterrorism, it won’t be sufficient to reduce risks to an acceptable level. Second, other physical chokepoints seem to receive comparatively little attention. RAND released an excellent report<\/a> on physical access controls and monitoring last year, but beyond that, public work on the topic is sparse.<\/p>\n\n\n\n

    We commissioned a leading biosecurity consultancy and assembled a dedicated in-house team of researchers \u2013 Alex Norman, Dana Gretton, and Reed Trende \u2013 to investigate alternative biotech access controls, including materials, reagents, equipment, and services like contract research organizations or cloud labs. <\/p>\n\n\n\n

    After evaluating over 200 alternative chokepoints, from lab equipment like biosafety cabinets to biological reagents like cell culture media, we concluded that nothing stands out as clearly superior to synthetic DNA. This comes down to three factors. First, most pathways to human-caused pandemic-level harm involve synthetic nucleic acids. Second, DNA sequences have a much stronger signal-to-noise ratio for inferring intent than common lab items like pipettes. Finally, gene-length DNA remains a hard-to-commodify product \u2014 unlike, say, home-made explosives, which can be manufactured with limited resources and expertise.<\/p>\n\n\n\n

    We also noticed a fundamental tension when evaluating other chokepoints: the more pathogen-agnostic the control, the worse the signal-to-noise ratio tends to be. Controls on liquid nitrogen delivery or biosafety cabinets may be useful, but they would also burden a majority of legitimate biology labs. Pathogen-specific controls, on the other hand, offer a clearer signal: some cell lines, for instance, are used almost exclusively for working with a small number of viruses. However, controls on these high-signal materials can often be circumvented by simply switching to a different pathogen. The challenge is finding the right balance between robustness and specificity \u2014 chokepoints that are relatively threat-agnostic but tractable enough to govern without imposing disproportionate costs on legitimate research.<\/p>\n\n\n\n

    We identified two chokepoints that could be exceptionally promising complements to nucleic acid synthesis security:<\/p>\n\n\n\n