{"id":1150632,"date":"2025-10-06T07:06:12","date_gmt":"2025-10-06T14:06:12","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/?post_type=msr-story&#038;p=1150632"},"modified":"2025-12-15T14:52:59","modified_gmt":"2025-12-15T22:52:59","slug":"the-paraphrase-project-designing-defense-for-an-era-of-synthetic-biology","status":"publish","type":"msr-story","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/story\/the-paraphrase-project-designing-defense-for-an-era-of-synthetic-biology\/","title":{"rendered":"The Paraphrase Project: Designing defense for an era of synthetic biology"},"content":{"rendered":"\n<div class=\"wp-block-cover has-parallax is-style-default\" style=\"min-height:398px;aspect-ratio:unset;\"><div role=\"img\" aria-label=\"Paraphrased proteins\" class=\"wp-block-cover__image-background wp-image-1151110 size-large has-parallax\" style=\"background-position:50% 50%;background-image:url(https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame8-HeroStill_2000-1333_V02-1024x682.png)\"><\/div><span aria-hidden=\"true\" class=\"wp-block-cover__background has-black-background-color has-background-dim-70 has-background-dim\"><\/span><div class=\"wp-block-cover__inner-container is-layout-constrained wp-container-core-cover-is-layout-2cb6a229 wp-block-cover-is-layout-constrained\">\n<div class=\"wp-block-group is-content-justification-left is-layout-constrained wp-container-core-group-is-layout-719fd2c2 wp-block-group-is-layout-constrained\">\n<div style=\"height:200px\" aria-hidden=\"true\" class=\"wp-block-spacer d-none d-sm-block\"><\/div>\n\n\n\n<h1 class=\"wp-block-heading is-style-display\" id=\"the-paraphrase-project-designing-defense-for-an-era-of-synthetic-biology\">The Paraphrase Project: Designing defense for an era of synthetic biology<\/h1>\n\n\n\n<div style=\"height:200px\" aria-hidden=\"true\" class=\"wp-block-spacer d-none d-sm-block\"><\/div>\n<\/div>\n<\/div><\/div>\n\n\n\n<article class=\"wp-block-group alignfull mt-0 is-layout-constrained wp-block-group-is-layout-constrained\">\n<div style=\"padding-bottom:0; padding-top:0\" class=\"wp-block-msr-immersive-section alignfull row has-background-gradient has-background-gradient-spectrum-3 wp-block-msr-immersive-section\">\n\t\n\t<div class=\"container\">\n\t\t<div class=\"wp-block-msr-immersive-section__wrapper\">\n\t\t\t<div style=\"height:40px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\t\t<\/div>\n\t<\/div>\n\n\t<\/div>\n\n\n\n<div class=\"wp-block-columns is-style-dark-mode p-4 z-20 container theme-dark is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:22%\"><\/div>\n\n\n\n<div class=\"wp-block-column headings-large is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:56%\">\n<div style=\"height:40px\" aria-hidden=\"true\" class=\"wp-block-spacer is-style-default d-none d-md-block\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading is-style-default-h3\" id=\"at-microsoft-we-believe-that-the-ability-of-generative-ai-to-learn-the-language-of-humans-is-equally-matched-by-its-ability-to-learn-the-language-of-nature-science-may-be-the-most-important-application-of-ai\">In the fall of 2023, breakthroughs in generative AI had researchers proclaiming a new era for medicine and healthcare.<\/h2>\n\n\n\n<div style=\"height:15px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div style=\"height:15px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>In fall 2023, as excitement grew over generative AI\u2019s role in medical breakthroughs, Microsoft\u2019s <a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/people\/horvitz\/\">Eric Horvitz<\/a> couldn\u2019t shake a nagging concern. The promise was undeniable, but his thoughts kept circling back to one hypothetical scenario: that open-source AI tools could, in theory, be used to reengineer toxins capable of evading existing biosecurity software.<\/p>\n\n\n\n<div class=\"annotations \" data-bi-aN=\"margin-callout\">\n\t<article class=\"annotations__list card depth-16 bg-body p-4 annotations__list--right\">\n\t\t<div class=\"annotations__list-item\">\n\t\t\t\t\t\t<span class=\"annotations__type d-block text-uppercase font-weight-semibold text-neutral-300 small\">Publication<\/span>\n\t\t\t<a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/strengthening-nucleic-acid-biosecurity-screening-against-generative-protein-design-tools\/\" data-bi-cN=\"Strengthening nucleic acid biosecurity screening against generative protein design tools\" data-external-link=\"false\" data-bi-aN=\"margin-callout\" data-bi-type=\"annotated-link\" class=\"annotations__link font-weight-semibold text-decoration-none\"><span>Strengthening nucleic acid biosecurity screening against generative protein design tools<\/span>&nbsp;<span class=\"glyph-in-link glyph-append glyph-append-chevron-right\" aria-hidden=\"true\"><\/span><\/a>\t\t\t\t\t<\/div>\n\t<\/article>\n<\/div>\n\n\n\n<p>That idea became the seed of what would grow into the Paraphrase Project, initially a biosecurity exploration, now the foundation of a landmark paper published October 2 in <em>Science<\/em>.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-style-spectrum is-layout-flow wp-block-quote-is-layout-flow\">\n<p>\u201cI tend to look out at the AI horizon all the time. And in scanning the horizon, I always reflect on dual use issues,\u201d said Horvitz, Microsoft\u2019s chief scientific officer. \u201cYou can design proteins to take on any structures now. What about known toxins?\u201d<\/p>\n<\/blockquote>\n\n\n\n<p>This question is what led Horvitz to spearhead the first biological \u201czero day\u201d: a term borrowed from cybersecurity to describe a previously unknown vulnerability in a computer system. In the realm of biosecurity, the analogy isn\u2019t perfect. This was about preemptively identifying cracks in the system before they could be exploited, not patching an active breach. But it was the closest analogy to what they were doing\u2014probing for hidden vulnerabilities and imagining how future misuse might unfold before it ever has the chance.&nbsp;<\/p>\n\n\n\n<p>At its core, the <a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/project\/paraphrase-project\/\">Paraphrase Project<\/a> calls for a shift in how we evaluate biological sequences, moving beyond surface-level identity checks to a deeper, semantic understanding of what proteins actually do. This approach could dramatically improve the safety and reliability of AI-driven biotechnologies, especially as synthetic biology becomes more accessible, Horvitz said.&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"yt-consent-placeholder\" role=\"region\" aria-label=\"Video playback requires cookie consent\" data-video-id=\"NtwlQdruK-0\" data-poster=\"https:\/\/img.youtube.com\/vi\/NtwlQdruK-0\/maxresdefault.jpg\"><iframe aria-hidden=\"true\" tabindex=\"-1\" title=\"What does it mean to paraphrase a protein?\" width=\"500\" height=\"281\" data-src=\"https:\/\/www.youtube-nocookie.com\/embed\/NtwlQdruK-0?feature=oembed&rel=0&enablejsapi=1\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><div class=\"yt-consent-placeholder__overlay\"><button class=\"yt-consent-placeholder__play\"><svg width=\"42\" height=\"42\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" aria-hidden=\"true\" focusable=\"false\"><g fill=\"none\" fill-rule=\"evenodd\"><circle fill=\"#000\" opacity=\".556\" cx=\"21\" cy=\"21\" r=\"21\"\/><path stroke=\"#FFF\" d=\"M27.5 22l-12 8.5v-17z\"\/><\/g><\/svg><span class=\"yt-consent-placeholder__label\">Video playback requires cookie consent<\/span><\/button><\/div><\/div>\n<\/div><\/figure>\n\n\n\n<div style=\"padding-bottom:0; padding-top:0\" class=\"wp-block-msr-immersive-section alignfull row wp-block-msr-immersive-section\">\n\t\n\t<div class=\"container\">\n\t\t<div class=\"wp-block-msr-immersive-section__wrapper col-lg-11 col-xl-9 px-0 m-auto\">\n\t\t\t<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<div class=\"wp-block-media-text has-vertical-margin-none  has-vertical-padding-none  has-media-on-the-right is-stacked-on-mobile\"><div class=\"wp-block-media-text__content\">\n<h3 class=\"wp-block-heading has-text-align-right\" id=\"insert-fmt-video-in-this-episode-of-the-microsoft-research-podcast-martin-and-daniela\">On the <a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/podcast\/ideas-more-ai-resilient-biosecurity-with-the-paraphrase-project\/\">Microsoft Research Podcast<\/a>, collaborators Eric Horvitz, Bruce Wittmann, Tessa Alexanian, and James Diggans explain AI-powered protein design, explore the Paraphrase Project, and present a new framework for publishing sensitive research.<\/h3>\n<\/div><figure class=\"wp-block-media-text__media\"><a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/podcast\/abstracts-september-30-2024\/\" target=\"_blank\" rel=\"noreferrer noopener\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"576\" src=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-1024x576.jpg\" alt=\"Illustrated headshots (from left to right): Eric Horvitz, Bruce Wittmann, Tessa Alexanian, and James Diggans.\" class=\"wp-image-1151087 size-full\" srcset=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-1024x576.jpg 1024w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-300x169.jpg 300w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-768x432.jpg 768w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-1066x600.jpg 1066w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-655x368.jpg 655w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-240x135.jpg 240w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-640x360.jpg 640w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-960x540.jpg 960w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788-1280x720.jpg 1280w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/EricBruceTessaJames-Ideas_Hero_Feature_River_No_Text_1400x788.jpg 1400w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a><\/figure><\/div>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\t\t<\/div>\n\t<\/div>\n\n\t<\/div>\n\n\n\n<div class=\"wp-block-group is-layout-constrained wp-block-group-is-layout-constrained\">\n<h2 class=\"wp-block-heading\" id=\"inside-synthetic-biology\">Inside synthetic biology<\/h2>\n\n\n\n<p>Here is an example of how synthetic biology works in practice: A scientist in Boston\u2014or one in Bangalore, Berlin or Buenos Aires\u2014wants to study a protein that could help treat a rare neurological disorder. To do that, they need a strand of DNA that encodes the protein. They send a request to a DNA synthesis company, one of many labs around the world that print custom DNA on demand. Within days, the company ships back a vial of genetic material, ready to be inserted into cells for exploration in a wet lab.<\/p>\n\n\n\n<p>Before that DNA reaches the lab bench, it passes through a digital checkpoint. Biosecurity screening software scans every order for sequences of concern, typically those linked to toxins or pathogens. These tools compare incoming DNA against regulated databases, often maintained by government agencies.<\/p>\n\n\n\n<p>The challenge is that these government databases aren&#8217;t curated by sequence. Part of the mission of the International Gene Synthesis Consortium (IGSC) is to curate a sequence database as a shared resource. In 2025 the IGSC spun out the Sequence Biosecurity Risk Consortium (SBRC), which is working with a broad community of experts to create a curated list of sequences that should be caught by screening systems.<\/p>\n\n\n\n<p>As AI tools become more powerful and accessible, the risk grows that someone could design a protein that slips past the screeners. It might look harmless to the software but behave like a toxin once inside a cell. The consequences could range from accidental lab mishaps to deliberate misuse. The safeguards we rely on may no longer be enough.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"testing-the-system\">Testing the system<\/h2>\n\n\n\n<p>To explore this, Horvitz teamed up with <a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/people\/bwittmann\/\">Bruce Wittmann<\/a>, a senior applied scientist at Microsoft with deep expertise in protein engineering and open-source biology tools. Together, they built a pipeline using models like <a class=\"msr-external-link glyph-append glyph-append-open-in-new-tab glyph-append-xsmall\" href=\"https:\/\/labs.ai.azure.com\/projects\/evodiff\/\" target=\"_blank\" rel=\"noopener noreferrer\">EvoDiff<span class=\"sr-only\"> (opens in new tab)<\/span><\/a>, which allowed them to generate thousands of synthetic variants of the highly potent toxin ricin. These variants weren\u2019t designed to be more dangerous, but to test the limits of current biosecurity screening systems.&nbsp;<\/p>\n\n\n\n<div style=\"height:10px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<figure class=\"wp-block-image aligncenter size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1920\" height=\"1080\" src=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame4-HeroStill_1920-1080_V04.png\" alt=\"Researchers discovered it was possible to preserve the active sites of the protein (illustrated by the letters\u00a0K E S),\u00a0while the amino acid sequence was rewritten.\u00a0\" class=\"wp-image-1151098\" srcset=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame4-HeroStill_1920-1080_V04.png 1920w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame4-HeroStill_1920-1080_V04-300x169.png 300w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame4-HeroStill_1920-1080_V04-1024x576.png 1024w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame4-HeroStill_1920-1080_V04-768x432.png 768w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame4-HeroStill_1920-1080_V04-1536x864.png 1536w\" sizes=\"auto, (max-width: 1920px) 100vw, 1920px\" \/><figcaption class=\"wp-element-caption\">Researchers discovered it was possible to preserve the active sites of the protein (illustrated by the letters&nbsp;K E S),&nbsp;while the amino acid sequence was rewritten.&nbsp;<\/figcaption><\/figure>\n\n\n\n<div style=\"height:10px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>The process was akin to paraphrasing a sentence: the meaning stays the same, but the words change. In this case, the structure and active sites of the protein were preserved, while the amino acid sequence was rewritten.&nbsp;&nbsp;<\/p>\n\n\n\n<p>To test their designs, Horvitz and Wittmann enlisted the help of two leading DNA providers: Twist Bioscience and Integrated DNA Technologies (IDT). They worked directly with the companies\u2019 top leadership, including CEOs and chief scientists, to evaluate how well existing screening systems could detect the AI-generated variants.<\/p>\n\n\n\n<p>What they found was sobering. The reformulated sequences made their way through existing filters undetected.&nbsp;&nbsp;<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-style-spectrum is-layout-flow wp-block-quote-is-layout-flow\">\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p>\u201cI don&#8217;t think we were necessarily surprised that it sailed right through,\u201d Wittmann told Microsoft Research blog. \u201cAnything that can be used for good can be used for bad. But providing a solution helps avoid a knee-jerk reaction that prevents the use of these tools for good.\u201d<\/p>\n<\/blockquote>\n<\/blockquote>\n\n\n\n<figure class=\"wp-block-image aligncenter size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1920\" height=\"1080\" src=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame7-HeroStill_1920-1080_V03.png\" alt=\"Simulation of the reformulated sequences bypassing the existing filters undetected, prior to the red-teaming patch. \" class=\"wp-image-1151171\" srcset=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame7-HeroStill_1920-1080_V03.png 1920w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame7-HeroStill_1920-1080_V03-300x169.png 300w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame7-HeroStill_1920-1080_V03-1024x576.png 1024w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame7-HeroStill_1920-1080_V03-768x432.png 768w\" sizes=\"auto, (max-width: 1920px) 100vw, 1920px\" \/><figcaption class=\"wp-element-caption\">Simulation of the&nbsp;reformulated sequences&nbsp;bypassing the&nbsp;existing filters undetected, prior to the red-teaming&nbsp;patch.&nbsp;<\/figcaption><\/figure>\n\n\n\n<div style=\"height:10px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"protecting-the-next-leap-in-biology\">Protecting the next leap in biology<\/h2>\n\n\n\n<div class=\"annotations \" data-bi-aN=\"margin-callout\">\n\t<article class=\"annotations__list card depth-16 bg-body p-4 annotations__list--right\">\n\t\t<div class=\"annotations__list-item\">\n\t\t\t\t\t\t<span class=\"annotations__type d-block text-uppercase font-weight-semibold text-neutral-300 small\">Blog<\/span>\n\t\t\t<a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/blog\/when-ai-meets-biology-promise-risk-and-responsibility\/\" data-bi-cN=\"When AI Meets Biology: Promise, Risk, and Responsibility\" data-external-link=\"false\" data-bi-aN=\"margin-callout\" data-bi-type=\"annotated-link\" class=\"annotations__link font-weight-semibold text-decoration-none\"><span>When AI Meets Biology: Promise, Risk, and Responsibility<\/span>&nbsp;<span class=\"glyph-in-link glyph-append glyph-append-chevron-right\" aria-hidden=\"true\"><\/span><\/a>\t\t\t\t\t<\/div>\n\t<\/article>\n<\/div>\n\n\n\n<p>The discovery underscored the urgency of expanding the initial study to address a critical question: is a solution possible? Horvitz and Wittmann sought to organize a cross-sector team to take on the challenge, with confidentiality and careful management of information hazards key to their success.<\/p>\n\n\n\n<p>That\u2019s where Jake Beal enters the story. A scientist at RTX BBN Technologies, Beal was tasked with developing the digital safeguards that could catch reformulated toxins before they slipped through. BBN\u2014the research arm of RTX Corporation\u2014has a long history of technological firsts, from helping build the internet precursor ARPANET to sending the first email and pioneering secure communications through quantum-based encryption systems.<\/p>\n\n\n\n<p>As one of the companies that makes biosecurity screening software. BBN\u2019s mission was to bring that same spirit of innovation to the Paraphrase Project.<\/p>\n\n\n\n<p>Beal teamed up with Horvitz, Wittmann, and a tight-knit group of colleagues to shape a response that felt both urgent and deliberate. In the early days of their collaboration, Beal and Horvitz found themselves circling a familiar idea. The threat they were facing didn\u2019t just resemble a biological risk\u2014it felt like a cybersecurity flaw. Horvitz leaned into the analogy. Maybe biosecurity tools needed to be treated like software, constantly updated to stay ahead of evolving threats. He imagined a future where AI safety followed the rhythm of a Windows Update, with patches rolling out in the background, keeping systems resilient without disrupting the flow.<\/p>\n\n\n\n<p>Among the questions Beal asked the coalescing Paraphrase team were: Who can we safely tell? How dangerous is this information? On one hand, the risks needed to be communicated. Transparency was essential for the broader scientific and security communities to understand what was possible and what was vulnerable. On the other hand, too much openness could inadvertently empower bad actors.<\/p>\n\n\n\n<p>But, they reasoned, if someone had the tools and expertise to replicate the experiment within a few hours, they were already close enough to the problem to warrant inclusion.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-style-spectrum is-layout-flow wp-block-quote-is-layout-flow\">\n<p>\u201cIf someone is already in the room, there\u2019s no point in trying to erect a door behind them,\u201d Beal said. \u201cBut there\u2019s also no reason to offer an open door to people on the outside.\u201d<\/p>\n<\/blockquote>\n\n\n\n<p>To further refine the response effort, Horvitz turned to Microsoft\u2019s top cybersecurity minds. He consulted with Executive Vice President for Microsoft Security Charlie Bell and team to explore best practices for handling zero-day vulnerabilities. The input from these experts helped steer the team toward a framework borrowed from the cybersecurity playbook\u2014a protocol known as the Computer Emergency Response Team, or CERT.<\/p>\n\n\n\n<p>Horvitz appreciated having experienced cybersecurity voices in the room. Their involvement gave the work a sense of grounding and made it easier to move forward with confidence.<\/p>\n\n\n\n<p>By developing updated detection algorithms trained to catch new variants, they showed the screening systems could be adapted to detect reformulated threats. It was a proof of concept that underscored both the vulnerability and an approach to updating the existing biosecurity screening software.<\/p>\n\n\n\n<div style=\"height:10px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<figure class=\"wp-block-image aligncenter size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1920\" height=\"1080\" src=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame8-HeroStill_1920-1080_V09-1.png\" alt=\"Simulation of patched screening systems detecting reformulated threats.  \" class=\"wp-image-1151176\" srcset=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame8-HeroStill_1920-1080_V09-1.png 1920w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame8-HeroStill_1920-1080_V09-1-300x169.png 300w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame8-HeroStill_1920-1080_V09-1-1024x576.png 1024w, https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2025\/10\/MS-Paraphrase_Frame8-HeroStill_1920-1080_V09-1-768x432.png 768w\" sizes=\"auto, (max-width: 1920px) 100vw, 1920px\" \/><figcaption class=\"wp-element-caption\">Simulation of&nbsp;patched&nbsp;screening systems&nbsp;detecting&nbsp;reformulated threats.&nbsp;&nbsp;<\/figcaption><\/figure>\n\n\n\n<div style=\"height:10px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"the-path-forward\">The path forward<\/h2>\n\n\n\n<p>For the DNA synthesis companies involved, the outcome brought a sense of relief. While access to DNA sits at the far end of a long chain of events in any hypothetical biosecurity breach, knowing the vulnerabilities have been identified and patched is reassuring.&nbsp;<\/p>\n\n\n\n<p>\u201cThe public at large wants to be able to trust that companies using these amazing technologies to build new products and services are safe and effective, and have their best interest in mind,\u201d said <a class=\"msr-external-link glyph-append glyph-append-open-in-new-tab glyph-append-xsmall\" href=\"https:\/\/ebrc.org\/diggans-james\/\" target=\"_blank\" rel=\"noopener noreferrer\">James Diggans<span class=\"sr-only\"> (opens in new tab)<\/span><\/a>, vice president of policy and biosecurity at Twist Bioscience and chair for the IGSC. \u201cA big piece of this is making sure you\u2019re a responsible steward of the technology you\u2019re developing.\u201d<\/p>\n\n\n\n<p>What began as a curiosity and concern raised by Eric Horvitz has culminated in a <em>Science<\/em> paper marking firsts in AI and biosecurity. The study demonstrates how artificial intelligence can \u201cparaphrase\u201d proteins\u2014reworking amino acid sequences with the aim of preserving structure and, potentially, biological function, while altering form. It\u2019s a concept that feels almost linguistic, but the implications are deeply molecular. Alongside this, the study establishes a protocol for red-teaming biosecurity screening tools, reports a global response to an AI-enabled biosecurity zero-day, and presents a framework for managing information hazards\u2014now recognized by <em>Science<\/em> as a model for publishing sensitive research in a way that balances openness with caution.<\/p>\n\n\n\n<p>But researchers are clear that this is only the beginning. As technologies continue to advance, protective measures must evolve with them. The work will need to be revisited, refined, and reinforced to ensure that innovation does not outpace safety.<\/p>\n\n\n\n<p>It also represents a budding community of scientists committed to working on the defensive tools and models necessary to keep these technologies safe at scale.\u202f And it\u2019s a reminder that in the age of intelligent design, understanding function is just as vital as recognizing form.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-style-spectrum is-layout-flow wp-block-quote-is-layout-flow\">\n<p>\u201cThis is about what the sequence does, not just how it looks,\u201d Horvitz said. \u201cEven if two sequences look different, they might still do the same thing\u2014like cause illness or perform the same job in a cell.\u201d<\/p>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<div class=\"wp-block-group is-layout-constrained wp-block-group-is-layout-constrained\">\n<div style=\"height:5px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p><em><strong>Paraphrase Project contributors:<\/strong><\/em> Bruce J.\u202fWittmann (Microsoft), Tessa\u202fAlexanian (The International Biosecurity and Biosafety Initiative for Science\/IBBIS), Craig\u202fBartling (Battelle), Jacob\u202fBeal (RTX BBN), Adam\u202fClore (Integrated DNA Technologies Inc\/IDT), James Diggans (Twist Bioscience), Kevin Flyangolts (Aclid), Bryan T.\u202fGemler (Battelle), Tom\u202fMitchell (RTX BBN), Steven T.\u202fMurphy (RTX BBN), Nicole E.\u202fWheeler University of Birmingham), Eric\u202fHorvitz (Microsoft)<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-group is-layout-constrained wp-block-group-is-layout-constrained\">\n<div style=\"height:5px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:22%\"><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-group theme-dark is-style-default container is-layout-constrained wp-block-group-is-layout-constrained\">\n\n\n<div style=\"padding-bottom:32px; padding-top:32px\" class=\"wp-block-msr-immersive-section alignfull row wp-block-msr-immersive-section\">\n\t\n\t<div class=\"container\">\n\t\t<div class=\"wp-block-msr-immersive-section__wrapper col-lg-11 col-xl-9 px-0 m-auto\">\n\t\t\t<p><em><em><strong>Story contributors:<\/strong><\/em> <em>Tetiana Bukhinska,<\/em><\/em> <em>Lucas Clark, <em>Jeremy Crawford<\/em><\/em>, <em><em>Kristina Dodge, <em>Chris Duryee<\/em><\/em><\/em>, <em><em>David Celis Garcia, Alyssa Hughes,&nbsp;<\/em>Lindsay Kalter, Jeremy Mashburn<\/em>, <em>Sarah McGee, <em>Amanda Melfi, <em>Matthew McGinle<\/em><\/em><\/em>y, <i>Wil Morrill, <\/i><em style=\"font-style: italic;\">Joe Plummer,<\/em> <em><em>Brenda Potts<\/em><\/em>, <em>Amber Tingle<\/em>, <em>Shauna Whooley<\/em><\/p>\n\n\n\n<p><em>Originally published on October 6, 2025<\/em><\/p>\t\t<\/div>\n\t<\/div>\n\n\t<\/div>\n\n\n\n<div style=\"height:60px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<h3 class=\"wp-block-heading is-style-default h2\" id=\"lightning-talks\">Other resources<\/h3>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:50%\">\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-vertically-aligned-top is-layout-flow wp-block-column-is-layout-flow\">\n<p><a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/podcast\/\">Microsoft Research Podcast<\/a><\/p>\n\n\n\n<p><a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/blog\">Microsoft Research Blog<\/a><\/p>\n\n\n\n<p><a href=\"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/story\/sep-2024-brief\/\">Microsoft Research Forum series<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-top is-layout-flow wp-block-column-is-layout-flow\">\n<p><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<div style=\"height:60px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n<\/article>\n","protected":false},"excerpt":{"rendered":"<p>In the fall of 2023, breakthroughs in generative AI had researchers proclaiming a new era for medicine and healthcare.<\/p>\n","protected":false},"featured_media":1151109,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","footnotes":""},"research-area":[13556],"msr-locale":[268875],"msr-post-option":[],"class_list":["post-1150632","msr-story","type-msr-story","status-publish","has-post-thumbnail","hentry","msr-research-area-artificial-intelligence","msr-locale-en_us"],"related-researchers":[{"type":"user_nicename","display_name":"Eric Horvitz","user_id":32033,"people_section":"Section name 0","alias":"horvitz"},{"type":"user_nicename","display_name":"Bruce Wittmann","user_id":43991,"people_section":"Section name 0","alias":"bwittmann"},{"type":"guest","display_name":"James Diggans","user_id":1151030,"people_section":"Section name 0","alias":""}],"related-publications":[1151114],"related-downloads":[],"related-videos":[],"related-projects":[1151019],"related-groups":[],"related-events":[],"related-posts":[1150818,1151021],"msr_impact_theme":[],"_links":{"self":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-story\/1150632","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-story"}],"about":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/types\/msr-story"}],"version-history":[{"count":61,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-story\/1150632\/revisions"}],"predecessor-version":[{"id":1158587,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-story\/1150632\/revisions\/1158587"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media\/1151109"}],"wp:attachment":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media?parent=1150632"}],"wp:term":[{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=1150632"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=1150632"},{"taxonomy":"msr-post-option","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-post-option?post=1150632"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}