AI crosses the genome design threshold

Overview

Stanford and Arc Institute researchers used an AI called Evo to write genetic code for 302 bacteriophage viruses from scratch. Sixteen of them worked—they replicated, killed bacteria, and some even outperformed the natural virus they were modeled on. It's the first time a machine has successfully designed complete, functional genomes without human guidance on what genes to include or how to arrange them.

In This Story

4 People

Phage Therapy Goes Mainstream Within 5 Years

3 Context

Craig Venter's JCVI-syn3.0 Minimal Genome (2016)

Key Indicators

16 of 302

AI-designed genomes that worked

5% success rate creating functional viruses from machine-generated code

63%

Minimum protein similarity to nature

Some AI-designed phages shared as little as 63% identity with natural proteins

1.27M

Annual deaths from antibiotic resistance

Global toll expected to reach 1.91 million by 2050

Resistant E. coli strains overcome

AI-phage cocktails rapidly evolved to kill bacteria resistant to natural phages

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People Involved

Brian Hie

Assistant Professor of Chemical Engineering, Stanford University (Lead researcher on Evo model and synthetic phage project)

Patrick Hsu

Co-Founder and Core Investigator, Arc Institute (Leading AI-driven genome editing and CRISPR research)

J. Craig Venter

Founder, J. Craig Venter Institute (Pioneer of synthetic genomics, commenting on AI-designed genomes)

Kevin Esvelt

Associate Professor, MIT Media Lab (Leading biosecurity voice calling for extreme caution)

Organizations Involved

Arc Institute

Independent Biomedical Research Institute

Status: Leading AI-driven synthetic biology research

Arc operates on an eight-year funding model designed to enable high-risk research that traditional academic cycles can't support.

Stanford University

Research University

Status: Academic partner in Evo development and phage research

Stanford's bioengineering and synthetic biology programs provide academic infrastructure for Arc Institute collaborations.

Timeline

Biosecurity Concerns Raised
Policy Response

Kevin Esvelt and other biosecurity experts issue warnings about dual-use risks of AI genome design capabilities.
September 18th, 2025
First AI-Designed Viral Genomes Announced
Scientific Breakthrough

Researchers reveal 16 functional bacteriophages created by Evo AI—first viable organisms designed entirely by machine intelligence without human genome specification.
September 17th, 2025
bioRxiv Preprint Posted
Research Publication

Stanford-Arc team uploads preprint describing AI-designed bacteriophage genomes, pending peer review.
September 12th, 2025
Evo 2 Scales to 9.3 Trillion Nucleotides
AI Development

Arc releases Evo 2, biology's largest AI model, trained on 128,000+ whole genomes and capable of identifying disease mutations in human genes.
November 15th, 2024
AlphaFold Wins Nobel Prize in Chemistry
Recognition

Demis Hassabis and John Jumper awarded Nobel for AlphaFold's protein structure predictions, validating AI's transformative role in biology.
October 9th, 2024
AlphaFold3 and RoseTTAFold All-Atom Expand Capabilities
AI Development

Both teams release next-gen models predicting structures of proteins bound to DNA, RNA, and small molecules—expanding beyond proteins alone.
May 1st, 2024
Evo Model Released in Science
AI Development

Arc Institute publishes Evo, a 7-billion parameter model trained on 2.7M genomes that can design functional CRISPR systems and predict across DNA, RNA, and proteins.
February 27th, 2024
Arc Institute Founded
Institutional

Patrick Hsu, Silvana Konermann, and Patrick Collison launch Arc with $650M, creating eight-year funding model for ambitious biology research.
December 15th, 2021
AlphaFold2 and RoseTTAFold Published
Scientific Milestone

Google DeepMind and David Baker's team simultaneously announce rival protein structure prediction systems, launching public databases.
July 15th, 2021
AlphaFold 2 Solves Protein Folding
Scientific Milestone

DeepMind's AlphaFold 2 predicts protein structures with unprecedented accuracy at CASP14, proving AI can decode biology's fundamental structures.
December 1st, 2020

Scenarios

Phage Therapy Goes Mainstream Within 5 Years

Discussed by: Nature Biotechnology, PLOS Biology, biotech analysts tracking clinical trials and FDA regulatory pathways

AI-designed phage cocktails enter Phase 3 trials and receive FDA approval for treating antibiotic-resistant infections. Companies like Locus Bioscience and BiomX, already in late-stage trials, incorporate AI genome design to rapidly customize therapies for evolving bacterial threats. Phage therapy becomes standard care for resistant infections in hospitals, with AI generating new therapeutic viruses faster than bacteria can evolve resistance. Cost curves for genome synthesis continue falling, making personalized phage treatments economically viable. Success hinges on whether AI-designed phages prove safe at scale and whether regulatory frameworks can handle therapies that evolve in real-time.

Biosecurity Incident Forces Research Moratorium

Discussed by: MIT biosecurity researchers, RAND Corporation analyses, Carnegie Endowment reports on synthetic biology governance

An accidental release from a lab working with AI-designed organisms, or a deliberate misuse attempt using published methods, triggers international alarm. Governments impose temporary moratorium on generative genome design research, similar to the 2015 gene editing summit response. SecureDNA-style screening becomes mandatory for all DNA synthesis globally. Research continues but under heavy regulation requiring pre-publication review of synthetic biology papers. The field fractures between open-science advocates and those prioritizing containment. Progress slows as promising applications get caught in bureaucratic review, while critics argue safeguards came too late.

AI Genome Design Becomes Routine Lab Tool

Discussed by: SynBioBeta industry publications, synthetic biology researchers, AI development labs extending capabilities

Within three years, AI genome design becomes as commonplace as CRISPR editing. Labs routinely use models like Evo to prototype genetic circuits, optimize metabolic pathways, and engineer microbes for industrial applications. The technology democratizes synthetic biology—lowering barriers to entry while raising stakes. DNA synthesis screening catches most dangerous sequences, but the sheer volume of experimentation means governance relies on lab-level responsibility rather than centralized control. Beneficial applications multiply: carbon-sequestering bacteria, programmable probiotics, phages that protect crops. The question becomes whether distributed safeguards scale faster than distributed risks.

Capabilities Plateau, Hype Deflates

Discussed by: Skeptical researchers noting low 5% success rate, technology critics tracking AI limitations in complex systems

The 16-out-of-302 success rate proves difficult to improve. AI can propose genomes, but most don't work for reasons models don't understand. The gap between generating sequences and predicting function remains vast—Venter's observation that 32% of essential genes have unknown functions still holds. Labs discover that AI-designed organisms often fail in unpredictable ways when moved from controlled experiments to real applications. Investment shifts back to traditional synthetic biology with AI as a supporting tool rather than autonomous designer. The breakthrough makes textbooks but doesn't transform the field's pace. Biology remains too complex for current AI to reliably engineer.

Historical Context

Craig Venter's JCVI-syn3.0 Minimal Genome (2016)

1995-2016

What Happened

After 20 years of research beginning with the first bacterial genome sequence, Craig Venter's team built JCVI-syn3.0—a synthetic bacterium with just 473 genes, the minimal genome for independent life. They designed it gene by gene through exhaustive testing, creating the first organism with a fully synthetic genome. The achievement required three design-build-test cycles and revealed that 149 of the 473 essential genes have unknown biological functions.

Outcome

Short Term

Proved humans could design and construct viable genomes through deliberate engineering, establishing synthetic biology's technical feasibility.

Long Term

Created a minimal chassis organism used by 50+ research groups to study fundamental cell biology, but highlighted how much we still don't understand about life's basic requirements.

Why It's Relevant Today

Venter's approach required two decades and human intuition to design 473 genes. Evo generated 302 complete viral genomes in days—a fundamentally different paradigm where AI proposes architectures humans couldn't design manually.

AlphaFold Protein Structure Revolution (2020-2024)

2020-2024

What Happened

DeepMind's AlphaFold 2 solved the protein folding problem at CASP14 in 2020, predicting 3D structures from amino acid sequences with accuracy matching experimental methods. By 2021, they released a database of 200 million protein structures. In 2024, AlphaFold 3 expanded to predict interactions between proteins, DNA, RNA, and small molecules. The achievement won the 2024 Nobel Prize in Chemistry and cut drug discovery timelines by up to 70%.

Outcome

Short Term

Transformed structural biology overnight, giving researchers instant access to protein shapes that previously required months of lab work per structure.

Long Term

Established AI as capable of solving biology's fundamental problems and created infrastructure for AI-driven drug design, though didn't eliminate need for experimental validation.

Why It's Relevant Today

AlphaFold showed AI could read biology's language—predicting what existing sequences do. Evo demonstrates AI writing that language—generating new sequences that do what you want. It's the difference between translation and authorship.

PhiX174 Synthetic Genome (2003)

1977-2003

What Happened

The bacteriophage φX174 was the first DNA genome ever sequenced by Fred Sanger in 1977. In 2003, Craig Venter's team synthesized the entire 5,386-base φX174 genome from chemically made DNA fragments in just 14 days—the first complete genome assembled in vitro. The synthetic virus was fully infectious and functional, proving DNA synthesized in a test tube could produce all features of natural life.

Outcome

Short Term

Demonstrated technical feasibility of genome synthesis and ushered in the age of synthetic biology, showing scientists could construct life from raw chemicals.

Long Term

Established φX174 as the standard model for genome synthesis research and raised first biosecurity questions about recreating pathogens from published sequences.

Why It's Relevant Today

The 2003 synthesis copied nature's design using human-directed assembly. The 2025 AI phages use φX174 as a template but generate novel variations—machines proposing genetic architectures that never existed in nature.