Balancing the Promise of Revolutionary Biotechnology with the Peril of Potential Misuse
In 2018, scientists at a leading biotechnology company assembled a complete horsepox virus using commercially synthesized DNA fragments. This breakthrough, while valuable for research, sent shockwaves through the biosecurity community—horsepox shares significant genetic similarity with smallpox, a devastating disease eradicated from nature but now potentially recreatable in laboratories worldwide 1 . This achievement highlighted a profound paradox: the same technology that promises revolutionary advances in medicine and biotechnology could also enable unprecedented biological risks.
The field of synthetic biology stands at a crossroads. DNA synthesis technology has advanced to the point where researchers can write genetic code as easily as we read it, enabling incredible advances in medicine, energy, and agriculture. But this powerful capability is becoming increasingly accessible, raising urgent questions about how to prevent misuse. As artificial intelligence begins to lower the technical barriers to designing dangerous pathogens, the security of DNA synthesis has emerged as one of the most pressing challenges at the intersection of science and security 1 .
Gene synthesis, often called DNA printing, refers to the process of artificially creating DNA sequences without a natural template. Unlike traditional genetic engineering that modifies existing DNA, synthesis builds molecules from scratch using chemical or enzymatic processes. This approach allows scientists to design entirely novel genetic sequences that may never have existed in nature, opening possibilities from bacteria that produce life-saving drugs to microorganisms that efficiently generate biofuels 3 .
The current workhorse technology, dominated the market in 2024 with approximately 48% share 2 .
The DNA synthesis market reflects the field's remarkable growth and diversification. By product type, the market divides into oligonucleotides (short DNA fragments) and synthetic genes (complete functional units). While oligonucleotides captured approximately 42% of the market in 2024, the synthetic genes segment represents the fastest-growing category, driven by demand for complete genetic pathways for therapeutic and industrial applications 2 .
| Category | Leading Segment | Market Share | Fastest-Growing Segment | Primary Drivers |
|---|---|---|---|---|
| Product Type | Oligonucleotides | 42% | Synthetic Genes | Gene therapies, metabolic engineering |
| Technology | Solid-Phase Synthesis | 48% | Enzymatic DNA Synthesis | Environmental benefits, longer sequences |
| Application | Research & Development | 44% | Therapeutics Development | Personalized medicine, genetic disorders |
| End User | Academic & Research Institutions | 39% | Biotechnology & Pharmaceutical Companies | Drug discovery, diagnostic development |
The therapeutic potential of synthetic DNA represents one of the most exciting application areas. "In gene therapy, DNA and RNA are used. Human gene therapy has the potential to be a useful tool in the fight against acquired immunodeficiency syndrome, cancer, diabetes, high blood pressure, coronary heart disease, peripheral vascular disease, neurodegenerative diseases, haemophilia, cystic fibrosis, and other genetic disorders," according to market analysis 2 . The therapeutics development segment is expected to be the fastest-growing application area in the coming years.
Recognizing the potential risks, the synthetic biology community has developed screening protocols to identify potentially dangerous orders before they're synthesized. The current U.S. Framework for Nucleic Acid Synthesis Screening establishes specific requirements for providers 5 .
Providers must screen orders against databases of "Sequences of Concern" (SOCs)—sequences from pathogens with significant potential for harm 5 .
Providers must screen customers for legitimacy, watching for red flags such as recipients whose identity isn't clear or unusual payment methods 5 .
Currently, DNA or RNA sequences of 200 nucleotides or longer must be screened (equivalent to about 66 amino acids) 5 .
The screening standards are scheduled to become significantly more stringent in the near future. By October 13, 2026, providers must 5 :
Decrease to 50 nucleotides (about 16 amino acids) from the current 200 nucleotides.
Screen for potential assembly of shorter sequences into dangerous pathways when ordered in bulk.
Screen for additional SOCs known to contribute to pathogenicity beyond those from regulated agents.
This evolution reflects growing recognition that dangerous sequences can be shorter than current thresholds, and that sophisticated actors might attempt to assemble hazardous pathogens from multiple small orders—a practice known as "split-order evasion" 5 .
In 2025, a coalition of biosecurity organizations conducted a red-team exercise to test whether current screening tools could detect potentially dangerous pathogens designed by artificial intelligence. The experiment proceeded through several critical phases 1 :
Researchers used specialized biological design tools—AI systems trained on biological data—to create novel pathogen sequences 1 .
The team employed multiple strategies to disguise the dangerous nature of the sequences, including species masking and chimeric designs 1 .
AI-designed sequences were submitted to various screening tools, including IBBIS's Common Mechanism and SecureDNA's algorithm 1 .
The findings revealed both vulnerabilities and potential solutions in the current screening landscape:
| Screening Method | Detection Rate for Natural Pathogens | Detection Rate for AI-Modified Pathogens | Strengths | Limitations |
|---|---|---|---|---|
| Sequence Similarity | 98% | 42% | Excellent for known threats | Poor against novel or disguised designs |
| Functional Prediction | 76% | 68% | Can identify hazardous function regardless of similarity | Computationally intensive |
| Random Adversarial Thresholds | 94% | 89% | Resilient against evasion attempts | Higher false positive rate |
The red-team study found that while traditional screening methods that relied primarily on similarity to known pathogens were easily evaded by AI-designed sequences, newer AI-resilient screening approaches showed promise. The study concluded that screening tools could potentially be "patched to catch most sequences disguised by current AI tools," but raised concerns about whether this capability could keep pace with rapidly advancing AI systems 1 .
Perhaps most alarmingly, the experiment demonstrated that large language models could help potential bad actors navigate technical challenges, identify evasion strategies, and troubleshoot experimental procedures—effectively lowering the expertise barrier for biological misuse 1 .
Whether constructing novel biologics or developing new diagnostic tools, researchers rely on a suite of essential reagents and resources. The following toolkit highlights critical components enabling advanced DNA synthesis and engineering:
| Reagent/Resource | Function | Application Examples |
|---|---|---|
| Oligonucleotides | Short DNA fragments (usually 15-200 bases) serving as building blocks | PCR primers, gene assembly, sequencing, probe development |
| Synthetic Genes | Complete functional genetic units designed for specific expression | Metabolic pathway engineering, therapeutic protein production |
| DNA Assembly Enzymes | Enzymes that join DNA fragments seamlessly | Gibson assembly, Golden Gate shuffling, modular construct development |
| Build-Optimization Software | Computational tools streamlining design-build transitions | BOOST software for optimizing synthetic biology workflows 3 |
| Biological Parts Registries | Platforms managing information about standardized biological components | Inventory of Composable Elements (ICE) for part management 3 |
| Genome Analysis Portals | Comparative genomics resources for sequence analysis | IMG/M for microbial genomes, Phytozome for plant genomes 3 |
These tools collectively enable the design, construction, and testing of synthetic genetic elements—from individual genes to entire metabolic pathways. As the field advances, integration between these components becomes increasingly important, with automated workflows reducing manual steps and potential errors.
Recent policy initiatives have created a stronger foundation for comprehensive screening. Significant developments include:
Signed on May 5, 2025, this order directs the Office of Science and Technology Policy to revise the Framework for Nucleic Acid Synthesis Screening within 90 days. The updated framework will require "verifiable" screening mechanisms with real enforcement accountability, including potential penalties such as immediate funding revocation and up to 5-year ineligibility for federal life-science grants for violations 6 .
On the technical front, several promising developments are enhancing screening capabilities:
Platforms like SecureDNA are implementing tamper-proof screening verification that provides mathematically secure proof of compliance while protecting intellectual property 6 .
Next-generation screening tools are incorporating detection of shorter hazardous sequences (down to 30 base pairs) and specialized algorithms to resist evasion attempts 6 .
To combat split-order attacks, researchers are developing systems that can detect patterns across multiple orders—even when placed with different providers 1 .
The challenge of ensuring safe, secure access to DNA synthesis technologies requires ongoing vigilance and adaptation. As AI capabilities advance and synthesis technologies become more accessible, the screening ecosystem must continuously evolve to address emerging risks. This demands not only technical innovations but also international cooperation, effective policy, and responsible scientific practices.
The scientific community, private sector, and government agencies all have critical roles to play in maintaining this delicate balance. As one analysis notes, "Securing DNA synthesis remains an open path for policymakers—a chance to close off a major national security threat from AI" 1 . The question is whether we can implement these protections effectively before potentially dangerous capabilities become widely available.
Collaborative Approach
The future of synthetic biology remains incredibly promising—with potential solutions to some of humanity's most pressing challenges in health, energy, and sustainability. By building robust, adaptive screening systems today, we can help ensure these powerful technologies develop safely and responsibly, maximizing their benefits while minimizing their risks. The path forward requires neither alarmism nor complacency, but rather determined, thoughtful action from all stakeholders in the biological research community.