Key Nucleic Acid Synthesis Policies

US Government Policies

Executive Order on the Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence

§4(b) of the October 2023 Executive Order on the Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence put forward several actions the federal government must take “[t]o reduce the risk of misuse of synthetic nucleic acids, which could be substantially increased by AI’s capabilities in this area, and improve biosecurity measures for the nucleic acid synthesis industry,” including:

(i) By April 27, 2024:

• The government will create a framework for screening synthetic nucleic acid orders.
• The government will establish criteria for identifying potentially dangerous nucleic acid sequences.
• The government will determine methods for screening orders and customers, and for reporting suspicious activities.

This resulted in the US Framework for Nucleic Acid Synthesis Screening (Framework), released on April 29, 2024 and detailed below.

(ii) By April 27, 2024:

• The government will initiate an effort to engage with industry and relevant stakeholders to develop Provider-focused guidance for adhering to the Framework, including: 
  • Specifications for effective nucleic acid order screening;
  • Best practices for managing databases of concerning nucleic acid sequences;
  • Technical guides for implementing screening; and
  • Best practices for assessing compliance with these guidelines.

This is an additional effort complementary to the Framework, currently being led by the White House Office of Science and Technology Policy (OSTP). Item (ii) also requires the National Institute of Standards and Technology (NIST) to partner with industry and other relevant stakeholders to develop compliance resources for the Framework, a process already underway by NIST via a 2-year cooperative agreement with the Engineering Biology Research Consortium (EBRC).

(iii) By October 26, 2024:

• Government agencies funding life sciences research must set a funding requirement for federally funded entities that synthetic nucleic acid is purchased only from providers or manufacturers who adhere to the Framework.

The National Institute of Allergy and Infectious Diseases, National Science Foundation, Department of Defense, Department of Agriculture, and Department of Energy all fund life sciences research and will be part of the Framework implementation. Each federal funding agency will establish requirements for Provider and Manufacturer adherence to the Framework under statutory and regulatory authorities applicable to them, such as through the terms and conditions of awards for life sciences research.

(iv) Regarding implementation:

• By October 26, 2024, the Department of Homeland Security (DHS) will develop a stress-testing framework for conformity assessment of Providers and Manufactures with the Framework.
• After developing this framework, DHS will submit annual reports to the White House on the results, including recommendations for strengthening the screening process.

US Framework for Nucleic Acid Synthesis Screening

To help manage the risks of AI and to safely seize its benefits in synthetic biology, the White House’s Office of Science and Technology Policy (OSTP) released the US Framework for Nucleic Acid Synthesis Screening (Framework) on April 29, 2024. The AI EO released in October 2023 required that, within 180 days of the publication of the Framework, all agencies that fund life sciences research will, as appropriate and consistent with applicable law, establish that, as a requirement of funding, synthetic nucleic acid procurement for federally funded research is conducted through providers of synthetic nucleic acids (Providers) and manufacturers of benchtop nucleic acid synthesis equipment (Manufacturers) that adhere to the Framework.

The Framework guides Providers and Manufacturers to screen purchase orders to identify sequences of concern (SOCs) and assess customer legitimacy. Adherence involves:

1. Self-attestation to implementing the Framework through a statement that either is posted on a public website or provided to the federally funded customer and federal funding agency; ​
2. Sequence screening of all purchase orders for synthetic nucleic acids to identify SOCs; ​
3. Customer screening to verify legitimacy of any customers submitting purchase orders of synthetic nucleic acids with SOCs, and purchase orders of benchtop nucleic acid synthesis equipment;​
4. Reporting potentially illegitimate purchase orders of synthetic nucleic acids involving SOCs or of benchtop nucleic acid synthesis equipment; ​
5. Retaining records of relevant information; and ​
6. Taking steps to ensure cybersecurity and information security.

The National Institute of Allergy and Infectious Diseases, National Science Foundation, Department of Defense, Department of Agriculture, and Department of Energy all fund life sciences research and will be part of the Framework implementation. Each federal funding agency will establish requirements for Provider and Manufacturer adherence to the Framework under statutory and regulatory authorities applicable to them, such as through the terms and conditions of awards for life sciences research.

Experts predict that the Framework will pertain to a significant portion of the nucleic acid synthetic sequence market, given the prevalence of federally funded life sciences research. However, biotechnology research (eg, research aimed at developing new molecules for biofuels, textiles, perfumes, etc.) is not captured by this estimate. It’s uncertain how much of that research is federally vs. non-federally funded and what the market size comparison is to research on pathogens and toxins. 

US State Policies

California State Policy 

In August 2022, California passed AB 1963, requiring the California State University (CSU) and requesting the University of California (UC) to develop systemwide guidance for purchasing gene synthesis equipment or gene synthesis products from gene synthesis providers who prevent the misuse of synthetic genes and safeguard the benefits of gene synthesis technology while minimizing risk, and to consider including International Gene Synthesis Consortium (IGSC) criteria in their guidance.  

The UC Guidance recommends, “Prior to purchasing gene synthesis equipment or gene synthesis products [purchasers], those placing orders, including researchers, lab managers, students, and local procurement offices, should ensure that the gene synthesis provider meets the IGSC criteria or that the provider applies protections commensurate to the IGSC criteria.” An explanation of the IGSC criteria and commensurate protections are provided in the guidance. At a high level, they include:  

1. Gene sequence screening;  
2. Customer screening;  
3. Record keeping;  
4. Order refusal and reporting; and  
5. Regulatory compliance.

The UC Guidance recommends that purchasers ensure providers meet these criteria/apply such protections by asking that the providers fill out this attestation form. Alternatively, the UC Guidance allows providers to present other written information demonstrating that they meet these criteria/apply such protections.

The CSU Guidance cannot be found online at this time.

To help purchasers comply with the guidance, UC and CSU created a “Smartsheet dashboard,” which lists the gene synthesis providers that meet the IGSC criteria. This dashboard also includes an online tool for requesting provider attestations.

The main differences between the California law, subsequent UC Guidance, and the US Framework for Nucleic Acid Synthesis Screening, are as follows: 

• Scope of Manufacturer Requirements: Manufacturers, as defined in the Framework, are not explicitly mentioned in the California law, while the Framework includes requirements for Manufacturers across the categories of self-attestation for compliance, nucleic acid sequence screening (beginning in October 2026), customer screening, reporting of concerning orders or customers to the relevant authorities, retaining records of relevant information, and cybersecurity and information security.
   
• Applicability: California law only applies requirements to the California State University (CSU), while the Framework applies to all federally funded life sciences research.
   
• Nucleic Acid Screening Order and Customer Protocol References: The UC Guidance defers to the nucleic acid synthesis order and customer screening requirements developed by the IGSC (ie, the Harmonized Screening Protocol), while the Framework sets screening requirements that build on top of the Administration for Strategic Preparedness and Response (ASPR)’s Screening Framework Guidance for Providers and Users of Synthetic Nucleic Acids and its corresponding Companion Guide to Assist in Implementing the Recommendations of the Screening Framework Guidance for Providers and Users of Synthetic Nucleic Acids.
   
  • Base Pair Thresholds for Screening: Potentially most significantly, the UC Guidance directs that Providers flag orders at 200 base pairs or more by relying on the IGSC’s Harmonized Screening Protocol. The Framework does the same, but additionally directs that Providers and Manufacturers begin flagging orders at 50 base pairs by October 2026 to comply with the Framework.
     
• Cybersecurity and Information Security: Neither the California law nor the UC Guidance specifically addresses Provider or Manufacturer cybersecurity and information security requirements, as does the Framework.
   
• Self-Attestation Requirements: The UC Guidance directs Providers to fill out a self-attestation form “to demonstrate that they apply the IGSC criteria or commensurate protections. Alternatively, gene synthesis providers may present other written information demonstrating that they prevent the misuse of synthetic genes and safeguard the benefits of gene synthesis technology while minimizing risk.” The Framework directs Providers and Manufacturers to self-attest by either posting a statement on a public website or providing it to both the federally funded customer and federal funding agency.
   
• Recordkeeping Duration: The UC Guidance has recordkeeping requirements for Providers for 3 years, while the Framework requires that both Providers and Manufacturers keep records for 3 years.

International Policies

International Gene Synthesis Consortium (IGSC)

As mentioned above, the International Gene Synthesis Consortium (IGSC) is an industry-led group of gene synthesis companies and organizations formed to design and apply a common protocol to screen both the sequences of synthetic gene orders and the customers who place them. In addition, the consortium works with national and international government organizations and other interested parties to promote the beneficial application of gene synthesis technology while safeguarding biosecurity. IGSC has created a Harmonized Screening Protocol for IGSC members and others to use for these purposes, which may be updated to align with the Framework.