NIH Requires Gain-of-Function Research Review by June 30

Overview

The U.S. biomedical research landscape is undergoing a sweeping policy transformation. On May 5, 2025, the White House issued an Executive Order titled “Improving the Safety and Security of Biological Research,” triggering immediate and far-reaching actions by the National Institutes of Health (NIH). Central to this response is a mandatory requirement for all NIH awardees: conduct a full review of your research portfolio by June 30, 2025, to identify any project that may qualify as dangerous gain-of-function (GoF) research.

This article breaks down the Executive Order’s central directives, NIH’s enforcement steps, and what research institutions and investigators urgently need to do to stay compliant.

Executive Order Overview: A New Era for Research Safety

President Trump’s Executive Order targets dangerous gain-of-function research that enhances the transmissibility, pathogenicity, or societal impact of infectious agents or toxins. It directs a government-wide halt and reassessment of such research, especially where the current administration considers oversight is weak or nonexistent.

Key Goals

• Terminate funding of GoF research in high-risk countries or other poorly regulated environments.
• Suspend domestic GoF research pending a revised biosecurity oversight policy.
• Require greater transparency, accountability, and regular auditing of all life-science research involving dangerous biological agents.
• Update and enforce nucleic acid screening frameworks for federally and non-federally funded research.

NIH’s Urgent Call to Action: Review by June 30, 2025

In its June 18, 2025 Notice (NOT-OD-25-127), the NIH clarified that awardees must immediately assess their NIH-funded research activities, including formal and unfunded collaborations, to identify projects that meet the new definition of dangerous gain-of-function research.

All portfolio reviews must be completed and submitted to NIH by June 30, 2025. Completing and submitting portfolio reviews is not optional. NIH is not accepting exception requests for projects identified as GoF. Failure to act will result in immediate enforcement actions, including funding suspension or termination.

NIH’s Immediate Actions Include:

• Terminating GoF projects involving foreign entities in countries deemed non-compliant with U.S. oversight standards.
• Suspending all other GoF research activities — even within the U.S. — until new policy guidance is finalized.
• Pausing new grant applications and contract proposals involving GoF research as of May 7, 2025.
• Requiring institutions to proactively notify NIH if any project aligns with the GoF definition but was not previously flagged.

What is “Dangerous Gain-of-Function” Research?

As defined in both the Executive Order and NIH policy, dangerous GoF research includes work that may:

• Increase the harmful effects, stability, or spread of an infectious agent.
• Undermine immune response or vaccine effectiveness.
• Confer resistance to treatment or facilitate evasion of detection.
• Change the host range or enhance transmissibility.
• Reconstitute eradicated or extinct pathogens.

If your research seeks or achieves any of these outcomes, it likely qualifies as GoF and is subject to new restrictions.

Compliance Checklist: What Institutions Must Do Now

Every NIH-funded institution, investigator, and research administrator should immediately take the following actions:

• Initiate a comprehensive review of all NIH-funded projects, including collaborative and unfunded workstreams, for potential GoF risk.
• Cross-check with the GoF definition outlined in Section 8 of the Executive Order.
• Notify your NIH Institute or Center of any relevant projects that match the criteria — even if NIH has not previously flagged them.
• Ensure no new GoF-related grant submissions are made after May 7, 2025.
• Document the review process for transparency and future audit readiness.

The NIH has made it clear that June 30, 2025 is a strict and final deadline. All institutions must act, or face automatic funding action with no option for exemption.

The Bigger Picture: Evolving Oversight in Biological Research

The Executive Order and NIH’s swift implementation signal a significant change in federal oversight of biological research, particularly in areas involving gain-of-function studies. These actions reflect a growing emphasis on risk management, accountability, and consistent standards for biosafety. While institutions may need to adjust internal processes in the short term, the updated framework being developed by the Office of Science and Technology Policy (OSTP) is intended to clarify expectations and ensure alignment across federally supported research initiatives.

Final Word: June 30 Is Closer Than You Think

The June 30 deadline leaves little time for delay or confusion. NIH awardees should act today to complete their reviews, notify the NIH of any covered projects, and safeguard their funding.