Comment from Edward Lee

I write in strong opposition to the proposed revisions to the regulation governing Federal financial assistance. As a physician-scientist leading research on Alzheimer’s disease and related dementias, I am deeply concerned that these changes would fundamentally weaken the scientific foundations that have made the United States the global leader in biomedical discovery. Several provisions are particularly troubling and, taken together, represent a profound shift away from a merit-based, expert-driven system: • Allowing political appointees to control grant awards introduces the risk of non-scientific influence in funding decisions that should be guided by technical expertise and peer evaluation. • Making peer review non-binding undermines the core mechanism that ensures rigor, feasibility, and impact in federally funded research. • Permitting termination of active grants at any time, for any reason would create unacceptable instability, particularly for long-term, resource-intensive studies such as those required in neurodegenerative disease research. • Allowing funding decisions based on organizational “affiliations” raises serious concerns about fairness, transparency, and the potential chilling effect on essential scientific collaboration. • Expanding centralized authority under OMB, including oversight of funding decisions and recipient institutions, risks displacing agency expertise with broad administrative control. The cumulative effect of these changes would be to replace a stable, predictable, and scientifically grounded funding system with one characterized by uncertainty, politicization, and administrative overreach. For dementia research, the implications are especially severe. Progress in this field depends on sustained funding, long-term patient cohorts, complex collaborations, and the ability to pursue high-risk, high-reward scientific questions. Disruptions to these elements will slow discovery and delay translation into therapies for patients facing progressive and fatal diseases. At a time when the burden of Alzheimer’s disease is rapidly increasing, we should be strengthening the mechanisms that enable scientific progress, not weakening them. These proposed changes would discourage investigators, destabilize research programs, and erode confidence in the fairness and integrity of federal funding. I strongly urge withdrawal or substantial revision of these provisions to preserve a system that is merit-based, stable, transparent, and guided by scientific expertise. The stakes for patients, the research enterprise, and public trust are simply too high.