How Animal Research Advances Physiology and Medicine

How Animal Research Advances Physiology and Medicine 

Explore the essential role of animal models in scientific discovery.

The ethical and scientific foundation of animal research has been well-established. But in today’s politicized climate, its role is being questioned now more than ever—loudly and often without scientific basis.

At the center of the debate is a fundamental misunderstanding that modern research technology can fully replace animal models. Tools such as organ-on-a-chip, microphysiological systems and artificial intelligence (AI) offer exciting possibilities—but they are not substitutes for the complex living systems required to understand how the body functions. For physiologists and biomedical researchers, there is no viable replacement for animal research, and understanding why is critical to protecting scientific progress. 

First introduced in 1959 in “The Principles of Humane Experimental Technique,” the principles of the 3Rs—reduction, refinement and replacement—have guided animal use in research for decades. These principles shape how investigators design experiments and write animal use protocols, and how institutional animal care and use committees function. The 3Rs are embedded into the Guide for the Care and Use of Laboratory Animals and the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. The 3Rs are not aspirational; they are standard. But of the three, replacement is the most frequently misunderstood—and the most politicized. 

Anti-animal research activists have long focused on replacement, arguing that the existence of alternatives—no matter how limited—makes continued animal use unethical. Recently, this argument has gained traction in policy circles. Proponents of organ-on-a-chip and microphysiological systems often present these technologies as side-by-side replacements for animals in research.  

Federal agencies are responding to this momentum. U.S. Health and Human Services Secretary Robert F. Kennedy Jr. said he intends to oversee a “dramatic reduction in animal testing,” in part because of the promise of AI to replace animals in research. His statement was followed by an announcement from the U.S. Food and Drug Administration about plans to phase out animal testing requirements for monoclonal antibodies and other drugs. 

However, this effort is not limited to clinical research and drug development. The National Institutes of Health (NIH) has announced an initiative to “prioritize human-based research technologies.” A new Office of Research Innovation, Validation and Application will validate alternative models. NIH announced in July that it will no longer issue Notices of Funding Opportunity that exclusively support animal models. 

Despite growing enthusiasm for alternatives, there is currently no full replacement for animal models. Studying organ systems or disease states requires approaches that are not limited to animal or non-animal based models.

APS member Caitlin Vonderohe, DVM, PhD, studies diseases primarily affecting infants and children. These conditions are rare, devastating and biologically distinct from disease states in adults. Her research program, like many others, seeks to leverage the strengths of all available models available. 

“The physiological differences between preterm infants and healthy adults who would be likely to volunteer for a clinical trial are insurmountable,” Vonderohe says. “Therefore, we’ve developed a research program that leverages the strengths of both animal and non-animal models.”

This kind of layered, multi-model design is common in physiology—and what the 3Rs intend to promote. APS remains committed to ensuring researchers have access to the range of resources they need to answer fundamental questions about life and health. This includes alternatives where appropriate and animal models where necessary.

Send questions or comments to tphysmag@physiology.org.

This article was originally published in the November 2025 issue of The Physiologist Magazine. Copyright © 2025 by the American Physiological Society.