Abstract
Organ-on-a-chip platforms have been widely promoted as imminent replacements for animal research, a theme prominently featured in Science (August 14, 2025, pp. 676-679). This commentary critically examines these claims in light of the current evidence base. While microphysiological systems provide useful adjunctive data, their predictive scope is limited by selective validation, material sorption effects, reliance on nonspecific endpoints, and unverified assumptions about metabolic competence. Economic projections of industry-wide savings rest on optimistic modeling rather than empirical demonstration. Moreover, premature policy initiatives to phase out animal studies risk undermining patient safety. This article argues for cautious integration of new approach methodologies (NAMs) alongside, rather than instead of established animal research, with emphasis on independent multisite validation and global regulatory harmonization.