The Subtle Crisis: Public Domain Genomes and the Ethics of Translational Infrastructure.

Public domain human genomic resources are infrastructure: tools researchers use to ask basic biological questions whose answers are then translated into products and care. Translational science now asks them to support an expanding set of tasks, including clinical variant interpretation for diverse populations, pharmacogenomic prescribing, polygenic risk prediction, and the training of clinical artificial intelligence. The corpus of public domain genomes, due in large part to upstream recruitment choices, is not fit for these purposes, and the gap between discovery and translation is widening. This essay argues that closing the gap requires treating public domain genomic infrastructure as a particular object of translational bioethics rather than a technical precondition for it. The limited number of genomes in the public domain relative to the broader genomic record, and the typology-friendliness of how that record represents human variation, are two faces of the same set of upstream choices. Reversing them is not a matter of more sampling under existing terms; it is a matter of building infrastructure of a particular kind; infrastructure made from people. That category, common in genomics but absent from the rest of science, demands an ethical apparatus the field has not yet built. Here we consider the commitments such an apparatus requires, and argue that where, how, and with whom we build genomic infrastructure is itself an ethics question the field has largely declined to ask.