arXiv:2507.19568v1 Announce Type: cross Abstract: Artificial intelligence (AI) has sparked immense interest in drug discovery, but most current approaches only digitize existing high-throughput experiments. They remain constrained by conventional pipelines. As a result, they do not address the fundamental challenges of predicting drug effects in humans. Similarly, biomedical digital twins, largely grounded in real-world data and mechanistic models, are tailored for late-phase drug development and lack the resolution to model molecular interactions or their systemic consequences, limiting their impact in early-stage discovery. This disconnect between early discovery and late development is one of the main drivers of high failure rates in drug discovery. The true promise of AI lies not in augmenting current experiments but in enabling virtual experiments that are impossible in the real world: testing novel compounds directly in silico in the human body. Recent advances in AI, high-throughput perturbation assays, and single-cell and spatial omics across species now make it possible to construct programmable virtual humans: dynamic, multiscale models that simulate drug actions from molecular to phenotypic levels. By bridging the translational gap, programmable virtual humans offer a transformative path to optimize therapeutic efficacy and safety earlier than ever before. This perspective introduces the concept of programmable virtual humans, explores their roles in a new paradigm of drug discovery centered on human physiology, and outlines key opportunities, challenges, and roadmaps for their realization.