The hegemony of empiricism: the opportunity for theoretical science in medicine.

Partly spurred by the rapid emergence of discovery tools, empirical science founded on experimental validation now dominates academic funding, publishing, and recognition while forums for theoretical science have been marginalized. Although this hegemony of empiricism instills useful discipline to the scientific process, it also limits the pace of science to sensor innovation and renders the ontogeny of scientific knowledge path-dependent, concealing potential discontinuities in intellectual trajectories. Theoretical science, founded on intuition, inspiration, and abstraction, can complement empirical science by creating disruptive paradigms that facilitate detection of spurious results and frame new hypotheses. For example, framing the compendium of human diseases as varying manifestations of buffer dysfunctions - insufficient or maladaptive responses to stress - portends new insights into disease mechanisms and treatments. As a specific incarnation of this theory, the "trauma hypothesis" suggests that the coordinated regulation of inflammation, coagulation, vasoconstriction, and fluid retention that evolved as a prehistoric adaptation to predatory stress and environmental injury conspires in modern times to produce acute coronary syndromes, heart failure, renal dysfunction, stroke, and pulmonary embolism. The theory also exposes the paradigmatic flaw behind the half-century detour perfecting balloon-deployed endovascular interventions. As the basis of buffer acquisition shifts from genetic to cognitive, phenoptosis - the theory that adaptive programmed death of organisms yields opportunity to successors - is rendered maladaptive, as an extended lifespan permits more efficient trait acquisition compared with life-death recycling. While forestalling death is a largely unfruitful medical game of "whack-a-mole" today, the recognition that aging and death may be programmed adaptations suggests they may also be amenable to systemic reprogramming. Epitomizing this opportunity are tumor cells, which reprogram themselves to escape their apoptotic fate and assume indefinite persistence. The prevalence and resilience of these cancer cells, and their ability to withstand the protean assaults of toxins, poisons, radiation, and host defenses, presage the potential robustness of life when appropriately programmed. Paradoxical medicine and dynamic range management may represent initial strategies to reprogram the neuroendocrine stress axes to modulate lifespan at the organism level, and many other strategies are anticipated. The key to theoretical science is original insight, but the prevailing pressure to conform to medicine's educational and practice standards dis-incentivizes independent thinking. A scientific future is envisioned when the commoditization of experimental science will enable its outsourcing, liberating health scientists from the tyranny of empiricism to engage in a more balanced process of discovery infused with theoretical considerations.