Causal fracture from biomarker to clinical performance: A critical reappraisal of the 2D:4D ratio in surgical skills and the developmental-stress-training interaction model.

The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic morphological trait widely used as a retrospective biomarker of prenatal androgen exposure. This critical review reappraises its causal validity as a predictor of complex behavioral phenotypes, using surgical technical performance as a test case, and proposes a Developmental-Stress-Training (DST) interaction model. Each inferential link-prenatal androgen exposure to the 2D:4D phenotype, the phenotype to central motor and visuospatial development, and neurodevelopmental differences to surgical technical performance-was examined for construct validity, measurement reliability, direct empirical association, and confounding by deliberate training. The causal chain fractures at all three links: the first holds only at the population level (individual classification accuracy 37.8%, approximately 60% between-group overlap); the second is biologically plausible but empirically unverified, with meta-analytic 2D:4D-spatial ability effect sizes negligible and heterogeneous; and the third is dominated by training effects, with baseline predictors collectively accounting for less than 15% of performance variance. Two paradigm-level confounders-reverse causation and methodological artifact-further destabilize the evidence base. Current evidence therefore does not support 2D:4D as a valid predictor of surgical skill or as a stand-alone selection instrument. The DST model repositions 2D:4D as a distal, weak developmental input gated by stress-resilience context and dominated by training-induced neuroplasticity, yielding six falsifiable propositions for longitudinal research on early developmental programming and human behavioral development.