Burgeoning research into early functional programming has opened a new perspective of developmental origins of disease and organ dysfunction. In examining the roots of this emerging paradigm, it appears that crucial observations were made already 25 years ago. Clear examples include the discoveries of foetal alcohol syndrome, cancer in daughters whose mothers had used diethylstilboestrol during pregnancy, and neurotoxicity of lead and methylmercury. However, this research was often considered controversial, scientific conclusions were cautiously hedged, and stakeholders demanded replication in excess. Recognition of the new paradigm was therefore delayed, preventive interventions even further so. In hindsight, and in light of the precautionary principle, the adverse effects incurred on public health and the environment would call for responsible judgment to balance reasonable scientific scepticism against the risks associated with inaction. The traditional scientific scrutiny whether confidence limits include the possibility of no effect must be modified to allow consideration of the likelihood of worst-case scenarios. Additional emphasis should be placed on the question: what could be known, given our study opportunities and methodologies? Our late insights into the early disease origins may then benefit science and prevention.