Darwin’s life can be read along two lines: one written into textbooks, and another preserved in private letters—recurrent nausea and vomiting, headaches and vertigo, palpitations and sweating, and sudden nighttime terror. Over two centuries he has been assigned more than 30 diagnoses, yet the sheer number of labels may be a clue in itself: this may not be a single-organ problem, but a paroxysmal, multi-system instability. Framed explicitly as a retrospective medical hypothesis, this piece uses mitochondrial energy instability to interpret a maternal pattern, and a “consanguinity magnifier” to understand why Darwin’s children may have appeared more fragile—without claiming certainty, but by re-ordering the clues into a more coherent physiological and genetic picture. Many symptom clusters that look like “anxiety” or “nervous exhaustion” can also arise from upstream physiology—unstable energy supply, a lower metabolic threshold, and recurring autonomic dysregulation. Darwin’s case offers a historical mirror: when the gut, vestibular system, autonomic nervous system, sleep, and emotion are all pulled into the same episodes, misdiagnosis becomes easy. This article does not claim a diagnosis—retrospective reasoning has strict limits—but it argues for one practical takeaway: don’t let “it’s purely psychological” end the trail too early. When the pattern is multi-system and episodic, it can be reasonable to include inherited metabolic disorders and mitochondrial-spectrum conditions in the differential.