Intended for healthcare professionals

Feature Christmas 2009: Diagnosis

Darwin’s illness revisited

BMJ 2009; 339 doi: (Published 14 December 2009) Cite this as: BMJ 2009;339:b4968

Re: Darwin’s illness revisited

Charles Darwin’s Illness – One step Forward, One step Back.

The diagnosis of Darwin’s illness may perhaps be moved forward and the actual mtDNA mutation that was the cause of his illness identified. The alternate diagnoses that have been suggested, in particular those of lactose intolerance and a Meniere type disorder can be explained by the same mutation. Darwin’s illness may also be traced back a further generation to his mother’s mother who had symptoms herself as well as three, perhaps four afflicted children.[1]

As well as symptoms that are commonly associated with CVS Darwin had several other symptoms, symptoms not seen in CVS – episodes of memory loss and partial paralysis.[2] These were stroke-like episodes, characteristic of the MELAS syndrome.[3] Headaches, visual disturbances, peripheral neuropathy and abdominal pain may occur in patients with CVS but also occur in the MELAS syndrome. 80% of patients with the MELAS syndrome have an A3243G mtDNA mutation; the same mutation has been described in patients with CVS.[4]

Patients with the A3243G mutation are known to have a variety of abdominal symptoms, including food allergies and intolerance to certain foods, nausea, vomiting, constipation, diarrhea, bloating and cramping.[3] This explains many of Darwin’s intestinal symptoms. The A3243G mutation has been shown to be associated with impaired vestibular function even in those patients without overt vestibular symptoms,[5] explaining Darwin’s seasickness and his Meniere type symptoms. An A3243G mtDNA mutation provides common ground for the diagnosis of CVS and the MELAS syndrome and also allows for symptoms of lactose intolerance and Meniere’s disorder.

Darwin inherited his mitochondria and his mitochondrial illness from his mother Susannah (1765-1816) and shared his illness with his maternal Uncle Tom (1771-1805). It is possible to take the illness one generation back, to their mother, Sally Wedgwood (1734-1815). Although living to old age, Sally was unwell, particularly after the birth of Tom.[1] She suffered from rheumatism and depression.

As well as Susannah and Tom, Sally had six other children, including Richard (1767-8) and Mary Ann (1778-86). Richard died in infancy with a gastric complaint; Mary Ann was sickly from birth and had periodic fits with partial paralysis and temporary blindness. She died at the age of eight.[1] She may be the first recorded case of the MELAS syndrome.

Sally, Charles Darwin’s grandmother, may or may not have had symptoms of a mitochondrial illness. She did however have abnormal mitochondria and passed these to three, perhaps four of her eight children. The disease that afflicted Charles Darwin had a matrilineal pattern of inheritance spanning three generations.


1. Wedgwood, B. and H. Wedgwood, The Wedgwood Circle 1730-1897. 1980, London: Macmillan Publishing Co.

2. Jones, H.B. (1867) Letter 5639 — Jones, H. B. to Darwin, Emma. Darwin Correspondence Project Database (letter no. 5639; accessed 9 December 2010).

3. Finsterer, J., Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation. Acta Neurol Scand, 2007. 116(1): p. 1-14.

4. Salpietro, C.D., et al., A mitochondrial DNA mutation (A3243G mtDNA) in a family with cyclic vomiting. Eur J Pediatr, 2003. 162(10): p. 727-8.

5. Iwasaki, S., et al., The mitochondrial A3243G mutation involves the peripheral vestibule as well as the cochlea. Laryngoscope, 2011. 121(8): p. 1821-4.

Competing interests: Original author

13 February 2012
John Hayman
The University of Melbourne
Parkville, Victoria, 3010, Australia