The illnesses of Charles Darwin and his children: a lesson in consanguinity

Abstract

Charles Darwin’s lifetime illness with its many disabling symptoms may be explained by an inherited pathological mtDNA mutation. Although such a diagnosis explains Darwin’s illness and the strange illnesses that afflicted his Wedgwood maternal forebears, it does not explain the illnesses that affected Darwin’s children. The sicknesses of the children were very different from those of the father and also different from each other. Although not directly inherited from their father, these illnesses may have been due, at least in part, to inbreeding since they were the inbred progeny from a consanguineous couple (Darwin and his wife were first cousins), a condition known to enhance susceptibility to recessive genetic disorders and infectious diseases. Darwin’s inherited illness may be traced back through three, perhaps four maternal generations. Consanguinity was present in the marriage of Darwin’s maternal grandparents, but the purported mitochondrial mutation appears to have been present prior to this union. The origin of any mutation appears lost in the mist of unrecorded history.

INTRODUCTION

Darwin’s illness and symptoms

Charles Darwin (1809–1882) suffered from a debilitating illness for much of his adult life with numerous symptoms, some of them bizarre (Colp, 2008). On 20 May 1865, Darwin wrote a note on his health for Dr. John Chapman describing his symptoms with the hope that treatment by Chapman would bring relief. Among the symptoms Darwin mentioned were vomiting, flatulence, shivering, ‘singing in ears’, problems in focusing, eczema, fatigue, ‘nervousness when Emma leaves me’ and hysterical crying (Burkhardt et al., 2003). First symptoms of this illness appeared when Darwin was still a student; unpleasant news from home would cause him to ‘lose a great many breakfasts’, and he suffered from attacks of eczema and lethargy (Darwin, 1887). His inability to witness surgical procedures when in Edinburgh and his persistent, severe seasickness on his Beagle voyage may also have been manifestations of this illness.

More than 40 separate and quite disparate diagnoses have been proposed for Darwin’s illness; most of these are incorrect or at best inadequate. Gastrointestinal diagnoses have been popular; these include Crohn’s disease (Orrego & Quintana, 2007), irritable bowel syndrome (IBS; Shanahan, 2012) and ‘systemic’ lactose intolerance (Campbell & Matthews, 2005, 2015) Darwin did have some symptoms that occur in some of the proposed disorders (IBS, chronic fatigue/fibromyalgia, lactose intolerance, panic disorder, paroxysmal tachycardia and atopic dermatitis), but these diagnoses do not account for the full spectrum of his illness. In general, the proponent of a disorder emphasizes those symptoms that may be consistent with the proposed diagnosis and ignores those that are inconsistent. As an example, the proponents of Crohn’s disease ignore Darwin’s seasickness, his headaches, his visual disturbances, his eczema and recurrent boils, his panic attacks, his heat and cold intolerance, his hysterical crying (dacrystic seizures) and his ‘stroke-like’ episodes in later life. Shanahan (2012) expressed the opinion that Crohn’s disease is an improbable diagnosis as Darwin’s weight as recorded from 1849 to 1855 did not decline and his illness improved in later life.

Similarly, the diagnosis of lactose intolerance would seem unlikely. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhoea (Lomer, Parkes & Sanderson, 2008). There may be occasional episodes of nausea and vomiting, but symptoms are predominantly lower intestinal in nature. It strains credulity to think that so excellent an observer as Darwin would not have made the connection between digestive upset and the consumption of dairy products, especially in view of his fondness for sweet puddings and Emma’s heavy use of milk and cream (Bateson & Janeway, 2008). The concept of ‘systemic lactose intolerance’ (Matthews et al., 2005) has not gained general credence; only one group has described this proposed diagnosis, and the condition is not listed in the International Classification of Diseases.

Darwin may well have had some symptoms that occur in IBS, but again the features of this disorder are mostly lower intestinal in nature. Furthermore, Darwin does refer to his stools as being ‘good’ (Burkhardt et al., 2003) – with IBS, they are seldom well-formed. IBS may be associated with functional dyspepsia, other upper intestinal and some systemic symptoms, but not the wide range of nonintestinal symptoms experienced by Darwin. The diagnoses of Crohn’s disease and IBS have previously been refuted at length (Sheehan, Meller & Thurber, 2008; Hayman, 2012, 2014). Those suggesting psychological illness ignore his sudden limb and facial swelling, his vomiting of blood and his constant search for medical help.

Most of the proposals have not considered Darwin’s early symptoms, before he sailed on HMS Beagle, a feature that should exclude diagnoses such as Chagas disease (Adler, 1959). This diagnosis, although comprehensibly refuted by Woodruff (1965), was later supported by his son (Adler, 1989) and his nephew (Adler, 1997) – it remains a romantic, but improbable diagnosis. None of the many proposed diagnoses have accounted for Darwin’s seasickness on HMS Beagle, and none have considered his strange maternal (Wedgwood) family history. A full discussion of these and other proposed diagnoses is available (Hayman, 2015).

Many of Darwin’s symptoms are those that may be experienced by patients diagnosed as having the cyclic vomiting syndrome (CVS; Hayman, 2009), including a susceptibility to motion sickness (in Darwin’s case, his persistent and worsening seasickness throughout the nearly 5-year Beagle voyage), and more unusual symptoms such as attacks of illness being brought on by pleasurable events (positive stress) and relief due to water exposure (Darwin’s ‘water cure’; Berra, 2009).

Mitochondria are organelles that provide most of the energy requirements for the cell, and in animals, their DNA (mtDNA) is the only genetic material located outside the cell nucleus. In humans, all mitochondria and subsequently mtDNA are inherited maternally (Fine, 1978). Today, new technology allows the use of a donor egg in which the nucleus has been removed leaving the cytoplasm that contains the mitochondria and other organelles. The nucleus of the biological mother’s egg is then inserted into the donor ovum, thus avoiding the defective mitochondria of the biological mother’s egg. The egg is then fertilized. A review by Clairborne, English & Kahn (2016) pointed out that the mitochondrial genome contains only 37 genes in comparison with the 20 000–30 000 genes in the nuclear genome, yet pathogenic mtDNA mutations may cause a host of serious diseases (Schaefer et al., 2008). The number of people harbouring such alterations may range from 1 in 200 to 1 in 5000 individuals (Elliott et al., 2008). Avoidance of faulty mitochondria in the unfertilized ovum is now possible, eliminating such defects and resulting in children with three genetic parents (Amato et al., 2014). However, Yamada et al. (2016) warn that if small amounts of the original deleterious mtDNA are carried over during nuclear transfer, this can lead to mtDNA genotype drift and reversion. A healthy three-parent boy was born on 6 April 2016 to a Jordanian couple treated by a US team in Mexico (Hamzelou, 2016).

Wedgwood–darwin family histories and illnesses

As well as being a diagnosis that accounts for the symptoms of Darwin’s lifetime illness, the same pathological mitochondrial mutation would explain the strange illnesses of Darwin’s elder brother, Erasmus (1804–1881), their mother Susannah (1765–1817) and her younger brother Tom Wedgwood (1771–1805; Fig. 1). The youngest sibling of that generation, Mary Ann (1778–1786), was of short stature, physically and mentally retarded and suffered from fits with episodes of cortical blindness (Wedgwood & Wedgwood, 1980; Fig. 2). She died at the age of 8 of a condition that had all the features of the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome, a disease recognized as due to a pathological mtDNA mutation (Pavlakis et al., 1984). Their mother, Sarah (1734–1815; Charles Darwin’s maternal grandmother), also had chronic illness, and as will be discussed, her mother, Charles Darwin’s great grandmother (Susan Irlam, 1703–1760), also had illness (Wedgwood & Wedgwood, 1980; Fig. 1).

Darwin married Emma Wedgwood (1808–1896), the daughter of his mother’s younger brother, in 1839 (Fig. 1). He and his wife were thus first cousins (Freeman, 1982; Berra, Álvarez & Ceballos, 2010a; Berra, Álvarez & Shannon, 2010b). Emma enjoyed relatively good health although she suffered from migraine and probable hyperemesis during her pregnancies (Healey, 2001). There is no record of her children having these difficulties, although they were a sickly lot. Concise biographies of Charles and Emma’s children can be found in Berra (2013). Many, including Darwin himself, have supposed that they inherited their illnesses from their father. In fact, Darwin expressed repeatedly in several letters to his second cousin William Darwin Fox and others that his own ill health led him to fear that his children might have inherited his medical problems (Keynes, 2001).

Since mitochondria are maternally inherited, the proposed pathological mtDNA mutation in Charles Darwin does not explain the illnesses of his children. Their illnesses appear contrary to the preferred diagnosis for their father’s affliction and should therefore be addressed. It is also necessary to take into account that Darwin’s children could not inherit the mtDNA mutation from the Wedgwood lineage through their mother Emma Wedgwood since Emma’s mother was Elizabeth Allen (Fig. 1).

ILLNESSES OF DARWIN’S CHILDREN

Background

Darwin’s children had a moderate–high inbreeding level due to the consanguinity of their parents (Berra et al., 2010a; Álvarez, Ceballos & Berra, 2015). Thus, the pedigree-based inbreeding coefficient computed for Darwin’s children was F = 0.0630, taking into account that Charles and Emma’s grandparents (Josiah Wedgwood I and Sarah Wedgwood) were third cousins (Fig. 1). On theoretical grounds, an increased risk of recessive genetic disorders is expected in Darwin’s children as the result of the increase of genome homozygosity produced by inbreeding (Charlesworth &Willis, 2009; Szulkin, Bierne & David, 2010; Álvarez, Quinteiro & Ceballos, 2011; Bittles, 2012; Hoffman et al., 2014).

A statistically significant inbreeding depression for both childhood survival and male fertility has been detected in the progeny of a number of marriages of the Darwin–Wedgwood dynasty (Berra et al., 2010a; Álvarez et al., 2015). The families included the first cousin marriages of Emma Wedgwood and her brothers Josiah III (married to Caroline Darwin, Charles Darwin’s sister), Hensleigh (married Frances Macintosh, his first cousin) and Henry (married to his double first cousin Jessie Wedgwood) as well as a number of nonconsanguineous marriages of the Darwin–Wedgwoods.

Much evidence supports the possibility of specific inbreeding effects on Charles Darwin’s progeny (Berra et al., 2010a; Álvarez et al., 2015). With regard to survival, three of Darwin’s ten children died at childhood (or infancy), Anne Elizabeth (1841–1851), Mary Eleanor (1842–1842) and Charles Waring (1856–1858). Compared with the childhood mortality of nonconsanguineous progeny of the Darwin–Wedgwoods, which was 9.34 ± 3.23%, the childhood mortality of Charles Darwin’s children (30%) was high. In addition, the cause of death of at least two of these three children is consistent with an inbreeding effect. Empirical evidence reveals that inbreeding is an important risk factor in susceptibility to infectious diseases such as tuberculosis and hepatitis (Lyons et al., 2009a, b); Anne Elizabeth most likely died of disseminated (miliary) tuberculosis and Charles Waring of scarlet fever (Keynes, 2001; Browne, 2002; Fenner, Egger & Gagneux, 2009).

Regarding the effects of inbreeding on fertility, it has been suggested that the unexplained infertility of three of Darwin’s children with long-term marriage history (William Erasmus, Henrietta and Leonard) could be caused by the increased homozygosity for recessive autosomal meiotic mutations due to the cousin marriage (Golubovsky, 2008). This is in accordance with the evidence of an adverse effect of male inbreeding on family size detected in the Darwin–Wedgwoods (Álvarez et al., 2015). Thus, the analysis of the number of children per woman through zero-inflated regression models showed a statistically significant adverse effect of male inbreeding coefficient, whereas statistically significant effects for female inbreeding coefficient and kinship coefficient of the couple were not detected. In particular, the mean number of children per woman for Darwin’s five sons who survive to adulthood (William Erasmus, George, Francis, Leonard and Horace) was 1.25 ± 0.65, whereas the mean family size for the non-inbred men of the Darwin–Wedgwoods was 2.10 ± 0.78 children per woman. This finding is consistent with the evidence of an adverse effect of inbreeding on sperm quality expressed in terms of the increased occurrence of sperm abnormalities in the ejaculate of the more inbred males, which has been reported in humans (Baccetti et al., 2001) as well as in other mammalian species (Roldan et al., 1998; Asa et al., 2007). As a whole, therefore, the evidence of a number of inbreeding effects on Darwin’s children due to the kinship of their parents is considerable and convincing (Berra et al., 2010a; Álvarez et al., 2015).

The above-mentioned studies on the possible inbreeding effects on Charles Darwin’s children have been focused on the inbreeding impact on reproductive fitness. However, it is necessary to take into account that inbreeding might influence a wide range of traits besides reproductive success. According to the principles of population genetics, consanguinity’s primary effect is the increase of genome homozygosity in the inbred offspring. Regarding the impact of inbreeding on morbidity, there is a large body of evidence of enhanced incidence of rare recessive Mendelian disorders in the progeny of consanguineous marriages. In this sense, the estimate of increased risk for congenital disorders in the progeny of first cousin marriages is about 1.7–2.8% compared to the offspring of nonconsanguineous marriages, and in most cases, those defects are attributable to autosomal recessive disorders (Bennett et al., 2002; Hamamy et al., 2011).

Furthermore, inbreeding has been shown to influence an important number of multifactorial or complex diseases such as hypertension, coronary heart disease, stroke, cancer, unipolar/bipolar depression, asthma and gout and peptic ulcer (Rudan et al., 2003a, b, 2006), and as mentioned above, inbreeding increases the susceptibility to infectious diseases (Lyons et al., 2009a, b). Therefore, it would be interesting to examine the health problems suffered by Charles Darwin’s ten children since some problems could be associated with the consanguinity of their parents, whereas some others could be directly inherited from their father.

Chronology of illnesses

If Darwin had a mitochondrial disorder as hypothesized above, this condition does not preclude the presence of other diseases at various times in his life. The severe illness he experienced in Valparaiso, Chile, in September and October 1834 was most likely typhoid (Pickering, 1974), and his terminal illness was ischaemic (coronary artery) heart disease, unrelated to the disease that afflicted him for most of his adult life. His lifetime illness, although initially progressive, troubled him less in his later years. The books he wrote during the last 7 years of his life were much less controversial than his earlier writings. There were botanical titles on climbing plants (1875), effects of cross- and self-fertilization (1876), different forms of flowers (1877), power of movement in plants (1880) and his last book on earthworms (1881). With the production of these books, he had no haste to publish, and there was no anxiety about public vilification.

Darwin was a healthy child whose health deteriorated progressively as an adult, but improved in later life. In addition to the reduction of stress alluded to above, there may also be pathophysiological reason why symptoms improved – mitochondria with mutant DNA may be at a survival disadvantage and decrease over time. Mitochondria with the commonest pathological mutant termed A3243G decrease with age in peripheral blood white cells and are thought to diminish in other tissues with dividing cells (Stewart & Chinnery, 2015).

Darwin’s children

The sicknesses that afflicted Darwin’s ten children had a different chronology from the illness of the father. Their illnesses were worse in childhood; the seven who survived infancy or childhood grew into essentially healthy adults with normal lifespan (Berra, 2013).

William Erasmus Darwin (1839–1914)

William’s infant development was studied intently by his father, and these studies were used in The Expressions of Emotions in Man and Animals (Darwin, 1872) and in an article in the journal Mind (Darwin, 1877). There is no record of William having any unusual illnesses. He remained active even after losing a leg in a hunting accident later in life. He was a successful banker, was married, but had no children.

Anne Elizabeth (Annie) Darwin (1841–1851)

Annie died at the age of 10 in 1851 after a protracted illness, an illness that appeared after an episode of acute infection (scarlet fever) that has been reliably proposed as being progressive miliary tuberculosis (Pickering, 1974; Keynes, 2001). Miliary tuberculosis is usually acquired from close contact with a person who has ‘open’ (pulmonary) tuberculosis, and one question is where Annie might have acquired this infection. Neither parent nor any grandparent appears to have had the infection, and suspicion lies with the town children, with whom Annie mingled freely, or perhaps the nursemaid, Jessie Brodie, who came to the Darwin’s from the Thackerays, a dysfunctional family that had previously lost a daughter in infancy from an unknown cause.

Mary Eleanor Darwin (1842)

Mary Eleanor, Charles and Emma’s second daughter, was born 4 weeks premature shortly after the move to Downe, never thrived from birth and died at 3 weeks of age (Keynes, 2009). Her premature birth in a house that had lain empty for 2 years, being closed and probably poorly ventilated during that time with an accumulation of mould spores and other indoor pollutants that may have impacted on this death.

Henrietta ‘Etty’ Emma Darwin (1843–1927)

Henrietta, their third daughter, also suffered from scarlet fever and a typhoid-like illness and relapsed into becoming a chronic invalid. Browne (2002) described this accurately: ‘Henrietta did make a full recovery in the end and lived to a great old age. But her parents worried over her smallest infirmity for years to come, solicitously hiring bed-carriages for journeys, keeping her indoors most of the time, consulting different doctors, sending health bulletins around the family and devising cautious routines that permitted only half an hour downstairs in the evenings, all of which tipped relatives and friends into regarding her as a permanent invalid. Henrietta emerged at the end of this illness as … a delicate daughter, prone to unspecified infirmities and relapses. … Being ill under Emma’s supervision was an opportunity for a daughter to be cherished, perhaps in contrast to Emma’s normally undemonstrative manner. … The same opportunity to be physically close probably also applied to her father. When she was ill, Henrietta received Darwin’s undivided attention.’ Gwen Raverat, Darwin’s granddaughter via his son George, remarked in Period Piece that ‘ill health became her profession and absorbing interest’ (Raverat, 1952).

This history of sickness is consistent with the diagnosis of a somatization disorder (Mai, 2004), today the most relevant of the numerous psychological or psychogenic diagnoses that have been proposed for Darwin’s own illness (Colp, 2008). This disorder is much more common in females and requires the subject to have a ‘role model’ on which to fashion their illness. Henrietta’s illness fulfils these requirements with her father being the necessary role model. As noted, she did improve and assisted her father with his later publications; she was married, later helped edit her father’s autobiography and her mother’s private papers and lived to the age of 84. She had no children.

George Howard Darwin (1845–1912)

George survived measles as a child and several dental extractions as a teenager. His father records how seeing George’s teeth extracted under chloroform brought on an episode of illness for Charles, similar to his discomfort when Emma gave birth (Burkhardt et al., 1994).

George became a mathematician, an astronomer and a professor of astronomy at Cambridge. He was elected as a Fellow of the Royal Society (FRS) and was president of the Royal Astronomical Society. He was knighted in 1905. He was married and had five children, one of whom died in infancy. The surviving children were also very accomplished. The Darwin family name is transmitted via George’s male offspring (Berra et al., 2010b).

Elizabeth ‘Bessy’ Darwin (1847–1926)

Bessy was regarded as an unusual, rather silent, and unknown entity. Darwin described her as having strange shivers and making extraordinary grimaces. In The Variation of Animals and Plants under Domestication (Darwin, 1868), Charles detailed his and Bessy’s habit, when pleased, of raising their moving fingers to their faces. The similarity of this one habit confirmed his fear that his children had also inherited his medical issues (Berra, 2013).

Bessy’s movements are consistent with a facial or motor tic, a condition not uncommon in children, although more common in males (Leckman et al., 2006). Tics may occur as part of the Tourette syndrome in which there may be an association with conditions such as attention disorder and depression. A mild form of Tourette syndrome would account for both Bessy’s abnormal movements and her unusual demeanour. The genetic basis of Tourette syndrome seems to be complex and not well understood (O’Rourke et al., 2009). Some studies provide evidence for an autosomal dominant inheritance, and consequently, an increase in susceptibility for this disorder in the progeny of consanguineous marriages is not expected. However, the possible contribution of rare recessive genes to this disorder has also been considered, and interestingly, the syndrome has been described in consanguineous families (Motlagh et al., 2008). Elizabeth never married.

Francis ‘Frank’ Darwin (1848–1925)

No record of significant illness is reported for Frank. He studied mathematics and botany at Cambridge and obtained a medical degree in 1875 from St. George’s Medical School, but never practised. His botanical experiments laid the foundation for plant physiology as a science. He was elected a Fellow of the Linnean Society and FRS. Frank assisted his father with plant experiments and contributed to The Power of Movements in Plants (Darwin, 1880) for which he received title-page recognition and edited Darwin’s autobiography and letters (Darwin, 1887). He was knighted in 1913. Francis had two children and outlived three wives (Berra, 2013).

Leonard ‘Lennie’ or ‘Leo’ Darwin (1850–1943)

Leonard was regarded as a delicate child, and his schooling was delayed because of illness. In 1862, he contracted scarlet fever, an illness that was followed by long periods of convalescence with his family in the south of England (Healey, 2001). However, he later attended the Royal Military Academy, Woolwich, being second in the entrance exams. He was commissioned in the Royal Engineers, reached the rank of major and went on several scientific expeditions. He was a fellow and later president of the Royal Geographical Society.

After retiring from 20 years of military service, he became an economist, was elected a Member of Parliament and, later, served as a mentor to population geneticist Ronald Fisher (Berra, 2013). He fully recovered from his childhood illnesses and was the longest lived of the Darwin children, dying at the age of 93. He was married twice but had no children.

Horace Darwin (1851–1928)

As well as childhood fevers, Horace experienced strange episodes as a child. At age 10, these episodes were termed ‘fits’ or shakes. His father described them as ‘the oddest of attacks, many times a day, of shuddering and gasping and hysterical sobbing, semi-convulsive movements, with much distress of feeling. These semi-convulsive movements have been less during these last few days and are never accompanied by loss of consciousness’ (Burkhardt et al., 1997). Darwin feared that his son was developing a neurological complaint related to his own neurological symptoms.

The episodes appear typical of a childhood monosymptomatic somatoform disorder (Garralda, 2010). Horace had developed intense attachment to the family’s German governess, Camilla Ludwig, and the episodes may have developed as a means of having her close to him. In any event, his symptoms improved when Camilla was sent on an extended visit to her mother in Hamburg. Apart from these episodes, he was regarded as frail. He suffered from what was considered indigestion and in 1863 preceded his father as a patient in the ‘water-cure’ resort in Malvern (Healey, 2001).

As an adult, he made a full recovery from these complaints; he went on to qualify as a civil engineer, founded the Cambridge Scientific Instrument Company, was elected FRS, was Mayor of Cambridge for one term and was knighted in 1918. He was married and had three children (Berra, 2013).

Charles Waring Darwin (1856–1858)

Charles was born when his mother was 48 years of age. In the one surviving photo with his mother, he shows features of Down syndrome, a condition much more common in the children of older mothers. Patients with this congenital disorder are more susceptible to infection (Ram & Chinen, 2011); this susceptibility may have been compounded by the consanguinity of his parents, which could have contributed to his death from scarlet fever (Berra et al., 2010a).

Charles darwin’s maternal ancestors

Charles mother, Susannah, was the eldest child of Josiah Wedgwood I (Fig. 1). She suffered from chronic illness as an adult, had ‘difficulties’ with her pregnancies and was famously ‘never quite well & never very ill’ (Wedgwood & Wedgwood, 1980). She died with an acute severe abdominal complaint that may have been one of several conditions. However, this could have been acute pancreatitis, a recognized occurrence in patients with mitochondrial dysfunction (Finsterer, 2007).

Susannah’s mother, Sarah Wedgwood, married a third cousin, Josiah Wedgwood I (1730–1795), and had seven surviving children (Berra et al., 2010a; Hayman, 2013). One child, Richard (1767–1768), died in infancy with an acute abdominal complaint, perhaps the same type of illness that caused the death of his older sister later in life. Sarah also had chronic illness, predominantly arthritis and also a spontaneous abortion after the birth of her fifth child (Wedgwood & Wedgwood, 1980; Fig. 1). This abortion was complicated by ‘inflammation of the liver’, most likely an acute fatty liver, a known complication both of pregnancy (Ko & Yoshida, 2006) and of mitochondrial disorders (Takahashi et al., 2008). As three (Susannah, Tom and Mary Ann) and possibly even more of her children and Sarah herself had evidence of mitochondrial disease, any pathological mtDNA mutation may already have been present.

Sarah’s mother was Susan (Susanna) Irlam of Buglawton, now a suburb of Congleton, Cheshire, who married Richard Wedgwood (1701–1780; Fig. 1). As well as Sarah, she had a daughter, Mary (1736) who died as a neonate, and a son, John (1732–1774). John died at the relatively young age of 42 with a sudden, catastrophic illness (Wedgwood & Wedgwood, 1980). As he had been previously well, conditions such as a perforated peptic ulcer or pancreatitis may be considered a possibility. Susan died after her childbearing years (then the commonest cause of early female death; Loudon, 1986); the cause or mode of death is not recorded. As she had one daughter with recorded illness, a daughter who died as a neonate and a son with a sudden catastrophic illness, she may well have harboured the mutation. There is no information on an elder sister, Hannah (born in 1696), who married a Matthew Wright in 1720.

There is good evidence that CD’s mother, maternal grandmother and, less conclusively, his maternal great grandmother had the proposed mitochondrial abnormality. There is no evidence of mitochondrial disease prior to this generation.

DISCUSSION

Charles Darwin’s children had differing illnesses; three died at an early age from essentially different causes. Infection played a significant role in the illnesses of four children and was most likely responsible for the death of two of these (Anne Elizabeth and Charles Waring). Their various illnesses were clearly different from the lifetime illness that afflicted Charles Darwin and were not directly inherited from their father. This is indirect evidence supporting the diagnosis of a mitochondrial disorder as the cause of many of Charles Darwin’s health problems (Hayman, 2013) since a mitochondrial cause of the ill health would not have been transmitted from father to children.

On the other hand, it is also interesting to examine the inheritance of the reproductive success considered as a biological trait in the Darwin family. The low reproductive fitness exhibited by Darwin’s children who experienced a high mortality at early age and a low male fertility at adult age does not seem to have been inherited in a simple fashion from their father as Charles and all his siblings survived to adult age (Berra et al., 2010a) and Darwin himself had normal fertility as evidenced by ten children. However, the low reproductive success of Darwin’s children can be satisfactorily explained in terms of the inbreeding depression phenomenon inferred in the Darwin–Wedgwood lineage (Berra et al., 2010a; Álvarez et al., 2015). The consanguinity of the parents, however, may have contributed to the children’s illnesses, in their susceptibility both to infection and, perhaps in one child, to the development of peculiar neuropsychiatric disorder (Tourette syndrome). Darwin may also have contributed to the sicknesses in another way, by acting as a ‘role model’ for the possible psychosomatic illnesses of Henrietta and perhaps also of Horace.

The study of the Darwin’s illnesses shows the value of family history in the diagnosis of chronic disorders.

CONCLUSION

The various illnesses of Charles Darwin’s children do not invalidate the favoured diagnosis of an inherited pathological mtDNA mutation with adult onset for Darwin’s own illness.

Although cousin marriage was common, there is no evidence that consanguinity contributed to the original occurrence of the proposed mtDNA mutation, the cause of CD’s illness, several generations earlier. The ills of the mother, rather than the ills of the father, were visited upon Charles Darwin but were not passed to his children.

Many of the health problems suffered by Charles Darwin and his children may be explained as the result of the confluence of two very different genetic processes in the Darwin family. Whereas most of Darwin’s health problems were probably caused by a mitochondrial genetic disorder inherited from his mother, a number of health problems that affected his children were probably associated with the consanguinity of Charles and his wife Emma Wedgwood.

Charles Darwin, in a letter to Asa Gray, botanist at Harvard University, on 11 November 1859 wrote about the theory of evolution via natural selection ‘…I fully admit that there are very many difficulties not satisfactorily explained by my theory of descent with modification, but I cannot possibly believe that a false theory would explain so many classes of facts as I think it certainly does explain. On these grounds I drop my anchor, and believe that the difficulties will slowly disappear…’ (Darwin, 1887). So may it be with the mitochondrial hypothesis of Darwin’s illness.

POSTSCRIPT

The present available evidence for an inherited pathological mtDNA mutation as the cause of Darwin’s lifetime illness is entirely circumstantial. This evidence, however, is considerable and is entirely consistent. Previously proposed diagnoses may account for some, perhaps many of Darwin’s symptoms but not one account for all the facets of this illness; none of the previous diagnoses have considered Darwin’s maternal (Wedgwood) family history. Mitochondrial dysfunction is the only entity that clinically would account for such a plethora of symptoms, once psychological or psychogenic illnesses are excluded. It is a parsimonious and credible contender for a unifying diagnosis.

Objective evidence is available; hairs from Darwin’s beard have been identified. These are a potential source of DNA, and mtDNA may be well preserved in such material. Portions of hair have been analyzed, and limited results have been released (Hayman, 2009). These restricted results do not invalidate the favoured diagnosis of an illness due to a pathological mtDNA mutation – a full analysis should either confirm or refute this diagnosis for Darwin’s illness. The reason for delay is not known.

FUNDING

The authors received no funding in support for this paper

ACKNOWLEDGMENTS

We are grateful to contributors the British Genealogy Forum website, particularly to the late ‘Dorothy’ (‘Thomasin’) for researched information on Darwin’s maternal ancestry, Footprints on the sands of time. Use was also made of the website ‘The Exciting Wedgwoods’ (http://www.familyhistorian.info/exciting/wedgwood/). We are grateful to Paul Fuerst, Ph.D., and Judith Westman, MD, both of The Ohio State University, for their comments on a previous draft of this manuscript. The comments of three anonymous reviewers for this article were very helpful. The mitochondrial hypothesis is the proposal of the first author; his arguments in favour of this diagnosis are propounded in his PhD thesis (https://minerva-access.unimelb.edu.au/handle/11343/48439). The co-authors support the publication of this idea so that it may be debated and confirmed or rejected as future evidence dictates.

REFERENCES

Author notes