Charles Darwin's studies of heredity, adaptation and evolution included many experiments into the effects of crossbreeding and inbreeding in both plants and animals. Such consanguineous pairing often resulted in weaker, more sickly descendants.







Ironically, his own lineage and marriage could have been experiments as well. At the age of 29, he proposed to his first cousin, Emma Wedgwood, the daughter of his mother's brother. Darwin realized the dangers of inbreeding and wondered if his close genetic relation to his wife had had an ill impact on his children's health, three (of 10) of whom died before the age of 11. In a letter to friend, Darwin noted his concern for his children, writing that "they are not very robust."







Darwin's marriage to his cousin was not the only mixing of blood in the two lines. The Darwin-Wedgwood family in fact had several instances of close family matches, and a new analysis, published online May 3 in the journal BioScience, shows that some of Darwin's concerns about his offspring's health might have been valid.







The analysis, led by Tim Berra, professor emeritus in the Department of Evolution, Ecology and Organismal Biology at the Ohio State University in Mansfield, found that Darwin's kids did have "a moderate level of inbreeding" and in the family's children, there was "a significant positive association between child mortality and inbreeding."







When two individuals mate, genetic material from both parents is passed on to the progeny. So even if one parent carries a harmful recessive trait, the other parent is likely to have a healthier version, which will manifest itself in the offspring. If both parents, however, carry a recessive allele—which is more likely to happen if they share much of their genetic material, as close relatives do—then they raise the chances that their child will have only the bad genes.







Berra and his colleagues' assessment of 25 nuclear families across four generations of Darwins and Wedgwoods found a slightly lower-than-average child mortality rate compared with the general population of the time. But in those nuclear families with higher levels of inbreeding, offspring had an estimated 5.4 percent reduction in fitness. And the autosomal genomes of Charles Darwin's children were likely more than 6 percent identical (that is, homozygous). That number represents about four times the amount of overlap than children of second cousins would be expected to have.







Although none of Darwin's children had obvious documented physical or mental deformities, the three who died appear to have suffered from infectious disease, which is more likely to be contracted in those with higher levels of inbreeding, Berra and his colleagues noted. One died at 23 days old, and another, who was not developing normally, died at 18 months. The third likely died of tuberculosis, for which inbreeding increases the contraction risk.







Many famous and powerful families have been renowned for their pairing of close relatives, including the Hapsburgs and some ancient Egyptian pharaohs, and marrying relatives—both close and distant—was in general more common historically when groups were smaller and more isolated. But by Darwin's time it was already assumed that "consanguineous marriages lead to deafness & dumbness, blindness [etc.]," Darwin wrote in a letter to parliamentarian John Lubbock in 1870. Darwin had been hoping the government could accumulate broad population-based data about the frequency of cousins marrying and the health of their offspring, and he requested questions to this effect be included in England's census.







Darwin's request was denied, but his concern lives on today. More than half of the states in the U.S. have explicit limits on first-cousin marriages.







Image of Charles Darwin and his son William Darwin taken in 1842, courtesy of Wikimedia Commons