(A) Louis Pasteur, the founder of the microbial theory of disease, lost three young daughters to “fever” between 1859 and 1866. A few years later, in 1870, he discovered that microbes caused disease in silkworms (95), paving the way for a general microbial theory of disease. Retrospectively, it is clear that his daughters died of infectious diseases. (B) Charles Darwin, the founder of the theory of natural selection, also lost three children to infectious diseases. Charles and Emma Darwin were first cousins. These two illustrious families are representative of most families worldwide and throughout history, until recent improvements in hygiene and the advent of vaccines and antibiotics, which resulted from the microbial theory. Prior to these medical advances, it was not uncommon for at least half the siblings in a family to die of infection. The microbial theory of disease identified the microbial cause of disease but did not resolve the question of intrafamilial clinical heterogeneity in families exposed to the same microbial environment. As illustrated in the pedigrees of Pasteur and Darwin, some children survived until adulthood, despite probable exposure to at least one of the microbes that killed their other siblings. It is possible that the children who died carried a Mendelian trait predisposing them to infectious diseases, or at least had some form of genetic predisposition to such diseases.