In the fifty years since the Venetian doctor's death, considerable new medical knowledge had come to the fore: physicians now knew that people breathed oxygen and that nerves carried both sensory and motor impulses for instance. But FFI remained vastly beyond the medical competency of the time. Giuseppe died shortly after Costante, his disease also a mystery. In retrospect, with our knowledge of how the mutation in Giuseppe's genes would spread and what misery it would bring, it might have been better if instead of having killed five of his children in infancy, disease had taken all eight, because with Angelo and Vincenzo, his two children who survived to adulthood, the mutation began to spread. Both men are obligate carriers -- that is, the pattern of those who have the FFI mutation today indicates that both brothers must have had it. Angelo, who was born in 1813, died of FFI, probably sometime in the 1870s, and Vincenzo, born in 1822, died of cancer of the lip before the disease could strike, in 1880.
Angelo had one child, of whom we know nothing. About Vincenzo we know more, because his branch of the family, the one Lisi descends from, made a family tree. Vincenzo was a farmer -- the parish books list him as contadino, or peasant, though he likely owned his own land, having inherited it from Giuseppe. His wife, Marianna, known for her full mane of red hair, survived him, and in her widowhood, she drove around in a sporty one-horse carriage called a calche, visiting her many children. It was a lucky mother who saw six of her eight children to adulthood as she had, and when she died in 1893, in the back room of her villa with its view of the sun setting behind the Dolomites, she had reason to believe that she had lived a blessed life.
But of her and Vincenzo's six descendants, four probably died from FFI: Angelo in his mid-thirties in 1901, Pierina in her early forties in 1906, Giovanni in his mid-forties in 1913, and Antonio in his mid-fifties in 1926. For each, a different cause of death is named in the parish book -- from dementia to pellagra. Also, at around this time a plague engulfed Europe: encephalitis lethargica, or Von Economo's disease. Its main symptom was either insomnia or endless sleepiness. At autopsy, encephalitis lethargica victims evinced swelling of the brain, but autopsy was still something only the poorest of the poor endured. So, many family members who died of FFI in this period were lumped in with the millions who, by chance, briefy joined them on their sleepless odyssey. In later years, when family members came to understand what had happened to them, they would blame Marianna for the disease -- "the accursed redhead," Lisi's mother would call her. Perhaps she was blamed because her family was not from the Veneto. Or it may have been because she had red hair, and family members believed that those who had red hair were more likely to come down with the malady. But she was not the carrier: her husband, Vincenzo, was.
Starting with their children, FFI followed an unfortunate pattern. Those branches that carried the mutation grew poorer, because they kept losing able-bodied adults. In response, like most poor families, they tended to have extra children to help with their labor, and as a hedge against high infant mortality rates. Because large families tend to suffer more from genetic diseases, those branches with the mutation fell further.