There were (and are) many scientists who disagree with this theory, and they challenged Prusiner to synthesize a prion in a test tube and show that it could cause infection. In the meantime, though, a prion plague came along that moved the center of the field back from molecular biology to epidemiology.

In the late 1980s, cows in England began shaking, falling over and sometimes charging their handlers. The first veterinarians to see the disease suspected that scrapie had jumped species—the symptoms and the pathology were quite similar—and after some opposition from the British government, which feared the economic consequences, a consensus formed that this was the case. Unfortunately, with that consensus came the assumption among many in government and the sciences that infected beef would be safe to eat, just as scrapie-infected sheep is. In fact, some manufacturers preferred the skinnier scrapie-infected sheep for pies. (The lack of infection presumably is based on the difference in shape between the sheep and the human prion protein.)

By the mid-1990s a more-than-ordinary number of Britons were coming down with CJD, the rare prion disease that is either inherited or occasionally simply develops by chance. And the victims were teenagers and young adults, whereas CJD is a disease of old age. The British government had gotten it wrong: Humans could “catch” mad cow disease (this type is now called variant CJD). There was suddenly a new pool of prion disease victims clamoring for an explanation of what was happening to them and, even more, for a cure.

For the Italian family living in the Veneto, mad cow disease was just something they read about in the newspapers. Fatal familial insomnia had by now spread throughout the various branches of the family, where it was known as “the family disease.” Hospitals could do little more than poke and prod the family members committed to their care in a vain attempt to understand their condition.

Then finally there was progress. In 1983, Silvano, the great-great-grandchild of Giuseppe, began to sweat and lose the ability to sleep. He was in his early fifties. His niece’s husband, Ignazio, a newly minted internist, grew intrigued. Ignazio took Silvano to the sleep clinic at the University of Bologna, where researchers observed an unprecedented EEG: a mixture of brain waves that was typical of neither sleep nor wakefulness. Silvano had no illusions about his fate. “I assume you’ll want the brain when it’s time,” he told the admitting neurologist. After Silvano died, the autopsy, conducted by Pierluigi Gambetti at Case Western Reserve in Cleveland, revealed that the disease, whatever its cause, ate away portions of the thalamus, setting off the insomnia and unregulated body functions.

A second key piece of the puzzle fell into place when, in the 1980s, Ignazio and his wife urged a distant family member to bring her sister to Bologna. The young woman, named Teresa, had a slower form of FFI (the difference would later be traced to a polymorphism on the prion gene). Teresa’s EEG was distinct from Silvano’s, and the sharp-eyed neurologist who headed the clinic, Elio Lugaresi, saw a resemblance between it and CJD. After Teresa’s death, Gambetti observed that the pattern of spongiform tissue and holes in her brain also resembled CJD. Antibodies he borrowed from Prusiner confirmed the presence of prions. Prusiner, in turn, used some of the family’s tissue to show that each kind of prion causes a distinct, specific disease in mice. He was now another step forward in establishing that the prion protein and only the prion protein was responsible for prion disease. In 1997 he was awarded the second Nobel Prize in the field. And at last FFI was not just a single family’s dreadful fate; it was one of a group of diseases that, because of the effort being expended to understand mad cow disease, might one day be cured.

Prion researchers never thought their work was just about a group of rare conditions. They hoped to shed light on a range of non-prion diseases that have always eluded medical understanding. This idea was already on Carleton Gajdusek’s mind in 1957, when, newly arrived in Papua New Guinea to study kuru, he promised the NIH that if he could “crack” the disease, “parkinsonism, Huntington’s chorea, multiple sclerosis, etc., etc.” might follow.

The list that Gajdusek drew up and that Prusiner elaborated on also includes such neurodegenerative disorders as Alz-heimer’s disease, such immune system disorders as Crohn’s disease and rheumatoid arthritis, and metabolic diseases like adult-onset diabetes.