In 1992 Gambetti's research team was able to sequence the family's genetic material and pinpoint the mutation that causes F.F.I. Armed with this information, they were able to administer a test to the family. Elisabetta persuaded reluctant members to participate. Half of the 50 relatives tested had the fatal gene.

Around this time, Gambetti called Stanley Prusiner and asked him if he wanted to use some of the family's brain tissue. Prusiner had mice with the human prion gene inserted, and Gambetti didn't -- without them he could not prove prions caused F.F.I. And Prusiner had been supportive of Gambetti. ''Without him we wouldn't have gotten the disease accepted so fast,'' Gambetti said. He sent the specimens. For Prusiner it was an unexpected break. He had been trying to show for more than 20 years that a certain class of diseases were caused by their own malignant proteins. It seemed counterintuitive, to say the least. Proteins have no nucleic acids and so no means of reproducing or replicating -- yet Prusiner was proposing that they could spread like an infection, taking over healthy proteins and making them lethal to the parent organism. It was not inconceivable; such patterns had been shown in yeast protein, for instance. Some proteins in the brain cells of people suffering from inherited Alzheimer's are also altered by adjoining proteins. One way to think of the model for a prion infection is what happens when you drop an extremely frozen ice crystal into a bucket of water. The rest of the water freezes, too, in response, from the nearest particle to the farthest. But what could be the biological purpose of this, since prions have no genes to pass on? Not being alive, they have no motive to kill.

Using the brain matter of Teresa and another relative, Prusiner in 1996 performed his key experiments. Having successfully caused F.F.I. in the mice, Prusiner was able to confirm his theory at last. Deviant prions caused the disease. Prusiner had met the basic standard of proof for an infectious agent. He would get his Nobel Prize a year later.

Not every scientist is convinced of the importance of prions. A small group of biologists still believe that hidden in these proteins is some sort of slow virus, something else that is getting into the brain tissue and making people sick. They point especially to the fact that no one has been able to convert a normal human prion into a lethal one in a test tube. Prusiner himself suspects there is some sort of helper protein in the process, which he vaguely calls ''protein X.'' But there is an increasing amount of circumstantial evidence to support his basic thesis. For one thing, there is never any sign of infection in those who die from prion diseases -- no swelling or dead white blood cells or other signs of inflammation. Patients are not contagious in the conventional sense. Nobody in Elisabetta's family has, for example, ever infected his neighbor or his wife or husband. But the main reason that prions remain credible is that there is simply no better answer. As Gambetti told me, ''With every year that no better solution comes forward, the evidence for prions grows stronger.'' It reminded me of the medieval proof of God, the one Giacomo would no doubt have heard from his parish priest if he ever wondered what he had done to deserve his awful death: If there is no God, who made the universe?

For Elisabetta and her family, Prusiner's Nobel did not change much. They continue to die. A new generation is now approaching the age of greatest risk. Some have begun to question if it made sense to go through all that work -- the blood tests, the publicity, the discrimination. Some family members wonder whether Elisabetta, who tested negative for the gene in 1993, and Ignazio are pursuing the research for their own purposes. They have not been able to find out whether or not they carry the F.F.I. gene; Bologna researchers refuse to tell them until there is a cure. ''Bring us news from Cleveland,'' they kept saying.

When I told this to Professor Gambetti, it caused him genuine pain. He is a tall man with his dark hair thinning on top and a stoop. At least in my imagination, this came from the thousands of hours he has spent looking at brain tissue under a microscope. His laboratory at Case Western is the United States surveillance center for outbreaks of prion diseases. There is a freezer with a biohazard sign on it outside his door full of pieces of brain suspected of infection. Other freezers in the basement have several hundred more, including the brains of many members of Elisabetta's family. The lab is, as much as the graveyard ringed by cypresses near Elisabetta's home, the true tomb of Giacomo's clan. If the electricity fails, Gambetti's phone at home will automatically ring. In the age of B.S.E., Gambetti's brain trove, one of the largest in the world, has great value.

During my visit to Gambetti's lab, the phone rang. I could hear only his part of the conversation, but it went this way: ''But you have a way to keep it frozen? You have a refrigerator? Well see if it fits in the freezer then. What about dry ice?''