Besides many having overlapping symptoms—diminishing coordination, stress-induced worsening, late onset—all these diseases also leave misfolded proteins behind. This shared characteristic is not something researchers who specialized in these ailments had paid much attention to historically. That all these diseases caused the buildup of the same gunk in the body was seen as incidental.

By contrast, prion researchers thought the misfolded proteins might be the cause of the disease. Strikingly, most of the diseases produced not just misfolded proteins but misfolded proteins of a particular kind, called amyloid plaques or amyloid fibril sheets, that developed when atoms bonded across the frames of damaged proteins, like the rungs of a fabulously strong ladder. Enzymes couldn’t digest them, and water didn’t dissolve them. There was nothing in biology as tough; it seemed safe to say that no cell could survive their presence.

“The amazing thing is how long it took us to see all these things that were right in front of our face,” says Fred Cohen, a molecular chemist at UCSF whose lab works with Prusiner’s. “The parallels were obvious.”

Through the decades the Italian family has kept on dying: 14 since 1973, eight in the past decade. In 2003, Vittorino, a Venetian living on the southern end of the lagoon, developed insomnia and uncontrolled sweating. His family read of the disease when the FFI family announced a foundation for research, and got in touch. Vittorino turned out to be a distant cousin, related through Giuseppe, the likely nephew of the original patient, the Venetian doctor. Though Vittorino’s death was no less brutal, at least the family knew they were not alone. Outside the church his daughters put out an offering receptacle with “For the Victims of Fatal Familial Insomnia” written on it.

Among the current generation, chance dictates that 25 more carry the gene that causes the disease. The question they face every day is, What can be done? There are two prion drug trials under way: one with quinacrine, an antimalarial synthetic; the other with pentosan, originally prescribed for bladder-lining infections. Though a victim of mad cow disease in Britain has remained alive now for six years thanks to pentosan treatments delivered with a shunt, scientists remain only cautiously optimistic about both drugs.

Meanwhile, the past few months have seen three discoveries. The genetic information for the prion protein resides on a gene on chromosome 20. It has long been known that mice whose prion genes have been removed live more or less normal lives, but no one knew whether this observation would also be true for larger mammals. Recently a pharmaceutical research company in Sioux Falls, S.D. successfully created eight cows with no prion proteins. The cows, which U.S. Department of Agriculture researchers have followed for a year and a half, seem to behave normally. While gene therapy in humans remains a hope, if it ever becomes a reality, prion disease, with its simple genetic basis, could be one of the first experimental targets.

At the same time a group of researchers in England has found a molecule called L13 that binds to the prion protein. In theory the blood of infected individuals could be purified in a filter containing the molecule. It could prevent the accumulation of malignant prions in the brain and the onset of the disease, assuming that scientists can find a way to filter them out of the central nervous system too.

And a third method of combating the disease has also recently been shown to have some success. Researchers in Germany have used a type of RNA that silences gene activity to prevent the prion gene from producing proteins. In tests on mice infected with scrapie, they found that mice genetically altered to produce this “interference RNA” for prion proteins lived significantly longer than the control group.

The Italian family has not consented to be a part of either drug trial, though they closely follow developments in the field. Perhaps one day gene therapy will allow them to live without a prion gene, or they will have their blood regularly cleansed. Maybe the science of interference RNA will advance far enough to allow for a drug to block the action of the prion gene. Meanwhile, the family members grow older, wondering what will happen to them. Some refuse to even have the genetic test to detect the mutation. As one family member who had just lost his father to the disease explained, “The stress of the test might even bring on the disease. Besides, what would I do with the information? There is no cure. I’d rather rely on my faith.”

  Dossier

1. Prion Diseases of Humans and Animals, edited by Stanley Prusiner, John Collinge, et al. (Chichester, England: Ellis Horwood, 1992). The definitive history of prion research.

2. Kuru: Early Letters and Field-Notes from the Collection of D. Carleton Gajdusek, by D. Carleton Gajdusek, edited by Judith Farquhar and D. Carleton Gajdusek (New York: Raven Press, 1981). This colorful compilation includes excerpts from Gajdusek’s journals and his correspondence with other researchers looking for kuru’s origins.

3. “Virus Paper Reignites Prion Spat,” by Heidi Ledford, Nature, February 2007. An overview of challenges to the prion orthodoxy, including the recent finding by prion doubter Laura Manuelidis, a Yale neuropathologist, that viruslike particles were present in cultured cells infected with the human form of mad cow disease.