ABSTRACT
The prion diseases (PrD) are a group of unusual neurodegenerative disorders that affect both
humans and animals, are associated with a variety of phenotypes, and are transmissible. The earliest
description of PrD was that of Creutzfeldt and then Jakob in the early 1900s (1,2) as a progressive
dementia associated with gait abnormalities and extensive vacuolation and astrocytic gliosis of
the brain. In the mid-1950s, while studying primitive cultures in the Highlands of New Guinea,
Carleton Gajdusek recognized and described a disease the Fore people, living in this region, called
“kuru.” Sufferers of kuru developed a progressive gait ataxia, unusual behavior, and a relatively
rapid progression to death. Gajdusek’s studies suggested that this disease was the result of
a transmissible agent carried within the brain of the affected individual that was horizontally
transmitted during rituals that involved cannibalism. Women and children were most affected by
the disease, likely due to their greater contact with infectious tissue during both the preparation
of the feast and the ritualistic ceremony. Pathologic examination of the kuru brain revealed the
same pattern of vacuolation (also called spongiform change) that was observed in the disease
described by Creutzfeldt and Jakob. Most importantly, however, this same pathology was astutely
recognized by the veterinarian William Hadlow as the same pathology present in scrapie, a known
transmissible disease of sheep associated with similar features of gait dysfunction, behavioral
changes, and a rapid progression to death. It was natural to speculate that Creutzfeldt-Jakob disease
(CJD) and kuru were similarly transmissible, which was confirmed in the mid-1960s (3,4). These
results led to the recognition of several other transmissible spongiform encephalopathies (TSEs).
Until relatively recently, the infectious agent of the TSEs was considered to be a slow virus (5), yet
despite considerable effort, evidence for a virus has not materialized. Instead, a wealth of data has
accumulated to implicate an abnormal isoform of the prion protein (PrP) as the etiologic agent in
these diseases (6). Several years after Gajdusek received the first Nobel Prize for linking the
transmissible nature of these diseases, Stanley Prusiner captured the second TSE-related Nobel
Prize for his discovery of the prion, the infectious protein of PrD.
