Fifteen years ago I evoked skepticism when I proposed that the infectious agents causing certain degenerative disorders of the central nervous system in animals and, more rarely, in humans might consist of protein and nothing else. Dogma held that the conveyers of transmissible diseases required genetic material (DNA or RNA) in order to establish an infection in a host.

Later, many scientists were similarly dubious when my colleagues and I suggested that these "proteinaceous infectious particles"-or "prions," as I called them-could underlie inherited, as well as communicable, diseases. Such dual behavior was then unknown to medical science. And we met resistance again when we concluded that prions multiply in an incredible way; they convert normal protein molecules into dangerous ones simply by inducing the benign molecules to change their shape.

Today, however, a wealth of experimental and clinical data have made a convincing case that we are correct: prions are indeed responsible for transmissible and inherited degenerative disorders.

The known prion diseases, all fatal, frequently cause the brain to become riddled with holes. These ills, which can brew for years (or even for decades in humans) are widespread in animals. The most common form is scrapie, found in sheep and goats. Afflicted animals lose coordination and eventually become so incapacitated that they cannot stand. They also become irritable and, in some cases, develop an intense itch that leads them to scrape off their wool or hair (hence the name "scrapie").

I first became intrigued by the prion disease in 1972, when as a resident in neurology at the University of California School of Medicine at San Francisco, I lost a patient to Creutzfeldt-Jakob disease. As I reviewed the scientific literature on that and related conditions, I learned that scrapie and Creutzfeldt-Jakob disease had been shown to be transmissible by injecting extracts of diseased brains into the brains of healthy animals. The infections were thought to be caused by a slow-acting virus, yet no one had managed to isolate the culprit.

In the course of reading, I came across an astonishing report in which Tikvah Alper and her colleagues suggested that the scrapie agent might lack nucleic acid. When the nucleic acid in extracts of scrapie-infected brains was destroyed by ultraviolet or ionizing radiation, the extracts retained their ability to transmit scrapie. This experiment, along with many experiments we have conducted since, shows that the scrapie agent is not a virus or any other known type of infectious agent that contains genetic material.

No one knows exactly how the accumulation of prions damages cells. In cell cultures, prions accumulate in intracellular vesicles known as lysosomes. In the brain, filled lysosomes could conceivably burst and damage cells. As the diseased cells died, creating holes in the brain, their prions would be released to attack other cells.

Common neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, show some marked similarities to the known prion diseases. Whether prions are responsible for these neurodegenerative diseases remains a possibility worthy of further research.

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