Prions

Sometimes a scientific discovery shakes the confidence of scientists, making

them question whether they truly understand nature's ground rules. That's exactly

what prions have done to scientists' understanding of the ground rules for

infectiousdiseases. Prions cause diseases,but they aren't viruses or bacteria or

fungi or parasites. They are simply proteins, and proteins were never thought to

be infectious on their own. Organisms are infectious, proteins are not. Or, at least,

they never used to be. Prions entered the public's consciousness during the mad

cow epidemic that hitEngland in 1986. For decades, however, scientists had

searched for unusual, atypical infectious agents that they suspected caused some

puzzling diseases that could not be linked to any of the "regular" infectious

organisms. One possibility was that slow viruses-viruses that spent decades

wreaking havoc in their hosts-might be the culprits, and these putative viruses

were not only leisurely about multiplying but also hard to isolate. Now researchers

are coming around, although reluctantly, to accepting the shocking fact that

naked proteins can be infectious.

Prions enter cells and apparently convert normal proteins found within the

cells into prions just like themselves. The normal cell proteins have all the same

"parts" as the prions- specifically the same amino acid building blocks -but they

fold differently. They are much like the toy "Transformers" that were around in

the 1980s. They could change themselves in to be different shapes with nothing

added and nothing subtracted.

Prions enter brain cells and there convert the normal cell protein PrPC to the

prion form of the protein, called PrPSC. When normal cell proteins transform into

prions, amino acids that are folded tightly into alpha helical structures relax into

looser beta sheets. More and more PrPC molecules transform into PrPSC

molecules, until eventually prions completely clog the infected brain cells. The

cells misfire, work poorly, or don't work at all. In mad cow disease, for example,

with their brain cells running amuck, the mad cows wobble and stagger and

appear fearful -their "madness" is craziness, not anger. Sheep and goats with the

disease scrapie, which is like mad cow disease, become so uncomfortable and

itchy that they frantically rub up against anything they can, finally scraping off -

hence, the name of the disease -most of their wool and hair.

Ultimately, infected prion-bloated brain cells die and release prions into the

tissue. These prions then enter, infect, and destroy other brain cells. And, as

clusters of cells die, the brain stops looking like a brain and starts looking more

like Swiss cheese. The medical term for the prion diseases is "spongiform

encephalopathies," in acknowledgement that the sick brains are riddled with holes

and have taken the form of sponges.

Shepherds and farmers whose sheep had scrapie never seemed to get scrapie

themselves. So, for a long time, scientists assumed that the prions of animals did

not cause infections in humans. But, between 1994 and 1996, 12 people in

England came down with Creutzfeld-Jakob disease (CJD), a human prion disease

whose symptoms are not unlike those of the mad cows, and all the victims had

eaten beef from cows suspected of having mad cow disease. In October, 1996,

scientists in England reported that the prions from ten of the British patients were

remarkably like those of the mad cows and not like those of people who died of

"classical" CJD. Scientists quickly realized that the occurrence of CJD in a dozen

people 19 to 39 years old was cause for alarm, because CJD had always been rare

-typically one new case might be diagnosed per million people each year -and

seldom occurred in people younger than 55. This epidemic was something new,

something extraordinary. Scientists now speculate that the prions that started out

in sheep suffering from scrapie made their way into cows and then moved more

recently into humans. Cattle are fed meal made from sheep, the bones and other

waste parts of sheep carcasses. Standard procedures for grinding up carcasses

were altered in the 1970s, and the new processing methods seem not to have been