Sometimes a scientific discovery shakes the confidence of scientists, making them question whether or not they really understand the basic rules of nature. That's exactly what prions have done to scientists' understanding of the rules concerning infectious diseases. Prions cause diseases, but they aren't viruses, bacteria, fungi or parasites; they are simply proteins which proteins have never been considered 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 disease epidemic that hit England in 1986. For decades, scientists had searched for unusual, atypical infectious agents that they suspected caused the puzzling diseases that they were unable to link to any of the "regular" infectious organisms. One possibility was that slow viruses, which spend decades wreaking havoc in their hosts, might be the culprits. These generally recognized viruses are not only leisurely about multiplying but also hard to isolate. Researchers are now reluctantly coming around to accepting the shocking fact that naked proteins can be infectious.

"More than one protein chemist has declared this to be insane--and yet this is precisely what is implied by a growing number of studies" was the way one news article put it (Nature 1996, 383: 666-667.).

Prions (pronounced pree-ahns) 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 Transformers, those awesome configurable robots that intrigued little kids in the 1980s. A sphinx could become a robot; a bug could become a warrior. Nothing was added; nothing subtracted. As a side note, I personally owned every Transformer from the first three series, and 90% of every other series up until the Action Masters series, which inevitably led to the end of that era of Transformers. But I digress…

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 (i.e. “scrapie”) most of their wool and hair.

Ultimately, the infected prion-bloated brain cells die, the sort of just disintegrate, and release prions into the tissue. These prions then enter, infect, and destroy other healthy brain cells. As clusters of cells die, the brain stops looking like a brain and starts looking more like Swiss cheese, which is what heralds the medical term for the prion diseases: "spongiform encephalopathy" (SE or BSE in the case of bovines). The term SE is an acknowledgement that the sick brains (encephalo is Greek for brain; pathy is Greek for disease) are riddled with holes and have taken the form of sponges.

Shepherds and farmers whose sheep had scrapie never seemed to get scrapie themselves. 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 Creutzfeldt-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 (3). 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, extraordinary, and worrisome. 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 "offal," 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 adequate for destroying scrapie prions. The cattle were exposed, through the offal, to sheep prions that eventually established themselves in their cow hosts. Later, they adapted further, infecting cells of people who had eaten hamburgers and steaks from infected cows. That’s a sad, sad steak.

At the moment, CJD and only a handful of other human diseases have clear links to prions. But it is likely that prions will turn out to be the agents of a variety of currently enigmatic diseases in which brain cells are destroyed and the nervous system deteriorates. Alzheimer's disease and Parkinson's disease are two prime candidates. Neither disease bodes much hope for the inflicted; however Michael J. Fox still seems to be making regular appearances on TV sitcoms.

So, a couple new ground rules now seem to govern infectious diseases. The first is that naked proteins can be infectious and can cause infectious diseases. The second and potentially more troubling is that, like other infectious agents, prions can jump the species barrier and cause deadly diseases in humans. Recently, and for the first time known, two farmers with mad cows in their herds died of CJD. Farmers, heed the warning: do not consume offal! Burn it!

Only time will tell how big a problem the prions will be both as the agents of dreadful diseases of the human nervous system, and as vectors of diseases from other species.