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. 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 hit England 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 1980's. 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,' 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 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. 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 1970's, 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, and the prions eventually established themselves in their cow hosts. Later, they adapted further, infecting cells of people who had eaten hamburgers from prion-bearing cows. 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. So, a couple new ground rules now seem to govern infectious diseases. The first is that naked proteins- prions -can be infectious and can cause infectious diseases. The second and potentially more troubling is that, like other infectious agents, prions can jump species' barriers and cause deadly diseases in humans. Recently, and for the first time known, two farmers with mad cows in their herds died of CJD. Humans might be infected by prions in 2 ways: 1.) Acquired infection (diet and following medical procedures such as surgery, growth hormone injections, corneal transplants) i.e. infectious agent implicated.
2.) Apparent hereditary mendelian transmission where it is an and dominant trait. This is not prima facie consistent with an infectious agent. This is one of the features that single out prion diseases for particular attention. They are both infectious and hereditary diseases. They are also sporadic, in the sense that there are also cases in which there is no known risk factor although it seems likely that infection was acquired in one of the two ways listed above. Kuru is the condition which first brought prion diseases to prominence in the 1950's.
Found in geographically isolated tribes in the Fore highlands of New Guinea. Established that ingesting brain tissue of dead relatives for religious reasons was likely to be the route of transmission. They ground up the brain into a pale grey soup, heated it and ate it. Clinically, the disease resembles CJD.
Other tribes in the vicinity with same religious habit did not develop the disease. It is speculated that at some point in the past a tribe member developed CJD, and as brain tissue is highly infectious this allowed the disease to spread. Afflicted tribes were encouraged not to ingest brain tissue and the incidence of disease rapidly declined and is now almost unknown. 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.
Is the juicy hamburger or the succulent lamb chop harboring microscopic 'wolves in sheep's clothing?'.