Spontaneous Prion Generation

One of the scarier health threats that has been in the news in the last few years is the family of neurodegenerative diseases, including Bovine Spongiform Encephalopathy [BSE, often called “Mad Cow Disease”], and the similar diseases scrapie in sheep and goats, and variant Creutzfeldt-Jakob Disease [vCJD] in humans.  Besides their devastating effects, they are frightening because they typically have a long incubation period, measured in years, between the time of first exposure to the disease and the appearance of symptoms, and are essentially always fatal.  They are thought to be caused by prions, a pathological form of a normally occurring protein that differs by being “folded” differently in space.

(Many biological molecules depend for their effects not only on their chemical composition, but also on their physical shape.  It is quite common, for example, to have two forms of the same compound that are mirror images of one another [these are called stereoisomers], where one form is biologically active, and the other is not..   To take another example, the three simple sugars — glucose, fructose, and galactose — all have the same basic formula, C6H12O6, but differ in the arrangement of those atoms within the molecule.)

The prions themselves are not in any sense living organisms; they contain no DNA or RNA.  Nonetheless, introduction of a small quantity of prions into normal protein causes the normal molecules to “re-fold” themselves into the pathological shape.   The mechanism of transmission of these diseases has been thought to be eating infected animals.  For example, the original outbreak of BSE in the United Kingdom was attributed to cattle (which are naturally vegetarians) being fed protein supplements derived from the meat of diseased cattle or sheep.   This transmission mechanism is reasonably well accepted, but it of course begs the question of how the whole thing got started — although a random mutation is always a possibility.

In a new study reported at the PhysOrg.com site, researchers from the Scripps Research Institute in Florida and the Institute of Neurology at University College London have shown that infectious prions can be spontaneously developed in normal tissue.  The scientists placed normal tissue on very fine steel wires, and were able to observe the spontaneous formation of infectious prions.  It is possible that the metal somehow acts as a catalyst for the formation of these molecules.  Dr. Charles Weissman, of Scripps, one of the study leaders, is careful to say that there is another possible explanation of the results:

Weissmann noted that an alternative interpretation of the results is that infectious prions are naturally present in the brain at levels not detectable by conventional methods, and are normally destroyed at the same rate they are created. If that is the case, he noted, metal surfaces could be acting to concentrate the infectious prions to the extent that they became quantifiable by the team’s testing methods.

The paper reporting the results is to be published in the Proceedings of the National Academy of Sciences, and is available online as a pre-publication open access article [doi:10.1073/pnas.1004036107]; the lead author is Julie Edgeworth of UCL.

I doubt that many people will find these results particularly reassuring, but at least we are making progress in understanding the mechanism of these strange diseases.

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