Sheep Trials Could Overturn Prion Theory

The discovery that prions may be an effect of scrapie rather than a cause could turn the conventional wisdom regarding diseases such as BSE and variant Creutzfeld-Jakob on its head, according to a report in this week’s New Scientist.

Prions are thought to trigger disease by getting into the body through food or cuts in the skin and triggering a chain reaction that transforms native prions into harmful ones. These accumulate in the brain with fatal consequences.

Prions eaten in contaminated food were thought to pass undigested through the gut wall into specialised lymphoid tissue called Peyer’s patches, where they multiplied up before spreading to the central nervous system.

Now, Martin Jeffrey of the UK Veterinary Laboratories Agency in Penicuik, Midlothian, has examined fifty sheep to see what happens to the prions thought to cause scrapie, the ovine equivalent of BSE, and found the opposite.

They injected enormous half gram doses of liquefied brain tissue from sheep that had died of scrapie directly into the gut lining of healthy sheep. They then monitored what happened to the millions of abnormal prions. Surprisingly, these prions didn’t migrate to Peyer’s patches as expected, but were digested or vanished into lymph nodes.

Separate experiments also revealed that abnormal prions can easily be digested by sheep stomach juices, so even if an animal ingested large quantities of infected feed, hardly any abnormal prions would survive.

The results don’t challenge the assumption that infected cattle feed and beef can cause disease. In the three sheep that developed scrapie after being injected with the diseased tissue, abnormal prions began accumulating in the Peyer’s patches 30 days later, even though all the prions from the original gut injections had long gone. Further investigations revealed that the prions were being formed afresh by cells in the Peyer’s patches.

Jeffrey suggests that another ingredient of the liquefied sheep brain may be responsible for triggering the cells to produce the abnormal prions – a highly controversial view (Journal of Pathology, vol 209, p 4). “It would be over-interpretation to say we have evidence for another infectious agent,” says Jeffrey. “But the prion hypothesis is less than satisfactory.”

Adapted from a New Scientist Press Release

4 thoughts on “Sheep Trials Could Overturn Prion Theory”

  1. I heard Stanley Prusiner speak at a scientific meeting about his prion work a few years ago, I think after he won the Nobel prize for it. I’m no expert in biochemistry, but I have to say it didn’t sound terribly convincing to me as a physicist.

    The question is, what IS behind the disease, if not the proteins? Or could it still be that, despite this present research, a tiny fraction of the protein does sometimes survive, enough to trigger the disease in the brain? Other than prions, the smallest infectious agents are viruses, so could this be some sort of virus still, remaining undetected all these years?

  2. I agree AP. It has always struck me as odd from a chemist’s point of view that somehow a rogue protein strand could get through the digestive system and trigger proteins beyond the blood-brain barrier to convert themselves into copies of said rogue…

    db

  3. We know that DNA can be its own model, as can RNA. Protein interacts with both, and autocatalytic RNA has been shown to exist as well.

    In certain microorganisms complex peptides can be formed in situ without being translated from RNA (from DNA). These aren’t anywhere as big as normal proteins, and the complexes that create them are large, but consist of nothing BUT protein. So we have peptides direct from protein without any nucleic acid intermediary.

    So far as I know nobody has asked (or looked to see) whether more complex peptides or even full proteins could be made by other protein complexes.

    Short of actual synthesis we have proteins which shoehorn nascent strings into preferred shapes- the prion theory depends on such a function going awry, and misshapen protein then auto-shaping others of its sequence into the wrong configuration by recruitment.

    I’ve often wondered how it is that prions could recruit their own and reshape them- isn’t charge/shape complementarity required to do this? Perhaps there is another species at work here- it might even be something as simple as a short peptide, or a piece of the prion, or of the shoehorn.

    Oh well, boys, back to the lab….

    Jess Tauber

  4. Not because I thought it was a good theory (I’ve never considered myself knowledgeable enough in subject to form an opinion either way), but because it felt like it was further blurring the boundary between life and non-life.

    Personally, I’ve always included viruses in my definition of life, but thought that prions made that categorization slightly more problematic. Of course, if prion theory turns out to be false, perhaps I can resurrect my nice, clean definition of what is “alive”. (Not meant to be useful, just a personal definition that helps me make sense of the world.)

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