Protein-Only Hypothesis

The prion continues to be a source of great scientific discovery as well as confusion. From this week’s reading, I delved more into the “protein-only” hypothesis by applying the concept of the scientific method to how the scientists tested such a hypothesis. Furthermore, I looked into sources of scrutiny and controversy in regards to the protein-only hypothesis.

With the hypothesis in mind, researchers experimented with animals to test the prion infectivity. The role of PrP was demonstrated through mice, which were resistant to prion inoculation. Scientists found that the disease could be transmitted by intracerebral inoculation of brain homogenates. The PrP could also spontaneously form infectious prions in vivo. The protein-only hypothesis is still subject to criticism, however, because the compelling evidence to prove such a hypothesis would only be verified by producing the infectious material used for intracerebral inoculation in vitro.

To clarify, the protein-only hypothesis proposes that the infectious agent is a mis-folded protein that does not contain a nucleic acid. The evidence supporting the protein-only hypothesis is strong. Firstly, researchers purified or isolated the protein from the infectious material. These purified forms of the protein preserved their infectivity and also provided insight into gene encoding. Studies have also shown that genetic diseases can be proliferated in an infectious manner. Moreover, evidence supplied by the Charles Weissmann group found that mice lacking the PrP gene became resistant to the infection of scrapies.

There are still missing pieces to the puzzle, however, which cause the hypothesis to be further questioned. One of the particular weaknesses of the hypothesis is that there is a lack of infectious origins for other neurodegenerative disorders linked to protein misfolding, including Parkinson’s disease. Furthermore, scientists still have not provided verification comprising of the generation of infectious prions in vitro.