The Nature of TSE Disease Transmission

Although critical to the understanding of TSE diseases, the most fundamental aspect of such is still controversial: i.e.
What is the nature of the agent that transmits these debilitating diseases?

The scientific community is divided between two possibilities:

Hypothesis A
Hypothesis B

Virino

TSEs are transmitted by a virino; a particle or organism that contains nucleic acids encoding the infectious agent.

Protein-Only

TSEs are transmitted by a mis-folded protein; the PrPSc molecule is infectious without the need of genetic material.
History
History
Theory first proposed in 1954 and 1959 by Sigurdsson or Hadlow when the transmitting agent was described as a "slow virus"

Theory first proposed by J.S. Griffith in 1967 with the idea that only protein was needed
Quote
Quote

"A nucleic acid is the only biological molecule we know about which could encode all this information. However we have not discovered it yet, perhaps because we scientists have not yet come up with the right experiments to find it. A nucleic acid encoding its protective protein would make an infective agent similar to other viruses. An informational molecule (presumably nucleic acid) protected by a host protein, PrP, is the prediction of the virino hypothesis. "


Robert A. Somerville
BBSRC & MRC Neuropathogenesis Unit
Institute for Animal Health, Edinburgh.
Source

"The protein-only hypothesis remains controversial because it breaks new conceptual ground. Those who have worked in this field under other paradigms (like the virus or virino hypotheses) are reluctant to accept this new paradigm. Scientists from other fields are more receptive to this hypothesis, however, and thus it has gained broad support. This hypothesis best explains all of the observations about these agents and the diseases they cause. If at some point it fails to do so, the hypothesis will need to be revised or rejected in favor of a better hypothesis. That is the nature of science."

David C. Bolton, Ph.D.
Department of Molecular Biology
New York State Institute for Basic Research
Source

Evidence
Evidence
History is the best supporting evidence for this hypothesis as there are currently no diseases that are known to be transmitted by proteins alone.

Purified materials that transmit various TSEs do not contain detectable genetic material. All materials that tranmit the various strains of TSE contain protein, specifically mis-folded prion protein: PrPSc.
All of the evidence from decades of experience indicate that diseases are transmitted by organisms. Contagious organisms contain genetic information in the form of DNA (or RNA that is reverse transcribed to DNA by the host organism). Human TSEs caused by genetic defects all contain PrPSc and can be tranmitted to new hosts by preparations of PrPSc without the need to transfer the genetic defect or any DNA from the founder
However, the DNA responsible (or necessary) for disease transmission has not been identified in any preparation of TSE transmissible material, but that does not prove it is absent.

In vitro, founder PrPSc has been shown to convert host PrPC to host PrPSc in the absence of detectible DNA or any living organism/cell. The resulting in vitro-formed PrPSc can transmit the founder strain of TSE with high fidelity.
  Several agents that destroy or inactivate DNA and RNA do not destroy the transmissibility of PrPSc preparations
  PrPSc can be mis-folded into several different conformations with varying protease resistance, thus providing the basis for multiple strains of TSE (each having its own mis-folding)
  Transmission of the disease requires active synthisis of host PrPC and its converion to PrPSc there is no evidence of virino replication and tranmission of its genetic material per se)
  Host PrPC sequence controls the ability of founder PrPSc to be transmitted, indicating that the protein itself controls transmission by determining the ability of founder PrPSc to interact with host PrPC, not the ability of a virino to propagate
Conclusion
Conclusion

Without evidence of genetic material involvement, should the 'protein-only' theory be accepted and the 'conventional' theory be dismissed?

Absolutely not!

The evidence available at this time indicates that PrPSc alone may be able to transmit TSE. Various forms of PrPSc may contain enough information to define each strain of TSE disease.

The important word in the above phrases is 'may.'
It is still possible that unidentified genetic material causes TSE or is at least involved in disease transmission. Abandoning research in this area could delay the discovery of the true cause of TSE.

As most scientists are taught early in their careers, no theory can be proven only dis-proven.

Until the 'protein-only' theory is disproven (possibly by the discovery of genetic material involvement), this theory has substantial evidence supporting its acceptance as a viable mechanism for disease transmission.

Considering the 'Protein-Only' Theory plausible, most of the information in this site is presented based on the probability that this theory is correct.