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Infectious Particles

Agent Hypotheses

Dominant belief

Normal host prion protein (PrP) spontaneously converts into an infectious amyloid, i.e., a “prion”;

Alternative view

TSE agents are environmental pathogens with a genome that encodes different agent strains;

These infectious agents need cell PrP to survive, and they provoke PrP amyloid as a late defense mechanism.

A) no infection without PrP host receptor; B) most agents induce same PrP-res; C) Amyloid stymies agent

Current Status (3/2014)

Attempts to fabricate an infectious PrP in a test tube

No reproducible infectivity for any pure PrP, including recombinant PrP (rPrP); more than 100 independent experiments fail to generate any infectivity from rPrP

Update: Dec 2015 Collinge lab reported 20,000 failed attempts to make rPrP infectious (Open Biol. 2015 Dec;5(12):150165. doi: 10.1098/rsob.150165) in contrast to previous Science publications.

Additional new data

  • Removal of PrP in brain homogenates does not reduce the infectivity PMID 21793014

  • When the “infectious” PrP amyloid increases, infectivity falls by 10,000 fold PMID 22509412

  • All infectious preparations contain circular DNAs of >500nt by molecular analysis PMID 21165784

  • CJD and scrapie agent particles, as viral structures, require nucleic acids to infect cells Download PDF

  • Infectious particles, stress, and induced prion amyloids Download PDF

  • Continuous production of prions after infectious particles are eliminated Download PDF

Are "established" Prion claims accurate?




1) "PrPSc (PrP-res amyloid) is proportional to titer"


diverse data from many labs falsify

2) "Procedures that hydrolyze PrPSc inactivate prions"


These also inactivate viruses

3) "No evidence exists for a virus-like particle"


discrete ~25nm viral particle

4) "Transmissible particles are devoid of nucleic acid"


all infectious matter contains long DNA

5) "PrP gene mutations cause formation of PrPSc"


toxic pathology, but not PrPSc

6) "PrP gene mutations cause transmissible disease"


Contamination with scrapie & irreproducible

7) "Prion diversity is enciphered by PrPSc" folding


unfolding PrP-res: no effect on strain or titer

9) "No immune response to foreign agent"


Early innate immune responses before PrP-res

10) "PrPSc associated with pathology"


PrPSc is a late response to infection

11) Protein X binds PrP to make it infectious

X not found

PrP itself not infectious; X is probably a virus

12) "Prions defy the rules of protein structure"


also of thermodynamics

13) CJD infectious agent arises spontaneously

No evidence for

An old & disproven concept of infection

14) recombinant PrP can be made infectious


Irreproducible: numerous failed attempts