If you're interested in what the father of the "Prion only" hypothesis is patenting, I suggest you look up USA patent #7,151,000 dated December 19, 2006 [Method of concentrating proteins from serum]. Here are a few comments which I found very interesting, and my commentary which ties up loose ends can be found at the end...
"Further, a prion which infects one species of animal (e.g., a human) will not readily infect another (e.g., a mouse)."
"It appears that the scrapie isoform of the prion protein (PrP.sup.Sc) is necessary for both the transmission and pathogenesis of the transmissible neurodegenerative diseases of animals and humans."
"The most common prion diseases of animals are scrapie of sheep and goats and bovine spongiform encephalopathy (BSE) of cattle [Wilesmith, J. and Wells, Microbiol. Immunol. 172:21 38 (1991)]. Four prion diseases of humans have been identified: (1) kuru, (2) Creutzfeldt-Jakob Disease (CJD), (3) Gerstmann-Strassler-Scheinker Disease (GSS), and (4) fatal familial insomnia (FFI) [Gajdusek, D. C., Science 197:943 960 (1977); Medori et al., N. Engl. J. Med. 326:444 449 (1992)]."
"Iatrogenic CJD has been caused by human growth hormone derived from cadaveric pituitaries as well as dura mater grafts [Brown et al., Lancet 340:24 27 (1992)]. Despite numerous attempts to link CJD to an infectious source such as the consumption of scrapie infected sheep meat, none has been identified to date [Harries-Jones et al., J. Neurol. Neurosurg. Psychiatry 51:1113 1119 (1988)] except in cases of iatrogenically induced disease."
"These cases of iatrogenic CJD underscore the need for screening pharmaceuticals that might possibly be contaminated with prions." [ie:
human to human]
"Another object of the invention is to provide a method which includes the initial steps needed to reveal a naturally occurring factor inhibitory for prion formation which inhibitory factor could be used in its naturally occurring or modified form as a therapeutic for the treatment of diseases related to disease conformations of certain proteins (e.g. prion diseases). "
"Another feature of the invention is that the complexing agent may be heteropoly acids or metal salts thereof, or biological agents such as peptides, small molecules, selective PrP.sup.Sc binding antibodies and PrP binding antibodies.
Another feature is that preferred complexing agents are metal salts of phosphotungstic acid, with sodium phosphotungstate being particularly preferred."
(back to Prusiner's patent):
"For example a complexing agent binds to the desired protein (PrP.sup.Sc) forming an agent/protein complex which has a higher specific gravity than the protein or agent alone. Accordingly, the agent/protein complex can be separated away via gravity which is preferably supplemental by the use of centrifugation. A preferred complexing agent which binds PrP.sup.Sc more readily than it binds PrP.sup.C and a particularly preferred agent binds PrP.sup.Sc with a high degree of affinity and does not bind PrP.sup.C at significant levels."
"As used herein, the term pathogenic may mean that the protein actually causes the disease or it may simply mean that the protein is associated with the disease and therefore is present when the disease is present. Thus, a pathogenic protein as used in connection with this disclosure is not necessarily a protein which is the specific causative agent of a disease."
"Particles are comprised largely, if not exclusively, of PrP.sup.Sc molecules encoded by a PrP gene. Prions are generally PrP.sup.Sc dimers."
"One conformation is associated with disease characteristics and is generally insoluble whereas the other conformation is not associated with disease characteristics and is soluble."
"After the serum is obtained the serum is treated in a manner which allows for the protein of interest to be concentrated. This is preferably done by adding a complexing agent which forms an agent/protein complex which complex has a higher specific gravity than either the complexing agent or protein of interest."
"No conclusive assertions can be made here with respect to why the present invention works. Thus, the scope of the present invention is not bound by any particular theory explaining the underlying mechanism. Notwithstanding such it appears as though proteins involved in clot formation have an inhibitory effect on the formation of the pathogenic conformation. Alternatively, the clot forming proteins remove some other inhibitor or factor which allows for the formation of the pathogenic form of the protein. Assuming such is the case, the isolation of this inhibitor would provide a valuable therapeutic for diseases. The inhibitor could be administered to any mammal including a human after first noting the signs of disease related to the pathogenic form of the protein. The administration of such an inhibitor would prevent further formation of the pathogenic formation of the protein and thereby halt progression of the disease."
"A particular class of heteropoly acids is the protonated form of heteropolymolybdates. These anions contain from 2 to 18 hexavalent molybdenum atoms around one or more central atoms. About 36 different elements have been identified as central atoms of these heteropolymolybdates. These anions are all highly oxygenated."
"In heteropolytungstates, the coordinating element is tungsten instead of molybdenum."
I will note here, that rats are extremely more tolerant of toxins than people. eg. in research on fluoride toxicity with rats, Dr. Mullenix had to increase the levels fed to rats 147 times in order to reach similar "blood levels" to that of humans. In the case of DU, to have wasting of the rats at only 5 times greater amounts than found in veterans, this is a serious wake-up call!
According to reknown scientist, Dr. Marion Fulk formerly of the "Manhatten Project" which developed the bombs dropped on Hiroshima and Nagasaki - depleted uranium nanoparticles act as "HETEROGENOUS CATALYSTS" need I say more? It needs to be laid out....
Dr. Vitaly Vodyanoy of Auburn University in Alabama found within blood (and other biological materials including plants, and soil), small non-ionic metallic nanoparticles containging 40-300 metal atoms which he calls PNCs (or proteon nucleating centers). These PNCs are capable of "nucleating" misfolded protein fragments, which are then referred to as "proteons". A single PNC can sequester approximately 100,000 mal-formed proteins. Dr. Vodyanoy found that the sequestering procedure with certain types of metallic PNCs is "reversible" (ie: "soluble"). There is no doubt in my mind, that other types of metallic PNCs create "non-reversible" or "insoluble" proteons.
Looking at USA patent 7,151,000 of Dr. Stanley Prusiner, the "father of the prion protein hypothesis" and comparing it to the knowledge surrounding:
Vodyanoy's PNCs, Fulk's DU heterogenous catalysts, and the consistent use by researchers of phosphotungstic acids (tungsten based - heavy metal), or salts thereof, to sequester PrPSc is all very interesting, and related.
When SB Prusiner comments in his new patent, that "Prions are generally PrP.sup.Sc dimers." I believe it is evident that prions alone are not capable of forming the so-called "infectious" particle ("agent/protein complex") responsible for transmission of TSEs. The malformed prion proteins must have a metal nucleating center that is a form of heteropoly acid. In the case of Transmissible spongiform encephalopathy, I hope that researchers will give serious consideration to "ACTINIDE based" heteropoly acids.
[wikipedia - Actinides]: (partial definition)
"The actinides display less similarity in their chemical properties than the lanthanide series, for instance exhibiting a wider range of oxidation states, which initially led to confusion as to whether actinium, thorium, and uranium should be considered d-block elements. All actinides are radioactive."
"Further, a prion which infects one species of animal (e.g., a human) will not readily infect another (e.g., a mouse)."
"It appears that the scrapie isoform of the prion protein (PrP.sup.Sc) is necessary for both the transmission and pathogenesis of the transmissible neurodegenerative diseases of animals and humans."
"The most common prion diseases of animals are scrapie of sheep and goats and bovine spongiform encephalopathy (BSE) of cattle [Wilesmith, J. and Wells, Microbiol. Immunol. 172:21 38 (1991)]. Four prion diseases of humans have been identified: (1) kuru, (2) Creutzfeldt-Jakob Disease (CJD), (3) Gerstmann-Strassler-Scheinker Disease (GSS), and (4) fatal familial insomnia (FFI) [Gajdusek, D. C., Science 197:943 960 (1977); Medori et al., N. Engl. J. Med. 326:444 449 (1992)]."
"Iatrogenic CJD has been caused by human growth hormone derived from cadaveric pituitaries as well as dura mater grafts [Brown et al., Lancet 340:24 27 (1992)]. Despite numerous attempts to link CJD to an infectious source such as the consumption of scrapie infected sheep meat, none has been identified to date [Harries-Jones et al., J. Neurol. Neurosurg. Psychiatry 51:1113 1119 (1988)] except in cases of iatrogenically induced disease."
"These cases of iatrogenic CJD underscore the need for screening pharmaceuticals that might possibly be contaminated with prions." [ie:
human to human]
"Another object of the invention is to provide a method which includes the initial steps needed to reveal a naturally occurring factor inhibitory for prion formation which inhibitory factor could be used in its naturally occurring or modified form as a therapeutic for the treatment of diseases related to disease conformations of certain proteins (e.g. prion diseases). "
"Another feature of the invention is that the complexing agent may be heteropoly acids or metal salts thereof, or biological agents such as peptides, small molecules, selective PrP.sup.Sc binding antibodies and PrP binding antibodies.
Another feature is that preferred complexing agents are metal salts of phosphotungstic acid, with sodium phosphotungstate being particularly preferred."
[Wikipedia definition] Heteropoly acid:
A heteropoly acid is a chemical compound composed of:
- a metal such as tungsten, molybdenum or vanadium;
- oxygen;
- an element from the p-block of the periodic table, such as silicon, phosphorus or arsenic;
- acidic hydrogen atoms.
The conjugate anion of a heteropoly acid is known as a polyoxometalate.
Heteropoly acids are widely used as heterogeneous catalysts.
[wikipedia definition] Polyoxometalate:
A polyoxometalate (abbreviated POM) is a metallate containing anion or molecule consisting of transition metal ions bonded to other ligands, generally oxygen atoms, though some derivatives might contain nitrogen or sulfur, and generally based upon MoO6 and/or WO6 octahedra (though not exclusively). Several of these POMs are polymeric in nature, while others are discrete anions/molecules The largest of these POM's currently known isolated molybdenum and number up to 368 molybdenum ions and over a 1000 atoms/ions in total. There are also numerous structures of tungsten and vanadium, not to mention the large mineral archetypes of the earlier transition metals (eg, rutile, hematite, spinel etc) and their laboratory snythesised analogues, along with numerous lanthanide and actinide complexes (often Keggin based).
(back to Prusiner's patent):
"For example a complexing agent binds to the desired protein (PrP.sup.Sc) forming an agent/protein complex which has a higher specific gravity than the protein or agent alone. Accordingly, the agent/protein complex can be separated away via gravity which is preferably supplemental by the use of centrifugation. A preferred complexing agent which binds PrP.sup.Sc more readily than it binds PrP.sup.C and a particularly preferred agent binds PrP.sup.Sc with a high degree of affinity and does not bind PrP.sup.C at significant levels."
"As used herein, the term pathogenic may mean that the protein actually causes the disease or it may simply mean that the protein is associated with the disease and therefore is present when the disease is present. Thus, a pathogenic protein as used in connection with this disclosure is not necessarily a protein which is the specific causative agent of a disease."
"Particles are comprised largely, if not exclusively, of PrP.sup.Sc molecules encoded by a PrP gene. Prions are generally PrP.sup.Sc dimers."
"One conformation is associated with disease characteristics and is generally insoluble whereas the other conformation is not associated with disease characteristics and is soluble."
"After the serum is obtained the serum is treated in a manner which allows for the protein of interest to be concentrated. This is preferably done by adding a complexing agent which forms an agent/protein complex which complex has a higher specific gravity than either the complexing agent or protein of interest."
"No conclusive assertions can be made here with respect to why the present invention works. Thus, the scope of the present invention is not bound by any particular theory explaining the underlying mechanism. Notwithstanding such it appears as though proteins involved in clot formation have an inhibitory effect on the formation of the pathogenic conformation. Alternatively, the clot forming proteins remove some other inhibitor or factor which allows for the formation of the pathogenic form of the protein. Assuming such is the case, the isolation of this inhibitor would provide a valuable therapeutic for diseases. The inhibitor could be administered to any mammal including a human after first noting the signs of disease related to the pathogenic form of the protein. The administration of such an inhibitor would prevent further formation of the pathogenic formation of the protein and thereby halt progression of the disease."
"A particular class of heteropoly acids is the protonated form of heteropolymolybdates. These anions contain from 2 to 18 hexavalent molybdenum atoms around one or more central atoms. About 36 different elements have been identified as central atoms of these heteropolymolybdates. These anions are all highly oxygenated."
"In heteropolytungstates, the coordinating element is tungsten instead of molybdenum."
[wikipedia taken from definition of depleted uranium]:
"A laboratory study on rats produced by the Armed Forces Radiobiology Research Institute [30] showed that, after a study period of 6 months, rats treated with chronical doses of depleted uranium coming from implanted pellets comparable to the levels (in μg/kg) found on average in the urines of Desert Storm veterans with retained DU fragments, had developed a slight (not statistically significant) tendency to lose weight with respect to the control group, as well as two isolated cases of total inability to eat, one of which caused by abnormal tooth growth. More importantly, the high dose group, which was maintained at a chronical level of DU roughly 5 times greater than found in veterans, had developed a significant tendency to lose weight with respect to the control group; substantial amounts of uranium were accumulating in their brains and central nervous systems, and showed a significant reduction of neuronal activity in the hippocampus in response to external stimuli. The conclusions of the study show that brain damage from chronic uranium intoxication is possible at lower doses than previously thought,"
I will note here, that rats are extremely more tolerant of toxins than people. eg. in research on fluoride toxicity with rats, Dr. Mullenix had to increase the levels fed to rats 147 times in order to reach similar "blood levels" to that of humans. In the case of DU, to have wasting of the rats at only 5 times greater amounts than found in veterans, this is a serious wake-up call!
According to reknown scientist, Dr. Marion Fulk formerly of the "Manhatten Project" which developed the bombs dropped on Hiroshima and Nagasaki - depleted uranium nanoparticles act as "HETEROGENOUS CATALYSTS" need I say more? It needs to be laid out....
Dr. Vitaly Vodyanoy of Auburn University in Alabama found within blood (and other biological materials including plants, and soil), small non-ionic metallic nanoparticles containging 40-300 metal atoms which he calls PNCs (or proteon nucleating centers). These PNCs are capable of "nucleating" misfolded protein fragments, which are then referred to as "proteons". A single PNC can sequester approximately 100,000 mal-formed proteins. Dr. Vodyanoy found that the sequestering procedure with certain types of metallic PNCs is "reversible" (ie: "soluble"). There is no doubt in my mind, that other types of metallic PNCs create "non-reversible" or "insoluble" proteons.
Looking at USA patent 7,151,000 of Dr. Stanley Prusiner, the "father of the prion protein hypothesis" and comparing it to the knowledge surrounding:
Vodyanoy's PNCs, Fulk's DU heterogenous catalysts, and the consistent use by researchers of phosphotungstic acids (tungsten based - heavy metal), or salts thereof, to sequester PrPSc is all very interesting, and related.
When SB Prusiner comments in his new patent, that "Prions are generally PrP.sup.Sc dimers." I believe it is evident that prions alone are not capable of forming the so-called "infectious" particle ("agent/protein complex") responsible for transmission of TSEs. The malformed prion proteins must have a metal nucleating center that is a form of heteropoly acid. In the case of Transmissible spongiform encephalopathy, I hope that researchers will give serious consideration to "ACTINIDE based" heteropoly acids.
[wikipedia - Actinides]: (partial definition)
"The actinides display less similarity in their chemical properties than the lanthanide series, for instance exhibiting a wider range of oxidation states, which initially led to confusion as to whether actinium, thorium, and uranium should be considered d-block elements. All actinides are radioactive."