Solving Alzheimers, Huntington, Prion diseases; Files150 and 151 of www.iw.net/~a_plutonium



A

Archimedes Plut

Guest
I am massively revising my website of
www.iw.net/~a_plutonium because it is written in a textbook
fashion that it requires massive editing and deleting and
adding onto about every 5 years. I have neglected this
website for about 10 years and so I have a big job ahead of
me. My other website of www.archimedesplutonium.com needs
no periodic editing because it is structured as a archive
that I merely collect the posts I post and enter or dump it
into the website. Archiving does not require editing
because it wants to save everything whether correct or
riddled with error.

Files 150 and 151 deal with Alzheimers Huntington and Prion
disease. I was fortunate to have a running dialogue and
conversation with at least 3 scientists from Berkeley and
Cambridge Univ about these diseases starting with the year
1997 and specifically these dates:

Oct-Nov 1997 Dec 1998 Feb-Mar 1999 Jan 2004 anyone
interested in that long history can view it at
www.archimedesplutonium.com website

I must have had over 2,000 posts to the internet in
conversations with 3 or more scientists about these
diseases. And my old practice of filling File150 and File151
with many of those past posts. That practice must cease
because my archived website handles all of those posts and
no need to repeat those posts in this textbook website where
I want to achieve understanding and clarity.

So that means I have to toss out old posts from this website
and to attempt to keep it current.

Let me just remark on the history of Alzheimers, Huntington,
and Prion. I dived into these 3 diseases back in October of
1997 noting the analogy similarity of a ant disease in the
tropics where a fungus infects an ant's brain and kills the
ant. I could not escape the notice of a analogy between
fungus ant disease and Prion disease. It then migrated theory-
wise to thinking that Prion disease is the analogy to sickle
cell anemia disease only with a deformed brain protein
instead of red blood cells. It migrated into many other
theories and hypothesis but then recently is news not of
Prion disease with metal-ions from phosmet and magnetic
manganese but news from Alzheimers in that the plaque
buildup (much like prion buildup) is caused by a scissors
that wrongly snips the APP protein into 2 segments wherein
the one segment ends up being toxic Alzheimers plaques.

So, is there a similar scissors mechanism or scissors-like
mechanism that causes Prion disease?

So I left the discussion of Alzheimers, Huntington, Prion
just January of 2004 with the open issue of a Scissors
mechanism for Alzheimers and whether Huntington and Prion
also have a scissors mechanism and whether magnetic
manganese is the metal ion culprit that causes Prion disease
and whether Huntington and Alzheimers also have a metal-ion
facilitator culprit.

One of the issues I stressed and harped and harped on from
1997 to present day is that the Nobel prize to Prusiner for
his Prion theory was a prize that was a huge mistake and
that it was perhaps 20 years too soon. To have given the
Nobel to Prusiner was so premature, that the Nobel should
have given a prize to any lead researcher of Alzheimers
circa 1995 to 1997 and to have given a prize to any lead
researcher for Huntington's disease circa 1995-1997. The
reason the Nobel Committee never awarded Alzheimers or
Huntington from 1990-2003 was because the mechanism for
Alzheimers and Huntington are still not understood. Prion is
not understand even to this very day, yet the Nobel
Committee blustered and rammed ahead giving a prize out for
Prion disease when it never should have. The Nobel to
Prusiner is one of the worst Nobel awards ever given. The
Nobel Committee in giving Prusiner the award were more
rambunctious and impetuous than Mr. Bush wanting to invade
Iraq in 2003. In fact, it can be argued that Mr. Bush had
more grounds to invade Iraq than the Nobel Committee had
grounds to award Mr. Prusiner the prize for his work on
Prion disease. And it is ironic that Mr. Blix is from Sweden
where the Nobel Committee is and that Mr. Blix is laying it
straight as far as the groundless claims of Weapons of Mass
Destruction.

One other item I want to mention for Files 150 and 151 is
that in that history of 1997 on Prion disease, is that I
attacked the Prusiner Model on two grounds and it is these
two grounds which convinced me back in 1995-March2004 that
the Prusiner Model is a complete fake.

(1) Thermodynamically it is impossible for a bad-prion-
molecule to turn a good-prion-molecule into an identical
copy. The energy equation does not give enough energy
for a similar protein to alter a different protein into
a identical copy. Just not enough energy.

(2) If prion proteins really did what the Prusiner Model
says then the lowest form of life is not the cell but
proteins like prion-proteins because replication or
reproduction is the main distinguishing characteristic
of life. And the Prusiner Model is that a protein thence
becomes the lowest form of life and makes the cell and
DNA as excess baggage.

On those two ground above convinced me that the Prusiner
Model was a fake and that it is only a matter of time before
the true mechanism of how Prion disease and how Huntington
and Alzheimers work.

Also I need to note that I suspect that Prion, Huntington
and Alzheimers are different but that they are very much
alike in several similarities. So that a mechanism of how
each works may have a family resemblance. Such that if metal-
ions plays a key role in Prion disease it is likely that metal-
ions plays a role in Huntington and Alzheimers and likewise
for the scissors mechanism in Alzheimers probably has a
scissors mechanism to be found in Huntington and Prion.

I believe these 3 diseases are related more than they are
not related.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies

(www.iw.net/~a_plutonium) website of the science of AP under
revision what used to be my old science website
www.newphys.se/elektromagnum/physics/LudwigPlutonium from
years 1993 to 2004
 
Archimedes Plutonium wrote:

> I am massively revising my website of
> www.iw.net/~a_plutonium because it is written in a
> textbook fashion that it requires massive editing and
> deleting and adding onto about every 5 years.

Yeah, that should keep it current.

I have neglected
> this website for about 10 years and so I have a big job
> ahead of me.

Well at least the information is all up to date.

> My other website of www.archimedesplutonium.com needs no
> periodic editing because it is structured as a archive
> that I merely collect the posts I post and enter or dump
> it into the website.

A trash can would be more appropriate.

Archiving does
> not require editing because it wants to save everything
> whether correct or riddled with error.

Good to know.
>
> Files 150 and 151 deal with Alzheimers Huntington and
> Prion disease. I was fortunate to have a running dialogue
> and conversation with at least 3 scientists from Berkeley
> and Cambridge Univ about these diseases starting with the
> year 1997 and specifically these dates:
>
>
> Oct-Nov 1997 Dec 1998 Feb-Mar 1999 Jan 2004 anyone
> interested in that long history can view it at
> www.archimedesplutonium.com website
>
> I must have had over 2,000 posts to the internet in
> conversations with 3 or more scientists about these
> diseases.

That's like 500 per scientist. I doubt that any
knowledgeable person would humour you for this long.

> I believe these 3 diseases are related more than they are
> not related.

Like a plane flies the same way a brick does not.
>
> Archimedes Plutonium whole entire Universe is just one big
> atom where dots of the electron-dot-cloud are galaxies

Depends on your perspective I suppose.
 
Archimedes Plutonium wrote:

> I am massively revising my website of
> www.iw.net/~a_plutonium because it is written in a
> textbook fashion that it requires massive editing and
> deleting and adding onto about every 5 years.

Yeah, that should keep it current.

I have neglected
> this website for about 10 years and so I have a big job
> ahead of me.

Well at least the information is all up to date.

> My other website of www.archimedesplutonium.com needs no
> periodic editing because it is structured as a archive
> that I merely collect the posts I post and enter or dump
> it into the website.

A trash can would be more appropriate.

Archiving does
> not require editing because it wants to save everything
> whether correct or riddled with error.

Good to know.
>
> Files 150 and 151 deal with Alzheimers Huntington and
> Prion disease. I was fortunate to have a running dialogue
> and conversation with at least 3 scientists from Berkeley
> and Cambridge Univ about these diseases starting with the
> year 1997 and specifically these dates:
>
>
> Oct-Nov 1997 Dec 1998 Feb-Mar 1999 Jan 2004 anyone
> interested in that long history can view it at
> www.archimedesplutonium.com website
>
> I must have had over 2,000 posts to the internet in
> conversations with 3 or more scientists about these
> diseases.

That's like 500 per scientist. I doubt that any
knowledgeable person would humour you for this long.

> I believe these 3 diseases are related more than they are
> not related.

Like a plane flies the same way a brick does not.
>
> Archimedes Plutonium whole entire Universe is just one big
> atom where dots of the electron-dot-cloud are galaxies

Depends on your perspective I suppose.
 
On 11 Mar 2004 12:49:20 -0800, [email protected] (Archimedes
Plutonium) wrote:

>
>One of the issues I stressed and harped and harped on from
>1997 to present day is that the Nobel prize to Prusiner for
>his Prion theory was a prize that was a huge mistake and
>that it was perhaps 20 years too soon.

You diminish whatever merit the scientific arguments may
have (and some are certainly worth discussion) by harping on
the Nobel. None of us have anything to do with it, and the
name calling is not constructive.

(I think I am already on record as having predicted
Prusiner's Nobel, but then being surprised how soon it
came -- and even more surprised that he got it alone.
But so what?)

> To have given the Nobel to Prusiner was so premature,
> that the Nobel should have given a prize to any lead
> researcher of Alzheimers circa 1995 to 1997 and to have
> given a prize to any lead researcher for Huntington's
> disease circa 1995-1997.

Well, I think the reason prion got it rather than those was
the implication for "new life form". And he dominated the
field unlike anyone in those, I think.

>
>One other item I want to mention for Files 150 and 151 is
>that in that history of 1997 on Prion disease, is that I
>attacked the Prusiner Model on two grounds and it is these
>two grounds which convinced me back in 1995-March2004 that
>the Prusiner Model is a complete fake.
>
>(1) Thermodynamically it is impossible for a bad-prion-
> molecule to turn a good-prion-molecule into an
> identical copy.

Then apparently you do not understand the model. I have
asked you about this before, but am still mystified what
your concern is. To declare impossible what has been shown
is not so helpful.

>
>(2) If prion proteins really did what the Prusiner Model
> says then the lowest form of life is not the cell but
> proteins like prion-proteins because replication or
> reproduction is the main distinguishing characteristic
> of life. And the Prusiner Model is that a protein
> thence becomes the lowest form of life and makes the
> cell and DNA as excess baggage.
>

Nonsense. The gene for the prion is a cellular gene.
Proteins do not self-replicate, according to Prusiner or
anyone else. Finding that the prion was encoded by a host
gene was a key (_the_ key?) to allowing a non-viral (not
containing nucleic acid) infectious agent to be accepted.

>
>Also I need to note that I suspect that Prion, Huntington
>and Alzheimers are different but that they are very much
>alike in several similarities.

It is interesting how similarities have been accumulating.
These similarities are all at the level of how an
aggregating protein (or perhaps a precursor to the
aggregating protein) causes neurodegeneration. But they are
all clearly very different in how that protein arises.

bob
 
Bob <[email protected]> wrote in message news:<[email protected]>...
> On 11 Mar 2004 12:49:20 -0800, [email protected]
> (Archimedes Plutonium) wrote:
>
> >
> >One of the issues I stressed and harped and harped on
> >from 1997 to present day is that the Nobel prize to
> >Prusiner for his Prion theory was a prize that was a huge
> >mistake and that it was perhaps 20 years too soon.
>
> You diminish whatever merit the scientific arguments may
> have (and some are certainly worth discussion) by harping
> on the Nobel. None of us have anything to do with it, and
> the name calling is not constructive.
>

True, but most people reading faintly have knowledge of the
science and mostly interested in the human history aspect
and it is that reason that I bring that into discussion. If
you hear Alzheimers or Prion discussed in news, it
invariably harps on the history.

> (I think I am already on record as having predicted
> Prusiner's Nobel, but then being surprised how soon it
> came -- and even more surprised that he got it alone. But
> so what?)
>

It holds back or retards progress in the field. And it can
be sensed at this time in year 2004 where progress is very
much being made in Alzheimers and in Parkinsons, but Prion
disease is thwarted and denied the real progress it should
be making. The Prusiner Model is a hurdle to progress in
that field.

>
> > To have given the Nobel to Prusiner was so premature,
> > that the Nobel should have given a prize to any lead
> > researcher of Alzheimers circa 1995 to 1997 and to have
> > given a prize to any lead researcher for Huntington's
> > disease circa 1995-1997.
>
> Well, I think the reason prion got it rather than those
> was the implication for "new life form". And he dominated
> the field unlike anyone in those, I think.
>

Bob, what if. What if when Alzheimers was first seen in
Germany in the early 20th century, what if Dr. Alzheimer had
said that the brain plaque was caused by a deformed protein
which when it comes in contact with a normal protein that it
deforms the normal protein. And that the Nobel committee
thence gives Dr. Alzheimers of Germany the prize in 1950.

A Prusiner Model can be claimed to be how Alzheimers works.
But every scientist in medicine knows that Alzheimers is not
a disease where protein molecule A deforms protein molecule
B into a copy of A.

So the Nobel Committee does not award for "true accurate
science" but instead awards more if a disease becomes
epidemic as in England in the early 1990s and the epidemic
social status forces the Swedes to award the person most
prominent in that disease field.

>
>
> >
> >One other item I want to mention for Files 150 and 151 is
> >that in that history of 1997 on Prion disease, is that I
> >attacked the Prusiner Model on two grounds and it is
> >these two grounds which convinced me back in 1995-
> >March2004 that the Prusiner Model is a complete fake.
> >
> >(1) Thermodynamically it is impossible for a bad-prion-
> > molecule to turn a good-prion-molecule into an
> > identical copy.
>
> Then apparently you do not understand the model. I have
> asked you about this before, but am still mystified what
> your concern is. To declare impossible what has been shown
> is not so helpful.
>

If you put a gallon of gasoline in your auto and asked to
drive it from Berkeley to New England, it is
thermodynamically impossible, for there just is not
enough energy.

It is impossible for a prion-bad-protein to deform a prion-normal-
protein into an identical copy. I know, Bob, you and Colin
have said years ago that the bad-prion protein garners
energy from its surrounding environment to deform the
normal prion but no-one is able to demonstrate such an
energy pathway.

In other words, bad-prion-proteins simply do not have enough
energy within the molecule and outside the molecule of its
environment to deform a normal-prion-protein.

>
> >
> >(2) If prion proteins really did what the Prusiner Model
> > says then the lowest form of life is not the cell but
> > proteins like prion-proteins because replication or
> > reproduction is the main distinguishing
> > characteristic of life. And the Prusiner Model is
> > that a protein thence becomes the lowest form of life
> > and makes the cell and DNA as excess baggage.
> >
>
> Nonsense. The gene for the prion is a cellular gene.
> Proteins do not self-replicate, according to Prusiner or
> anyone else. Finding that the prion was encoded by a host
> gene was a key (_the_ key?) to allowing a non-viral (not
> containing nucleic acid) infectious agent to be accepted.
>
>
> >
> >Also I need to note that I suspect that Prion, Huntington
> >and Alzheimers are different but that they are very much
> >alike in several similarities.
>
>
> It is interesting how similarities have been accumulating.
> These similarities are all at the level of how an
> aggregating protein (or perhaps a precursor to the
> aggregating protein) causes neurodegeneration. But they
> are all clearly very different in how that protein arises.
>
>
> bob

It is interesting how Alzheimers is converging with Prion.
Parkinsons is out of the picture but I am hoping that
Parkinsons will also have similarities and be a member of
what I call a Family of brain wasting diseases.

Bob, back in 1997 when you first started discussing diseases
with me, I never would have guessed that the convergence of
Alzheimers with Prion would be so intense by year 2004 but
it is shaping up that way.

The scissors that snips the APP protein in Alzheimers
disease snips the protein in two segments which is abnormal
for the small segment becomes the plaque buildup. So if
scissors snipping of proteins is the cause of Alzheimers,
then it is highly likely that the cause of Prion disease is
a rogue scissors.

Now, how is a rogue scissors in Prion able to transfer by
eating, while in Alzheimers, the rogue scissors is not
transmitted through eating-- at least it is not known
whether Alzheimers is transmittable through eating.

Bob, your comment "new life form" is the heart of the
argument against the Prusiner Model. RNA and DNA are life
forms and their smallest particle is a virus which manages
to use the energy of its environmental surroundings--the
cell. So, Bob, back in the 1980s or 1990s, you should have
asked yourself about the Prusiner Model that if he was
correct then this prion protein particle would be a lower
life form than even the RNA of the lowest virus. And Bob,
you have been a scientist longer than I have, so did you
ever ask yourself the reasonableness of whether a prion
protein could ever be the Lowest form of life and usurp RNA
as the lowest form of life. I suspect you never spent the
time on that question, Bob, because if you had, you would
never have endorsed the Prusiner Model to the extent you
endorsed it.

I am surprized also that Alzheimers is solving Prion disease
whereas back in 1997, I would have bet that prion disease
research would have solved prion disease itself and
Alzheimers a disconnect. I do not know if there is a lesson
or theme to be learned from this, even though prematurely.
Whether the lesson is that when baffled by a disease, then
the best avenue of attack is to find a Family Resemblance of
Diseases and then be eclectic and use parts and pieces of
one disease to guide oneself in the other disease.

Bob, question: where is Colin from Cambridge England these
days; I sort of miss his contributions, perhaps too busy.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies

(www.iw.net/~a_plutonium) website of the science of AP under
revision what used to be my old science website
www.newphys.se/elektromagnum/physics/LudwigPlutonium from
years 1993 to 2004
 
Bob <[email protected]> wrote in message news:<[email protected]>...
> On 11 Mar 2004 12:49:20 -0800, [email protected]
> (Archimedes Plutonium) wrote:
>
> >
> >One of the issues I stressed and harped and harped on
> >from 1997 to present day is that the Nobel prize to
> >Prusiner for his Prion theory was a prize that was a huge
> >mistake and that it was perhaps 20 years too soon.
>
> You diminish whatever merit the scientific arguments may
> have (and some are certainly worth discussion) by harping
> on the Nobel. None of us have anything to do with it, and
> the name calling is not constructive.
>

True, but most people reading faintly have knowledge of the
science and mostly interested in the human history aspect
and it is that reason that I bring that into discussion. If
you hear Alzheimers or Prion discussed in news, it
invariably harps on the history.

> (I think I am already on record as having predicted
> Prusiner's Nobel, but then being surprised how soon it
> came -- and even more surprised that he got it alone. But
> so what?)
>

It holds back or retards progress in the field. And it can
be sensed at this time in year 2004 where progress is very
much being made in Alzheimers and in Parkinsons, but Prion
disease is thwarted and denied the real progress it should
be making. The Prusiner Model is a hurdle to progress in
that field.

>
> > To have given the Nobel to Prusiner was so premature,
> > that the Nobel should have given a prize to any lead
> > researcher of Alzheimers circa 1995 to 1997 and to have
> > given a prize to any lead researcher for Huntington's
> > disease circa 1995-1997.
>
> Well, I think the reason prion got it rather than those
> was the implication for "new life form". And he dominated
> the field unlike anyone in those, I think.
>

Bob, what if. What if when Alzheimers was first seen in
Germany in the early 20th century, what if Dr. Alzheimer had
said that the brain plaque was caused by a deformed protein
which when it comes in contact with a normal protein that it
deforms the normal protein. And that the Nobel committee
thence gives Dr. Alzheimers of Germany the prize in 1950.

A Prusiner Model can be claimed to be how Alzheimers works.
But every scientist in medicine knows that Alzheimers is not
a disease where protein molecule A deforms protein molecule
B into a copy of A.

So the Nobel Committee does not award for "true accurate
science" but instead awards more if a disease becomes
epidemic as in England in the early 1990s and the epidemic
social status forces the Swedes to award the person most
prominent in that disease field.

>
>
> >
> >One other item I want to mention for Files 150 and 151 is
> >that in that history of 1997 on Prion disease, is that I
> >attacked the Prusiner Model on two grounds and it is
> >these two grounds which convinced me back in 1995-
> >March2004 that the Prusiner Model is a complete fake.
> >
> >(1) Thermodynamically it is impossible for a bad-prion-
> > molecule to turn a good-prion-molecule into an
> > identical copy.
>
> Then apparently you do not understand the model. I have
> asked you about this before, but am still mystified what
> your concern is. To declare impossible what has been shown
> is not so helpful.
>

If you put a gallon of gasoline in your auto and asked to
drive it from Berkeley to New England, it is
thermodynamically impossible, for there just is not
enough energy.

It is impossible for a prion-bad-protein to deform a prion-normal-
protein into an identical copy. I know, Bob, you and Colin
have said years ago that the bad-prion protein garners
energy from its surrounding environment to deform the
normal prion but no-one is able to demonstrate such an
energy pathway.

In other words, bad-prion-proteins simply do not have enough
energy within the molecule and outside the molecule of its
environment to deform a normal-prion-protein.

>
> >
> >(2) If prion proteins really did what the Prusiner Model
> > says then the lowest form of life is not the cell but
> > proteins like prion-proteins because replication or
> > reproduction is the main distinguishing
> > characteristic of life. And the Prusiner Model is
> > that a protein thence becomes the lowest form of life
> > and makes the cell and DNA as excess baggage.
> >
>
> Nonsense. The gene for the prion is a cellular gene.
> Proteins do not self-replicate, according to Prusiner or
> anyone else. Finding that the prion was encoded by a host
> gene was a key (_the_ key?) to allowing a non-viral (not
> containing nucleic acid) infectious agent to be accepted.
>
>
> >
> >Also I need to note that I suspect that Prion, Huntington
> >and Alzheimers are different but that they are very much
> >alike in several similarities.
>
>
> It is interesting how similarities have been accumulating.
> These similarities are all at the level of how an
> aggregating protein (or perhaps a precursor to the
> aggregating protein) causes neurodegeneration. But they
> are all clearly very different in how that protein arises.
>
>
> bob

It is interesting how Alzheimers is converging with Prion.
Parkinsons is out of the picture but I am hoping that
Parkinsons will also have similarities and be a member of
what I call a Family of brain wasting diseases.

Bob, back in 1997 when you first started discussing diseases
with me, I never would have guessed that the convergence of
Alzheimers with Prion would be so intense by year 2004 but
it is shaping up that way.

The scissors that snips the APP protein in Alzheimers
disease snips the protein in two segments which is abnormal
for the small segment becomes the plaque buildup. So if
scissors snipping of proteins is the cause of Alzheimers,
then it is highly likely that the cause of Prion disease is
a rogue scissors.

Now, how is a rogue scissors in Prion able to transfer by
eating, while in Alzheimers, the rogue scissors is not
transmitted through eating-- at least it is not known
whether Alzheimers is transmittable through eating.

Bob, your comment "new life form" is the heart of the
argument against the Prusiner Model. RNA and DNA are life
forms and their smallest particle is a virus which manages
to use the energy of its environmental surroundings--the
cell. So, Bob, back in the 1980s or 1990s, you should have
asked yourself about the Prusiner Model that if he was
correct then this prion protein particle would be a lower
life form than even the RNA of the lowest virus. And Bob,
you have been a scientist longer than I have, so did you
ever ask yourself the reasonableness of whether a prion
protein could ever be the Lowest form of life and usurp RNA
as the lowest form of life. I suspect you never spent the
time on that question, Bob, because if you had, you would
never have endorsed the Prusiner Model to the extent you
endorsed it.

I am surprized also that Alzheimers is solving Prion disease
whereas back in 1997, I would have bet that prion disease
research would have solved prion disease itself and
Alzheimers a disconnect. I do not know if there is a lesson
or theme to be learned from this, even though prematurely.
Whether the lesson is that when baffled by a disease, then
the best avenue of attack is to find a Family Resemblance of
Diseases and then be eclectic and use parts and pieces of
one disease to guide oneself in the other disease.

Bob, question: where is Colin from Cambridge England these
days; I sort of miss his contributions, perhaps too busy.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies

(www.iw.net/~a_plutonium) website of the science of AP under
revision what used to be my old science website
www.newphys.se/elektromagnum/physics/LudwigPlutonium from
years 1993 to 2004
 
Bob <[email protected]> wrote in message news:<[email protected]>...
> On 11 Mar 2004 12:49:20 -0800, [email protected]
> (Archimedes Plutonium) wrote:
>
> >
> >One of the issues I stressed and harped and harped on
> >from 1997 to present day is that the Nobel prize to
> >Prusiner for his Prion theory was a prize that was a huge
> >mistake and that it was perhaps 20 years too soon.
>
> You diminish whatever merit the scientific arguments may
> have (and some are certainly worth discussion) by harping
> on the Nobel. None of us have anything to do with it, and
> the name calling is not constructive.
>

True, but most people reading faintly have knowledge of the
science and mostly interested in the human history aspect
and it is that reason that I bring that into discussion. If
you hear Alzheimers or Prion discussed in news, it
invariably harps on the history.

> (I think I am already on record as having predicted
> Prusiner's Nobel, but then being surprised how soon it
> came -- and even more surprised that he got it alone. But
> so what?)
>

It holds back or retards progress in the field. And it can
be sensed at this time in year 2004 where progress is very
much being made in Alzheimers and in Parkinsons, but Prion
disease is thwarted and denied the real progress it should
be making. The Prusiner Model is a hurdle to progress in
that field.

>
> > To have given the Nobel to Prusiner was so premature,
> > that the Nobel should have given a prize to any lead
> > researcher of Alzheimers circa 1995 to 1997 and to have
> > given a prize to any lead researcher for Huntington's
> > disease circa 1995-1997.
>
> Well, I think the reason prion got it rather than those
> was the implication for "new life form". And he dominated
> the field unlike anyone in those, I think.
>

Bob, what if. What if when Alzheimers was first seen in
Germany in the early 20th century, what if Dr. Alzheimer had
said that the brain plaque was caused by a deformed protein
which when it comes in contact with a normal protein that it
deforms the normal protein. And that the Nobel committee
thence gives Dr. Alzheimers of Germany the prize in 1950.

A Prusiner Model can be claimed to be how Alzheimers works.
But every scientist in medicine knows that Alzheimers is not
a disease where protein molecule A deforms protein molecule
B into a copy of A.

So the Nobel Committee does not award for "true accurate
science" but instead awards more if a disease becomes
epidemic as in England in the early 1990s and the epidemic
social status forces the Swedes to award the person most
prominent in that disease field.

>
>
> >
> >One other item I want to mention for Files 150 and 151 is
> >that in that history of 1997 on Prion disease, is that I
> >attacked the Prusiner Model on two grounds and it is
> >these two grounds which convinced me back in 1995-
> >March2004 that the Prusiner Model is a complete fake.
> >
> >(1) Thermodynamically it is impossible for a bad-prion-
> > molecule to turn a good-prion-molecule into an
> > identical copy.
>
> Then apparently you do not understand the model. I have
> asked you about this before, but am still mystified what
> your concern is. To declare impossible what has been shown
> is not so helpful.
>

If you put a gallon of gasoline in your auto and asked to
drive it from Berkeley to New England, it is
thermodynamically impossible, for there just is not
enough energy.

It is impossible for a prion-bad-protein to deform a prion-normal-
protein into an identical copy. I know, Bob, you and Colin
have said years ago that the bad-prion protein garners
energy from its surrounding environment to deform the
normal prion but no-one is able to demonstrate such an
energy pathway.

In other words, bad-prion-proteins simply do not have enough
energy within the molecule and outside the molecule of its
environment to deform a normal-prion-protein.

>
> >
> >(2) If prion proteins really did what the Prusiner Model
> > says then the lowest form of life is not the cell but
> > proteins like prion-proteins because replication or
> > reproduction is the main distinguishing
> > characteristic of life. And the Prusiner Model is
> > that a protein thence becomes the lowest form of life
> > and makes the cell and DNA as excess baggage.
> >
>
> Nonsense. The gene for the prion is a cellular gene.
> Proteins do not self-replicate, according to Prusiner or
> anyone else. Finding that the prion was encoded by a host
> gene was a key (_the_ key?) to allowing a non-viral (not
> containing nucleic acid) infectious agent to be accepted.
>
>
> >
> >Also I need to note that I suspect that Prion, Huntington
> >and Alzheimers are different but that they are very much
> >alike in several similarities.
>
>
> It is interesting how similarities have been accumulating.
> These similarities are all at the level of how an
> aggregating protein (or perhaps a precursor to the
> aggregating protein) causes neurodegeneration. But they
> are all clearly very different in how that protein arises.
>
>
> bob

It is interesting how Alzheimers is converging with Prion.
Parkinsons is out of the picture but I am hoping that
Parkinsons will also have similarities and be a member of
what I call a Family of brain wasting diseases.

Bob, back in 1997 when you first started discussing diseases
with me, I never would have guessed that the convergence of
Alzheimers with Prion would be so intense by year 2004 but
it is shaping up that way.

The scissors that snips the APP protein in Alzheimers
disease snips the protein in two segments which is abnormal
for the small segment becomes the plaque buildup. So if
scissors snipping of proteins is the cause of Alzheimers,
then it is highly likely that the cause of Prion disease is
a rogue scissors.

Now, how is a rogue scissors in Prion able to transfer by
eating, while in Alzheimers, the rogue scissors is not
transmitted through eating-- at least it is not known
whether Alzheimers is transmittable through eating.

Bob, your comment "new life form" is the heart of the
argument against the Prusiner Model. RNA and DNA are life
forms and their smallest particle is a virus which manages
to use the energy of its environmental surroundings--the
cell. So, Bob, back in the 1980s or 1990s, you should have
asked yourself about the Prusiner Model that if he was
correct then this prion protein particle would be a lower
life form than even the RNA of the lowest virus. And Bob,
you have been a scientist longer than I have, so did you
ever ask yourself the reasonableness of whether a prion
protein could ever be the Lowest form of life and usurp RNA
as the lowest form of life. I suspect you never spent the
time on that question, Bob, because if you had, you would
never have endorsed the Prusiner Model to the extent you
endorsed it.

I am surprized also that Alzheimers is solving Prion disease
whereas back in 1997, I would have bet that prion disease
research would have solved prion disease itself and
Alzheimers a disconnect. I do not know if there is a lesson
or theme to be learned from this, even though prematurely.
Whether the lesson is that when baffled by a disease, then
the best avenue of attack is to find a Family Resemblance of
Diseases and then be eclectic and use parts and pieces of
one disease to guide oneself in the other disease.

Bob, question: where is Colin from Cambridge England these
days; I sort of miss his contributions, perhaps too busy.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies

(www.iw.net/~a_plutonium) website of the science of AP under
revision what used to be my old science website
www.newphys.se/elektromagnum/physics/LudwigPlutonium from
years 1993 to 2004
 
"Archimedes Plutonium" <[email protected]> wrote in message
news:[email protected]...
> Bob <[email protected]> wrote in message
news:<[email protected]>...
> > On 11 Mar 2004 12:49:20 -0800, [email protected]
> > (Archimedes Plutonium) wrote:
> >
> > >
> > >One of the issues I stressed and harped and harped on
> > >from 1997 to present day is that the Nobel prize to
> > >Prusiner for his Prion theory was a prize that was a
> > >huge mistake and that it was perhaps 20 years too soon.
> >
> > You diminish whatever merit the scientific arguments may
> > have (and some are certainly worth discussion) by
> > harping on the Nobel. None of us have anything to do
> > with it, and the name calling is not constructive.
> >
>
> True, but most people reading faintly have knowledge of
> the science and mostly interested in the human history
> aspect and it is that reason that I bring that into
> discussion. If you hear Alzheimers or Prion discussed in
> news, it invariably harps on the history.
>
>
> > (I think I am already on record as having predicted
> > Prusiner's Nobel, but then being surprised how soon it
> > came -- and even more surprised that he got it alone.
> > But so what?)
> >
>
> It holds back or retards progress in the field. And it can
> be sensed at this time in year 2004 where progress is very
> much being made in Alzheimers and in Parkinsons, but Prion
> disease is thwarted and denied the real progress it should
> be making. The Prusiner Model is a hurdle to progress in
> that field.
>
> >
> > > To have given the Nobel to Prusiner was so premature,
> > > that the Nobel should have given a prize to any lead
> > > researcher of Alzheimers circa 1995 to 1997 and to
> > > have given a prize to any lead researcher for
> > > Huntington's disease circa 1995-1997.
> >
> > Well, I think the reason prion got it rather than those
> > was the implication for "new life form". And he
> > dominated the field unlike anyone in those, I think.
> >
>
> Bob, what if. What if when Alzheimers was first seen in
> Germany in the early 20th century, what if Dr. Alzheimer
> had said that the brain plaque was caused by a deformed
> protein which when it comes in contact with a normal
> protein that it deforms the normal protein. And that the
> Nobel committee thence gives Dr. Alzheimers of Germany the
> prize in 1950.
>
> A Prusiner Model can be claimed to be how Alzheimers
> works. But every scientist in medicine knows that
> Alzheimers is not a disease where protein molecule A
> deforms protein molecule B into a copy of A.
>
> So the Nobel Committee does not award for "true accurate
> science" but instead awards more if a disease becomes
> epidemic as in England in the early 1990s and the epidemic
> social status forces the Swedes to award the person most
> prominent in that disease field.
>
> >
> >
> > >
> > >One other item I want to mention for Files 150 and 151
> > >is that in that history of 1997 on Prion disease, is
> > >that I attacked the Prusiner Model on two grounds and
> > >it is these two grounds which convinced me back in 1995-
> > >March2004 that the Prusiner Model is a complete fake.
> > >
> > >(1) Thermodynamically it is impossible for a bad-prion-
> > > molecule to turn a good-prion-molecule into an
> > > identical copy.
> >
> > Then apparently you do not understand the model. I have
> > asked you about this before, but am still mystified what
> > your concern is. To declare impossible what has been
> > shown is not so helpful.
> >
>
> If you put a gallon of gasoline in your auto and asked to
> drive it from Berkeley to New England, it is
> thermodynamically impossible, for there just is not
> enough energy.
>
> It is impossible for a prion-bad-protein to deform a prion-normal-
> protein into an identical copy. I know, Bob, you and Colin
> have said years ago that the bad-prion protein garners
> energy from its surrounding environment to deform the
> normal prion but no-one is able to demonstrate such an
> energy pathway.
>
> In other words, bad-prion-proteins simply do not have
> enough energy within the molecule and outside the molecule
> of its environment to deform a normal-prion-protein.

I've tried this before but... AP, try looking at Pathologic
conformations of prion proteins. (1998) Annu Rev Biochem 67
p793-819 Also, I like to look at the serpin analogy http://-
eagle.mmid.med.ualberta.ca/publications/JMB293p449.pdf

AP, do you claim that crystallisation is thermodynamically
impossible?

Amyloid is just a great big Conga line of drunk proteins
at a New years party, and the normal proteins just aint
drunk enough to join in... yet. Until it hits midnight...
An I know its not thermodynamically impossible to get
drunk. Trust me
 
"Wyrin" <[email protected]> wrote in message news:<[email protected]>...

>
> I've tried this before but... AP, try looking at
> Pathologic conformations of prion proteins. (1998) Annu
> Rev Biochem 67 p793-819 Also, I like to look at the serpin
> analogy http://eagle.mmid.med.ualberta.ca/publications/JM-
> B293p449.pdf
>
> AP, do you claim that crystallisation is thermodynamically
> impossible?
>
> Amyloid is just a great big Conga line of drunk proteins
> at a New years party, and the normal proteins just aint
> drunk enough to join in... yet. Until it hits midnight...
> An I know its not thermodynamically impossible to get
> drunk. Trust me

Crystallization is thermodynamically possible, and you know
what Wyrin, thousands perhaps millions of chemists and their
students have worked out enthalpies and entropies and
whether the reaction will go and the rates of reaction. But
why is it Wyrin that no-one ever worked out whether bad-
prions react and change good prions. Is it because Mr.
Prusiner is unable to do any such calculations? So why have
you Wyrin not given any website that shows the entropy and
enthalpies for prion reactions? Is it because they are
nonexistant?

Also a question Wyrin, in that you so heartily believe in
the Prusiner Model. What would you assign a probability of
correctness for a Prusiner Model when in the decade of the
1980s and in the decade of the 1990s and even from the years
2000 to March of 2004, it is still unknown and vastly
unclear as to the role and function of normal-prions. In the
past it was said that normal prions build or help build cell
walls but as of March 2004 there is not a chemist or
biologists in the entire world who is confident of what
normal prions do or function as or their purpose. So, the
question I have for you Wyrin, is what sort of probability
would you assign for any scientist who claims to have a
correct theory as to the mechanism and causes of a disease
and to offer such a Model, yet still has no clue or firm
clue or understanding of what the particle of his Model what
that particles role or function or purpose was.

Would you say Wyrin that the chances of any scientist
finding a correct model for a disease wherein that scientist
has little to no clue as to what the function or role of
their main-element or main molecule of the disease (in this
case normal-prions). Would you say that the chances of the
Model being wrong is something about 99% with maybe a 1%
chance that the Model is correct? Because that is where I
would place the numbers.

Any scientist in any field whether biology, medicine,
chemistry, physics, if they do not know the role or function
of their main issue under investigation, then any Model or
theory constructed around that main issue is by all chances
and probabilities going to be wrong.

Analogy: suppose Sherlock Holmes or other famous detectives
operated in the same manner that Mr. Prusiner operated to
form his Model. Then Sherlock would be arresting people left
and right without ever knowing whether anyone had been
killed. We would have Sherlock Holmes stories where he goes
out and looks for and hunts criminals yet no dead bodies.
That is a similar analogy to Mr. Prusiner running out and
running off concocting Models without ever knowing what
Normal Prions function or role was.

A good scientist knows that unless he fully knows and
understands what normal and good Prions do and function,
unless he knows that, his Models on prion disease are
nothing but wild-speculation.

Sorry if it sounds like I am picking on you Wyrin, but you
deserve it with your scatterbrained tidbits above.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies

(www.iw.net/~a_plutonium) website of the science of AP under
revision what used to be my old science website
www.newphys.se/elektromagnum/physics/LudwigPlutonium from
years 1993 to 2004
 
On 14 Mar 2004 23:30:17 -0800, [email protected] (Archimedes
Plutonium) wrote:

>> >
>> >One other item I want to mention for Files 150 and 151
>> >is that in that history of 1997 on Prion disease, is
>> >that I attacked the Prusiner Model on two grounds and it
>> >is these two grounds which convinced me back in 1995-
>> >March2004 that the Prusiner Model is a complete fake.
>> >
>> >(1) Thermodynamically it is impossible for a bad-prion-
>> > molecule to turn a good-prion-molecule into an
>> > identical copy.
>>
>> Then apparently you do not understand the model. I have
>> asked you about this before, but am still mystified what
>> your concern is. To declare impossible what has been
>> shown is not so helpful.
>>
>
>If you put a gallon of gasoline in your auto and asked to
>drive it from Berkeley to New England, it is
>thermodynamically impossible, for there just is not
>enough energy.

agreed, but that is irrelevant.

>
>It is impossible for a prion-bad-protein to deform a prion-normal-
>protein into an identical copy.

You still have not answered the question. Why do you think
that? Proteins fold and refold and adjust their folding all
the time. This is basic protein chemistry. The total net
energy of protein folding is very slight. Offhand I have no
idea what the energetics of the proposed reaction is, but no
one with the slightest understanding of proteins would think
there is any problem with it.

>
>The scissors that snips the APP protein in Alzheimers
>disease snips the protein in two segments which is abnormal
>for the small segment becomes the plaque buildup. So if
>scissors snipping of proteins is the cause of Alzheimers,
>then it is highly likely that the cause of Prion disease is
>a rogue scissors.

The logic of that statement is zilch. In fact, it is known
to be incorrect. There are many ways to make bad proteins.

>
>Bob, your comment "new life form" is the heart of the
>argument against the Prusiner Model. RNA and DNA are life
>forms and their smallest particle is a virus which manages
>to use the energy of its environmental surroundings--the
>cell. So, Bob, back in the 1980s or 1990s, you should have
>asked yourself about the Prusiner Model that if he was
>correct then this prion protein particle would be a lower
>life form than even the RNA of the lowest virus. And Bob,
>you have been a scientist longer than I have, so did you
>ever ask yourself the reasonableness of whether a prion
>protein could ever be the Lowest form of life and usurp RNA
>as the lowest form of life. I suspect you never spent the
>time on that question, Bob, because if you had, you would
>never have endorsed the Prusiner Model to the extent you
>endorsed it.

What the prion model does is to show that the prion is not
alive, any more than a virus is. Cells are the lowest form
of life known. Viruses and prions use cells. The prion model
resolved what had seemed to be a problem by showing how
prions use cells. The prion is coded for by a cellular gene.
Problem solved. (That we still may not agree on all the
details of the prion transformation is not relevant to that
basic issue. And how they cause disease has no relevance at
all to the question of what a prion is.)

>
>I am surprized also that Alzheimers is solving Prion
>disease whereas back in 1997, I would have bet that prion
>disease research would have solved prion disease itself and
>Alzheimers a disconnect. I do not know if there is a lesson
>or theme to be learned from this, even though prematurely.
>Whether the lesson is that when baffled by a disease, then
>the best avenue of attack is to find a Family Resemblance
>of Diseases and then be eclectic and use parts and pieces
>of one disease to guide oneself in the other disease.

well, that's progress.

bob
 
Bob <[email protected]> wrote in message news:<[email protected]>...
> On 14 Mar 2004 23:30:17 -0800, [email protected]
> (Archimedes Plutonium) wrote:

> >
> >It is impossible for a prion-bad-protein to deform a prion-normal-
> >protein into an identical copy.
>
> You still have not answered the question. Why do you think
> that? Proteins fold and refold and adjust their folding
> all the time. This is basic protein chemistry. The total
> net energy of protein folding is very slight. Offhand I
> have no idea what the energetics of the proposed reaction
> is, but no one with the slightest understanding of
> proteins would think there is any problem with it.

Would you not agree Bob that when two molecules collide and
interact, that changes in one or both of the molecules is
induced. That is normal collision and interaction. But would
you not agree Bob that when a collision between protein
molecules occurs and they interact and they go off as
identical to one another, would you not agree that such was
so implausible as to be unbelievable.

It is what I said back in 1997, that unless you say the bad-
prion molecule is a catalyst where a catalyst is unchanged
at the end of the interaction. But that still makes the prion-
catalyst unique amoung all other catalysts because the prion
catalyst is the only 2 party catalyst and all other
catalysts like platinum in the gasoline industry is a 3
party catalyst.

Bob, I agree proteins fold and refold and adjust their
folding all the time, but your opinion of Prions as per the
Prusiner Model is a superspecial sort of folding that no
thermodynamical enthalpies or entropies can support.

Toyota makes a car called Prius, sort of hybrid electric
that gives more then 50 miles per gallon. Suppose cars were
like protein collision and interaction. Suppose there was a
Prion car out there and it collided and interacted with many
other cars. Whenever a Prius collided or interacted with a
GM or Ford or BMW or VW both are folded and misshapened
after the event. But when a Prion collides and interacts
with a Prius, both are undamaged and both drive off from the
accident as brand new Prion cars-- totally unbelievable,
forgive the expression, someone would say Twilight Zone
science or X-files science.

Protein folding in normal interactions is commonplace, but
when 2 proteins collide and interact and leave the scene of
the event as identical molecules, well, that needs special
attention for it is against the rules of Thermodynamics and
even the 2nd Law of Thermodynamics.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies
 
Bob <[email protected]> wrote in message news:<[email protected]>...
> On 14 Mar 2004 23:30:17 -0800, [email protected]
> (Archimedes Plutonium) wrote:

> >
> >It is impossible for a prion-bad-protein to deform a prion-normal-
> >protein into an identical copy.
>
> You still have not answered the question. Why do you think
> that? Proteins fold and refold and adjust their folding
> all the time. This is basic protein chemistry. The total
> net energy of protein folding is very slight. Offhand I
> have no idea what the energetics of the proposed reaction
> is, but no one with the slightest understanding of
> proteins would think there is any problem with it.
>

Bob, I am rusty on calculating enthalpy and entropy for
whether a reaction will go or not and the rate of reaction.
I am please asking for you to calcalute those numbers for
platinum and for gold. We all know that platinum is a
catalyst but not a super catalyst that the Prusiner Model
expects of a prion protein. Platinum is a normal catalyst in
that it speeds up the rate of reaction and it ends up
unchanged by the end of the reaction. In fact, there
probably does not exist a supercatalyst for which this
calculation I am asking of you Bob would demonstrate.

We all know that platinum cannot change gold into more
platinum, but please Bob work through the numbers and please
give me a number for enthalpy and entropy that proves number
wise that such a reaction is impossible.

Working through the numbers Bob, it should be a huge
negative energy to have to put into the reaction in order
for Platinum to alter Gold atoms into making more Platinum
Atoms. And, or, please work the reverse route of starting
with Gold atoms and expecting them to change Platinum atoms
into more gold atoms.

Bob, I appreciate you constantly asking me to clarify why
prions of the Prusiner Model are thermodynamically
impossible. I keep answering that question. I keep telling
you that if his model were correct implies Supercatalysts,
implies chemistry of not just normal catalysts like platinum
in the gasoline distilling industry but supercatalysts where
platinum turns gold atoms into more platinum atoms. Chemical
Reactions alter the molecules of shape and form-- this is
normal. But it is not normal that molecule A when it bumps
into molecule B and alters B into an identical copy, that is
not normal. That is not allowed by thermodynamics and the
Prusiner Model is just another way of saying SuperCatalysts
exist when that is a falsehood.

Bob, I am very rusty as it was over 30 years ago when at UC
that I computed enthalpy and entropy and rates of chemical
reactions. So please assist me. Please compute the numbers
that shows that it is impossible for Platinum to convert
Gold and vice versa. Show me the numbers that proves it is
impossible in Chemistry for Platinum to convert gold into
more platinum.

Once those numbers are displayed, then it is easier to go
the reaction of taking a Prion bad molecule and expecting it
to convert a Prion good molecule into an identical copy.

Yes, the flaw of the Prusiner Model is that it expects the
world of science to have a Supercatalyst, but the world of
science has no supercatalysts and these are impossible. A
supercatalyst is more than a catalyst in that it is party to
2 molecules whereas a normal-catalyst is party to at least 3
molecules.

Bob, I cannot find the numbers or work the numbers for prion
proteins and it seems from your above reply that you cannot
also. But you are more of a chemist than I will ever be, and
thus you should be able to provide me with a number solution
of enthalpy and entropy of a reaction between Platinum and
Gold and why platinum cannot alter gold into an identical
platinum copy and vice versa.

ARchimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies
 
"Archimedes Plutonium" <[email protected]> wrote in message
news:[email protected]...
> "Wyrin" <[email protected]> wrote in message
news:<[email protected]>...
>
> >
> > I've tried this before but... AP, try looking at
> > Pathologic conformations of prion proteins. (1998) Annu
> > Rev Biochem 67 p793-819 Also, I like to look at the
> > serpin analogy http://eagle.mmid.med.ualberta.ca/public-
> > ations/JMB293p449.pdf
> >
> > AP, do you claim that crystallisation is
> > thermodynamically impossible?
> >
> > Amyloid is just a great big Conga line of drunk proteins
> > at a New years party, and the normal proteins just aint
> > drunk enough to join in... yet. Until it hits
> > midnight... An I know its not thermodynamically
> > impossible to get drunk. Trust me
>

> Sorry if it sounds like I am picking on you Wyrin, but you
> deserve it with your scatterbrained tidbits above.

It didnt sound like you were picking on me - just that you
were spouting a diatribe with little basis in fact. Those
scatterbrained titbits - IF YOU ACTUALLY BOTHRERED TO READ
THEM - would answer some of your questions

> Crystallization is thermodynamically possible, and you
> know what Wyrin, thousands perhaps millions of chemists
> and their students have worked out enthalpies and
> entropies and whether the reaction will go and the rates
> of reaction. But why is it Wyrin that no-one ever worked
> out whether bad-prions react and change good prions. Is it
> because Mr. Prusiner is unable to do any such
> calculations? So why have you Wyrin not given any website
> that shows the entropy and enthalpies for prion reactions?
> Is it because they are nonexistant?

If you looked at the first reference I gave you, you would
find some of the answer to this Pathologic conformations of
prion proteins. (1998) Annu Rev Biochem 67 p793-819 http://-
arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioche-
m.67.1.793 Go to a local library and ask for this article,
or purchase it online

What do you think of the existance of prions in yeast?

> Would you say Wyrin that the chances of any scientist
> finding a correct model for a disease wherein that
> scientist has little to no clue as to what the function or
> role of their main-element or main molecule of the disease
> (in this case normal-prions). Would you say that the
> chances of the Model being wrong is something about 99%
> with maybe a 1% chance that the Model is correct? Because
> that is where I would place the numbers.

What is the probability of correctness of the opinion of a
person who is so inherently biased against Prusiner? He
proposed a dogma-breaking theory and got a nobel prize for
it. Ok, it might have been earlier than he deserved, but
that doesnt invalidate the growing body of evidence that has
been compiled to sugest his theory could be true

> Analogy: suppose Sherlock Holmes or other famous
> detectives operated in the same manner that Mr. Prusiner
> operated to form his Model. Then Sherlock would be
> arresting people left and right without ever knowing
> whether anyone had been killed. We would have Sherlock
> Holmes stories where he goes out and looks for and hunts
> criminals yet no dead bodies. That is a similar analogy
> to Mr. Prusiner running out and running off concocting
> Models without ever knowing what Normal Prions function
> or role was.

Irrelevant

>A good scientist knows that unless he fully knows and
>understands what normal and good Prions do and function,
>unless he knows that, his Models on prion disease are
>nothing but wild-speculation.

A good scientist basis his opinions on observations with as
little speculation as possible. Here's a bit from my thesis
where I try to put a balanced view on it. The first
theories put forward to explain the observed infectivity
and strain variation of prion diseases, such as scrapie in
sheep and kuru in humans, suggested the existence of a
parasite or 'slow virus' (Eklund and Hadlow, 1969; Hadlow,
1995). However, the infectivity was resistant to
decontamination by UV irradiation at 254 nm, which argued
against the presence of a nucleic acid (Alper et al.,
1967). Other properties of the agent included resistance to
heat, including autoclaving at 120 °C, formalin treatment
and ionising radiation (Gordon, 1946; Prusiner, 1998a). An
'unconventional virus' was suggested but no actual details
offered. No bacteria or virus has been found consistently
associated with prion disease (Prusiner, 1998a). The term
prion (from proteinaceous-infectious particle, lacking a
nucleic acid) was put forward following evidence that
procedures that modified or destroyed proteins could reduce
scrapie infectivity (Griffith, 1967; Prusiner, 1982).
Prusiner proposed, therefore, that the endogenous prion
protein was the infectious agent, and a mutated PrP
responsible for the inherited disease. This model has since
been widely accepted, since it has been shown that PrP is
the only factor that has been found to be associated with
disease so far, and endogenous PrP is required for disease
transmission (Bolton et al., 1982; Hope et al., 1986;
Prusiner et al., 1993b).

Nevertheless, some researchers still maintain that viral
mechanisms are important in prion disease and to account for
the observed strain variation, citing other viruses that are
known to cause dementia and spongiform change in the brain,
and that display resistance to classical decontamination
techniques (Manuelidis, 1994a Manuelidis, 1995 #787).
Furthermore, neither refolded PrPSc nor purified recombinant
protein have yet been shown to be infective (Prusiner et
al., 1993a; Manuelidis, 1994b). However, studies with yeast
prions, and in vitro demonstration that resistance to prion
infectivity correlates with the degree of homology between
the host PrPC and exogenous PrPSc, are strong arguments in
favour of the prion hypothesis (Bossers et al., 1997;
Liebman, 2002).
 
On 15 Mar 2004 23:53:32 -0800, [email protected] (Archimedes
Plutonium) wrote:

>Would you not agree Bob that when two molecules collide and
>interact, that changes in one or both of the molecules is
>induced. That is normal collision and interaction. But
>would you not agree Bob that when a collision between
>protein molecules occurs and they interact and they go off
>as identical to one another, would you not agree that such
>was so implausible as to be unbelievable.

??? Why is this not believable?

Steve Turner
 
On 16 Mar 2004 10:39:39 -0800, [email protected] (Archimedes
Plutonium) wrote:

>We all know that platinum cannot change gold into more
>platinum, but please Bob work through the numbers and
>please give me a number for enthalpy and entropy that
>proves number wise that such a reaction is impossible.

This is a nuclear transformation, not a chemical one.
Chemical thermodynamics do not apply.

Steve Turner
 
"Wyrin" <[email protected]> wrote in message news:<[email protected]>...
> "Archimedes Plutonium" <[email protected]> wrote in
> message
> news:[email protected]...
> > "Wyrin" <[email protected]> wrote in message
> news:<[email protected]>...
> >
> > >
> > > I've tried this before but... AP, try looking at
> > > Pathologic conformations of prion proteins. (1998)
> > > Annu Rev Biochem 67 p793-819 Also, I like to look at
> > > the serpin analogy http://eagle.mmid.med.ualberta.ca/-
> > > publications/JMB293p449.pdf
> > >
> > > AP, do you claim that crystallisation is
> > > thermodynamically impossible?
> > >
> > > Amyloid is just a great big Conga line of drunk
> > > proteins at a New years party, and the normal proteins
> > > just aint drunk enough to join in... yet. Until it
> > > hits midnight... An I know its not thermodynamically
> > > impossible to get drunk. Trust me
> >
>
> > Sorry if it sounds like I am picking on you Wyrin, but
> > you deserve it with your scatterbrained tidbits above.
>
> It didnt sound like you were picking on me - just that you
> were spouting a diatribe with little basis in fact. Those
> scatterbrained titbits - IF YOU ACTUALLY BOTHRERED TO READ
> THEM - would answer some of your questions

some files I cannot access for it interfers with my killfile
such as pdf

>
> > Crystallization is thermodynamically possible, and you
> > know what Wyrin, thousands perhaps millions of chemists
> > and their students have worked out enthalpies and
> > entropies and whether the reaction will go and the rates
> > of reaction. But why is it Wyrin that no-one ever worked
> > out whether bad-prions react and change good prions. Is
> > it because Mr. Prusiner is unable to do any such
> > calculations? So why have you Wyrin not given any
> > website that shows the entropy and enthalpies for prion
> > reactions? Is it because they are nonexistant?
>
> If you looked at the first reference I gave you, you would
> find some of the answer to this Pathologic conformations
> of prion proteins. (1998) Annu Rev Biochem 67 p793-819 ht-
> tp://arjournals.annualreviews.org/doi/pdf/10.1146/annurev-
> .biochem.67.1.793 Go to a local library and ask for this
> article, or purchase it online
>

If you were scientifically objective about prion disease
then you would not be in these newsgroups with the attitude
of saying "you are wrong and here, I deposit for you sites
in which to correct your misconceptions" Your trouble Wyrin
is that you take some lofty high ground that you are the
authority on prions and that you are here to correct
everyone else. When you fact you are an incompetent in
Prion science.

> What do you think of the existance of prions in yeast?
>

If you had a gram of science objectivity, Wyrin, you would
thence realize that since yeast which is chock full of prion
proteins yet is utter harmless to animals, would indicate
strongly that the Prusiner Model for prions is false. Why
should prions in yeast never act like prions in animals,
unless of course the Prusiner Model is a fake science model.
But you, Wyrin, just does not have the science objectivity.

> > Would you say Wyrin that the chances of any scientist
> > finding a correct model for a disease wherein that
> > scientist has little to no clue as to what the function
> > or role of their main-element or main molecule of the
> > disease (in this case normal-prions). Would you say that
> > the chances of the Model being wrong is something about
> > 99% with maybe a 1% chance that the Model is correct?
> > Because that is where I would place the numbers.
>
> What is the probability of correctness of the opinion of a
> person who is so inherently biased against Prusiner?

No, I am both biased against Prusiner but also _able_ to be
biased for Prusiner. But you, Wyrin, is incapable of being
biased against Prusiner. Perhaps it is because you are part
of the establishment with your job and career at stake. This
is a common problem with most scientists in that they know a
science theory is wrong but they cannot speak out against it
because of their biweekly paycheck.

> He proposed a dogma-breaking theory and got a nobel prize
> for it. Ok, it might have been earlier than he deserved,
> but that doesnt invalidate the growing body of evidence
> that has been compiled to sugest his theory could be true
>

There is no growing body of evidence in support of Prusiner.
There is evidence of variant types of bad prion proteins
which disproves the Prusiner Model. How can that Model
reconcile over 13 type flavors of bad prion proteins just
for cows. And the growing evidence that a protein scissors
is the cause of prion accumulation. That the scissors
creates the bad prions. And the growing evidence that
Alzheimers is very much like Prion disease and no-one
expects the Prusiner Model to work for Alzheimers.

> > Analogy: suppose Sherlock Holmes or other famous
> > detectives operated in the same manner that Mr. Prusiner
> > operated to form his Model. Then Sherlock would be
> > arresting people left and right without ever knowing
> > whether anyone had been killed. We would have Sherlock
> > Holmes stories where he goes out and looks for and hunts
> > criminals yet no dead bodies. That is a similar analogy
> > to Mr. Prusiner running out and running off concocting
> > Models without ever knowing what Normal Prions function
> > or role was.
>
> Irrelevant
>
> >A good scientist knows that unless he fully knows and
> >understands what normal and good Prions do and function,
> >unless he knows that, his Models on prion disease are
> >nothing but wild-speculation.
>
> A good scientist basis his opinions on observations with
> as little speculation as possible. Here's a bit from my
> thesis where I try to put a balanced view on it.

You do not put a balanced view on this issue of Prion
disease. It is your unbalance view of this entire issue that
prevents you from making any progress.

Example, you cannot even answer my question put to you. I
asked you what you think is the likelihood of success of a
science theory when the proponents of the theory have no
clue or no firm basis of the purpose and design of what the
prion protein molecule functions as? I asked you Wyrin, what
is the chances of a theory about Prion disease of the
Prusiner Model being correct when Mr. Prusiner never had a
clear understanding of the role and function of the prion
protein as of this very date?

How likely is it for a Prion Disease Model to be correct
when the authors of that model have little to no idea of
what a prion protein does or functions or its purpose or its
behaviour in the body.

Wyrin, I said the probability is that of 99% wrong for the
model and perhaps a low 1% that Mr. Prusiner guessed it
correctly. For it would have to be a guess when a scientist
constructs a Model around a disease but has little to no
understanding of the protein function of prions.

And funny how the Nobel Committee when it evaluated the
giving of the award to Mr. Prusiner that not a single one of
those Swedish scientist had a bell and light go off in their
brains and said--- hey, how likely is it that the Prusiner
Model is correct when Mr. Prusiner does not even know what
the function of a prion protein molecule is, nor any other
scientist of that time period.

So, Wyrin, please answer my question: what is the likelihood
that the Prusiner Model is correct when it was constructed
without knowing or understanding of what a prion protein
functions as within the body. I said the probability was 99%
wrong and only a 1% chance that Mr. Prusiner had guessed it
correctly.

> The first theories put forward to explain the observed
> infectivity and strain variation of prion diseases, such
> as scrapie in sheep and kuru in humans, suggested the
> existence of a parasite or 'slow virus' (Eklund and
> Hadlow, 1969; Hadlow, 1995). However, the infectivity was
> resistant to decontamination by UV irradiation at 254 nm,
> which argued against the

Tell me, did anyone ever think that Alzheimers was a virus
led disease? Or that Parkinsons was a virus led disease?
That is old history.

But what Alzheimers and Parkinsons and Prion have in common
is the cutting edge of science as far as prion disease is
concerned. Don't keep bringing up Prusiner baloney because
nothing of what Mr. Prusiner espoused in the 20th century is
turning out correctly. Almost all of
Mr. Prusiner's espousals of prion disease are turning out
to be wrong.

It is scissors that is the cause of Prion disease as it is
scissors that is the cause of Alzheimers and Parkinsons. It
maybe metal-ions such as magnetic manganese that corrupts
the prion-scissors and that when meat is eaten from infected
prion those prion-scissors or magnetic-manganese get lodged
into the new victims brains.

> presence of a nucleic acid (Alper et al., 1967). Other
> properties of the agent included resistance to heat,
> including autoclaving at 120 °C, formalin treatment and
> ionising radiation (Gordon, 1946; Prusiner, 1998a). An
> 'unconventional virus' was suggested but no actual details
> offered. No bacteria or virus has been found consistently
> associated with prion disease (Prusiner, 1998a). The term
> prion (from proteinaceous-infectious particle, lacking a
> nucleic acid) was put forward following evidence that
> procedures that modified or destroyed proteins could
> reduce scrapie infectivity (Griffith, 1967; Prusiner,
> 1982). Prusiner proposed, therefore, that the endogenous
> prion protein was the infectious agent, and a mutated PrP
> responsible for the inherited disease. This model has
> since been widely accepted, since it has been shown that
> PrP is the only factor that has been found to be
> associated with disease so far, and endogenous PrP is
> required for disease transmission (Bolton et al., 1982;
> Hope et al., 1986; Prusiner et al., 1993b).
>
> Nevertheless, some researchers still maintain that viral
> mechanisms are important in prion disease and to account
> for the observed strain variation, citing other viruses
> that are known to cause dementia and spongiform change
> in the brain, and that display resistance to classical
> decontamination techniques (Manuelidis, 1994a
> Manuelidis, 1995 #787). Furthermore, neither refolded
> PrPSc nor purified recombinant protein have yet been
> shown to be infective (Prusiner et al., 1993a;
> Manuelidis, 1994b). However, studies with yeast prions,
> and in vitro demonstration that resistance to prion
> infectivity correlates with the degree of homology
> between the host PrPC and exogenous PrPSc, are strong
> arguments in favour of the prion hypothesis (Bossers et
> al., 1997; Liebman, 2002).

The Prusiner Model is equivalent to saying that the world
has a supercatalyst. Platinum is a normal catalyst and used
in the gasoline distilling industry. Where a normal catalyst
like platinum speeds up the rate of reaction and is
unchanged at the end and so platinum is party to at least 3
molecules/atoms. If the Prusiner Model were correct then the
world of chemistry has a Supercatalyst wherein it is party
to only 2 molecules, not 3. And if platinum were a
supercatalyst then it would be able to alter gold atoms into
more platinum atoms.

I don't expect you to understand any of the above paragraph
Wyrin because your mind is so polluted in bias favor of the
Prusiner Model that it is too much for you to handle.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies
 
Steve Turner <[email protected]> writes:

>On 16 Mar 2004 10:39:39 -0800, [email protected]
>(Archimedes Plutonium) wrote:

>>We all know that platinum cannot change gold into more
>>platinum, but please Bob work through the numbers and
>>please give me a number for enthalpy and entropy that
>>proves number wise that such a reaction is impossible.

>This is a nuclear transformation, not a chemical one.
>Chemical thermodynamics do not apply.

A better example would be if platinum catalyzed the
conversion of, let's say, platinum chloride into platinum
and chlorine. Start out with a beaker of pure platinum
chloride, let's say one molecule decomposes spontaneouely,
producing a Pt atom. This atom catalyzes a second molecule,
resulting in 2 Pt atoms. Then you'd get 4, 8, 16 and I'd
guess the result is it would appear to suddenly decompose.
 
[email protected] wrote in message news:<[email protected]>...

>
> A better example would be if platinum catalyzed the
> conversion of, let's say, platinum chloride into platinum
> and chlorine. Start out with a beaker of pure platinum
> chloride, let's say one molecule decomposes spontaneouely,
> producing a Pt atom. This atom catalyzes a second
> molecule, resulting in 2 Pt atoms. Then you'd get 4, 8, 16
> and I'd guess the result is it would appear to suddenly
> decompose.

I probably did not use the best example with platinum
catalyzing gold into more platinum. I am after the numbers
and chemists would never compute these numbers because they
automatically know that it is impossible for such reactions
to go forth. But I want the numbers so as to "emphasize and
show how impossible".

I could restate the problem by asking for platinum and
gold mix and what energy it takes for a platinum atom to
steal away a electron from a gold atom to make another
platinum atom.

Or I could ask for the energies involved in a CO and CO2 mix
where the CO converts CO2 into more CO.

Or I could ask for the energies involved in ethylene-glycol
to convert glycerol into more ethylene-glycol.

I am keeping focused on the main issue-- Supercatalysts --
that they do not exist because it takes too much energy for
a molecule or atom that when it collides, it remains the
same and yet still has energy coming from out of nowhere to
convert other molecules into identical copies.

Take any two molecules that are almost identical and compute
the amount of energy required for one of those molecules to
convert the other into an identical copy. I see it as
impossible because the one molecule would be changed also
and would not be the original itself, as well as the second
being changed.

Chemists never figure these energies because they never have
a need to do so since they instinctively know that the
reaction will never take place and that the energies are
prohibitively large.

But this is the only way to convince people who are enamored
with the Prusiner Model that they are on false science
grounds. If Prusiner were correct then the world has in
existance at least one Supercatalyst-- bad-prions. But I am
sure that Prusiner is utterly wrong and that the world has
no supercatalyst. The closest the world has to chemical that
in part acts like a supercatalyst is RNA and DNA in mitosis,
but even there they are not catalysts.

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies
 
On 15 Mar 2004 23:53:32 -0800, [email protected] (Archimedes
Plutonium) wrote:

>Bob <[email protected]> wrote in message
>news:<[email protected]>...
>> On 14 Mar 2004 23:30:17 -0800, [email protected]
>> (Archimedes Plutonium) wrote:
>
>> >
>> >It is impossible for a prion-bad-protein to deform a prion-normal-
>> >protein into an identical copy.
>>
>> You still have not answered the question. Why do you
>> think that? Proteins fold and refold and adjust their
>> folding all the time. This is basic protein chemistry.
>> The total net energy of protein folding is very slight.
>> Offhand I have no idea what the energetics of the
>> proposed reaction is, but no one with the slightest
>> understanding of proteins would think there is any
>> problem with it.
>
>Would you not agree Bob that when two molecules collide and
>interact, that changes in one or both of the molecules is
>induced. That is normal collision and interaction. But
>would you not agree Bob that when a collision between
>protein molecules occurs and they interact and they go off
>as identical to one another, would you not agree that such
>was so implausible as to be unbelievable.

No, would not agree. But it has no relevance anyway. That is
not what happens. Prion A joins prion B, and takes the B
conformation (loosely).

>
>It is what I said back in 1997, that unless you say the bad-
>prion molecule is a catalyst where a catalyst is unchanged
>at the end of the interaction. But that still makes the prion-
>catalyst unique amoung all other catalysts because the
>prion catalyst is the only 2 party catalyst and all other
>catalysts like platinum in the gasoline industry is a 3
>party catalyst.
>

I hope you are not getting hung up on the word catalyst.
Prion conversion is probably not truly catalytic, since the
"catalyst" ends up bound to the protein it changed.

The point is that prion conversions have been amply
demonstrated, and are within the normal behavior of
proteins.

Nothing you have said suggests that we are deceiving
ourselves. I still await an argument why the conversion is
impossible -- and there is a tremendous burden there, since
it is well understood to occur and to be reasonable.

If you want to argue that mammalian prions may have
additional complexities (eg beyond yeast prions), fine. It
is true that no one has yet demonstrated conversion to
infective material in a cell-free system for a mammalian
prion. But the prion basics are amply demonstrated, and
there is no reason that the additional complexities cannot
be accommodated within the current models. Time will tell.

>Bob, I agree proteins fold and refold and adjust their
>folding all the time, but your opinion of Prions as per the
>Prusiner Model is a superspecial sort of folding that no
>thermodynamical enthalpies or entropies can support.

nope, not at all.

>
>Toyota makes a car called Prius, sort of hybrid electric
>that gives more then 50 miles per gallon. Suppose cars were
>like protein collision and interaction. Suppose there was a
>Prion car out there and it collided and interacted with
>many other cars. Whenever a Prius collided or interacted
>with a GM or Ford or BMW or VW both are folded and
>misshapened after the event. But when a Prion collides and
>interacts with a Prius, both are undamaged and both drive
>off from the accident as brand new Prion cars-- totally
>unbelievable, forgive the expression, someone would say
>Twilight Zone science or X-files science.

cute, but irrelevant.

Try driving a Prion!

Your analogies really are not helping. In fact, they seem to
be causing you to be misled.

bob
 
Bob <[email protected]> wrote in message news:<[email protected]>...
> On 15 Mar 2004 23:53:32 -0800, [email protected]
> (Archimedes Plutonium) wrote:
(some snipping)
> >
> >Would you not agree Bob that when two molecules collide
> >and interact, that changes in one or both of the
> >molecules is induced. That is normal collision and
> >interaction. But would you not agree Bob that when a
> >collision between protein molecules occurs and they
> >interact and they go off as identical to one another,
> >would you not agree that such was so implausible as to be
> >unbelievable.
>
>
> No, would not agree. But it has no relevance anyway. That
> is not what happens. Prion A joins prion B, and takes the
> B conformation (loosely).
>

Are you saying that prion A and prion B after the collision
and interaction are not identical when they disjoin and move
off? And that only a *part* of prion A is identical to a
*part* of prion B? So the identicalness is not the entire
prion molecule but only a small surface area of each
molecule? If so, that would help explain better the
thermodynamical energies and also explain better various
prion variety types in that only a small portion of the
prion is identical or made identical.

I had always thought of the Prusiner Model as identicalness
for the entire molecule. Partial identicalness could have a
ring of truth. I guess partial identicalness could be the
conversion of helices to that of sheets, so that a bad prion
converts a portion of a helix into a sheet geometry.

But I need to know something. Bob, can you tell me of the
most similar protein molecule that behaves in this manner
and is not prions. Tell me if there are any bio-molecules
that act and behave in the manner of bad prions. Are there
any? Or are bad prions a unique case.

>
>
> >
> >It is what I said back in 1997, that unless you say the
> >bad-prion molecule is a catalyst where a catalyst is
> >unchanged at the end of the interaction. But that still
> >makes the prion-catalyst unique amoung all other
> >catalysts because the prion catalyst is the only 2 party
> >catalyst and all other catalysts like platinum in the
> >gasoline industry is a 3 party catalyst.
> >
>
>
> I hope you are not getting hung up on the word catalyst.
> Prion conversion is probably not truly catalytic, since
> the "catalyst" ends up bound to the protein it changed.
>
> The point is that prion conversions have been amply
> demonstrated, and are within the normal behavior of
> proteins.
>
> Nothing you have said suggests that we are deceiving
> ourselves. I still await an argument why the conversion is
> impossible -- and there is a tremendous burden there,
> since it is well understood to occur and to be reasonable.
>

I could go along with a "partial conversion"

>
>
> If you want to argue that mammalian prions may have
> additional complexities (eg beyond yeast prions), fine. It
> is true that no one has yet demonstrated conversion to
> infective material in a cell-free system for a mammalian
> prion. But the prion basics are amply demonstrated, and
> there is no reason that the additional complexities cannot
> be accommodated within the current models. Time will tell.
>

The best explanation to date why infective material in a cell-
free system is a no-go is that the disease is caused by the
protein scissors and you need cells to create the scissors,
and thus the disease is not caused by prion converting other
prion particles, but that the scissors is the culprit.

Bob, I have asked Wyrin whether the alpha-synuclein in
Parkinsons and whether the two proteins that accumulate
in Alzheimers come in several varieties and types. Or do
they come in one and only one brand or type? Would you
happen to know?

Also, I am trying to find out the most current state of
knowledge as to the number of varieties or types of CJD and
of Mad-Cow-Disease, and also of sheep scrapie. I vaguely
remember 6 varieties for CJD and 13 for Mad Cow Disease.
Bob, are you current on those numbers?

Archimedes Plutonium whole entire Universe is just one big
atom where dots of the electron-dot-cloud are galaxies