🚀 go-pugleaf

Note that I see no need to continue cross-posting this to seven or eight 
groups and have set followups to rec.pets only.

In article <31A13661.6E0C@megafauna.com>,
Steve Barnard  <steve@megafauna.com> wrote:
>
>The leading theory about "mad cow" disease, which is in fact a widely 
>accepted theory, is that it is caused by a "prion," which is a 
>self-replicating protein molecule.  This was once ridiculed as heresy in 
>biochemical circles, but it's accepted now.

"Ridiculed" is pretty strong.  "Not widely accepted, but considered 
plausible enough for further examination" would be closer.  

>cause "scabies" in sheep and are known to cause a brain disease in 

"Scrapie", not "scabies".  The latter is a mite different.

>cannabilistic human societies.  (This is sometimes called "laughing 

No, only in some New Guinea tribes.  It's being questioned as to the 
societies in question (or for that matter, any society, ever) was 
cannibalistic.  There are other plausible and even probable methods by 
which the prion could spread.

There are also many other human prion diseases.

>I wouldn't be at all surpised if prions are eventually determined to 
>cause all sorts of mysterious diseases, especially neurological diseases 
>such as MS, ALS, and Altsheimer's.

Possibly but unlikely.  This has been looked at fairly closely and there 
hasd been no convincing link found.

The following quick-n-dirty guide to prions has probably already been 
seen and yawned over by many of you.  Feel free to hit 'n' now.

-=-=-
There are many excellent web sites on prions:
  http://www.kcc.com.msu.edu/CAI/Pathology/cns_infections
  http://www.airtime.co.uk/bse/welcome.htm
  http://www.nmia.com/~mdibble/prion.html
  http://www.iah.bbsrc.ac.uk/institut/public/3wtse.htm
  http://www.cowtown.org/nca4315.html

Wot's a prion?  It's the cause of a number of animal diseases which have 
in common a slow course, a lack of an immune response, and 'spongiform 
encephalopathies" - the brain gets holes appearing in it so it looks 
like a sponge under the microscope.  Prions are apparently unique among 
infectious thingies in that they're solely protein - there's no nucleic 
acid (i.e. RNA and DNA) involved.  The word was coined by Stan Prusiner 
and it's short for "proteinaceous infectious" particle, which should 
therefore be "proin" but that didn't sound so good so he changed it to 
prion.  (T).  

There are a bunch of prion disease.  The most common is a sheep disease
called "scrapie".  Bovine and mink and a couple others get 'bovine (or
mink) spongiform ecephalopathies".  In humans, there's Kuru, and there's
Creutzfeldt-Jacob disease, fatal familial insomnia,
Gerstmann-Straussler-Scheinker Syndrome, and some others that don't have
names as far as I can find. 

They're all fatal.

Most importantly, prion protein is a normal component of normal cells.  
All of you are happily churning out prion proteins by the billion right 
now.  Actually, you're churning out prion precursor protein - the normal 
protein is innocuous (although its functiuon is unknown, it's presumably 
required for normal cell function).  When something changes the protein 
to another form then it becomes Evil.  

There are fundamentally three causes of prion protein changes.  (1)  
Spontaneous. No cause known.  There may be a precipitating event or it 
may be a truly random event.  This is very rare - something like 
1/1000000 or less - but is probably the most common cause of prion 
diseases in humans.  (2)  Inherited mutations.  Note that it is, for 
example, fatal FAMILIAL insomnia.  (3)  Infection.  

What seems to happen is that the prion protein can exist in two forms, but
that form 2 (the dangerous one) causes form 1 to convert to form 2.  In
other words, a catalytic feedback reaction.  Hence, the infectious nature.
The familial cases occur because there's a mutation that makes the protein
more likely to assume position 2.  In fact, even spontaneous diseases are
infectious - that is, if someone has CJD from a spontaneous change, the
prion particles from that person are infectious (catalyze the formation of
type 2), even though she was not infected originally.  If you see what I
mean. 

For example, CJD may be sporadic (case 1), familial (case 2) or 
iatrogenic (case 3).  

Recently it was shown that yeast have an analagous process (although it's 
not fatal in yeast) in which a normal yeast protein has two switch 
positions and position 2 converts position 1 to position 2.

It's common for the prions from one species to be able to infect another
species, but it's not inevitable.  Thus scrapie agent (from sheep) can
infect a number of lab rodents; but it's not very infectious at first, and
takes some acclimatization for it to become very infectious in that
species.  Scrapie agent probably originally caused BSE (that's not
certain) and probably originated the mink encephalopathy as well.  On the
other hand, scrapie has been around in sheep for a long time, and there's
never been any epidemiological evidence that scrapie agent would infect
humans. (And people have looked very hard for such a link.) This is one
reason it was originally believed that BSE was unlikely to infect humans. 

One thing about prions is that they're incredibly hardy.  You can't
destroy them with anything, including autoclaving.  (Actually, autoclaving
will eventually destroy them, but it takes a long, long time.) They can
also be present in very high levels, so you can destroy 99% of them and
still be left with billions of infectious particles.  This isn't entirely
unique in proteins - there are some other proteins which can be boiled and
autoclaved and still be functional.  For example, the purification
protocol for the RNase A protein begins "boil a pancreas in sulpheric acid
..." 

The infection process is poorly understood.  In the lab animals infected 
with scrapie agent, it's known that the particles have a blood phase, 
collect in the spleen briefly, then infect the brain and start causing 
gradual problems.  The blood and spleen phase is less easily found in 
some other cases, and apparently in BSE it's very difficult to show this 
at all.  In BSE essentially all the prions are found in the brain and 
spinal cord.  

And that about sums up the current knowledge.  They're a bitch to study -
the process is slow, so you're looking at years for a single experiment
often, and until recently it was difficult to mimic the human processes in
lab rodents.  Until recently, also, there wasn't a great deal of interest
in them - these are very rare sporadic human diseases, and until BSE and
the fear of spread to humans there was little funding for the work. 
(Another argument against directed research?) Also people had to assume
that the first time you used the damn things your whole lab was thereafter
forever a scrapie lab, because you can't disinfect them. 

-- 
      Ian York   (iayork@panix.com)  <http://www.panix.com/~iayork/>
      "-but as he was a York, I am rather inclined to suppose him a
       very respectable Man." -Jane Austen, The History of England