[sci.nanotech] Prions

mvp@hsv3.uucp (Mike Van Pelt) (01/04/91)

In article <Dec.31.18.35.03.1990.25921@athos.rutgers.edu> cphoenix@csli.stanford.edu (Chris Phoenix) writes:
>Several years ago I heard of something called prions, which the
>discussion of self-replicating chemicals reminded me of.

I was told recently that prions were just a hypothesis, which
turned out not to be true after all.  I know I haven't seen
anything about them in years -- Anyone else have more info?
-- 
Mike Van Pelt                          Here lies a Technophobe,
Headland Technology/Video 7               No whimper, no blast.
...ames!vsi1!headland!mvp              His life's goal accomplished,
                                          Zero risk at last.

toms@fcs260c2.ncifcrf.gov (Tom Schneider) (01/07/91)

In article <Jan.3.21.51.17.1991.2385@athos.rutgers.edu> mvp@hsv3.uucp
(Mike Van Pelt) writes:

>I was told recently that prions were just a hypothesis, which
>turned out not to be true after all.  I know I haven't seen
>anything about them in years -- Anyone else have more info?

They were a hypothesis TO EXPLAIN CERTAIN DISEASES.  They were not a "just a
hypothesis" floating in the air.  The diseases are rather strange, that have
long incubation periods (years) and cause brain degeneration.  One was called
Kuru (spelling?).  Apparently it was transmitted when certain peoples ate the
brains of dead relatives.  The factor did not appear to contain any nucleic
acid.  The last report I saw confirmed this.  There does seem to be a gene in
the body that makes something similar to the prion protein, but I don't have
the latest information on this.  Perhaps if an abnormal form of the prion
protein enters the body, it triggers the body to create more copies of that
abnormal form.  One could dream up many reasonable mechanisms.  For example,
the abnormal form could be created by a bad RNA splicing event that only occurs
when the protein itself is in the cell.  Although this does not explain the
origin of the disease, it does explain the continuation.  The disease could
have originated as a mistaken RNA splicing event.

>Mike Van Pelt
>Headland Technology/Video 7
>...ames!vsi1!headland!mvp

  Tom Schneider
  National Cancer Institute
  Laboratory of Mathematical Biology
  Frederick, Maryland  21702-1201
  toms@ncifcrf.gov

heskett@titan.tsd.arlut.utexas.edu (Donald Heskett) (01/08/91)

Today's issue of the Wall St. Journal has a front page article on
spongiform encephalopathy and talks briefly about prions as a possible
infectious agent.  It mentions one test in which candidate infectious
material was held at over 600 degrees Fahrenheit for an hour...and
remained, apparently, infectious; that doesn't sound like organic
matter, much less genetic material.

toms@fcs260c2.ncifcrf.gov (Tom Schneider) (01/10/91)

I just came a review on prions from last September!

@article{Aiken1990,
author = "J. M. Aiken
 and R. F. Marsh",
title = "The Search for Scrapie Agent Nucleic Acid",
journal = "Microbiology Reviews",
volume = "54",
pages = "242-246",
year = "1990"} 

Kru was a disease of natives in New Guinea.
 
There is now evidence for genes in the host to be involved, but studies of the
infective agent itself have failed to identify a nucleic acid.  Still!  The
last sentence says it all for this modern mystery:  "The search continues."

  Tom Schneider
  National Cancer Institute
  Laboratory of Mathematical Biology
  Frederick, Maryland  21702-1201
  toms@ncifcrf.gov

gwilliam@mrc-crc.ac.uk (Gary Williams x3294) (01/12/91)

In article <Jan.9.15.30.10.1991.11777@athos.rutgers.edu>, toms@fcs260c2.ncifcrf.gov (Tom Schneider) writes:
> 
> I just came a review on prions from last September!
> ...
> Kru was a disease of natives in New Guinea.
> ...
> There is now evidence for genes in the host to be involved, but studies of the
> infective agent itself have failed to identify a nucleic acid.  Still!  The
> last sentence says it all for this modern mystery:  "The search continues."

The last theory I heard of was that 'slow-viruses' or Prions (Kuru,
Creutzfeld-Jacob Disease, Scrapie, Bovine Spongiform Encepalopathy etc.)
are caused by a protein that is a natural product of the brain cells and
which performs some essential function; however it has two forms.

It is normally present as a trimer of three subunits.  As an example,
(Using a dimer because the ASCII character set isn't up to displaying
trimers very well) let one subunit of the protein be represented by a
'[' character, then the sticky bits of the protein that recognise itself
to bind the dimer together would be the horizontal bits of the character
and the dimer can be represented as '[]'. 

So the protein dimer are normally floating about in brain cells like:

                []          []

                    []    []
                []

Now (says the theory) when the brain cell is infected with some material
from an affected brain, the second form of the protein is introduced.
This second form is a rod-like protein made from a chain of the subunits
like this:

                            [
                              ]
                            [
                              ]
                            [
                              ]
                            [

Note that it has sticky bits at the ends of the chain.  The proteins are
constantly being knocked around in the thermal motion (37 C) of the cell
contents and sometimes the dimers are knocked apart for an instant.  In
the normal state they would quickly re-bind, but when there is the
rod-form around there is a small probability that the protein subunits
will join onto the end of the rod of subunits instead of reforming the
dimer, thus the rod grows.  The general effect is much the same as if
your car engine slowly started growing a steel girder inside itself. 
The cell dies - slowly.  Big regions of dead cells appear in the brain. 
The brain looks spongy because it now has holes in.  The affected
individual starts having co-ordination problems etc.  The condition is
chronic and fatal. 

Questions:

How does the cell's machinery construct the protein so that it forms the
dimer (trimer) rather than the rod-form?

Is there a difference in stability between these two forms?

How did the rod-form originate? (Presumably a rare event can occur such
that two dimers can bang into each other, disassemble and snap back
in the rod-form)

Are there more than one type of protein that has these two stable forms?
(Many proteins occur in the form of two or more subunits bound together,
eg Hemoglobin is formed from two alpha-type and two beta-type subunits)
If so why don't we see more of these slow diseases? (Maybe we do but
don't recognise them for what they are because cell damage is so much
more obvious in the brain - would decay of the cartilage covering of the
joints be called anything other than 'yet another type of
osteoarthritis'?)

For those of you interested in the esoterica of molecular biology, here
are two DNA sequences for Human prions and one for Sheep.  There are
many more in the DNA databases, but your patience probably wouldn't
stretch that far :-)

ID   HSPRP      standard; RNA; PRI; 2415 BP.
AC   M13899;
DT   20-MAY-1987 (last revised)
DE   Human prion protein (PrP) mRNA, complete cds.
KW   prion protein.
OS   Homo sapiens
OC   Eukaryota; Metazoa; Chordata; Vertebrata; Tetrapoda; Mammalia;
OC   Eutheria; Primates; Anthropoidea; Hominoidea; Hominidae.
RN   [1] (bases 1-2415)
RA   Kretzschmar H.A., Stowring L.E., Westaway D., Stubblebine W.H.,
RA   Prusiner S.B., Dearmond S.J.;
RT   "Molecular cloning of a human prion protein cDNA";
RL   DNA 5:315-324(1986).
FH   Key             Location/Qualifiers
FH
FT   mRNA            <1. .2415
FT                   /note="PRP mRNA"
FT   CDS             50. .811
FT                   /note="prion protein precursor /map="20""
FT   CDS             50. .115
FT                   /note="prion protein signal peptide"
FT   CDS             116. .808
FT                   /note="prion protein (PrP 33-35-C)"
SQ   Sequence  2415 BP;  666 A; 499 C; 578 G; 672 T; 0 other;

   embl:hsprp  Length: 2415  January 11, 1991 13:38  Check: 4378  ..

       1  CGGCGCCGCG AGCTTCTCCT CTCCTCACGA CCGAGGCAGA GCAGTCATTA 
      51  TGGCGAACCT TGGCTGCTGG ATGCTGGTTC TCTTTGTGGC CACATGGAGT 
     101  GACCTGGGCC TCTGCAAGAA GCGCCCGAAG CCTGGAGGAT GGAACACTGG 
     151  GGGCAGCCGA TACCCGGGGC AGGGCAGCCC TGGAGGCAAC CGCTACCCAC 
     201  CTCAGGGCGG TGGTGGCTGG GGGCAGCCTC ATGGTGGTGG CTGGGGGCAG 
     251  CCTCATGGTG GTGGCTGGGG GCAGCCCCAT GGTGGTGGCT GGGGACAGCC 
     301  TCATGGTGGT GGCTGGGGTC AAGGAGGTGG CACCCACAGT CAGTGGAACA 
     351  AGCCGAGTAA GCCAAAAACC AACATGAAGC ACATGGCTGG TGCTGCAGCA 
     401  GCTGGGGCAG TGGTGGGGGG CCTTGGCGGC TACATGCTGG GAAGTGCCAT 
     451  GAGCAGGCCC ATCATACATT TCGGCAGTGA CTATGAGGAC CGTTACTATC 
     501  GTGAAAACAT GCACCGTTAC CCCAACCAAG TGTACTACAG GCCCATGGAT 
     551  GAGTACAGCA ACCAGAACAA CTTTGTGCAC GACTGCGTCA ATATCACAAT 
     601  CAAGCAGCAC ACGGTCACCA CAACCACCAA GGGGGAGAAC TTCACCGAGA 
     651  CCGACGTTAA GATGATGGAG CGCGTGGTTG AGCAGATGTG TATCACCCAG 
     701  TACGAGAGGG AATCTCAGGC CTATTACCAG AGAGGATCGA GCATGGTCCT 
     751  CTTCTCCTCT CCACCTGTGA TCCTCCTGAT CTCTTTCCTC ATCTTCCTGA 
     801  TAGTGGGATG AGGAAGGTCT TCCTGTTTTC ACCATCTTTC TAATCTTTTT 
     851  CCAGCTTGAG GGAGGCGGTA TCCACCTGCA GCCCTTTTAG TGGTGGTGTC 
     901  TCACTCTTTC TTCTCTCTTT GTCCCGGATA GGCTAATCAA TACCCTTGGC 
     951  ACTGATGGGC ACTGGAAAAC ATAGAGTAGA CCTGAGATGC TGGTCAAGCC 
    1001  CCCTTTGATT GAGTTCATCA TGAGCCGTTG CTAATGCCAG GCCAGTAAAA 
    1051  GTATAACAGC AAATAACCAT TGGTTAATCT GGACTTATTT TTGGACTTAG 
    1101  TGCAACAGGT TGAGGCTAAA ACAAATCTCA GAACAGTCTG AAATACCTTT 
    1151  GCCTGGATAC CTCTGGCTCC TTCAGCAGCT AGAGCTCAGT ATACTAATGC 
    1201  CCTATCTTAG TAGAGATTTC ATAGCTATTT AGAGATATTT TCCATTTTAA 
    1251  GAAAACCCGA CAACATTTCT GCCAGGTTTG TTAGGAGGCC ACATGATACT 
    1301  TATTCAAAAA AATCCTAGAG ATTCTTAGCT CTTGGGATGC AGGCTCAGCC 
    1351  CGCTGGAGCA TGAGCTCTGT GTGTACCGAG AACTGGGGTG ATGTTTTACT 
    1401  TTTCACAGTA TGGGCTACAC AGCAGCTGTT CAACAAGAGT AAATATTGTC 
    1451  ACAACACTGA ACCTCTGGCT AGAGGACATA TTCACAGTGA ACATAACTGT 
    1501  AACATATATG AAAGGCTTCT GGGACTTGAA ATCAAATGTT TGGGAATGGT 
    1551  GCCCTTGGAG GCAACCTCCC ATTTTAGATG TTTAAAGGAC CCTATATGTG 
    1601  GCATTCCTTT CTTTAAACTA TAGGTAATTA AGGCAGCTGA AAAGTAAATT 
    1651  GCCTTCTAGA CACTGAAGGC AAATCTCCTT TGTCCATTTA CCTGGAAACC 
    1701  AGAATGATTT TGACATACAG GAGAGCTGCA GTTGTGAAAG CACCATCATC 
    1751  ATAGAGGATG ATGTAATTAA AAAATGGTCA GTGTGCAAAG AAAAGAACTG 
    1801  CTTGCATTTC TTTATTTCTG TCTCATAATT GTCAAAAACC AGAATTAGGT 
    1851  CAAGTTCATA GTTTCTGTAA TTGGCTTTTG AATCAAAGAA TAGGGAGACA 
    1901  ATCTAAAAAA TATCTTAGGT TGGAGATGAC AGAAATATGA TTGATTTGAA 
    1951  GTGGAAAAAG AAATTCTGTT AATGTTAATT AAAGTAAAAT TATTCCCTGA 
    2001  ATTGTTTGAT ATTGTCACCT AGCAGATATG TATTACTTTT CTGCAATGTT 
    2051  ATTATTGGCT TGCACTTTGT GAGTATCTAT GTAAAAATAT ATATGTATAT 
    2101  AAAATATATA TTGCATAGGA CAGACTTAGG AGTTTTGTTT AGAGCAGTTA 
    2151  ACATCTGAAG TGTCTAATGC ATTAACTTTT GTAAGGTACT GAATACTTAA 
    2201  TATGTGGGAA ACCCTTTTGC GTGGTCCTTA GGCTTACAAT GTGCACTGAA 
    2251  TCGTTTCATG TAAGAATCCA AAGTGGACAC CATTAACAGG TCTTTGAAAT 
    2301  ATGCATGTAC TTTATATTTT CTATATTTGT AACTTTGCAT GTTCTTGTTT 
    2351  TGTTATATAA AAAAATTGTA AATGTTTAAT ATCTGACTGA AATTAAACGA 
    2401  GCGAAGATGA GCACC

ID   HSPRP0A    standard; RNA; PRI; 2420 BP.
AC   M13667;
DT   30-JUN-1987 (last revised)
DE   Human prion protein 27-30 mRNA, complete cds.
KW   amyloid; prion; sialoglycoprotein.
OS   Homo sapiens
OC   Eukaryota; Metazoa; Chordata; Vertebrata; Tetrapoda; Mammalia;
OC   Eutheria; Primates; Anthropoidea; Hominoidea; Hominidae.
RN   [1] (bases 1-2420)
RA   Liao Y.C.J., Lebo R.V., Clawson G.A., Smuckler E.A.;
RT   "Human prion protein cDNA: Molecular cloning, chromosomal mapping,
RT   and biological implications";
RL   Science 233:364-367(1986).
CC   A single prion protien gene is found on chromosome 20 per haploid
CC   genome.
FH   Key             Location/Qualifiers
FH
FT   mRNA            <1. .2420
FT                   /note="PrP mRNA"
FT   CDS             77. .814
FT                   /note="prion protein"
SQ   Sequence  2420 BP;  669 A; 500 C; 583 G; 668 T; 0 other;

  embl:hsprp0a  Length: 2420  January 11, 1991 13:38  Check: 4907  ..

       1  CGAGCAGCCA AGGTTCGCCA TAATGACTGC TCTCGGTCGT GAGGAGAGGA 
      51  GAAGCTCGCG GCGCCGCGGC TGCTGGATGC TGGTTCTCTT TGTGGCCACA 
     101  TGGAGTGACC TGGGCCTCTG CAAGAAGCGC CCGAAGCCTG GAGGATGGAA 
     151  CACTGGGGGC AGCCGATACC CGGGGCAGGG CAGCCCTGGA GGCAACCGCT 
     201  ACCCACCTCA GGGCGGTGGT GGCTGGGGGC AGCCTCATGG TGGTGGCTGG 
     251  GGGCAGCCTC ATGGTGGTGG CTGGGGGCAG CCCCATGGTG GTGGCTGGGG 
     301  ACAGCCTCAT GGTGGTGGCT GGGGTCAAGG AGGTGGCACC CACAGTCAGT 
     351  GGAACAAGCC GAGTAAGCCA AAAACCAACA TGAAGCACAT GGCTGGTGCA 
     401  GCAGCTGGGG CAGTGGTGGG GGGCCTTGGC GGCTACATGC TGGGAAGTGC 
     451  CATGAGCAGG CCCATCATAC ATTTCGGCAG TGACTATGAG GACCGTTACT 
     501  ATCGTGAAAA CATGCACCGT TACCCCAACC AAGTGTACTA CAGGCCCATG 
     551  GATGAGTACA GCAACCAGAA CAACTTTGTG CACGACTGCG TCAATATCAC 
     601  AATCAAGCAG CACACGGTCA CCACAACCAC CAAGGGGGAG AACTTCACCG 
     651  AGACCGACGT TAAGATGATG GAGCGCGTGG TTGAGCAGAT GTGTATCACC 
     701  CAGTACGAGA GGGAATCTCA GGCCTATTAC CAGAGAGGAT CGAGCATGGT 
     751  CCTCTTCTCC TCTCCACCTG TGATCCTCCT GATCTCTTTC CTCATCTTCC 
     801  TGATAGTGGG ATGAGGAAGG TCTTCCTGTT TTCACCATCT TTCTAATCTT 
     851  TTTCCAGCTT GAGGGAGGCG GTATCCACCT GCAGCCCTTT TAGTGGTGGT 
     901  GTCTCACTCT TTCTTCTCTC TTTGTCCCGG ATAGGCTAAT CAATACCCTT 
     951  GGCACTGATG GGCACTGGAA AACATAGAGT AGACCTGAGA TGCTGGTCAA 
    1001  GCCCCCTTTG ATTGAGTTCA TCATGAGCCG TTGCTAATGC CAGGCCAGTA 
    1051  AAAGTATAAC AGCAAATAAC CATTGGTTAA TCTGGACTTA TTTTTGGACT 
    1101  TAGTGCAACA GGTTGAGGCT AAAACAAATC TCAGAACAGT CTGAAATACC 
    1151  TTTGCCTGGA TACCTCTGGC TCCTTCAGCA GCTAGAGCTC AGTATACTAA 
    1201  TGCCCTATCT TAGTAGAGAT TTCATAGCTA TTTAGAGATA TTTTCCATTT 
    1251  TAAGAAAACC CGACAACATT TCTGCCAGGT TTGTTAGGAG GCCACATGAT 
    1301  ACTTATTCAA AAAAATCCTA GAGATTCTTA GCTCTTGGGA TGCAGGCTCA 
    1351  GCCCGCTGGA GCATGAGCTC TGTGTGTACC GAGAACTGGG GTGATGTTTT 
    1401  ACTTTTCACA GTATGGGCTA CACAGCAGCT GTTCAACAAG AGTAAATATT 
    1451  GTCACAACAC TGAACCTCTG GCTAGAGGAC ATATTCACAG TGAACATAAC 
    1501  TGTAACATAT ATGAAAGGCT TCTGGGACTT GAAATCAAAT GTTTGGGAAT 
    1551  GGTGCCCTTG GAGGCAACCT CCCATTTTAG ATGTTTAAAG GACCCTATAT 
    1601  GTGGCATTCC TTTCTTTAAA CTATAGGTAA TTAAGGCAGC TGAAAAGTAA 
    1651  ATTGCCTTCT AGACACTGAA GGCAAATCTC CTTTGTCCAT TTACCTGGAA 
    1701  ACCAGAATGA TTTTGACATA CAGGAGAGCT GCAGTTGTGA AAGCACCATC 
    1751  ATCATAGAGG ATGATGTAAT TAAAAAATGG TCAGTGTGCA AAGAAAAGAA 
    1801  CTGCTTGCAT TTCTTTATTT CTGTCTCATA ATTGTCAAAA ACCAGAATTA 
    1851  GGTCAAGTTC ATAGTTTCTG TAATTGGCTT TTGAATCAAA GAATAGGGAG 
    1901  ACAATCTAAA AAATATCTTA GGTTGGAGAT GACAGAAATA TGATTGATTT 
    1951  GAAGTGGAAA AAGAAATTCT GTTAATGTTA ATTAAAGTAA AATTATTCCC 
    2001  TGAATTGTTT GATATTGTCA CCTAGCAGAT ATGTATTACC TTTCTGCAAT 
    2051  GTTATTATTG GCCTTGCACT GTGTAGTATT CTATGTAAAA ATATATATGT 
    2101  ATATAAAATA TATCATTGCA TAGGACAGAC TTAGGAGTTT TGTTTACAGC 
    2151  AGTTAACATC TGAAGTGTCT AATGCATTAA CTTTTGTAAG GTACTGAATA 
    2201  CTTAATATGT GGGAAACCCT TTTGCGTGGT CCTTAGGCTT ACAATGTGCA 
    2251  CTGAATCGTT TCATGTAAGA ATCCAAAGTG GACACCATTA ACAGGTCTTT 
    2301  GAAATATGCA TGTACTTTAT ATTTTCTATA TTTGTAACTT TGCATGTTCT 
    2351  TGTTTTGTTA TATAAAAAAA TTGTAAATGT TTAATATCTG ACTGAAATTA 
    2401  AACGAGCCAA GATGAGCACC 

ID   OAPRP      standard; DNA; MAM; 4226 BP.
AC   M31313;
DT   22-JAN-1990 (last revised)
DE   Sheep prion protein (PrP) gene, complete cds.
KW   prion protein.
OS   Ovis aries
OC   Eukaryota; Animalia; Metazoa; Chordata; Vertebrata; Mammalia;
OC   Theria; Eutheria; Artiodactyla; Ruminantia; Pecora; Bovidae.
RN   [1] (bases 1-4226)
RA   Goldmann W., Hunter N., Foster J.D., Salbaum J.M., Beyreuther K.,
RA   Hope J.;
RT   "Two alleles of a neural protein gene linked to scrapie in sheep";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:2476-2480(1990).
CC   Draft entry and computer-readable sequence for [1] kindly submitted
CC   by W.Goldmann, 16-JAN-1990, for release after publication.
FH   Key             Location/Qualifiers
FH
FT   iDNA            <1. .61
FT                   /note="prion protein (PrP) intron"
FT   CDS             72. .842
FT                   /note="prion protein (PrP) precursor"
FT   CDS             72. .144
FT                   /note="prion protein (PrP) signal peptide"
FT   CDS             145. .839
FT                   /note="prion protein (PrP)"
SQ   Sequence  4226 BP;  1283 A; 780 C; 966 G; 1197 T; 0 other;

   embl:oaprp  Length: 4226  January 11, 1991 13:39  Check: 1989  ..

       1  CTGCAGACTT TAAGTGATTC TTACGTGGGC ATTTGATGCT GACACCCTCT 
      51  TTATTTTGCA GAGAAGTCAT CATGGTGAAA AGCCACATAG GCAGTTGGAT 
     101  CCTGGTTCTC TTTGTGGCCA TGTGGAGTGA CGTGGGCCTC TGCAAGAAGC 
     151  GACCAAAACC TGGCGGAGGA TGGAACACTG GGGGGAGCCG ATACCCGGGA 
     201  CAGGGCAGTC CTGGAGGCAA CCGCTATCCA CCTCAGGGAG GGGGTGGCTG 
     251  GGGTCAGCCC CATGGAGGTG GCTGGGGCCA ACCTCATGGA GGTGGCTGGG 
     301  GTCAGCCCCA TGGTGGTGGC TGGGGACAGC CACATGGTGG TGGAGGCTGG 
     351  GGTCAAGGTG GTAGCCACAG TCAGTGGAAC AAGCCCAGTA AGCCAAAAAC 
     401  CAACATGAAG CATGTGGCAG GAGCTGCTGC AGCTGGAGCA GTGGTAGGGG 
     451  GCCTTGGTGG CTACATGCTG GGAAGTGCCA TGAGCAGGCC TCTTATACAT 
     501  TTTGGCAATG ACTATGAGGA CCGTTACTAT CGTGAAAACA TGTACCGTTA 
     551  CCCCAACCAA GTGTACTACA GACCAGTGGA TCGGTATAGT AACCAGAACA 
     601  ACTTTGTGCA TGACTGTGTC AACATCACAG TCAAGCAACA CACAGTCACC 
     651  ACCACCACCA AGGGGGAGAA CTTCACCGAA ACTGACATCA AGATAATGGA 
     701  GCGAGTGGTG GAGCAAATGT GCATCACCCA GTACCAGAGA GAATCCCAGG 
     751  CTTATTACCA AAGGGGGGCA AGTGTGATCC TCTTTTCTTC CCCTCCTGTG 
     801  ATCCTCCTCA TCTCTTTCCT CATTTTTCTC ATAGTAGGAT AGGGGCAACC 
     851  TTCCTGTTTT CATTATCTTC TTAATCTTTG CCAGGTTGGG GGAGGGAGTG 
     901  TCTACCTGCA GCCCTGTAGT GGTGGTGTCT CATTTCTTGC TTCTCTCTTG 
     951  TTACCTGTAT AATAATACCC TTGGCGCTTA CAGCACTGGG AAATGACAAG 
    1001  CAGACATGAG ATGCTATTTA TTCAAGTCCC ATTAGCTCAG TATTCTAATG 
    1051  TCCCATCTTA GCAGTGATTT TGTAGCAATT TTCTCATTTG TTTCAAGAAC 
    1101  ACCTGACTAC ATTTCCCTTT GGGAATAGCA TTTCTGCCAA GTCTGGAAGG 
    1151  AGGCCACATA ATATTCATTC AAAAAAACAA AACTGGAAAT CCTTAGTTCA 
    1201  TAGACCCAGG GTCCACCCTG TTGAGAGCAT GTGTCCTGTG TCTGCAGAGA 
    1251  ACTATAAAGG ATATTCTGCA TTTTGCAGGT TACATTTGCA GGTAACACAG 
    1301  CCATCTATTG CATCAAGAAT GGATATTCAT GCAACCTTTG ACTTATGGGC 
    1351  AGAGGACATC TTCACAAGGA ATGAACATAA TACAAAAGGC TTCTGAGACT 
    1401  AAAAAATTCC AACATATGGA AGAGGTGCCC TTGGTGGCAG CCTTCCATTT 
    1451  TGTATGTTTA AAGCACCTTC AAGTGATATT CCTTTCTTTA GTAACATAAA 
    1501  GTATAGATAA TTAAGGTACC TTAATTAAAC TACCTTCTAG ACACTGAGAG 
    1551  CAAATCTGTT GTTTATCTGG AACCCCAGGA TGATTTTGAC ATTGCTTAGG 
    1601  GATGTGAGAG TTGGACTGTA AAGAAAGCTG AGTGCTGAAG AGTTCATGCT 
    1651  TTTGAACTAT AGTGTTGGAG AAAACTCTTG AGAGTCCCTT GGACTGAAAG 
    1701  GAGATCAGTC CTGAATATTC ATTGGAAGGA CTGATGCTGA AGCTGAAACT 
    1751  CCAGTACTTT GGTCACCTGA TGGGAAGAAC TGAAGGCAGG AGGGATGCTA 
    1801  GGAAAGACTG AAGGCAGGAG GAGAAGGGGA CGACAGAGGA TGAGATGGCT 
    1851  AGATGGCATC ATGGACTCAA TGGACATGAG CTTAAGTAAA CTCCAGGAGT 
    1901  TGGCAATGGA CAGGGAGACC TGGCGTCCTG CAGTCCATGG TGTCGCAGAG 
    1951  TCGGACACGA TTGAGTGACT AAATTGAGGT GACCCAGATT TAACATAGAG 
    2001  AATGCAGATA CAAAACTCAT ATTCATTTGA TTGAATCTTT TCCTGAACCA 
    2051  GTGCTAGTGT TGGACTGGTA AGGGTATAAC AGCATATATA GGTTATGTGA 
    2101  TGAAGAGATA GTGTACATGA AATATGTGCA TTTCTTTATT GCTGTCTTAT 
    2151  AATTGTCAAA AAAGAAAATT AGGTCCTTGG TTTCTGTAAA ATTGACTTGA 
    2201  ATCAAAAGGG AGGCATTTAA AGAAATAAAT TAGAGATGAT AGAAATCTGA 
    2251  TCCATTCAGA GTAGAAAAAG AATTGCATAC TGTATTAAGA AGTCAAATAT 
    2301  TCCTGAATTG TTCAATATTG TCACCTAGCA GATAGACACT ATTCTGTACT 
    2351  GTTTTTACTA GCTTGCACCT TGTGGTATCC TATGTAAAAA CATATTTGCA 
    2401  TATGACAAAC TTTTTCTGTT AGAGCAATTA ACATCTGAAC CACCTAATGC 
    2451  ATTACCTGTT TTTGTAAGGT ACTTTTTGTA AGGTACTAAG GAGATGTGGG 
    2501  TTTAATCCCT AGGTCAGGTA AATCCCCTAG AGGAAGAAAT GGCAACCCAC 
    2551  TCCAGTATTC TTGCCAGGAA AATCCAGTGG GCAGAGGAGC CTGGCAGGGT 
    2601  ACAGTCTGAG CATGGGGTTG CAAAGAGTGA GACAAGACTT GAGCTACTGA 
    2651  ACAATAAGGA CAATAAATGC TGGGTCGGCT AAAAGGTTCA TTAGGTTTTT 
    2701  TTTCTGTAAG ATGGCTCTAG TAGTACTTGT CTTTATCTTC ATTCGAAACA 
    2751  ATTTTGTTAG ATTGTATGTG ACAGCTCTTG TATCAGCATG CATTTGAAAA 
    2801  AAACATCACA ATTGGTAAAT TTTTGTATAG CCATCTTACT ATTGAAGATG 
    2851  GAAGAAAAGA AGCAAAATTT TCAGCATATC ATGCTGTACT TATTTCAAGA 
    2901  AAGATAACCA AAATGCAAAA ATGTATTTGT GAAGTGTATG GAGAAGGGGC 
    2951  TGCAACTGAT CAAGCTTGTC AAAGTAGTTT GTGAAGTTTC GTGCTGGAGA 
    3001  TTTCTTATTG GACGATGCTC CACAGTTGGA TATACCAGTT GAAGTTGATA 
    3051  GTGATCAAAT TGAGATATTG AGAATAATCG ATGTTATACC ACGCGGGAGA 
    3101  TAGCTGACAT ACTCAAAATA TCCAAATAGA ACCTTGAAAA CCATTTGCAC 
    3151  CATCTCAGTT ATGTTAATCA CTTTGATGTT TGAGTTCCAC ATAAGCAAAA 
    3201  AAACAACAAC AAAAAAAAAT ACAACCTTGA CCATATTTGC GCATGCAGTT 
    3251  CTCTACTGAA ATGATTGAAA ACACTTTGTT TTTAAAAACA GATTTTGATT 
    3301  AACAGTGGGT ACGATACAAT AACGTAGATG GAAGAAATTG TAGGGTGAGC 
    3351  AAAATGAACC ACACCACCAA AGGCCAGTCT TCCTCTAAAG AAGATGTGTG 
    3401  TATGGTGGGA TTGGAAAGTA ATCCTCTATT ATGAATTCTT CTGGAAAACA 
    3451  CTGCTCCTAA TTAGACCAAC TGAAAACAGC ACTCAACGAA AAGCATCCAG 
    3501  AATTAGTCAA TAGAAAACAT AATCTTCCAT CAGGATAACG CAAGACTACA 
    3551  TATTTCTTTG ATGACCCAGC ATGGCTGGAG TTTCTGATTC ATCTGTTGTA 
    3601  TCAGACGTTG CATCTTGGAT TTTTCATTAT TCAGTCTACA AATTATATAT 
    3651  GAAAATTCAT CCTTGTAAGA TGTAAGTGCA TCTGGAAAAT TTCTTTGCTC 
    3701  AAAAAGATAA AAAGTTTTGT GAACACAGAA TTATGACGTT GCCTGAAAAA 
    3751  TGGCAGAAGG TAGTGGAACA AAAGAGTGAC TATGTTGTTT GGTAAAGTTC 
    3801  TTAGTGAAAA TGAAAAATGT GTCTTTTATT TTTATTTAAA CACCAAAGGC 
    3851  ACATTTGCAC ACCAACTGTA ATCTAAGAAC CTCGGTGTCC TAGCCTTACA 
    3901  GTGTGCACTG ATAGTTTGTA TAAGAATCCA GAGTGATATT TGAAATACGC 
    3951  ATGTGCTTAT ATTTTTTATA TTTGTAACTT TGCATGTACT TGTTTTGTGT 
    4001  TAAAAGTTTA TAAATATTTA ATATCTGACT AAAATTAAAC AGGAGCTAAA 
    4051  AGGAGTATCT TCCACGGAGT GTCTGGCTGT GTTCACCAGT GTGCACACCA 
    4101  TGTTGGCAGC TTCATTTGGG GGGTTAATAT GAGAAAAGTG ACACATTCAG 
    4151  TCCTCACACT GCCAATTGCA GGAGGAGGGC TACTCCTGAT CCTGCTTCAG 
    4201  CCTTATTCCC AGTCACATGC CAGCTG


-- 
GARY WILLIAMS,  Computing Services Section,  Janet:       G.Williams@UK.AC.CRC
MRC-CRC & Human Genome Mapping Centre,       Internet:    G.Williams@CRC.AC.UK
Watford Rd, HARROW, Middx, HA1 3UJ, UK       EARN/Bitnet: G.Williams%CRC@UKACRL
Tel 081-869 3294   Fax 081-423 1275     Usenet: ...!mcsun!ukc!mrccrc!G.Williams

KPURCELL@liverpool.ac.uk (Kevin Purcell) (01/16/91)

On Thu, 3 Jan 91 21:51:23 EST hsv3!mvp@edu.rutgers.cs said:

>
>In article <Dec.31.18.35.03.1990.25921@athos.rutgers.edu>
> cphoenix@csli.stanford.edu (Chris Phoenix) writes:
>>Several years ago I heard of something called prions, which the
>>discussion of self-replicating chemicals reminded me of.
>
>I was told recently that prions were just a hypothesis, which
>turned out not to be true after all.  I know I haven't seen
>anything about them in years -- Anyone else have more info?
>--
>Mike Van Pelt                          Here lies a Technophobe,
>Headland Technology/Video 7               No whimper, no blast.
>...ames!vsi1!headland!mvp              His life's goal accomplished,
>                                          Zero risk at last.

Prions are alive(?) and well and still belived to be a possible cause for:

1. Kuru (a degenerative brain disease in sheep).
2. Crutfeldt-Jakob disease (a degenerative brain disease in man.)
3. Bovine Spongiform Encephalopathy (a degenerative brain disease in cattle).

This may all be caused by the same agent (that has species-hopped).

All agents involved are resistant to chemical attack and normal heat treatments
with a consequent worry of transmission from cattle to humans of BSE.

Kevin
                                                      _   .
Kevin Purcell          | kpurcell@liverpool.ac.uk   _/ \ / \   kgp@cxa.dl.ac.uk
Surface Science,       |                           /----/^^^\
Liverpool University   | There is now a damm fine /TWIN PEAKS\ email discussion
Liverpool L69 3BX, UK  | list for TPers. Mail me /    /       \ for details.

lfk@eastman1.mit.edu (Lee F. Kolakowski) (01/22/91)

There is a good review of Scrapie agents and the arguement for Prions
in September 1990 Microbiological Reviews (an ASM journal).

Prions and the prion protein are alive and well.

Whats not is the infectious nucleic acid theory.

--

Frank Kolakowski

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