Confirmatory cultural and gene-detection
studies: an examination
'La théorie des germes
de Louis Pasteur est une fiction ridicule.' Pierre Pachet,
professor of physiology, Toulouse (1872)
The evidence for a causal association
between a potentially treatable Chlamydia pneumoniae infection
and majority subsets of Multiple Sclerosis, as detailed on the
first page, is very strong. It is far stronger than hypothesis.
Why, then, is this evidence almost unknown within the medical
establishment? MS is often a devastating illness which usually
strikes during the most productive years. It is the commonest
neurological illness in young adults. No present treatment is
anywhere near satisfactory, and, as the disease becomes progressive,
present-day medicine has little to offer.
The problem is one of collation. A multitude of scientific studies
- some of great elegance - can be linked together to support
the causal association very powerfully, but this information
has not been brought together in a broad, comprehensive manner
within a widely-read multidisciplinary medical journal. The reason
for this delay is the process by which scientific papers are
selected for publication.
Editors must be selective. Scientific studies vary in their quality.
No editor would wish to publish worthless material. At the same
time no editor can be expected to possess the expertise necessary
to evaluate the material he receives. One of the editorial staff
will read the manuscript. If it is obviously poor then it will
be filed in the basement and a polite note of rejection will
be sent to the author. If it passes preliminary scrutiny as being
reasonable and worthwhile, copies will be sent to two or three
referees who are considered knowledgeable in the subject. The
referees will read the manuscript and submit a report. This is
the peer-review system, and is generally considered to be the
least bad way of selecting scientific work for publication. Its
advantages are that it can pick up sloppy or improbable work;
work which places hypotheses upon hypotheses, or work which does
not stand up to analysis.
It has drawbacks, though. The biggest drawback is that it resists
any change to the underlying Weltanschauung  or 'mindset'
on which the subject rests. The peers are senior establishment
figures; their reputations are built solidly on a thesis of ideas
which they share with each other. Thus it is that any work which
casts doubt on the validity of the prevailing ethos is likely
to be treated very harshly. Its principles are likely to be pulled
to pieces in an unfair way; its findings, even when clear, are
made to sound doubtful, and the argumentation in the discussion
made to sound improbable. None of this is (one hopes) conscious.
(A few days ago I happened to bring up this subject on meeting
a friend in the hospital; she immediately took a copy of the
Guardian from under her arm and said, 'you might like
to have a look at this.' It was an article by Cordelia Fine.
It is indeed apposite. I've put a few quotes at the bottom of
In the case in point the 'peers' are dedicated to the theory
of inflammatory autoimmunity as the primary flywheel of the disease.
They have made an enormous investment into this: years of their
lives, ongoing research projects, academic reputations, lucrative
connections to pharmaceutical companies eager to profit by expensive
agents such as monoclonal antibodies. No-one is going to fund
a large trial of out-of-patent antibiotics and unpatentable supplements.
The establishment wishes that any idea of infection being at
the root of MS would go away. That is why, if you study the literature,
you'll find that negative studies  are given equal weight
with studies that detected Chl pneumoniae in the CSF,
and grew the organism and found specific antibodies
. Another (again one hopes) unconscious method of down-rating
evidence which counters the established view is to side-line
those who have made the positive discoveries. 'I know that Chlamydia
pneumoniae has been found in the CSF of people with MS,'
said a world-respected MS neurologist recently, 'but those early
findings have never been repeated.' He is stating a half-truth,
but only a half-truth.
Those early findings have indeed been repeated. There are, in
fact, many good, worldwide, confirmatory studies which have detected
Chl pneumoniae in the CSF of persons with with MS by culture
or specific gene detection. Here is a précis.
The preliminary work was carried
out by workers at Vanderbilt University, Nashville, TN in the
US. 27 patients with MS and 27 patients with other neurological
disease were studied. Polymerase chain reaction assays demonstrated
the presence of C pneumoniae MOMP gene in the CSF of 97%
of MS patients versus 18% of patients with other neurological
disease (OND)  The same workers isolated C pneumoniae
from the CSF in 64% of MS patients and 11% of OND controls. 86%
of MS patients had increased CSF antibodies to C pneumoniae
elementary body antigens as shown by enzyme-linked immunosorbent
assay absorbance values that were 3 SD greater than those seen
in OND controls. The specificity of this antibody response was
confirmed by western blot assays of the CSF, using elementary
body antigens. Moreover, CSF isoelectric focusing followed by
western blot assays revealed cationic antibodies against C
pneumoniae. The authors are careful to say that this gives
evidence for but does not prove and aetiological link.
In 2000 Layh-Schmitt and colleagues in Heidelberg, Germany, reported
the presence of Chl pneumoniae in 5 of 10 patients with
MS using PCR. In a further study they detected the organism in
2 of 20 patients with MS, 3 of 17 patients with possible/probable
MS and 0 of 56 patients with other neurological disease (OND)
In 2001 Ikejima and colleagues, in the USA, reported the presence
of Chl pneumoniae genes in the CSF of 11 of 16 patients
with MS. These workers used a commercial kit rather than an in-house
Also in 2001 Geiffers and colleagues in Lubeck, Germany, detected
Chl pneumoniae DNA in the CSF of 12 of 58 patients with
MS and 20 of 47 patients with OND. However, Chl pneumoniae
DNA was not detected in the CSF of any of 67 neurologically healthy
persons. These authors conclude that Chl pneumoniae is probably
a highly neurotropic pathogen [6.]
In 2002 Hao and colleagues, in Japan, reported the presence of
Chl pneumoniae in 9 of 28 patients with MS and in 2 patients
with inflammatory disease in 15 patients with OND. Elevated titres
of specific antibody was found in the CSF of 42 of 84 patients
with MS and in 28% of patients with OND [7.]  Interestingly
these workers observed a higher rate of Chl pneumoniae gene
transcription in the patients with MS; this suggests a more active
bacterial metabolism, and may point to host factors playing a
part in the disease [7.]
In 2003 Grimaldi and colleagues, in Italy, detected Chl pneumoniae
gene-sequences in the CSF of 23 of 107 patients with MS and 2
of 77 patients with OND .
In 2003 another study from the Heidelberg group detected the
chlamydia-specific ompA gene in the CSF of 50% of patients with
MS and in 28.1% of 89 OND patients [9.] In a most interesting
further study, these authors found chlamydial HSP60-mRNA in the
CSF of 75% of patients with MS, indicating active bacterial activity:
chlamydiae are known to upregulate HSP60. This has the effect
of preventing host cell apoptosis.
In 2002 a conjoint study of Chlamydia pneumoniae gene-sequences
in the CSF was undertaken by workers at Vanderbilt University
Medical Centre and the University of South Florida. The two laboratories
used different DNA extraction and PCR techniques. In definite
MS patients the detection rates were 72% (VUMC) and 61% (USF);
in probable monosymptomatic patients the detection rates were
41 and 54% respectively; in OND controls the signal was positive
in 7% and 16% respectively .
This repeated confirmation by different centres - using different
methodology and targets - leaves little room for doubt about
the association of Chl pneumoniae with MS. We have recently
reviewed the evidence in some detail [11.]
Those who have read the above
compilation will note, in the PCR findings within the CSF of
persons with MS, a wide range of results, ranging from 10% to
97% positive signal. What is the cause of this diversity? Three
possibilities might be considered: differences in methodology;
geographical differences in strains; very small organism numbers.
A very clear account of PCR in the detection of bacterial gene-sequences
in the CSF is given by Yamamoto, who brings clarity to a difficult
subject [12.] One of the most problematic issues, this paper
says, is that of organism numbers. For one thing, Chl pneumoniae,
under chronic stress conditions, drastically curtails EB production.
Extracellular EB nucleic acids and proteins are thus likely to
be present in minute quantities within the CSF, and, furthermore,
are likely to be swept away very rapidly. The CSF is often considered
to be a slow-moving - even sluggish - stream; this is not the
case. The body of fluid is exchanged some three times in a 24
hour period; the volume of the CSF-containing cavities is about
150ml and approximately 500ml of CSF is produced every day. The
anatomy of the CSF circulatory pathway is such that there are
no 'dead spaces'. EBs will be quickly removed. The determination
of positivity or negativity may well lie at the edge of
chance; any slight advantage of methodology would be critical.
It is possible that EB release may be intermittent. It will be
noted that the positive reports are from centres round the world;
little is known about geographical variation in the external
proteins of the EB, or whether there are functional strain-differences;
some strains might, for instance, produce more EBs than others
while in the persistent state. An elucidation of the possible
events which may happen in the course of persistent infective
states with this organism will present one of the greatest challenges
in medical microbiology in this century.
The information is present,
but is not as yet collated. This is the reason why, if you want
to stand a chance of recovery from MS, you will have to trawl
through the millions of pages of journals listed in PubMed, using
appropriate search terms: and when you find the material you
will have to edit it to remove the establishment bias. Or else
find someone who has done this for you and who has put the information
on the Internet.
Speaking of the Internet, it is worthwhile examining the bona
fides of any web-forum in which you may wish to participate.
Some are sponsored by business organisations which do not permit
discussion antithetical to their commercial interests. Posts
which allude to treatable infection as a component of the MS
syndrome tend to be removed. www.cpnhelp.org and www.thisms.com
can be recommended as being forums which allow truly independent
Notes and References
1. Weltanschauung: the accepted
scheme of things or an 'axiomatic framework'. It is usually translated
as 'world view' and refers to a person's or group's culturally
constructed version of reality. A term given philosophical currency
by the phenomenologist Edmund Husserl.
2. Boman J, Roblin PM, Sundstrom P, Sandstrom M, Hammerschlag
MR. Failure to detect Chlamydia pneumoniae in the central
nervous system of patients with MS. Neurology. 2000 Jan 11;54(1):265.
3. Sriram S, Stratton CW, Yao S, Tharp A, Ding L, Bannan JD,
Mitchell WM. Chlamydia pneumoniae infection of the central nervous
system in multiple sclerosis. Ann Neurol. 1999 Jul;46(1):6-14.
4. Layh-Schmitt G, Bendl C, Hildt U, Dong-Si T, Juttler E, Schnitzler
P, Grond-Ginsbach C, Grau AJ. Evidence for infection with Chlamydia
pneumoniae in a subgroup of patients with multiple sclerosis.
Ann Neurol. 2000 May;47(5):652-5.
5. Ikejima H, Haranaga S, Takemura H, Kamo T, Takahashi Y, Friedman
H, Yamamoto Y. PCR-based method for isolation and detection of
Chlamydia pneumoniae DNA in cerebrospinal fluids. Clin
Diagn Lab Immunol. 2001 May;8(3):499-502.
6. Gieffers J, Pohl D, Treib J, Dittmann R, Stephan C, Klotz
K, Hanefeld F, Solbach W, Haass A, Maass M. Presence of Chlamydia
pneumoniae DNA in the cerebral spinal fluid is a common phenomenon
in a variety of neurological diseases and not restricted to multiple
sclerosis. Ann Neurol. 2001 May; 49(5):585-9.
7. Hao Q, Miyashita N, Matsui M, Wang HY, Matsushima T, Saida
T. Chlamydia pneumoniae infection associated with enhanced
MRI spinal lesions in multiple sclerosis. Mult Scler. 2002 Oct;8(5):436-40.
8. Grimaldi LM, Pincherle A, Martinelli-Boneschi F, Filippi M,
Patti F, Reggio A, Franciotta D, Allegra L, Comi G, Blasi F.
An MRI study of Chlamydia pneumoniae infection in Italian
multiple sclerosis patients. Mult Scler. 2003 Oct;9(5):467-71.
9. Dong-Si T, Weber J, Liu
YB, Buhmann C, Bauer H, Bendl C, Schnitzler P, Grond-Ginsbach
C, Grau AJ. Increased prevalence of and gene transcription by
Chlamydia pneumoniae in cerebrospinal fluid of patients
with relapsing-remitting multiple sclerosis. J Neurol. 2004 May;
10. Sriram S, Yao SY, Stratton C, Calabresi P, Mitchell W, Ikejima
H, Yamamoto Y. Comparative study of the presence of Chlamydia
pneumoniae in cerebrospinal fluid of Patients with clinically
definite and monosymptomatic multiple sclerosis. Clin Diagn Lab
Immunol. 2002 Nov; 9(6): 1332-7.
11. Stratton CW, Wheldon DB. Multiple sclerosis: an infectious
syndrome involving Chlamydophila pneumoniae. Trends
Microbiol. 2006 Nov;14(11):474-9.
12. Yamamoto Y. PCR in diagnosis of infection: detection of bacteria
in cerebrospinal fluids. Clin Diagn Lab Immunol. 2002 May;9(3):508-14.
'So evidence that fits with our beliefs is quickly waved through
the mental border control, while counter-evidence must submit
to close interrogation and, even then, will probably not be admitted.
As a result, people can end up holding their beliefs even more
strongly after seeing the counter-evidence. . .
'Part of this attachment may
be because there is a sense in which our important beliefs are
an integral part of who we are. To bid a belief adieu is to lose
a cherished part of our identity. . .
[Cordelia Fine: The Vain Brain
The Guardian 26th January 2006 Pp G 2 16 - 17 ]
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page created 28th January 2006;
last edited 18th March 2011