One of the biggest issues in the question of whether or not CPn is present in MSi brains is the publication of work that finds no CPn in MS. It puts us in the uncomfortable position of saying that we choose to think that this researcher is correct and that one is incorrect. Since few of us are lab experts, such discernment may be based on bias and not facts. Yet there may be some very good reasons to find the work that says CPn is not in MS brains is biased itself.
To look at this chronologically we start with the Vanderbilt University (VU) work found here. This paper is the whole citation. In that original work the team at VU found that pwMS (people with MS)were more likely to have CPn detected by PCRi in the brain.
A top chlamydia expert, Margaret Hammerschlag MD, found the theory intriguing and conducted her own experiments in her labs. They found no CPn in any sample. The abstract may be found HERE
Following that work, Dr Sriram came out and said it is very difficult to find in the brain and that it was not surprising htey did not find it. What follows is taken from HERE (note: this paper was overall negative about the MS/CPn connection. It is an older paper talking about what was known at that time)
Quote from that paper:" Sriram responded by saying, "The fact that they can't find it in the brain is not surprising at all" because of difficulties his group had finding C. pneumoniae after injecting it into the brains of mice. "We know we put the bug there," he said. "But we're having difficulty finding out exactly what the conditions are to extract it from brain tissue. I don't know why."
To help settle the dispute, Sriram agreed to participate in a blinded study with three other teams. All received spinal fluid from patients with MS and controls, sent by Michael Kaufman, MD, of the MS Center of the Carolinas Medical Center in Charlotte, NC. The results, presented at the 2000 meeting of the American Neurology Association, further isolate the Vanderbilt team, who found C. pneumoniae DNA in 22 (73%) of 30 MS cases and in 5 (23%) of 22 controls. The other teams, at Johns Hopkins, the Centers for Disease Control and Prevention, and Umeå University, detected no traces of the organism.
Hammerschlag said the mass of evidence points to contamination or a lack of experience with delicate screening tests on the part of Sriram and his colleagues. "All of his work is being published in neurology journals, and they just kind of accept the methods. None of it would get published in microbiology journals," she said" end quote
This is very important. Please do note that in the teams other than VU they found no CPn. None. There have been many published papers since then by many experts all over the world finding CPn in brain samples of MS and other neurological diseases. It is peculiar that in this particular test they found absolutely none at all. But this was a long time ago as science goes and techniques have advanced since then, so the various researchers finding CPn since then may well be using much better techniques.
Let's note the VU findings in this interesting contest between labs. VU found CPn in 22 of 30 of the MS patients and in only 5 of 22 of controls. If Sriram contaminated his samples how did he manage, in a blinded sample, to contaminate primarily his MS samples? Why not contaminate most samples if his work is sloppy? Or even finding it in all of them?
It seems to me personally it would be very difficult, and statistically improbable to contaminate mainly the MS samples in a blinded study of that nature. Adding to the evidence that the VU laboratory test for CPn in CFSi is finding real CPn in MS is the fact that the numbers of positive samples discovered were very similar to his previously stated numbers of positive MS samples. The VU team seems to find CPn in about 60-95% of MS CSF (multiple sclerosis cerebrospinal fluid).
Another comment in that article which points out the human side of research is in the final line of the quoted piece as it shows the opinion of one researcher stated as if it were fact. It is not exactly "scientific" but opinion, and peevish at that, to state that the neurology journals are somehow naive in what they accept and that the VU protocol "would never be published in microbiology journals". In fact, the VU lab protocol was published in a laboratory journal two years later HERE
And in another paper HERE we have the VU team and a team of researchers at the University of South Florida using split samples to compare results with one another. "Split samples", which were also used in the first lab contest above, means they send half any given sample to lab A and half to lab B and see if they get similar results. (Some few samples were too small to split, and VU got all of those samples resulting in the odd numbers)
In this comparison between USF and VU they both found positive samples of CPn in the MS brains using different CPn tests, confirming that it is possible to culture CPn in MS brains. The conclusion of the paper was quote "In clinically definite MS patients, the VUMC and USF detection rates were 72 and 61%, respectively, and in patients with monosymptomatic MS, the VUMC and USF detection rates were 41 and 54%, respectively. The PCR signal was positive for 7% of the OND controls at VUMC and for 16% at USF. These studies confirm our previous reports concerning the high prevalence of C. pneumoniae in the CSF of MS patients. The presence of C. pneumoniae in patients with monosymptomatic MS would also suggest that infection with the organism occurs early in the course of the disease." end quote
What we have here is a batch of evidence that indicates the VU approach is fairly effective at finding CPn in MS CSF, that at USF they also have the ability to find this, and the fact that these labs used split samples indicates that there is some concordance. In comment Sriram has been quoted as saying that the problem with the other contests where others found no CPn is that the other labs use formalin preserved brain samples, which ruins the possibility of detecting CPn. According to VU, the lab must use frozen tissue to find the CPn in these samples. USF also uses frozen samples, though they use their own unique test. This is the kind of technical detail that makes the difference, but takes time to prove the value of conclusively so everyone "knows" we must use frozen samples. Clearly in the Hammerschlag lab it is not considered important to use frozen samples.
Dr Hammerschlag is still convinced that MS has nothing to do with CPn though. As recently as 2005 she was asked to comment on some work being published by VU connecting CPn to MS and once again she talked about the 2000 lab contest in which her labs found no CPn. This comment was titled "The role of chlamydia pneumoniae in multiple sclerosis:real or fictitious? She remains adamant that the original work in which no CPn was found remains unchallenged, apparently rejecting the work of so many in the interveneing years in spite of the fact that various researchers all over the world have found at least some CPn in brain samples of many kinds. She seems very confident of her test results in which she found on CPn in MS CSF samples.
Interestingly enough though, Dr Hammerschlag herself has since authored a paper which in and of itself may offer support for the CPn theoretical model of MS causation. In this most recent work she states that we cannot culture persistent infection as it is undetectable. Now this is interesting, if a persistent infection is undetectable using currently available lab techniques, then what does it mean if you do a CPn test and it's negative? We know that CPn even in it's persistent state can cause inflammation (see smoking guns next page) so if that is true and you have an inflammatory disease of unknown etiology how can you say conclusively it is not CPn simply because you had a negative test if your own research says that persistent infections produce negative tests? It might be more accurate for her to say I do not agree with the VU methods, but I do not know if MS is related to CPn. The opinion paper indicating that we cannot culture persistent infections that she wrote is found HERE
If you read it carefully, you will see she is saying that while CPn might cause chronic illness like atherosclerosis and asthma, we can't design good studies since we can't test to know if eradication of CPn occurred. She suggests that without lab work to tell you if the patient got better from eradication of the germ, you can't know why the patient got better and your study is meaningless. From a purely scientific standpoint this is correct. But we are not lab experiments as individuals, and should this be applied to patients in general, it denies that the physician is a diagnostician who has been trained to evaluate people and their physical status based on a variety of findings, not just lab work. It would be naive to imagine labwork is flawless and perfect or the the MD is helpless without it to make clinical decisions. Good grief, if this were so why see an MD at all? Why not just see the lab tech, they're the ones who do the tests!
I would again like to mention the human side of science. Science has a certain inertia. People at this level and of this stature begin to get locked in to certain points of view for a variety of reasons. Not least is that once you publish a notable finding, you may be granted funding by interested organizations to do more of the same research. This leads you to work again along the same lines and after some time goes by you have a considerable paper trail clearly placing you on one side of the scientific debate. And you really believe your point of view, witness the absolute tanacity of the autoimmune model of MS in light of the research indicating it appears that autoimmunity does not explain the facts. It is difficult for someone who has done a lot of work on an issue to go back and say, "Oh, by the way, all this work I did before was wrong the other guy was right". You could be forced into that eventually, but it will not happen without a lot of weight on the other side to pull you over. Furthermore, the sheer numbers of people on that autoimmune side of the debate means there is a real sense that "most of us are over here and of course we are right, everybody thinks so...." It might help to recognize that Freud and Jung had a lifelong debate as did Einstein and several of his compatriots. Eventually some other finding may clarify a key issue making it possible to finally see what was missed before so everything falls into place. In this debate about CPn nd MS that would be something like a conclusive photo that shows CPn in the key structures of the MS brain. For example, if someone develops a way to see CPn inclusions in oligodendrocytes and we have an unmistakeable picture of such in an MS brain, maybe in a client that also cultured negative for CPn using traditional methods, we'd have extremely persuasive material wouldn't we? We do not have anything like that now however.
At this point in time there is still considerable debate over this issue. If we had Dr Hammerschlag here she would undoubtedly discuss the technical details of this work in ways I cannot. I am not a chlamydial lab expert. But then again, Dr. Sriram is a neurologist and the director for VU's Multiple sclerosis center. He is teamed up with Dr. Stratton a microbiologist (like MH), and Dr Mitchell an MD PhD pathologist, and they have studied this material and they have made it their business to say this IS happpening in MS and have published extensively on the subject. I am not swayed to believe that Dr Hammerschlag is correct and that the VU team is off base.
So what about other researchers beyond MH and VU? Well, if you go on pubmed and put "multiple sclerosis chlamydia pneumoniae" in the search box you will get a whole list of this kind of work done all over the world by othe people. Some will support the idea, some will not. This is the way science goes, it is a back and forth process until eventually something conclusive and reproducible is put forth. As you read the research, these are the questions to keep in mind;
If a study suggests that there were no people with CPn in the brain, what tests did they use to establish that? Often we see something like the VU study which utilized several highly technical and detailed methods on CSF samples to establish that CPn was there being "countered" with a study that used a single test, sometimes even a blood test.
Or sometimes the author finds not one single case of CPn in the tissue, and you wonder, considering how often other people find it even in seemingly healthy people, how does this author find none at all?
Or sometimes we lay people cannot judge without a tip from someone inside the study, as in the case where the formalin fixed samples were used. To find that out you might need to read comments or editorials in later issues of the publishing journal.
And finally, we have the notion that persistent CPn cannot be cultured at all. If you accept this might be a possibility then testing and it's positivity becomes a somewhat moot point, the germaine issue then being who will develop a test that will find persistent CPn, and importantly, has VU done it already?
So now we come full circle to where I began this page, we are in the uncomfortable position of saying I believe this researcher and not that one, and this question becomes vitally important to us if we are in the unenviable position of suffering from MS and having no results from traditional treatment. Dare we try this treatment in spite of it's not being fully proven and in light of the fact there are some people vehemently stating it is incorrect?
I offer this and this is entirely my personal opinion: The talented and highly qualified team at VU who have published several peer reviewed papers on the subject claiming that CPn is present in at least a subset of MS patients has been focused on this specific issue now for 9 years. That's 9 years of refining their PCR techniques, 9 years of making the tests more robust and redoing tests to remove doubt, 9 years of watching the few people they've treated experimentally with antibiotics get some level of improvement (which is documented) and 9 years of focus. From this multifaceted effort they say it appears to be there in at least a subset of patients. 9 years is long enough for an MD to become a specialist in a couple of disciplines. In my book I find it impossible to imagine the VU team is not utterly expert at this by now, and more expert than any other researcher because of their focus. Add to that the fact that USF gets similar results using a different test, and that some others all over the world are also weighing in on this side of the debate and we have a good weight of evidence agreeing that CPn appears to be there in MS in at least a subset of patients.
Considering the fact that this would be treated with currently available antibiotics and it is clear that these drugs are not patent drugs and therefore not going to make anyone anywhere any money, there is no commercial interest here in manipulating the data at all, which is always a concern with commercial patent drug research. I can find no reason for the people at VU to be anything but honest in their work; it appears legitimate even if still not widely accepted yet. We will hope for some large blinded studies down the road that will make it clear to every one the exact extent of CPn incidence in MS and or some interesting other data that clarifies the issue. Another important point related to the fact CPn is treated with antibiotics is that there is no interest on the part of any drug firm to rush to VU with a large grant to further the research either. This is the reality of our commercial research system. It might be worth noting that the year before Barry Marshall proved beyond a shadow of a doubt that h.pylori caused almost all ulcers, he was still correct, even though few agreed with him. A physician I know of made the comment that "CPn could be neurology's h. pylorii". The original resistence to the idea on the part of doctors who treated ulcers with surgery and bland diets and who mocked the idea of h pylorii causing ulcers are not unlike the neurolosits who reject Cpni/MS idea.
So that is the debate as it pertains to multiple sclerosis. I did not talk about PCR specifically or other issues about the labwork. For that please consult the other book pages.
So if we accept that labwork is not in 100% consensus about how to culture CPn in the CSF of the MS patient, nor is it even clear that persistent infection CAN be cultured, is there other circumstantial evidence that supports the theoretical model that CPn plays a role in MS? The next page is smoking guns and it talks about this issue...and I'd like to say for the person who has been into MS research for a long time, it is there that the correlations uncannily begin to fall into place, although once again we are talking about an idea, not a scientifically proven fact at this point.