Throw away your Vitamin D3!

Here is the bottom line I believe about this issue:

There are more effective ways to treat most of the conditions that are somewhat helped by zero Vitamin D3 intake, etc.

So, even though there is thought to be some truth of the Vitamin D3 problem in a small set of patients, they are still better off resorting to other therapies that do not involve avoidance of D3, with Sarcoidosis as one exception.

So in other words, if a patient has Lyme, or say autoimmune thyroiditis or some other infectious condition....rather than avoiding D3, it would be more effective to find the specific infections and treat those accordingly.

I share this opinion with many who treat these cases. They do not totally discount D3 problem, but they see better results from other treatments in these patients without having to avoid D3.

CS,

Don't mean to be a pain. You've taught me a great deal of info! I guess one thing that could be remembered of me is my firm stance on the subject, lol.

Anyway, please ponder this info. Took me a great deal of time for it to finally "click." When it does, it really does click.

When exposed to infection and damage, especially that which is caused by pathogens, the body begins to convert the inactive form 25-D into the active form, 1,25-D.

... bacteria create ligands, which like 25-D, inactivate the VDR and, in turn, the innate immune response. This allows the microbes to proliferate. In response[microbes proliferating], the body increases production of 1,25-D from 25-D, leading to one of the hallmarks of chronic inflammatory disease: a low 25-D and a high 1,25-D.

This pattern is a result of the disease process rather than a cause.

http://mpkb.org/home/pathogenesis/vitamind/metabolism

This is why a good percentage of people 10 minutes of sun exposure isn't enough.

a research team at the University of Wisconsin Osteoporosis Clinic, ... seemed puzzled by the results of a study which revealed that some participants getting abundant sun exposure still displayed low levels of 25-D. ...51% of this population had low vitamin D status " = http://jcem.endojournals.org/cgi/content/abstract/jc.2006-2250v1

For instance, look how common EBV virus is. EBV downregulates VDR receptor 10 fold and is found in 95% of population. Lyme downregulates 50 fold. Lyme being very common with around 20% of all stinging, biting insects being infected.



So again, 51% of the studies population had low 25 D levels despite getting abundant sun exposure. And again, low 25 D levels doesn't always equate to having health problem. In fact, can be quite the opposite.



A<R, For the vast majority not really. Hard to come back from immune suppression. Not getting further worse would be the goal.

The Microbial Metagenome
Published by Mark Crislip under Basic Science,Medical Ethics,Science and Medicine
Comments: 30

First some background. I was first directed to the Marshall protocol by a reader who wondered about the information the found on the web. So I went to the web and looked at the available information, much as any patient would, and discussed what I found there.

I have subsequently been lead to believe that none of the information on the website http://www.marshallprotocol.com can be considered up to date or accurate. As as result of, I have told that my post is chockablock with errors, although, outside of writing doxycycline where I should have put minocycline, I am left in the dark as to exactly what my errors are. I am told that it is my responsibility to locate the errors in the last post, yet I can find none when compared to the website.

However, to remedy the deficiency of having reviewed inaccurate and out of date material, I have been sent 6 articles that I am informed represent the state of the art in understanding the science behind the Marshall protocol. Ah, the peer reviewed medical literature. An opportunity to carefully read and critique new ideas. It is one of the reasons people publish: to see if their ideas can withstand the scrutiny of others.

Several of these papers concern Vitamin D, the Vitamin D receptor, and olmesartan which I will review, perhaps, another time. I don’t find them a compelling read, but it not an area about which I have more than a standard medical knowledge. The other papers concern the role of infection in autoimmune diseases, which I will discuss here. It is easier as an infectious disease doctor to read this literature as I am, as least as far as the American Board on Internal Medicine is concerned, a specialist in the field. Alternatively, I am a closed minded tool of the medical industrial complex who only seeks to push his own twisted, narrow agenda at the expense of suffering patients (1). We can’t all be perfect.

The main article, which was published in July of this year, is “Autoimmune disease in the era of the metagenome (2)” will be discussed along with several (2, 3) references that are, as of the writing of this post, not yet published. For the clarity, footnotes in ‘()’ are mine, footnotes in ‘[]” are from the referenced material. I added any bold face type.

The article starts with an interesting sentence.

“According to the NIH, a mere 10% of the cells that comprise the organism known as Homo sapiens are human cells. The remaining 90% are bacterial in origin. Thus, Homo sapiens is best described as a superorganism in which a large number of different organisms coexist as one (1).”

That is certainly a curious way to think about the microbial ecosystem we carry around with us. It is true that there are 10 to 100 times more bacteria on us than there are cells that make us up (for the sake of clarity, bacteria on the skin and in the GI tract I will refer to as on us even though from one perspective the bacteria in our gastrointestinal tract are in us. Prepositions can be imprecise. But the GI tract is contiguous with the environment, so I will use the word on. To be in us, the bacteria will have had to breech the cells that line us and be in the blood, the cytoplasm, the nucleus, the interstitial spaces, etc.).

We are covered in bacteria and carry a complex ecosystem that we are just beginning to understand and of which we can grow or, by molecular techniques, identify a minority. However those cells are not us. While we do have some interaction with these bacteria, they are not the cells that make us. It would be the same as saying that the cells of the fleas on a dog are part of what constitutes a dog or the cells of a monkey in a tree are part of what constitutes a tree. There is self, and there is not-self, and our bacteria are not-self. Our genome is what we pass on to our children with reproduction. So the opening sentence does not inspire confidence in the authors understanding of what constitutes being human. From my understanding of human-microbial interaction the opening sentence is wrong.

“Medicine is now comfortable with the bacterial populations that exist in the gut and areas of the body in contact with the external environment, such as the mouth, ears, nose and skin. Yet, components of the human microbiota also likely persist in many other body tissues, including those which become inflamed in autoimmune disease [5] (1).”

Reference 5 is a video of a lecture of one of the authors which is a keynote address summarizing the ideas found in the articles discussed here. You evaluate a review by the quality of the arguments and the quality of the referenced material. It has more credence if the information is based on first class, reproduced research in high impact journals. Linking to your own lectures? Well, no so much. I should put up YouTube video of me reading this blog and link to it as proof of the assertions in this entry as I suppose an on line video constitutes now constitutes valid, scholarly reference material. See. It’s on the interwebs, so it must be true.

What they appears to be saying is the complex microbiology found on us is also to be be found in us, in our cells and tissues, and are involved in the pathogenesis of autoimmune diseases. We shall see.

They continue with

“Such bacteria can persist inside the very cells of the immune system that are supposed to kill them [6], or in biofilm communities in which they are protected from the immune response by a self-created polymeric matrix [7].”

The reference in regards to persisting bacteria is scanning electron microscopy (EM) of white cells in three patients with eye disease and the alleged pathogens were never shown as living organisms nor have the findings of the paper ever been reproduced or verified by others. Dr. Witosko, the author of reference 6, published a number of studies in the 1980′s where he found what he considered to be mycoplasms in several diseases, the proof of an infection being based on EM and response to antibiotics. Unfortunately since that time, his findings have not been confirmed by other researchers. Searching Pubmed for mycoplasms and uveitis, sarcoid, Crohn’s and JRA yield next to nothing. If the primary references to support your hypothesis, at least the ones that are not internet videos, are one off’s, never reproduced or verified, then the foundation upon which your are building your argument may be less than solid.

Bacteria can persist for short times in phagocytic cells during acute infections. However, extrapolating from this paper to bacteria living for years in phagocytes for the lifetime of the patient with an autoimmune disease is a leap across the Grand Canyon of medical hypothesis. Biofilms are important in persisting infections associated with prosthetic material and osteomyelitis but the role of biofilms in other diseases not associated with inert material is uncertain.

So they are building an argument for disease pathogenesis, based in large part on examples and parallel, for infections due to colonies of as of yet undiscovered organisms that evade the immune system and live in biofilms.

Because some organisms cannot be isolated, ours exist and cannot be isolated.
Because some organisms can evade the immune system, ours evade the immune system.
Because some organisms live in biofilms, ours live in biofilms.

The next paragraph concerns the easy exchange of bacterial DNA and how calling an organism E. coli may by old fashioned. I am sympathetic to this view of bacteria, because at one level, given their ability to exchange and utilize DNA, bacteria are a metagenome and our classification of bacteria can be imprecise. I tend to think of bacterial identification as probability functions rather than an absolute characteristic. They are fuzzy, and not in a good way.

“Due to their small size, hundreds, or even thousands, of bacterial cells can fit inside a human cell [6]. The combined genetic contributions of these microbes inevitably provide myriad gene products not encoded by our own relatively small genomes. This means that the human genome is only one of the many genomes that affect Homo sapiens function. In reality, the organism we call Homo sapiens is controlled by a metagenome, a tremendous number of different genomes working in parallel. “

Sorry, this seems ludicrous to me. Sure. We have covered with millions of bacterial genes and in some places there is an ongoing interaction between the bacteria and us. But to suggest that these genes in bacteria are part of our genes and controlling us is an unwarranted extrapolation and, in my understanding, more science fiction than science fact. And just because thousands of bacteria could fit into a cell it doesn’t mean they do. One would think, given the last 50 years of light and other forms of microscopy and the ongoing search for infectious etiologies of most autoimmune diseases (a search that keeps coming up negative) that someone, some time, would have noticed huge numbers of bacteria stuffed into cells. And that such findings would be easily reproduced by others. Curiously, that hasn’t happened. So if the bacteria don’t seem to fit, we must acquit…. sorry for that one.

Then another odd example:

“Bacterial gene products can be very similar to our own. For example, the metabolism of glucose-6-phosphate by both the human body and E.coli is nearly identical, so that remarkably similar metabolites are produced by both species [11]. With this in mind, the interaction between an E.coli genome and the human genome, as they exchange nutrition and toxins, increases the complexity of transcription and translation for both species.”

Thanks to evolution, we do share many common metabolic pathways with many bacteria; it is why some antibiotics will affect human cells and some anticancer drugs will affect bacteria. However, the role of the interaction of bacterial metabolic products, out side of locally, is currently speculative in disease. They then mention that in a test tube system that probiotic bacteria grown in skim milk make enzymes that inhibit angiotensin 1 converting enzyme. How this is relevant to human systems requires another huge leap. It is always a question whether test tube examples have clinical relevance. In this case, unlikely, as we are not skim milk and the bacterial strains in probiotics are usually different than the strains found in us. Possible, but I would not generate a treatment plan based on it.

The authors then give examples of how two genes are altered by bacteria in the test tube: one up regulated, one down regulated. No argument here. When infected the body responds in a variety of ways. Genes get up regulated and down regulated. It is always a question whether these test tube phenomena are of clinical relevance or if they are lost in the complex human metabolic system. Often these effects are the equivalent of tossing a rock in the Oregon ocean and to increase the size of the waves in Hawaii. The effects are too small to be noticed, butterflies and hurricanes not withstanding.

Then the move on to capnine:

“Created by the gliding bacteria that are present in biofilm, the sulfonolipid Capnine provides a specific example of how a bacterial metabolite could manipulate human gene expression in order to dramatically alter the progression of autoimmune and other chronic diseases.Capnine has the capacity to disrupt transcription by the VDR, one of the body’s most prolific nuclear receptors [15].”

Note could, not does. And the proof? The reference is from a paper that is from computer modeling of the interaction of capnine and the VDR. Again with the computer modeling. No real data to show an interaction of this molecule and the VDR. No data to show that this molecule has ever been found outside of biofilm where it could have pharmacologic effects. Going from computer modeling to disease pathogenesis and treatment is another huge stretch. As a clinician I am not impressed. Computer models are interesting but have to be compared to that pesky reality before they can be taken seriously. It is a shame that one cannot jump straight from the computer model to real life, as I would love a computer model that would makes me a Powerball winner.

“Thus, if Capnine was deregulating the VDR, it would greatly hamper the innate immune response. VDR dysfunction would cause the active vitamin D metabolite 1,25-D to rise to excessively high levels where it could inhibit expression by the bulk of the body’s other nuclear receptors -including alpha thyroid, the glucocorticoid receptor, and the androgen receptor [20]. This would result in hormonal imbalances and also interfere with expression of the dozens of other AmPs expressed by these receptors. In vivo, the microbiota appears to gradually shut down the innate immune response over a person’s lifetime, resulting in the increased accumulation of chronic bacteria and other pathogens [21]. “

If wishes were horses, Beggars would ride: If turnips were watches, I would wear one by my side. If capnine was pathogenic, Bacteria would more than glide.

All an unproven speculation presented as fact, all following from could and if. There is no in vitro or in vivo data to suggest that capnine is involved in anything but the production of biofilms. Reference 21 leads to a speculative review that will be discussed later, not original research. But none of this is based on original research in real biologic systems. The shutting down of the immune system by bacteria, while stated as fact, is yet more unproven speculation.

“Eventually, genes from the accumulating microbial metagenome may determine a clinical disease symptomatology such as an autoimmune diagnosis, or simply drive the inflammation associated with the aches and pains of aging [5]. This accumulation is an extremely logical evolutionary survival mechanism. Components of the human microbiome have evolved to dysregulate the VDR receptor that would otherwise activate a potent immune response against its presence.”

No. Most bacteria in our microbial metagenome are simply not pathogenic and lack the capacity to invade and cause disease. Bacteria need to have the capacity to cause disease, and most do not. They live outside of us, on us, and in symbiosis with us. Even if you wipe out most of the immune system with chemotherapy or AIDS and patients become ill with their own bacteria invading, the number of pathogens in these patients is limited relative to the number of bacteria they have. Of our thousand bacterial species, I only have to worry about a couple dozen. Of the millions of microbial species in the world, less than a thousand have the ability to infect humans. Most bacteria simply can’t cause disease. They do not need to have evolved to dysregulate the Vitamin D receptor to survive. Unless, of course, they are forming large, unseen, intracellular colonies, which as best as I can tell, they do not.

“As Royston Goodacre comments in Journal of Nutrition, we are born with a genome that, aside from the genes of species that can survive in the womb and endometrium [22], is largely human. But we inevitably die with a genome that is at least 90% bacteria.”

Nonsense. The genome that is on us is not the genome that is in us. Our genome, what makes us human, is what we pass on with reproduction and those genes are most certainly not bacterial in origin. I suppose under this paradigm, that if you were to drown in a sewage pit, then you would die with an even greater genome.

They move on to discuss antibody production as a result of infection with the metagenome.

“Yet now that Homo sapiens is understood to be the product of multiple genomes, it is equally possible that the antibodies observed in autoimmune disease result from alteration of human genes and gene products by the bacterial metagenome.”

If we take one unsupported hypothesis as true then anther unsupported hypothesis is equally true. We are not the product of multiple genomes, that is hyperbole. But if you repeat something frequently enough, maybe it will be considered true despite a lack of evidence. Works for politicians. Are they saying that the metagenome alters our genes to cause disease? That the bacteria lead to genetic mutations? They are not talking natural selection here.

They are saying that the DNA is altered by the bacteria. News to me, and, if true, leads to a new understanding of disease pathophysiology. It is only “equally possible,” although I would classify that speculation as extremely unlikely.

Next is a discussion of how the bacterial flora varies in time and in location and as a result the products of that bacterial flora will change with time. No argument here, the ongoing ebb and flow of out bacterial flora is just beginning to be elucidated. How this alters disease manifestation is hinted at in the text, but I infer that different microbiota in people will lead to different autoimmune diseases. Which would be good excuse for the not finding a consistent pathogen causing a given disease in each patient. Each patient has a different microbial metagenome causing their sarcoid or RA or whatever disease is present. I admit to being wedded to the idea that one bug causes one disease. For over a century that concept, at the core of Koch’s postulates (5), have helped to discover the cause of everything from AIDS to Zygomycetes. If inference is true, it may make the pathophysiology espoused in this paper unable to be tested or falsified. It would also make the it impossible to isolate the infecting organisms and test it to see what is the optimal antibiotic to be used to kill it. A clinician could never say that the patient DIDN’T have a disease, which is often important information to give a patient.

Then they move on to where and how the microbiota cause disease:

“Persistent bacteria including Francisella tularensis [25], Mycobacterium tuberculosis [26], Rickettsia massiliae [27], Brucella spp. [28], Listeria monocytogenes [29], Salmonella typhimurium [30] and others, use a variety of mechanisms to evade the immune response and survive inside macrophages and other phagocytic cells.”

It is the rare pathogen that survives, usually for a relatively short time, in the cytoplasm of cells. Eventually it either kills the host in relatively short order or is cured. Chronic infection of cells is not the norm of these organisms, although extracellular persistent infections can occur. As will be discussed later, it is postulated that cell wall deficient organisms persist in the cytoplasm to cause autoimmune disease. What is curious about the organisms above is that is the mechanisms by which these organisms evade the immune system are often part of, well, er, the cell wall. Often what allows bacteria to evade the immune system and survive intracellularly is due to constituents on the cell wall and I would suppose that cell wall deficient organisms would lack that mechanism.

“Furthermore, various species of bacteria have been detected inside the cells of patients with juvenile rheumatoid arthritis [31],sarcoidosis [6], and other inflammatory diseases [32].”

The search for a reproducible infection in these and other autoimmune diseases continues and I will not be surprised if one day one or more microbes are found at the center of a sarcoid granuloma. Or in a JRA joint. But the consistent, reproducible demonstration of an infectious agent in any of these autoimmune diseases is still pending. When they discover an infectious cause of some of these autoimmune diseases, it will probably be one lone organism, not a colony. If it takes a village of bacteria to cause a metropolis of diseases, that would be a novel pathophysiology.

“This suggests that disease-causing microbiota largely persist in the cytoplasm of nucleated cells, where it has access to both the DNA transcription and protein translation machinery of Homo sapiens. “

Really? It does? If so, where are they? Colonies of bacteria should be seen by light or electron microscopy and yet for 100 years these bacteria have evaded detection. Romulan cloaking technology is probably beyond their capacity. It might be suggested, but it has never been noticed. There are the occasional reports of quasi bacterial products found in the cells on EM, never reproduced, never confirmed by alternative techniques. Just where are they in all the specimens in all the pathology labs all over the world? It should be easy enough to find the microbiota, should they not?

“Microorganisms are also capable of integrating their DNA with our own [36]. This results in alteration of the human DNA by the microbiota over time, potentially leading to genetic mutations associated with autoimmune diagnoses. Genetic haplotypes observed in autoimmune disease frequently have very low statistical significance, as would be expected based on knowledge that the metabolome varies from population to population and individual to individual. In addition, host DNA repair mechanisms are susceptible to modification by the products of the metabolome. In fact, bacteria may hijack DNA repair mechanisms to generate genetic diversity without losing genomic stability [37, 38].”

The microorganisms referred to is a herpes virus, and there are a few viruses, herpes and retrovirus, that can insert its DNA into ours. The paper refers to bacteria as the constituents of the microbiota and then they switch to a virus and do not bother to mention it. That is disingenuous at best and misleading to anyone who did not bother to go to the footnotes. This kind of scholarship is not reassuring to the reader. However, higher organisms (bacteria, mycoplasma etc) do not put their DNA into ours. There is zero data to suggest that the accumulation of bacterial DNA in humans accounts for autoimmune disease. This is stated as if it were fact, when it is closer to science fiction. Reference 37 is in an insect and reference 39 is computer modeling. Quite a leap from a bug and a PC to the cause of human disease.

So what do we have?

Humans have in them colonies of unseen and undiscovered bacteria that persist undetected in the cytoplasm and alter our genome in ways as of yet proven to suppresses the immune system by way of uncharacterized and unproven metabolites interacting with the Vitamin D receptor to cause a wide variety of autoimmune diseases ranging from sarcoid to diabetes. Hey, I’m convinced. Nothing like lots of speculation and extrapolation from primary sources that are poor in quality and never reproduced or validated by alternative lines of data, and are unsupported by primary in vivo or in vitro studies.

Maybe the reader can see why I am less than enamored of the validity of the pathophysiology noted above. I read dozens of papers a month to keep up in my field. This one is not going to rank high of the compelling review list.

So how does that translate into treating infections? For that we must turn to “Reversing Bacteria-Induced Vitamin D Receptor Dysfunction is Key to Autoimmune Disease. (2)”, which is in press. Sorry. I have a copy and you do not.

Here is the basic hypothesis from the introduction:

“An intraphagocytic bacterial microbiota is proposed to be the primary cause of VDR dysfunction. Because the VDR is key to the innate immune response, its dysfunction would lead to chronic infections with a wide range of pathogens, leading to inflammation and frequent elevation in autoimmune disease markers.”

The first part of the article is a review of the same issue discussed above. Intracytoplamsic colonization of colonies of bacteria make products that interfere with the VDR. No new data, no primary research, many of the same references. I am again going to focus on the infectious disease aspect of the paper, rather than the vitamin D.

“The use of pulsed, subinhibitory, bacteriostatic antibiotics is an important part of this approach. Research indicates that most standard antibiotic protocols used so far to treat chronic inflammatory diseases are ineffective, and so new ways of using antibiotics are called for to deal with the relative treatment resistance of the bacteria involved.”

I read this and my jaw dropped. I promised myself not to be snotty when I evaluated these papers, but such statements really do deserve ridicule. Maybe they are ineffective because the disease do not have infectious etiology? Maybe? The new ways of giving antibiotics? Dose them so that they cannot be effective.

In the practice of infectious diseases when patients do not respond to therapy, there can be a multitude of reasons for the failure. One is that the patient does not have an infection. Another is that the organism is resistant to the antibiotics being used. In the context of the e pathophysiology of the paper, what they say is that since standard antibiotics at standard doses do not work, they will give the same antibiotic, but dosed intermittently and in small amounts, or in such a way that it should have no effect on the infecting organism.

Your infection is not getting better, so we will continue the antibiotic that is not working, but we will give you less of it. That would only make sense to a homeopath but if I were to treat infections this way we would have no shortage of cases for morgue conference. However, novel infections get novel therapies, right?

That’s assuming that bacteria are involved, which as we have noted, while interesting, is far from proved. Antibiotics are presumed not to work against the bacteria in autoimmune disease as the bacteria are cell wall deficient and the antibiotics are dosed too high.
The first part I understand. If there are indeed L forms persisting in the cytoplasm, which have never been demonstrated definitively in autoimmune diseases, then cell wall active agents will not work. Which is why the tetracycline class (minocycline) and macrolides are used against these bugs.

There is a long history in infectious disease of the concept of the minimal inhibition concentration. It takes many more than one antibiotic molecule to inhibit an organism. How many depends on the antibiotic and the organism, but is takes hundreds of antibiotic molecules to have an effect on a bacterium. If you fall below the MIC, the organism still grows, although perhaps more slowly. Using subtherapeutic concentrations of antibiotics are the quick and easy way to develop resistance to the antibiotics. What doesn’t kill it makes it stronger. Currently for most infections you give maximal dose for as short a period of time to maximize killing and minimize the development of resistance. The opposite of what is suggested in this paper. Of course I am biased by 60 years of the successful treatment of infectious diseases and am stuck in my ways.

“The survival of “persister” cells when constant dosages are used means that pulsed antibiotics are likely to be more effective.[18] The ability of bacteriostatic antibiotics to be effective at low dosage levels has been documented.[37]“

To date, there is not an infection treated with pulsed antibiotics. Intermittent antibiotics helps breed resistance. Reference 37 does not concern the ability of low doses of antibiotics to be effective against bacteria, it is an article about the effect on antibiotics on the phagocytosis of bacteria, the ability of cells to ingest bacteria. In the context of the paper, this appears to be a misrepresentation of primary sources. Since the alleged bacteria in autoimmune disease are already intracellular, one wonders about the relevance of this reference as it applies to the use of antibiotics as proposed in this paper.

“The existence of communities of multiple bacterial species, like those occurring in biofilms, means that combinations of antibiotics are likely to be necessary to fully target all species. Thus, there is increasing support for the use of pulsed, low dosages of combinations o bacteriostatic antibiotics.”

Where are these biofilms? In the cells? Extracellular? Never quite certain where the biofilm is in the context of autoimmune diseases. Where are the multiple bacterial species? One does not necessarily need multiple antibiotics just because there are multiple species of bacteria. Often the judicious and rational use of antibiotics allows one to kill multiple organisms with one antibiotic. Rather than delaying the development of resistance in bacteria (bacteria, not mycobacteria, so do not use Tb as an example of why I am wrong), multiply antibiotics may intensify the evolutionary pressure on bacteria to become resistant. There is no support outside the extrapolations of this paper for the use of pulsed, low dose combination antibiotics in any disease that I treat (and cure) for a living.

“The waxing and waning of symptoms that typically follows each of the pulsed antibiotic doses supports the model’s contention that bacteria are involved in autoimmune disease. The fact that these immunopathological responses decline over time, as the patient improves during treatment, provides evidence of disease reversal.”

This is the most risible statement in the paper. An equally unjustified conclusion from a similar paper:

“Perez showed that 81% of a group of 54 patients representing 20 different autoimmune diagnoses reported continual improvement after treatment durations of 18-53 months with aVDR agonist and antibiotics – further pointing to bacteria as a causative agent in autoimmune disease.[21] (4)”

Here is the reasoning: we dose antibiotics in a manner that should have no effect on bacteria (pulsed and subinhbitory).
We therefore conclude that because the ineffectively dosed antibiotics are having an effect, the diseases have an infectious etiology.
That’s a clinical paradox that would shut down an M-5 multitronic unit.

I emphasize with the residents that unless you have firm evidence of infection (culture, serology, PCR etc), response to therapy is not a good way to prove an infectious disease etiology. If they were to make such a suggestion, I would pat them on the head, smile patronizingly and point out that there are four solutions to an alleged antibiotic response:

The patient improved because they had in infection that responded to antibiotics.

The patient improved because they had a self limited infection and the antibiotics did nothing. Treating a viral pneumonia with ampicillin as an example.

The patient improved because they had a non infectious disease and the antibiotics did nothing. They received antibiotics for their stasis changes in their legs misdiagnosed as cellulitis but responded to elevation.

The patient improved because they had a non infectious disease that responded to the antibiotics.

It is the last that makes the treatment success problematic to prove. I used to think that the immunomodulatory effects of antibiotics and other agents were too minor to be of clinical importance. Now I am not so sure. The association of NSAID use and the development of group A streptococcus necrotizing fascitis and the possible decreased mortality with infections in patients who are on statins are non-antibiotic examples of possibly clinically relevant effects of minor immunomodulation.

Both the tetracycline and the macrolide classes of antibiotics are immunomodulatory, and several recent studies have demonstrated decreased mortality for infections resistant to macrolides that are treated with adjunctive macrolides. An animal model suggests that the decrease in mortality from macolides is due to a decrease in cytokines. The minor immunomodulatory effects may, much to my surprise, be clinically relevant.

So assuming that tetracycline and macrolide antibiotics are indeed effective in decreasing the symptoms of autoimmune diseases, in the absence of a well defined infection, you cannot know for sure of the result is from the antimicrobial drug treating an infection or the result of an immunomodulatory drug altering immune function. I bet, since they are dosed at levels to low to be effective against bacteria, that it is the latter that will be the mechanism of action, if, indeed, they are demonstrated in clinical trials to be effective.

“Diseases responding to treatment include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren’s syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter’s syndrome, type I and II diabetes mellitus and uveitis8 and sarcoidosis. [3] Fibromyalgia, though not generally established as an autoimmune disease, has also responded favorably to this approach.”

If there is a recurrent theme in this blog, it is the difficulty of assigning causality to therapeutic interventions, especially when the underlying treatment has no or unproven biologic plausibility. The acupuncturists say their interventions are effective and that chi exists because of anecdotes of efficacy and poorly controlled studies. Yet when rigorous trials are done, acupuncture is no better than twirling toothpicks on the skin. The plural of anecdote is anecdotes, not data. With diseases that can naturally wax and wane there is always a question of true causality with anecdotal information. Until you do a placebo controlled trial, anecdotal evidence may be interesting but is not definitive.

So perhaps you can see why, as an infectious disease doctor, I am less than convinced about the infectious diseases component of the pathogenesis of autoimmune diseases as presented in these papers.

No reproducible, credible evidence that colonies of organisms and their biofilms exist inside of human cells.
No evidence outside of in silico (I love that term. It means computer modeling, but suggests parallel validity with in vivo and in vitro) data to suggest that bacteria make molecules to alter the VDR to suppress immune function.
 No controlled trials to suggest that patients are having a response to the antibiotics due its antimicrobial, rather than immunomodulatory, effects. 
Antibiotics are used in a manner that has a long history of being ineffective and aids in the development of resistance.

Lots of extrapolation, hypothesis and anecdote. To me it is all, as Shakespeare might say, all sound and fury, signifying nothing.

All aspects of the pathophysiology are amenable to testing, so I could easily be proven wrong. I can easily imagine a clinical trial that would prove or disprove the therapies independent of the theory behind it. It could be that they have the right therapeutic idea for all the wrong reasons. It wouldn’t be the first time in medicine. Take a well defined population of sarcoid or another illness. 4 treatment groups: 2 placebos, one placebo plus antibiotics, one placebo plus olmesartan and both antibiotics and olmesartan. Everyone blinded. It also makes me wonder: what research would the proponents consider valid in falsifying the pathyphysiology and treatment in the Marshall protocol?

Much is made by the fact that these articles are peer reviewed. After reading the papers closely, what peers and what they were reviewing, I am uncertain. Perhaps spelling and punctuation? They didn’t pay a whole lot of critical attention to the arguments or the references. Certainly, peer reviewed does not mean true; much of the published literature in medicine is subsequently shown to be incorrect. It is good to have speculative ideas published, it drives innovation. To use speculative ideas as the basis of a complex treatment protocol is not, to mind, the safe and prudent practice of medicine. I have in my mind a factoid, and I am not sure where I read it, it so it may be in error, that if you have no data to support a therapeutic intervention, the odds are you will do more harm than good. I heard that, I think, as a resident almost 25 years ago and could be misremembering, but I am sure the commentators will set me straight.

“It should be noted that the immunopathological reactions resulting from this approach are sometimes strong enough to be life-threatening in patients with more advanced disease.[3]“

It is good to note that you may be killing people with an intervention. The ethics of almost killing people with unproven treatments is problematic. The ethical guidelines for doing research are found in the Declaration of Helsinki, I will quote from the Wikpedia summary, which I sure will lead to derision.

“Research should be based on a thorough knowledge of the scientific background (Article 11), a careful assessment of risks and benefits (Articles 16, 17), have a reasonable likelihood of benefit to the population studied (Article 19) and be conducted by suitably trained investigators (Article 15) using approved protocols, subject to independent ethical review and oversight by a properly convened committee (Article 13). The protocol should address the ethical issues and indicate that it is in compliance with the Declaration (Article 14). Studies should be discontinued if the available information indicates that the original considerations are no longer satisfied (Article 17). Information regarding the study should be publicly available (Article 16). Ethical publications extend to publication of the results and consideration of any potential conflict of interest (Article 27). Experimental investigations should always be compared against the best methods, but under certain circumstances a placebo or no treatment group may be utilized (Article 29). The interests of the subject after the study is completed should be part of the overall ethical assessment, including assuring their access to the best proven care (Article 30). Wherever possible unproven methods should be tested in the context of research where there is reasonable belief of possible benefit (Article 32).”

I am not so certain that these (nonbinding) guidelines are being adhered to. But if you are almost killing people, it really behooves the proponents to subject the therapies to careful clinical trials to make sure the potential for death is worth the benefit.

Which brings us to China, an internationally recognized center of human rights and ethics. A press release has noted that the Marshall protocol is to be used in the biggest hospital in China. Bigger, of course, is always synonymous with quality. What is being done in China is not clear: a clinic to make money and turn out more anecdotes? Like the fake stem cell clinics? Or is a protocol finally to be put to the test with a placebo control blinded trial in a well defined patient population. If the former, well, I can go to Mexico for a cheaper alternative. If the latter, I look forward to eating my words when a well done clinical trial demonstrates the efficacy of the Marshall protocol.

===

References

(1) For the record, I have not talked to a drug rep not accepted anything, not even pizza at a conference, for over 25 years. I am, however, the Head of the Vitamin D subcommittee of the trilateral commission.
(2) Autoimmune disease in the era of the metagenome
Amy D. Proal, Paul J. Albert, Trevor G. Marshall
Autoimmunity Reviews. Jul;8(:677-81. Epub 2009 Feb 13.
(3) Reversing Bacteria-Induced Vitamin D Receptor Dysfunction is Key to Autoimmune Disease
Joyce C. Waterhouse, Thomas H. Perez, Paul J. Albert, 
in press.
(4) Dysregulation of the Vitamin D Nuclear Receptor may contribute to the higher prevalence of some autoimmune diseases in women
Amy D. Proal, Paul J. Albert, Trevor G. Marshall, 
in press.
(5) From Wikipedia
Koch’s postulates are:
1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.
2. The microorganism must be isolated from a diseased organism and grown in pure culture.
3. The cultured microorganism should cause disease when introduced into a healthy organism.
4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.
There are ethical and practical limitations to these postulates, but they serve as a reasonable starting point for determining causality.

Not sure why the above author is so sarcastic. When someone is so sarcastic always reminds me of this quote

“Every truth passes through three stages before it is recognized In the first it is ridiculed, in the second it is opposed, in the third it is regarded as self-evident”


Regarding a rebuttal, most all is done if the author read the work of Zimmer for one

explains that by scrutinizing the bacteria's genome, scientists have discovered that genes can jump from one species to another and how virus DNA has become tightly intertwined with the genes of living creatures all the way up the tree of life to humans.

http://www.amazon.com/Microcosm-Coli-Science-Vintage/dp/0307276864/ref=sr_1_2?ie=UTF8&qid=1290722727&sr=8-2

rest of work the author is looking for is explained via oncoviruses.

Either way, from very first post always stated hated bringing up the why as there are always those who will disagree. Would rather just focus on the results such as this http://www.curezone.com/forums/fm.asp?i=1727457#i

jdp701 wrote:Not sure why the above author is so sarcastic. When someone is so sarcastic always reminds me of this quote

“Every truth passes through three stages before it is recognized In the first it is ridiculed, in the second it is opposed, in the third it is regarded as self-evident”


Regarding a rebuttal, most all is done if the author read the work of Zimmer for one

explains that by scrutinizing the bacteria's genome, scientists have discovered that genes can jump from one species to another and how virus DNA has become tightly intertwined with the genes of living creatures all the way up the tree of life to humans.

http://www.amazon.com/Microcosm-Coli-Science-Vintage/dp/0307276864/ref=sr_1_2?ie=UTF8&qid=1290722727&sr=8-2

rest of work the author is looking for is explained via oncoviruses.

Either way, from very first post always stated hated bringing up the why as there are always those who will disagree. Would rather just focus on the results such as this http://www.curezone.com/forums/fm.asp?i=1727457#i

His sarcastic tone is partly due to the fact that amy proal had commented on his blog posts and refused to address any of his points. It was always "tl;dr off to china".

The vitamin D issue is better left to trained professionals like IH.

Jdp, you don't even work in this field. You did a three-month Internet study, and exchange posts with friends at the curezone. However interesting and intriguing this may be to you, it does not trump or negate the results and recommendations from those, again trained professionals, at say, Harvard University who recommend vitamin D3 supplementation.

jdp701 wrote:Not sure why the above author is so sarcastic. When someone is so sarcastic always reminds me of this quote

“Every truth passes through three stages before it is recognized In the first it is ridiculed, in the second it is opposed, in the third it is regarded as self-evident”

http://en.wikipedia.org/wiki/Survivorship_bias


Regarding a rebuttal, most all is done if the author read the work of Zimmer for one

explains that by scrutinizing the bacteria's genome, scientists have discovered that genes can jump from one species to another and how virus DNA has become tightly intertwined with the genes of living creatures all the way up the tree of life to humans.

http://www.amazon.com/Microcosm-Coli-Science-Vintage/dp/0307276864/ref=sr_1_2?ie=UTF8&qid=1290722727&sr=8-2

rest of work the author is looking for is explained via oncoviruses.

Either way, from very first post always stated hated bringing up the why as there are always those who will disagree. Would rather just focus on the results such as this http://www.curezone.com/forums/fm.asp?i=1727457#i

I'm not going to read that book for a rebuttal, I want to see studies I can view online.

I'm aware you don't agree with the marshal protocol but It would figure that if any part of the vitamin d theories were true people would be getting better with it. I can guarantee you thats just not happening. Not one person off abx, not one person off benicar, not one person exposing themselves to vit-d, not one person getting rid of their sunglasses. Everyone of those interviews with patient recoveries you've seen are bs. Anyone with phase 2 access can see they "relapse" and go back on abx/benicar.

abc123 wrote:Not one person off abx, not one person off benicar, not one person exposing themselves to vit-d, not one person getting rid of their sunglasses. Everyone of those interviews with patient recoveries you've seen are bs. Anyone with phase 2 access can see they "relapse" and go back on abx/benicar.

Must not be reading my links but we don't do the Marshall Protocol.

jdp701 wrote:

abc123 wrote:Not one person off abx, not one person off benicar, not one person exposing themselves to vit-d, not one person getting rid of their sunglasses. Everyone of those interviews with patient recoveries you've seen are bs. Anyone with phase 2 access can see they "relapse" and go back on abx/benicar.

Must not be reading my links but we don't do the Marshall Protocol.

Yea I didnt read this whole thread just skimmed it, only saw you referenced them at several points.

What do you recommend.

High vit-d through sun/no supplemental or low both?

This post responds to abc123's post not to offer a specific stance on vitamin D biology. I have my own observations, hypotheses, and theories---regarding hair loss, vitamin D, and microorganisms---yet I'll withhold those at the moment. I am responding to the extremely common yet utter error of presuming that medical microbiology---which is merely an applied science---offers scientific realism, namely accurate portrayal of the natural world. Medical microbiology was built upon the early presumption of Robert Koch's bacteriology, developed in the 1870s, that bacteria are monomorphic---hold constant form form and function no matter environment. By now bacteriology is merely applied science---a medical science---whereas the basic science, also called pure science, microbiology has long recognized that bacteria are pleomorphic, rather, and can take very many forms.

"Bacteria in nature exist as films, mats, colonies, aggregates, and chains and rarely as isolated cells. The concept of bacteria as unicellular organisms, a very successful strategy that began with the research successes of Robert Koch, is about to undergo a major paradigm shift in microbiology. Koch invented the pure (axenic) culture method in which monomorphic traits remain constant, but studies in mixed cultures proved difficult and frustrating because they often produced pleomorphism; that is, any microbe could become any other. Pure culture methodology was soon adopted by mycologists to study fungi for essentially the same reasons. The legacy of Koch's method was that it eliminated as many variables as possible form the tangled web that normally exists in nature and opended the way to a reductionist approach to studying the causes of infectious diseases. After more than 100 years, an alternative view of microbiology is gathering momentum" [Paracer S, Ahmadjian V, Symbiosis: An Introduction to Biological Associations, 2nd ed (New York: Oxford University Press, 2000), chapter 1 "Introduction", subchapter 1.3 "Symbiosis in all forms of life", section "Bacteria as multicellular organisms", p 10, books.google.com/books?id=OmZ6CfHQIZ8C&pg=PA10].

The monomorphist tenet, however, apparently underlay the biomedical presumption that the blood is normally sterile and thus that biomedical products extracted from patients and animals were sterile unless the animal was acutely ill. (This confusion has had trenchant implications as to the longterm effects of injected biomedical products, yet I won't review those here.)

"Yet medical journals often contain poor science. Basic scientists who work in biology and chemistry are regularly scornful of the, mostly, applied science that appears in medical journals" [Smith R, "The trouble with medical journals"---section "The poor science of medical journals", J R Soc Med, 2006;99(3)-9, ncbi.nlm.nih.gov/pubmed/16508048]. As science for the unscientific, their "science" is statistics [Smith R, 2006, section "Science for the unscientific"]. Medical peer review seldom catches basic scientific or philosophical errors [Smith R, 2006, section "Peer review: More evidence of harm than benefit"]. A short quote of abc123's post illustrates the vast gaps both in content and philosophy between pure science (microbiology) and applied science (medical microbiology).

Proal et al had published a 2009 article saying, "Studies of autoimmune disease have focused on the characteristics of the identifiable antibodies. But as our knowledge of the genes associated with the disease states expands, we understand that humans must be viewed as superorganisms in which a plethora of bacterial genomes---a metagenome---work in tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease. Thus, we must re-examine how human gene transcription is affected by the plethora of microbial metabolites" [Proal AD et al, "Autoimmune disease in the era of the metagenome", Autoimmun Rev, 2009 Jul;8(8):677-81, ncbi.nlm.nih.gov/pubmed/19393196].

Rather innocently if naively, being faithful to medical ideology, abc123 explains that the microorganisms merely live on body surfaces---skin and intestinal lining---yet do not live systemically in the human organism or reside inside human cells.

abc123 wrote:
Sorry, this seems ludicrous to me. Sure. We have covered with millions of bacterial genes and in some places there is an ongoing interaction between the bacteria and us. But to suggest that these genes in bacteria are part of our genes and controlling us is an unwarranted extrapolation and, in my understanding, more science fiction than science fact. And just because thousands of bacteria could fit into a cell it doesn’t mean they do. One would think, given the last 50 years of light and other forms of microscopy and the ongoing search for infectious etiologies of most autoimmune diseases (a search that keeps coming up negative) that someone, some time, would have noticed huge numbers of bacteria stuffed into cells. And that such findings would be easily reproduced by others. Curiously, that hasn’t happened. So if the bacteria don’t seem to fit, we must acquit. Sorry for that one.

It is apt in biology---pure science---to point out that the gastrointestinal tract is more or less a closed tube merely running through and yet external to the human system. Proal at al have the microbiology correct, however. The human metagenome does not merely live on the human body---it lives both on and within the human body. The pleomorphic microorganisms not only can reside systemically, within the human system, yet live within human cells, emerge from human cells, and can fuse with human cellular components. The Marshall Protocol's treatment effects---a matter of medicine---is a different question. Yet there is probably a better chance of treatment success if treatment is grounded in more accurate theory.

Pleomorphic variants of classical bacteria have long been recognized by basic scientists---microbiologists---who call them spheroplasts, protoplasts, and L forms [Smith DG, "Bacteria with their coats off: Spheroplasts, protoplasts, and L-forms", Sci Prog, 1969 Summer;57(226):169-92, ncbi.nlm.nih.gov/pubmed/4893484]. When the bacterial cell wall is destroyed, an L form develops from 10% to 80% of the time [Makemson CJ & Darwish RZ, "Calcium requirement and magnesium stimulation of Escherichia coli L-form induction", Infect Immun, 1972 Nov;6(5):880–2, ncbi.nlm.nih.gov/pmc/articles/PMC422624]. L forms can be considered undifferentiated cells that, depending on the stimulus and environment, can transform along several different routes, and, evading immune survellience, they might sometimes integrate with host cells' organelles [Domingue GJ, "Demystifying pleomorphic forms in persistence and expression of disease: Are they bacteria, and is peptidoglycan the solution?", Discov Med, 2010 Sep;10(52):234–46, ncbi.nlm.nih.gov/pubmed/20875345].

"It had long been assumed that a bacterial cell was dead when it was no longer able to grow on routine culture media. We now know that this assumption is simplistic, and that there are many situations where a cell loses culturability but remains viable and potentially able to regrow", a state called viable but nonoculturable (VBNC) [Oliver JD, "The viable but nonculturable state in bacteria", J Microbiol, 2005 Feb;43 Spec No:93-100, ncbi.nlm.nih.gov/pubmed/15765062]. Classical E coli cells subjected to boiling or autoclaving---the sterilization method applied in hospitals---can transform into L forms that survive, calling for modification of current sterilization notions [Markova N et al, "Survival of Escherichia coli under lethal heat stress by L-form conversion", Int J Biol Sci, 2010 Jun 9;6(4):303–15, ncbi.nlm.nih.gov/pubmed/20582223].

Medical sciences frame discussion of the immune system as that of keeping the system sterile. A 1900 clinical bacteriology textbook says, "Bacteria are ubiquitous: they are found everywhere; only the internal organs of the human and animal body not in communication with the atmosphere are free from them" [Klemperer F, Levy E, Elements of Clinical Bacteriology for Physicians and Students, 2nd ed (Philadelphia: W B Saunders, 1900), p 25, books.google.com/books?id=pu8q1wGBHsUC&pg=PA25]. A 2009 a medical textbook echoes, "Occasionally a patient will need to have blood collected for culture. The culture will determine if the patient has pathogens in the blood. Normally blood is sterile" [Lindh WQ, Pooler M, Tamparo C, Dahl BM, Comprehensive Medical Assisting: Administrative and Clinical Competencies (Canada: Delmar Cengage Learning, 2009), p 1162, books.google.com/books?id=AUhJKmKJ_eEC&pg=PA1162], which is false.

Formerly called PPLO, mycoplasma have long been known to occupy hosts undetected for long periods but, upon a particular stress to the host, proliferate and result in disease ["Microbiology: The elusive PPLO", Time, 1 Oct 1965, time.com/time/magazine/article/0,9171,834435,00.html]. Pleomorphic bacteria---L forms of classical bacteria as well as the genus Mycoplasma---live all throughout the blood of healthy humans [McLaughlin RW et al, "Are there naturally occurring pleomorphic bacteria in the blood of healthy humans?", J Clin Microbiol, 2002 Dec;40(12):4771-5, ncbi.nlm.nih.gov/pubmed/12454193]. Watkins, a clinician, applied this understanding in the early 20th century [Watkins RL, "Blood examination", Health Culture, 1913 Jun;19(6):289-90, books.google.com/books?id=5vqfAAAAMAAJ&pg=PA290].

In 1921, in Memoirs of the National Academy of Sciences of the United States of America, Felix Löhnis, reviewing the published scientific literature of Europe, Russia, and America during the 80-year period from 1838 till 1918, concluded that the monomorphist tenet was "utterly untenable", and pointed out the even Koch himself soon withdrew from it, whereas merely Koch's followers tenaciously upheld the monomorphist tenet. Löhnis summarizes with seven points. Point 1 opens, "The monomorphistic theory of F Cohn, R Koch, and their followers, still accepted by many bacteriologists as being correct, is irreconcilable with numerous facts, which prove conclusively that all bacteria are pleomorphic".

Point 2 explains how "it was possible to uphold the monomorphistic theory for a considerable length of time, despite its erroneousness". Point 2 has four subpoints: (a) differences in appearance were merely assumed to be different species, and so cultures showing such differences were called contaminated; (b) bacteria that showed budding, branching, or other peculiarities not predicted by monomorphist theory were simply called not bacteria; (c) when a pure culture showed various cell forms, only one was called typical or legitimate, the others dismissed as atypical or degenerate; (d) the culture methods developed by the founders of the monomorphist doctrine enable fairly constant proliferation of a single cell type, but when variation was observed, anyway, it was labeled 'contamination' or 'involution forms', in other words damaged forms.

Point 3 remarks, "In practically all cases where the so-called involution forms have been properly studied, it has been found that it was a mistake to classify them as such". Point 6 indicates, "It is a grave, though often repeated, logical mistake to believe that the acknowledgement of pleomorphism of the bacteria be equivalent to a negation of the existence and constancy of bacterial species. Just as all studies upon the pleomorphism of the fungi, algae, and protozoa did not minimize, but have increased, the accuracy in distinguishing between the various genera and species, so also systematic bacteriology will win considerably by every thorough investigation upon the life cycles of the different species". And yet, "the old monomorphistic form genera and form species of F Cohn, of R Koch, and of their followers will have to be thoroughly revised" [Löhnis F, "Studies upon the life cycles of the bacteria, Part I, Review of the literature, 1838–1918", Mem Natl Acad Sci U S A, 1921;16(2):1–335, books.google.com/books?id=bfAjAQAAIAAJ&pg=RA1-PA88 = books.google.com/books?id=6lbZAAAAMAAJ&pg=PA89].

L forms cannot be detected by traditional culture methods, namely pure culture, as used in allopathic medicine, however, because the are tiny and lack the classical cell wall that binds the chemical stains used in microscope-slide preparation. Only a relative handful of clinicians have acknowledged L forms, usually under the name of microzymas. In 2002 Young explained, "This lost chapter of history reveals that there is something living independently in cells and body fluids that is capable of evolution into more complex forms. These elements are known as microzymas..., and all living things contain them. Degeneration and regeneration both originate with the microzymas. All cells evolve form them to begin with. In the right circumstances and environment, microzymas evolve into more complex forms, including bacteria and fungi. It is a two-way street: bacteria also devolve back to microzymas. Everything [in biology] begins and ends with microzymas. What happens in between depends on the environment" [Young RO, Young SO, The pH Miracle: Balance Your Diet, Reclaim Your Health (New York: Warner Books, 2002), p 21, books.google.com/books?id=rC7PV5oJNXkC&pg=PT22].

In 1912 Watkins acknowledged, "Béchamp has demonstrated that the microzymas are the constituent and physiological basis of all anatomical life. Starting with this premise it would follow that the microzymas are the constituent of the liver, lungs, bones, cells, and the blood, and are therefore the basis of the work the hematologist" [Watkins RL, "The microzymas in the hen's egg", Med Times, 1912 Oct;40(10):292–3, books.google.com/books?id=2wEUAAAAYAAJ&pg=PA292]. In current biology literature the host's own microzymas are called membrane vesicles---framed linguistically as merely shed by host cells---with variants called microvesicles and exosomes, things that till recently were generally labeled mere debris [Lee TH et al, "Microvesicles as mediators of intercellular communication in cancer---the emerging science of cellular 'debris'", Semin Immunopathol, 2011 Feb 12;[Epub ahead of print], ncbi.nlm.nih.gov/pubmed/21318413]. In 1934 Kritschewski and Ponomarewa, microbiologists, explained about the monomorphist tenet, "This doctrine has paved a most important part in the development of our science, but its authority has too long prevailed over microbiological thought and has prevented free progress. ... Summary: 1) The bacillary form of B. paratyphi B, Schottmuller, though more frequently found, may be regarded as only one of many possible forms of existence of this microrganisms. Because of this, pleomorphism of bacteria should be considered as a proven fact. 2) The doctrine of mononmorphism contradicts reality and should be substituted by the statement that bacterial species are pleomorphic" [Kritschewski IL & Ponomarewa IW, "On the Pleomorphism of Bacteria: I, On the Pleomorphism of B Paratyphi B", J Bacteriol, 1934 Aug;28(2):111–26, ncbi.nlm.nih.gov/pubmed/16559732].

A 2005 a medical journal published a systematic review of clinical literature starting from 1934---using only the search term cell wall deficient bacteria and clinical significance and infections although cell all deficient bacteria is a relatively new term---acknowledged that cell wall deficient bacteria (CWDB), known for over a century, are pleomorphic bacterial forms, occurring either naturally or after artificial induction, yet the authors concluded that despite many reports of association between these "atypical" forms and disease, "evidence for the clinical significance...in disease is not compelling" [Onwuamaegbu ME et al, "Cell wall-deficient bacteria as a cause of infections: A review of the clinical significance", J Int Med Res, 2005 Jan-Feb;33(1):1–20, ncbi.nlm.nih.gov/pubmed/15651712], which, anyway, is a question of medical application, a question different from whether they exist, pure science. Whether they are clinically significant is a matter of opinion. In 2000 medical microbiologist Lida Mattman's textbook, published in its third edition, discussed mainly Mycoplasma---a genus of bacteria that appears to always lack cell wall---and L forms, which, being pleomorphic variants of classical bacteria, can construct cell well to transform into the classical classical bacteria [Mattman L, Cell Wall Deficient Forms: Stealth Pathogens, 3rd ed (Boca Raton FL: CRC Press, 2000), chapter 6 "Disclosures by electron microscopy", p 47, books.google.com/books?id=mincr2Hi81UC&pg=RA1-PA47].

As to Koch's postulates, putatively to answer whether a microorganism is the cause of disease, even Koch himself---who actually did not even formulate these hypotheses---acknowledged that in many instances they did not apply, and the quest is still on to try to develop a practical system of determining causation [Inglis TJ, "Principia aetiologica: Taking causality beyond Koch's postulates", J Med Microbiol, 2007 Nov;56(Pt 11):1419-22, ncbi.nlm.nih.gov/pubmed/17965339] [Fredericks DN, Relman DA, "Sequence-based identification of microbial pathogens: A reconsideration of Koch's postulates", Clin Microbiol Rev, 1996 Jan;9(1):18-33, ncbi.nlm.nih.gov/pubmed/8665474] [Evans AS, "Causation and disease: The Henle-Koch postulates revisited", Yale J Biol Med, 1976 May;49(2):175-95, ncbi.nlm.nih.gov/pubmed/782050]. So abc123 was quite correct to say that Koch's postulates are just a start---a start---the point that ought to be emphasized. Peer review cannot determine absolute truth, yet the peer-review team of the journal Autoimmunity Reviews, which published Proal et al's paper, probably is familiar with the extremely simplistic Koch's postulates.

Till the late 19th century bacteria were detected by direct visualization in natural samples. In the 1870s Robert Koch developed bacteriology---at the time intended as basic science---by standardizing pure culture methods, using agar plates to culture and grow bacteria, aiding the bacteria's visualization. For microscopic examination, a sample is fixed and stained. In fixation, the bacterial structure is chemically fixed, killing the bacteria and fixing the form. In staining, the bacteria are treated with 'crystal violet', which colors the bacteria blue, and then iodine is applied to fix the stain, whereupon alcohol or another solvent is applied in an effort to decolorize the specimen: bacteria that hold the crystal violet stain are gram positive, and examined like so under the microscope, whereas bacteria that lost the crystal violet stain are gram negative, get counterstained with safranin, and, now pink, are examined like so under the microscope [Fox A, figure 2, Chapter 2 "Culture and identification of infectious agents", Bacteriology, Microbiology and Immunology On-line, Univ S Carolina School Med, 15 Feb 2010, pathmicro.med.sc.edu/fox/culture.htm]. The monomorpist tenet philosophically presumed---during this slide preparation then microscopic examination---that bacteria could not have become any different in form if they had been left alive.

Some bacteria eluded culturing, for instance Mycobacterium tuberculosis, associated with tuberculosis. Soon immunology brought recognition of antigens. Antigenic reaction permitted indirect detection of bacteria when antibody molecules ligated---in other words binded to---bacterial structures or secreted proteins. Thus M tuberculosis infection could be detected by injection of tuberculin to see whether the host's body reacted [Fox A, Chapter 2 "Culture and identification of infectious agents", Bacteriology, Microbiology and Immunology On-line, Univ S Carolina School Med, 15 Feb 2010, pathmicro.med.sc.edu/fox/culture.htm]. And now we have enzyme linked immnosorbent assay (ELISA). Monomorpist philosophy presumes that if a particular antigen is absent from a sample, no entities in the sample can construct the antigen later---a false assumption. Buxton and Phllips reported, "The use of special microbiological media and modified techniques has resulted in the stimulation of growth and development of bacterial L forms in samples of blood and egg yolk free from mature bacteria and derived from normal healthy chickens. After prolonged cultivation the majority of these L form cultures reverted to staphylococci" [Buxton A & Phillips JE, "Isolation of staphylococcal L-phase variants from the blood and egg yolks of normal chickens", Res Vet Sci, 1980 Jul;29(1):51-6, ncbi.nlm.nih.gov/pubmed/7192878].

In 1928 Fred Griffith, medical officer at the Ministry of Health, in London, reported that a strain of Streptococcus pneumonia---involved in most serious cases of pneumonia as called lobar pneumonia and thus medically called pneumococcus---could transform from a strain avirulent into another strain virulent as well as switch antigenic types, back and forth. As the monomorhpist tenet maintained that these different strains and antigenic types must have evolved from separate evolutionary lineages altogether, America's most prominent pneumococcus expert, Oswald Avery, The Rockefeller Hospital, The Rockefeller Institute, New York, disbelieved Griffith's findings and presumed that Griffith had applied inadequate control measures. In other words, Avery presumed that Griffith's samples had been contaminated. In 1944 Avery's laboratory at The Rockefeller Hospital published the landmark paper identifying the transformation factor as DNA---opening the door to molecular genetics---yet medical sciences mostly ignored the epidemiological and pathological implications rendered by Griffith. (I wrote most of the Wikipedia.org page on Frederick Griffith, and that page reviews this in more detail.)

DNA is recognized and then intricate molecular machinery negotiates its transport, recombination, and integration [Chen I et al, "The ins and outs of DNA transfer in bacteria", Science, 2005 Dec 2;310(5753):1456–60, ncbi.nlm.nih.gov/pubmed/16322448] [Burton B & Dubnau D, "Membrane-associated DNA transport machines", Cold Spring Harb Perspect Biol, 2010 Jul 1;2(7):a000406, dx.doi/org/10.1101/cshperspect.a000406]. What Griffith described is now, in microbiology, called transformation. Joshua Lederberg described conjugation, whereby bacteria in effect have sex in a process whereby one bacterium endowed with the F factor can construct an F pilus, connect with another bacterium, and insert genes [Babić A et al, "Direct visualization of horizontal gene transfer", Science, 2008 Mar 14;319(5869):1533–6, dx.doi.org/10.1126/science.1153498]. The phage group---who studied prophages which are the viruses of bacteria---developed much of our understanding of the function of animal cells and described transduction whereby virus genes get installed into the bacterial genome.

By now an entire genome can be sequenced---its genetic code determined---still a large and expensive task, not one performed in a clinical laboratory, as a bacterial genome contains millions of nucleotides (nts). More practical techniques are usually applied toward genetic recognition. In DNA hybridization, for instance the polyermerase chain reaction (PCR), a relatively short portion of the genome is tested for its binding affinity to a sequence within a putatively homologous genome, and the greater the binding affinity, the more homologous the genomes---a high affinity suggesting a species match. Bacterial genomes are not constant, however. Horizontal gene transfer, also called lateral gene transfer, occurs by way of transformation, conjugation, and transduction [Ragan MR & Beiko RG, "Lateral genetic transfer: Open issues", Phil Trans R Soc B, 2009 Aug;364(1527):2241–51, dx.doi.org/10.1098/rstb.2009.0031]. More genetically stable seqences of nucleic acid---DNA or RNA---occur as ribosomal RNA (rRNA), found in the cell's organelles called ribosomes. 16S rRNA---1600 sequences long---can be extracted and sequenced. 16S rRNA is highly conserved within and sometimes even across species.

By the 1980s the genomic era left microbiologists to widely accept that as many as 99% of microorganisms in certain environments cannot be cultured by standard techniques [Singh J et al, "Metagenomics: Concept, methodology, ecological inference and recent advances", Biotechnol J, 2009 Apr;4(4):480–94, ncbi.nlm.nih.gov/pubmed/19288513]. Medical personnel have the habit of repeating mere snippets of such information to convert them into platitudes and then dismiss them in order to propound medical ideology as if it were pure science and then claim such notions as offering scientific realism. Apparently this has left the public severely confused, believing by way of faith in medical personnel that this ideology is positively proved scientific facts and truths [Clarke JN et al, "The paradoxical reliance on allopathic medicine and positivist science among skeptical audiences", Soc Sci Med, 2007 Jan;64(1):164-73, ncbi.nlm.nih.gov/pubmed/17045377]. Allopathic medical education developed the applied science called medical microbiology and retained bacteriology within medical microbiology, apparently the lens of abc123's discussion. As to introductory medical microbiology, abc123's indications are accurate. Simply, medical sciences---which are applied science and not pure science---do not offer scientific realism [Zalewski Z, "Importance of philosophy of science to the history of medical thinking", Croat Med J, 1999 Mar;40(1):8-13, ncbi.nlm.nih.gov/pubmed/9933889].

UsernameK,

Surprised that you didn't pick up on the fact that I did not write that. If you're looking for a response I suggest you write a comment on the authors blog http://www.sciencebasedmedicine.org/index.php/the-microbial-metagenome/.

I will set some time aside to read your post later.

Hello, abc123. Thank you for responding and for indicating that you'll take the time to read my post. I saw your post's header, yet it mostly just confused me. It seemed to not make clear that the content was quoted, so, although I tried to discern the source, I defaulted to presuming that you wrote the content. I actually didn't read it closely, since every portion that I did read fit very tightly mere allopathic medical dogma thoroughly nullified in biology consistently over decades by now, and so, lest it somewhere said, "This is just a gag!", I took it as apparent what the argument invoked. I now accept the correction---that you did not write it---yet it remains a useful illustration that you have offered us of simplistic yet dogmatic medical rhetoric. I'll try to tailor this post---as I did my previous post---for general reading, not to you per se.

The clinic is a facility of medical treatment, and so the clinical is the medical. I'm loosely familiar with the website ScienceBasedMedicine.org, published by a group of physicians opposed to evidence-based medicine (EbM). The group presumes that their own grasp of biology---basic science---and its branch physiology is so enlightened that they know what treatments should be clinical tested to standards of clinical epidemiology, versus and which should be dismissed before testing in clinical epidemiology. They call this approach science-based medicine (SBM). Spouting rhetoric against treatments that have not been subjected to clinical epidemiology, they are practicing faith-based medicine by violating EbM's hierarchy of evidence [Lundberg GD, "Evidence-based medicine or faith-based medicine?", MedGenMed, 2004;6(4), ncbi.nlm.nih.gov/pmc/articles/PMC1480548].

I lack interest in posting at the SBM website, for they appear sectarian and belligerent, seeking to maintain yet expand their own biomedical cult. Biomedicine is the encompassing socioeconomic institution that arose via the 1910 merger, via the Flexner report published by the Carnegie Foundation, of allopathic medicine (American Medical Association), scientific medicine (William H Welch), and biomedicine (The Rockefeller Institute for Medical Research). Biomedicine is mere applied science, the application of snippets of biology---the basic science or pure science---to develop medical technology or technique in the manner commissioned and funded. Preceding America's biomedicine was Germany's biomedical industry, yet this was crushed---relative to America's---by way of World War I (1914-18) and World War II (1935-45), and America's emerged globally dominant.

The SMB group is fighting to cling to the philosophies of the late 19th century when Germany was overtaken by reductionist zeal to purge physiology of vitalism and to reinforce the monomorphist notion of bacteria, which William H Welch, trained in German pathology and bacteriology, spread throughout America---scientific medicine---and this is still the model of today's medical education [Tauber AI, "The two faces of medical education: Flexner and Osler revisited"---section "Laboratory versus bedside", J R Soc Med, 1992 Oct;85(10):598-602, ncbi.nlm.nih.gov/pmc/articles/PMC1293684/?page=2]. As to integrating pure science into the training of medical practice, medical schools fell out of step with biology---and thus its branch called physiology---around 1945 [Arky RA, figure 1, "Abe Flexner, where are you? We need you!", Trans Am Clin Climatol Assoc, 2007;118-96, ncbi.nlm.nih.gov/pubmed/18528492]. In the early 1970s Archie Cochrane's Effectiveness And Efficiency: Random Reflections on Health Services discussed that most medical practices had scant evidence of their effectiveness [Shah HM & Chung KC, "Archie Cochrane and his vision for evidence-based medicine", Plast Reconstr Surg, 2009 Sep;124(3):982-8, ncbi.nlm.nih.gov/pubmed/19730323]. By 1983 historian of medicine Lester King published in JAMA a series of articles acknowledging that medicine was never quite scientific to begin with [King LS, "Medicine in the USA: Historical vignettes, XI, Medicine seeks to be 'scientific'", JAMA, 1983 May 13;249(18):2475-9, jama.ama-assn.org/content/249/18/2475].

Guyatt explains EbM's origins: "In 1981, a group of clinical epidemiologists at McMaster University, led by Dave Sackett, published the first of a series of articles advising clinicians how to read clinical journals. Although a huge step forward, the series had its limitations. After teaching what they called 'critical appraisal' for a number of years, the group became increasingly aware of both the necessity and the challenges of going beyond reading the literature in browsing mode and [on to] using research studies to solve patient management problems on a day-to-day basis.

"In 1990, I assumed the position of residency director of the Internal Medicine Programe at McMaster. Through David Sackett's leadership, critical appraisal had evolved into a philosophy of medical practice based on knowledge and understanding of the medical literature (or lack of such knowledge and understanding) supporting each clinical decision. We believed that this represented a fundamentally different style of practice and required a term that would capture this difference.

"My mission as residency director was to train physicians who would practice this new approach to medical practice. In spring 1990, I presented our plans, for changing the program, to the members of the Department of Medicine, many of whom were not sympathetic. The term [that I] suggested to describe the new approach was 'scientific medicine'. Those already hostile were incensed and disturbed at the implication that they had previously been 'unscientific'. My second try at a name for our philosophy of medical practice, 'evidence-based medicine', turned out to be a catchy one" [Guyatt G, Rennie D, Meade M, Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 2nd ed (New York: McGraw-Hill Professional, 2008), "Preface", p xxi].

EbM hit the worldstage in 'JAMA' in 1992. In 2002 BMJ editor Richard Smith parodied physicians opposed to EbM, alleging it a new religion disempowering physicians to the detriment of patients [CRAP, "EBM: Unmasking the ugly truth", BMJ, 2002;325(7378)-8, ncbi.nlm.nih.gov/pubmed/12493681]. Some complaint can be legitimate only insofar as the sociopolitical manipulation to reduce EbM to its mere mantlepiece, clinical epidemiology (CE), developed in the 1960s by David Sackett, importing epidemiology's statistical methodology into clinical science---the clinical investigation of treatment effects---whose results are published in medical journals. Even EbM and CE---not defining biology, patient choices, or who becomes a patient---are for MD practice.

"Clinical medicine can be complex, and EBM will never provide easy answers to difficult problems, which means that there will always be an art to clinical medicine. As well, EBM is practised in complex, semirational, constantly changing healthcare systems, which sometimes actually establish barriers to the incorporation of evidence into practice" [Can J Clin Pharmacol, 2001;8(Suppl A)A-9A, ncbi.nlm.nih.gov/pubmed/11586371]. Unspoken assumptions---tacit knowledge---operate even in EbM [Theor Med Bioeth, 2009;30(3)-98, ncbi.nlm.nih.gov/pubmed/19548116]. Despite EbM's definition---"an integration of best research evidence, clinical expertise, and patient values"---new areas of knowledge are obstructed by sociopolitical hierarchy in research communities, carriage of institutional power by individuals, and clinician resistance [J Eval Clin Pract, 2008;14(5)-9, ncbi.nlm.nih.gov/pubmed/19018888].

The SBM group refutes EbM, but apparently to continue practicing a romantic myth of scientific medicine, which, versus EbM, is actually vehemence-based medicine, asserting mere volume and stridency of rhetoric as evidence, along with eminence-based medicine: "The more senior the colleague, the less importance he or she placed on the need for anything as mundane as evidence. Experience, it seems, is worth any amount of evidence" [Isaacs D & Fitzgerald D, "Seven alternatives to evidence based medicine", BMJ, 1999;319(7225):1618, ncbi.nlm.nih.gov/pubmed/10600968].

Guyatt and colleagues explain, "EBM is about solving clinical problems. In 1992, we described EBM as a shift in medical paradigms. In contrast to the traditional paradigm of medical practice, EBM places lower value on unsystematic clinical experience and pathophysiologic rationale, stresses the examination of evidence from clinical research, suggests that interpreting the results of clinical research requires a formal set of rules, and places a lower value on authority than the traditional medical paradigm. Although we continue to find this paradigm shift a valid way of conceptualizing EBM, the world is often complex enough to invite more than one 1 useful way of thinking about an idea or a phenomenon.... As a distinctive approach to patient care, EBM involves 2 fundamental principles. First, EBM posits a hierarchy of evidence to guide clincal decisionmaking. Second, evidence alone is never sufficient to make a clinical decision. Decisionmakers must always trade off the benefit and risks, inconvenience, and costs associated with alternative management strategies and, in doing so, consider their patients' values and preferences" [Guyatt, Rennie, Meade, Users' Guides to the Medical Literature, 2008, section "Philosophy of EbM", p 10].

Guyatt and colleagues ask, "What is the nature of evidence in EBM? We suggest a broad definition: any empirical observation constitutes potential evidence, whether systematically collected or not. Thus, the unsystematic observations of the individual clinician constitute one source of evidence; physiologic experiments constitute another source. Unsystematic observations can lead to profound insights, and wise clinicians develop a healthy respect for the insights of their senior colleagues in issues of clinical observation, diagnosis, and relations with patients and colleagues" [Guyatt, Rennie, Meade, 2008, p 10].

As to clinical epidemiology, Guyatt and colleagues indicate, "Our clinical questions have a correct answer that corresponds to an underlying reality or truth. ... Research studies attempt to estimate that underlying truth. [Yet] we will never know what that true impact really is (Table 5-1). Studies may be flawed in their design or conduct and introduce systematic error (bias). Even if a study could be perfectly designed and executed, we would remain uncertain whether we had arrived at the underlying truth" [Guyatt, Rennie, Meade, 2008, p 78]. Large trial size seeks statistical significance to overcome random error if intervention effect is modest. "Truth claims in the medical literature rely heavily on statistical significance testing", but "most physicians misunderstand the underlying probabilistic logic of significance tests and consequently often misinterpret their results", a "near-universal misunderstanding" [BMC Med, 2011;9, ncbi.nlm.nih.gov/pubmed/21356064].

(Meta-analysis pools numerical data from multiple clinical trials and applies statistical methods to discern what outcome remains across multiple trials. Systematic review, which might include but isn't meta-analysis, poses a question, states 'search terms', fields returned articles, states 'selection criteria', and uses 'critical appraisal'---not statistical methods---to interpret clinical research articles. ["Glossary", Cochrane Collaboration, 2010, cochrane.org/glossary])

As explained in 2004, "The difference that needs to be marked is not that before EBM people did not use the evidence. Rather, the real failure was the lack of a framework and a set of rules to use the evidence in a systematic and explicit fashion. Seen in this way the current fight around EBM and its nature could be advanced by moving the discussion from principles [of what is or isn't evidence] to a more pragmatic perspective where the attention is centered on a 'better use of evidence in clinical decisionmaking'. ...

"Struggling for a better use of evidence in medicine also has other important advantages. It challenges the paternalistic and authoritarian nature of much medical practice and helps increase awareness that---even when based on scientific methods---there is a selective and structural imbalance in the nature of the evidence that is available, because that evidence is skewed and biased toward therapeutic versus preventive interventions, and toward simple pharmacological versus complex behavioural/social care. Acquiring critical appraisal skills---one of the most important tenets of the EBM movement---is the necessary (though not sufficient) and best immunisation against ignoring that there is a structural imbalance in the research agenda, an imbalance that should be overcome in order to make fully available the sort of evidence that is needed to provide effective and comprehensive healthcare to all patients.

"There is no doubt that EBM does not, and cannot, answer all the epistemological [questions]"---what we can know, how we can know it, and limits of knowledge---"and practical questions surrounding the practice of medicine. On the contrary, it is important that expectations of EBM are appropriate in order to prevent conceptual and practical mistakes. ... Culturally, its anti-authoritarian spirit is important in increasing the participation of different stakeholders and the opportunity for a multidisciplinary approach to healthcare problems.

"It is clear that, thus far, the potential of EBM has not been fully exploited, and that views of it which are too narrow have created avoidable confrontations with those who may be concerned that an 'EBM dominated view' can do more harm than good. As efforts by methodologists have chiefly focused on how to design, conduct, and interpret studies aimed at assessing the efficacy/effectiveness of drugs, EBM is today mostly 'evidence based therapy' with robust tools---that is, randomised controlled trials---especially for assessing the worth of relatively simple interventions. The fact that we currently have limited ability to reliably assess complex interventions, preventive care in general, and diagnosis as well as prognosis, should be seen not only as the result of the greater intrinsic complexity of these areas but also as the consequence of lower intellectual investments. This is a reflection, in turn, of the more limited commercial interests at stake here" [Liberati A & Vineis P, "Introduction to the symposium: What evidence based medicine is and what it is not", J Med Ethics, 2004;30(2)-1, ncbi.nlm.nih.gov/pubmed/15082801].

In 2010 one philosopher of science indicated, "Obviously medicine should be evidence-based. The issues lie in the details: what exactly counts as evidence? ... When it comes to these details, the [EbM] movement has got itself into a mess.... In order to start to resolve this mess, we need to go 'back to basics'---and that means turning to the philosophy of science" [Worrall J, "Evidence: Philosophy of science meets medicine", J Eval Clin Pract, 2010;16(2)-62, ncbi.nlm.nih.gov/pubmed/20367864]. Individuals who try to turn EbM into a framework of physiological epistemology---what we can know, how we can know it, and the limits of knowledge as to physiology---as well as the SBM medicine group, too, promote pseudoscience. They seek to set up experiments only to confirm their predictions, and yet assert proved theory as to physiology. This approach to scientific method is called verificationism, the substrate of the philosophy of science called positivism, which philosopher of science Sir Karl Popper overturned decades ago and described as pseudoscience [Int J Nurs Pract, 2007;13(6)-30, ncbi.nlm.nih.gov/pubmed/18021160].

Not testing theory, clinical science tests a positive hypothesis---hypothetical events whose predicted success is derived from the theorised natural law---yet confirmation of the hypothesis remains explainable by over one theory. So no theory was actually proved, in the positivistic approach, to be the sole accurate theory. This is a philosophical error called overdetermination, overstepping the demarcation of the domain of science, and thus positivists exit the domain of science and propound metaphysics, rather, the branch of philosophy concerning traits of the natural world beyond those open to test and observation. Pure science, for instance physiology, in order to test theory, tests a null hypothesis---an impossibility according to the theorised natural law---for refutation and thus can overturn a theory. If it's overturned, a new theory of natural law is posited. Any positive results simply establish apparent probability. It is called induction when one observes particulars and infers general law---seeming likely to the observer---whereas deduction is applies general law to particulars in such a manner where the particulars are necessarily true.

As my previous post cites, the theories of the SBM group as to microorganisms---their notions of general law---in the human body have been nullified countless times in basic research. Still, the SBM group insists to deduce from these long-nullified laws as if they were positively proved facts, yet they were merely induced via severely limited testing equipment. The SBM group ignores and denies this. So they operate in merely a sociocultural paradigm of philosophical error [Skurvydas A, "Paradigm errors in the old biomedical science", Medicina (Kaunas), 2008;44(5)-65, ncbi.nlm.nih.gov/pubmed/18541951]. They use rhetoric and deception to establish their medical ideology as putative scientific facts and truths ["Paul Feyerabend: Science and the anarchist", Science, 1979 Nov 2;206(4418):534-7, dx.doi.org/10.1126/science.386510]. There are other individuals, not this SBM group, trying to give medicine a scientific footing [Hopayian K, "Why medicine still needs a scientific foundation: Restating the hypotheticodeductive model---part one", Br J Gen Pract, 2004 May;54(502):400-1, ncbi.nlm.nih.gov/pubmed/15372723] [Hopayian K, "Why medicine still needs a scientific foundation: Restating the hypotheticodeductive model---part two", Br J Gen Pract, 2004 May;54(502):402-3, ncbi.nlm.nih.gov/pubmed/15372724].

Perhaps later I'll offer my views on vitamin D biology, the Marshall Protocol, versus other approaches, and hair loss.

Don't think it's entirely the fault of those who would ignore subtle evidence, it's not a simple subject. The idea of looking at this subject in standard terms, our current "understanding" of biology is absurd. The idea of bacteria changing based on environment and interaction makes an infinitely complex math equation that is severly non-linear, the change of bacteria (or at that the flourishing of bacteria) makes the bacteria themselves a part of the interaction that could allow them to get up to trouble in the first place.

a
Don't think it's entirely the fault of those who would ignore subtle evidence, it's not a simple subject. The idea of looking at this subject in standard terms, our current "understanding" of biology, is absurd.

Biology, which has a branch called microbiology, has overturned such simplistic notions of bacteria over 100 years ago, and has continually reinforced this position---that a classical bacterium is merely one variant of a pleomorphic microorganism and that many of the other variant forms normally reside in cells of healthy animal hosts---in every decade since. In microbiology, these are standard terms decades old. The mere applied science called medical microbiology---retaining long nullified principles of 19th century bacteriology in medical education---is not the pure science called microbiology. On Proal et al's paper versus the science-based medicine group's response to it, this is a stark contrast between pure science versus pseudoscience.

Naively characterizing this as a matter of ignoring "subtle evidence" illustrates the power of medical dogma to utterly confuse the public about what is biology and what is medical ideology. Whether it's entirely the fault of particular physicians for being ignorant of microbiology is different from whether it is their place to assert omniscience in microbiology while actually mocking microbiology and promulgating misconceptions under the banner of putative scientific credentials.

If I have misinterpreted the gist of the post that I've replied to here, I can scarcely decipher its import other than blurring the answer to whether microorganisms do reside systemically in host cells and in host fluids. Perhaps the science-based medicine group, rather, could use some of the caution about "subtle evidence". There is a difference between being ignorant in a particular branch of science versus proclaiming irrefutable omniscience in every branch of biology. We are all ignorant of some things and even a scientist in one branch can be virtually illiterate in another branch [Levy-Leblond JM, "About misunderstandings about misunderstandings", Public Understand Sci, 1992 Jan;1(1)-21, pus.sagepub.com/content/1/1/17.extract]. Taking this crusade of asserted supreme scientific knowledge even so far as opposing in medicine the practice of evidence-based medicine, because the science-based medicine group has its own ideas for proper medicine while the science-based medicine group jeers at other clinicians for sharing mainstream microbiology with the public, is, in my view, egregious.

"Bertolt Brecht's Galileo (Vesey, 1963) states, 'The chief cause of poverty in science in imaginary wealth. The chief aim of science is not to open a door to infinite wisdom but to set a limit to infinite error'. The stance of science is doubting, uncertain, and skeptical; it is this which offers the possibility of 'setting a limit to infinite error'" [McCormick J, "Scientific medicine: Fact or fiction? The contribution of science to medicine"---section "Science as a way of thinking", Occas Pap R Coll Gen Pract, 2001 Jul;(80):3–6, ncbi.nlm.nih.gov/pmc/articles/PMC2560978]. Why one would presume to formalise in mathematical equations---whether linear or nonlinear---putative universal laws of microorganism behavior and interaction with hosts in the first place remains a mystery to me. The science-based medicine group would probably do better to educate the public about the difference between drug marketing---impelling a national craze reducing humans to mathematical models of serotonin levels---versus a medical hypothesis that over the span of decades remained unconfirmed in the literature [Lacasse JR & Leo J, "Serotonin and depression: A disconnect between the advertisements and the scientific literature", PLoS Med, 2005 Dec;2(12):e392, ncbi.nlm.nih.gov/pubmed/16268734]. This is not a subtle difference, either.

Exhibiting pleomorhism and multicellular behavior, bacteria exhibit far more plasticity than do humans. Microorganisms exhibit consciousness, intelligence, and learning, and arrange themselves into animal-like formations applying networks that operate like nerves [Baluska F & Mancuso S, "Deep evolutionary origins of neurobiology: Turning the essence of 'neural' upside-down", Commun Integr Biol, 2009;2(1):60-5, ncbi.nlm.nih.gov/pubmed/19513267]. Before trying to form any sort of mathematical model, first it remains to be quite acknowledged---in allopathic medical eduction and in the biomedical industry and therefore in public education---whether and where the microorganisms even exist. Voluminous findings reported in biology and even medical journals have indicated for roughly 150 years their existence within animal systems and residing in animal cells [Kendall AI, "The filtration of bacteria: Studies in bacterial metabolism CIII", Science, 1932 Mar 18;75(1942):295-301, dx.doi.org/10.1126/science.75.1942.295] [Klieneberger-Nobel E, "Filterable forms of bacteria", Bacteriol Rev, 1951 Jun;15(2)-103, ncbi.nlm.nih.gov/pubmed/14847983].

Smells like SPAM

Spam or not, very good posts he's making. Sadly what he's saying is going to be lost save for a couple users, what he's saying (and perhaps could not be said in any other way) is going to get lost in the symbolic mess of my ex's panties. Way too much going on down there.

a<r wrote:Spam or not, very good posts he's making. Sadly what he's saying is going to be lost save for a couple users, what he's saying (and perhaps could not be said in any other way) is going to get lost in the symbolic mess of my ex's panties. Way too much going on down there.

I am still trying to get through his posts lol. It's not something I'm happy just skim reading, I like to look into all of the references as well.

I am also surprised someone this articulate would bother registering just to post this.

UsernameK, feel free to post your theories on vitamin D and hair loss too.

abc123 wrote:

I am also surprised someone this articulate would bother registering just to post this.

Sport?

I couldn't care less why he's posting really. The site has been far too slow lately, preoccupied with a lot of trivia, Hoppi, etc.

It's good that this subject is being brought back up because no matter what we're going to end up coming back to this subject if we're to untangle the mysteries of disease.

I agree w/y action.


But posts from that user are meaningless, actually what's his point? Pure rambling and copy-paste.

And I'm far from being close minded... yes I can listen to what other have to say.

I hope more people brings useful insight and well thought theories to the table, we need them.

There's so many points in those posts that it really doesn't seem like there's a point, but what I take away from it most strongly (besides its literal assertions) are that the representation of the information that does certainly exist regarding pleomorphism and bacteriology, is poor at best.

Bump, UsernameK where did you go? Can you post your theories on d and hairloss?

I know the Marshall Protocol is not the point of the argument here, but people seem to be bringing up points from his theories, so perhaps this might explain some criticisms of his protocol. Warning: its long

http://stuff.mit.edu/people/london/universe.htm

liverock wrote:I know the Marshall Protocol is not the point of the argument here, but people seem to be bringing up points from his theories, so perhaps this might explain some criticisms of his protocol. Warning: its long

http://stuff.mit.edu/people/london/universe.htm

This was posted before.

ABC brought more that enough evidence in favor of D3 that wasn't/couldn't be refuted. That's enough for me. I can accept that for a few conditions, D3 might be contraindicated, but you also have to give evidence for that.

New and complex theories ARE NOT automatically true. Seems that a lot of people are sold to them because of those characteristics.

Quite interesting that no one further discussed the mysterious usernameK's three posts, which were quite something. I wonder what kind of health approaches he would have suggested.

Biofilms, l-form bacteria, 90 percent of cells in the human body are microorganisms; and they are constantly changing. Then I am not I, am I? So much for vanity of self!

9rugrats5 wrote:Quite interesting that no one further discussed the mysterious usernameK's three posts, which were quite something. I wonder what kind of health approaches he would have suggested.

Biofilms, l-form bacteria, 90 percent of cells in the human body are microorganisms; and they are constantly changing. Then I am not I, am I? So much for vanity of self!

Exactly!

" 'I' is another. If brass wakes up a bugle, it's not its own doing. This is
clear to me: I'm a witness at the flowering of my own thought. I watch it and listen to it.
I draw a stroke of the bow, and the symphony makes its stir in the depths, or comes upon
the stage in a leap."

Rimbaud


"The minute you or anybody else knows what you are you are not it, you are what you or anybody else knows you are and as everything in living is made up of finding out what you are it is extraordinarily difficult really not to know what you are and yet to be that thing. "

Gertrude Stein

usernameK was talking about pleomorphism. This first came out in 1942 and is a good treatise on the subject:
http://www.whale.to/a/b/pearson.html

Here is a short blog post on the subject, which got 58 responses. Apparently this concept is still very controversial.
http://personalliberty.com/2008/11/17/the-germ-theory-of-disease/