This month yet another paper was published whose results confirm that the Petri dish is a thing of the past. The study, which was published in BMC Microbiology, used a series of molecular techniques to identify the species of biofilm bacteria present inside several different kinds of wounds.

Bioflims are formed when a complex and varied group of bacteria aggregate together inside a protective and adhesive protein matrix. The bacteria inside a biofilm cooperate to promote their own survival and the chronic nature of an infection. While dentists have long realized that bacteria in the mouth often reside inside biofilms – they form much of the goo that they remove from teeth – researchers are just starting to investigate bioflim communities that form in other areas of the body.

Since few studies have performed extensive surveys of the bacterial populations within different types of chronic wound biofilms, the BMC team, comprised of individuals from the United States Department of Agriculture, the Medical Biofilm Research Institute in Texas, and the Center for Biofilm Engineering at Montana State University, used several advanced molecular techniques to survey the major populations of bacteria in the pathogenic biofilms of three types of chronic wounds:

• diabetic food ulcers
• venous leg ulcers
• pressure ulcers

The researchers used several different molecular methods – ribosomal amplification and cloning, Sanger sequencing (FRACS), partial ribosomal amplification, density gradient gel electrophoresis (DGGE), and Sanger sequencing (PRADS) – to provide a comprehensive survey of microbial populations.

Together, these molecular techniques revealed that some specific populations of bacteria were evident in the biofilms of all chronic wound types. These bacteria included Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia.

But there were also marked difference between the bacterial populations in each of the wounds. For example, in pressure ulcers, 62% of the populations identified were from a class of bacteria called obligate anaerobes – bacteria that do not require oxygen for growth and may even die in its presence.

In fact, every wound that the research team tested with new molecular technology was also tested for the presence of bacteria using traditional based culture methods. When the results of molecular analysis were compared to the bacteria obtained using these traditional methods, the team found that culture methods were only able to correctly identify the primary bacterial population in one wound type.

“Here we show that culturing failed to identify major contributing populations, especially strict anaerobes, within the given wound types,” state the team, “Standard culturing techniques are inherently biased as they only examine only the 1% of all microorganisms which are able to grow fairly rapidly in pure culture.”

The team also commented on the fact that it takes several days for bacteria grown by culturing methods to be identified, whereas molecular methods such as PCR can typically be completed within several hours. They also stress the fact that some forms of bacteria can simply not grow under the conditions required for standard cultivation, stating that “In addition, certain of the isolates that we have shown to be primary populations within a wound type may never be cultured in the laboratory due to reduced metabolic activity, obligate cooperation with other bacteria, requirements for specialized nutrients, or growth in specific environmental conditions.”

They also argue that molecular methods, unlike culture methods, have more potential to provide quantitative data, stating “arguably, we have shown that molecular methods will allow populations residing within biofilms to be more fully characterized.”

Furthermore, they make it clear that doctors will greatly benefit by knowing the exact composition of bacteria that each of their individual patients harbors. “The continued development of molecular methods may lead to vastly improved tools or diagnostics that will identify and provide quantification of the diverse species potentially present in chronic wounds thereby allowing physicians to better tailor their treatment to each patient’s unique pathogenic biofilm populations,” states the team.

Thus, much like other teams who are using molecular methods to detect bacteria, the researchers make an urgent call for the standardized use of improved diagnostic methods. Not only that, but they also hope the results of their study might actually “foster the pioneering, and development of new diagnostic tools.”

One of the study’s findings that also bears pertinence to the Marshall Protocol is the fact that the bacterial species Staphylococcus was found inside all chronic wound types. Two of the other largest studies to date to seek bacteria using molecular technology (one which looking at bacteria removed prosthetic joints, and another that looked at bacterial populations in patients with Cystic Fibrosis) also found Staphylococcus to be a common pathogen in their samples. Since minocycline is one of the antibiotics that best targets Staphpylococcus, these findings suggest that the decision to use minocycline as the base antibiotic for the Marshall Protocol was well warranted.

Also interesting is that researchers at the University of Turku in Finland just released the results of a study which found that infants who harbor the Staphylococcus aureus are more likely to become overweight and obese later in life. Again, this suggests that Staphylococcus is a common cause of Th1 symptoms, and that obesity should respond to the MP antibiotic regimen that allows the bacterial species to be killed.

The team analyzed 490 skeletons from a London cemetery for Black Death victims – the name given to those people who succumed to the plague epidemic of 1347 to 1351. Black Death – named after the black spots the bubonic form of the plague caused on the skin – was one of the deadliest recorded in human history, killing about 75 million people, according to some estimates, including more than a third of Europe’s population.

Experts have long believed that the Black Death killed indiscriminately regardless of age, sex or level of health because it was so virulent. But anthroplogists Sharon deWitte and James Wood, who led the Penn State team, have demonstrated that the infection did not affect everyone equally.

The anthropologists found that while many perfectly healthy people certainly were cut down, those already in poor health prior to the arrival of the plague were more likely to have perished.

“A lot of people have assumed that the Black Death killed indiscriminately, just because it had such massive mortality,” states DeWitte. “People already in poor health often are more vulnerable in epidemics. “But there’s been a tradition of thinking that the Black Death was this unique case where no one was safe and if you were exposed to the disease that was it. You had three to five days, and then you were dead.”

DeWitte analyzed skeletons unearthed from the East Smithfield cemetery in London, dug especially for plague victims and excavated in the 1980s, for bone and teeth abnormalities that would show that people had health problems before they died of plague.

She found such abnormalities in many skeletons, suggesting these people had experienced malnutrition, iron deficiencies and infections well before succumbing to the Black Death.

Today we understand that, due to the chronic nature of bone deterioration and dental problems, these infections were almost certainly caused by L-form bacteria.

Bone loss results after L-form bacteria create substances that block the Vitamin D Receptor – preventing it from transcribing an enzyme that keeps the level of the hormone/cytokine 1,25-D in check. As 1,25-D rises above a certain range (around 43 pg/ml), it stimulates bone osteoclasts, or cells that remove minerals from the bone. Stimulated osteoclasts dissolve bone material, causing it to be reabsorbed into the bloodstream – leading to osteoporosis and osteopenia.

We are also familiar with the “anemia of chronic disease”, or the fact that people with Th1 disease are frequently deficient in iron. This deficiency is the direct result of the fact that L-form and biofilm bacteria secrete iron-binding complexes called siderophores that remove iron from host proteins, making it available for use by the pathogens.

Futhermore, tooth decay is almost certainly impacted by L-form bacteria, as a wide range of treatment resistant bacteria, including those that persist in bioflims, have been detected in the mouth, not to mention the fact that dental immunopathology and subsequent improvement of dental issues is common among patients on the Marshall Protocol.
Thus it comes as no surprise that DeWitte and team found that the proportion of people with such signs of Th1 disease in the cemetery, compared to those who appeared to have been of robust health before the epidemic, indicate that Black Death was somewhat selective in who it killed.

“The Black Death was highly virulent and undoubtedly killed many otherwise healthy people who would have been unlikely to die under normal-mortality conditions,” they wrote. But people already in poor health were more likely to die.”

Those people in poor health were certainly immunosuppressed, thanks to the fact that as L-form and other stealth bacteria accumulate, the pathogens produce substances that block the VDR, causing the innate immune system to become increasingly compromised. It’s no wonder their lives were claimed by the Black Death, just as today people with Th1 disease are easy victims for the HIV virus.

Several months ago, two international trials aimed at testing an experimental AIDS vaccine were stopped after it became clear that the vaccine did not prevent infection with the AIDS virus. The trials were conducted in the United States, Peru, Brazil, Dominican Republic, Haiti, Jamaica, Australia and South Africa. Today, the researchers conducting the trial are faced with another problem. Earlier this month they reported “worrying” indications that the thousands of people who received the vaccine are now at greater risk for infection. They have already begun counseling volunteers about the fact that they could be at higher risk for acquiring HIV – the fatal and incurable virus that causes AIDS.

To test vaccines and new drugs, researchers always aim for what are called placebo-controlled, double-blinded trials. This means that neither the researchers nor the volunteers know who gets a placebo and who gets an active ingredient – the goal being to minimize any biases in determining whether the treatment works.

But Merck and the academic researchers who conducted the vaccine trial are planning to “unblind” the study – meaning that participants will find out who got an active shot and who got a dummy injection.

“All study volunteers will be encouraged to continue to return to their study sites on a regular basis for ongoing risk reduction counseling and study-related tests,” the researchers said in a statement.

Were the vaccines contaminated with L-form bacteria? It’s quite probable. Especially since L-form bacteria are now known to create ligands that bind and block the Vitamin D Receptor (VDR). Since the VDR controls the activity of the innate immune system and the antimicrobial peptides, people who acquire L-form bacteria begin to suffer from immune dysfunction – much like the study participants in the trial described above.

Ensuring that the vaccines, injections, and blood transfusions we receive are not contaminated by L-form bacteria only strengthens the reality that the pathogens need to be brought into the spotlight immediately. In the meantime, people such as those unlucky enough to receive the actual vaccine in the Merck trial will continue to get sick after taking a measure ironically aimed at preventing disease.

In the case of the more commonly studied classical bacterial forms, the creation of a septum, or a wall separating two cavities or spaces, is an essential requisite for cell division. The main structure of a septum is composed of chains of amino acids made from the substance peptidoglycan. In fact, classical bacterial divide only after a double layer of peptidoglycan is laid down in the middle of the cell. The septum subsequently splits – forming two daughter cells. The septum itself is formed by several different proteins that unite to form a ring-like complex.

Interestingly, according to the standard view of L-form bacteria, the pathogens lack peptidoglycan and thus do not form a septum when they divide. This belief stems from the work of prominent L-form scientist Louis Dienes who, when looking at the pathogens under the electron microscope during the 1930s, saw that, in contrast to classical bacteria, they are not surrounded in peptidoglycan.

But if Dienes’ observation is correct, then how are L-form bacteria able to reproduce? “A major enigma raised by L-forms is how they manage to free cell division of its normal dependence on peptidoglycan synthesis,” states Casadesus. “This question has in fact puzzled the experts on cell division over the decades.”

It turns out that the classical definition of L-forms as consistently cell-wall-less bacterial variants may need a revision in order to accommodate recent observations by Richard d’Ari and coworkers at the Institut Jacques Monod in Paris.

Pictures of the E. Coli L-forms cultured by D’Ari’s group.

The team recently published the results of a study demonstrating that in order for classical forms of bacteria to be converted to the L-form – a feat usually accomplished by exposing the classical forms to one of the beta-lactam antibiotics – some components of a cell wall are indeed formed at the time of division.

The researchers used the beta-lactam antibiotic cefsulodin to convert classical cells of E. coli into its L-form. They proceeded to investigate which (if any) of the known E. coli cell division functions were required for L-form propagation. But how? The team grew L-form mutants, each without a specific enzyme needed to create a different protein that makes up the E. coli septum used for division. These proteins included D-glutamate, diaminopimelic acid, and muramic acid. Interestingly, when the synthesis of each of these cell wall proteins was blocked, the mutant L-forms were unable to divide or propagate.

After performing further biochemical analyses on his L-forms, D’Ari found that the cefsulodin-induced L-forms do actually contain peptidoglycan – about 7% of what their classical counterparts would harbor. This amount of peptidoglycan is far too small to allow them to form cell walls that would span their entire circumference, but the researchers believe it is just enough peptidoglycan to allow for the creation of septums when the L-forms need to divide.

The bottom line: L-form bacteria may indeed form small, temporary cell walls when they divide. “L-forms retain the ability to synthesize small amounts of peptidoglycan and this residual synthesis is essential for their propagation,” states Casadesus. Whether D’Ari’s findings will apply to all species of L-form bacteria remains to be seen.

Diameter distributions of the E. Coli L-forms in all 248 cells were measured.

Interestingly, Casadesus pauses frequently throughout his discussion of the bacterial cell wall to discuss how L-form bacteria are likely to be the pathogens responsible for causing many illnesses of “unknown cause.” “Of special interest for human health is the formation of L-forms as a consequence of specific antibiotic treatments, and the potential involvement of L-forms in persistent and relapsing infections,” states the scientist.

In fact, Casadesus seems quite convinced that L-form bacteria are responsible for causing a wide array of chronic diseases. One can’t help but wonder if part of this author’s impetus for writing was to, once again, remind the medical community of the key role that L-form bacteria play in causing disease.

According to Casadesus, the idea that L-forms might underlie chronic and relapsing bacterial infections is supported by:

1. studies which show that the pathogens are spared from the killing actions of antibodies which act only on bacteria that possess complete cell walls.

2. The fact that the pathogens can persist inside white blood cells of the immune system called phagocytes and perhaps emerge in more virulent forms if a patient becomes immunocompromised.

3. The reality that L-forms can survive for long periods of time within the macrophages (white blood cells), explaining “both the difficulty of showing the presence of L-forms in human blood cultures and the failure of certain antibiotic treatments.”

Right on, Dr. Casadesus! Luckily, biomedical researcher Trevor Marshall has created a treatment that can kill L-form bacteria despite the survival mechanisms presented above – meaning that for the first time in history patients are recovering from a wide array of chronic diseases.

Returning to the subject of bacterial cell walls, Casadesus concludes, “Not only has D’Ari’s work provided novel support to the idea that peptidoglycan synthesis is absolutely needed for cell division, but it has also corrected an old, insufficiently grounded dogma.”

Casadesus’ effort to rethink dogma is admirable. Let’s hope it’s the first of many, many more to come that will gradually wear away at the conventional wisdom surrounding so many aspects of chronic disease – finally ushering us into an era that embraces a new understanding of the immune system and the pathogens making us sick.

New insights into culturing L-forms

And yet, D’Ari’s insights into the characteristics of L-form bacteria do not stop at cell wall division. In what is also groundbreaking work, his research team was also able to come up with a new, more effective protocol for culturing L-form bacteria in the first place.

In a review article published in the Journal of Bacteriology that also discusses D’Ari’s L-form research, Dr. Kevin Young at the North Dakota School of Medicine describes how other research teams have, up until this point, spent long hours in the lab generating L-forms by “incubating the cells in complex media in the presence of high concentrations of penicillin, growing them as embedded colonies in a specific percentage of agar, and passaging them multiple times for several years,” D’Ari’s team has broken new ground by discovering a way to culture L-forms using a new advanced technique.

According to Young, the novel procedure is “extremely straightforward” and centers on incubating the pathogens for only one night in the presence of the antibiotic cefulodin.

D’Ari’s team developed their procedure by studying the substances that play a role in the process of L-form transformation. According to D’Ari, in the lab, classical forms of bacteria transform into the L-form only if they are denied the ability to form a normal cell wall. The beta-lactam antibiotics work towards this end by blocking the creation of proteins known as penicillin-binding proteins (PBPs) – the proteins responsible for forming the cross-linked chains that compose a proper cell wall. When the ability of the PBPs to create a full cell wall is blocked, “the cells become spherical, osmosensitive [sensitive to water], and heterogeneous in size” – in essence they become L-form bacteria.

However, there are several different PBPs, and one of D’Ari’s most important discoveries is that in order to most effectively create L-forms, only some, and not all PBPs must be inactivated at the time of formation. For example, when creating E. coli L-forms, PBPs 1a and 1b should be inactivated, but PBP 3 and PBP 2 should remain active if the pathogens are to grow correctly.

A chart showing the activation and inactivation of certain PBPs.

Unfortunately, several of the beta-lactam antibiotics that researchers have used to grow L-forms in the past (including penicillin) inactivate ALL the PBPs. That means that in the future, it will be of extreme importance for L-form researchers to work with an antibiotic (such as cefulodin) that controls the activity of the PBPs in the correct manner. D’Ari’s new procedure “finally achieves a proper balance between the set of reactions (involving PBPs) to be inhibited versus those that must be retained,” states Young.

This is big news. Looking back, it’s not hard to understand why, without these recent insights, researchers trying to create L-forms often used the wrong antibiotics, forcing them to resort to using much more complicated and time-consuming laboratory procedures in order to create the pathogens. One of the major reasons behind why L-form research has often been marginalized is because, over the past century, few scientists have possessed the patience or the knowledge to use such complex culturing techniques. But now that the process of creating L-forms has been streamlined, perhaps more microbiologists will be enticed to study these pathogens in more detail.

The history of L-form research is also haunted by scientists who tried and failed to culture the pathogens, because the laboratory methods used to grow them were so complicated. For the most part, instead of acknowledging possible errors, these researchers chose to explain the failure of their experiments by simply concluding that there were no L-form bacteria in their samples. This caused many researchers to miss the connection between L-form bacteria and a variety of chronic diseases and goes a long way towards explaining why, even today, many doctors and researchers are not even aware that L-form bacteria can exist within the human body.

Now that we know more about the exact methods needed to successfully grow L-forms, errors in cultivation should become much less common, meaning that perhaps awareness of these pathogens and the diseases they cause will also grow.

“This [D’Ari’s work] should place the investigation of L forms on a much firmer foundation and should revive interest in, and reinvigorate the study of, this interesting mode of prokaryotic existence,” states Young.

These findings also sparked my interest for another reason. If it holds true that in order for L-form bacteria to form from classical bacteria, some of the PBPs must be inactivated, could scientists in the future create drugs that work to keep all PBPs active, thus maintaining a stable cell wall that prevents L-form formation? After all, the Marshall Protocol effectively kills L-form bacteria and stops their ability to replicate once they have formed, but the key to truly quelling illness will be to stop these bacteria from being created from classical forms in the first place. Blocking inactivation of the PBPs seems like a tantalizing prospect to slow or stop the formation of L-form bacteria in the first place….at least in my mind! Whether this will actually prove possible remains to be seen.

The wear and tear created by the inflammatory response plays a large role in generating the stress and tissue damage that leads to old age.

In a 2006 paper in the Journal of Immunity and Aging, Italian researcher Sergio Giunta argues that inflammation and aging are intricately connected, to the point where the term “Inflammaging” has been coined “to explain the now widely accepted phenomenon that ageing is accompanied by a low-grade chronic, systemic up-regulation of the inflammatory response and that the underlying inflammatory changes are also common to most age-associated diseases.”

Essentially, the wear and tear created by the inflammatory response plays a large role in generating the stress and tissue damage that perpetuate old age and eventually death. Central to this response? According to Giunta, the release of cytokines, or proteins that generate pain and fatigue.

Although Giunta attributes this release of cytokines to the effects of “autoimmune” disease, those of us familiar with Marshall’s research and the emerging understanding of the role that bacteria play in chronic disease realize that, in reality, the cytokine release and subsequent persistent inflammation observed in inflammatory disease is likely the result of infection with a chronic intraphagocytic metagenomic microbiota (often referred to as the Th1 pathogens).

“We have shown much chronic inflammation results from the body’s innate immune response [to the Th1 pathogens], and we agree it seems likely that ‘Inflammaging’ may also result from this same pathogenesis,” Marshall argues in a letter published in response to Giunta’s article. “Clearly we still have a lot to learn about the processes which society categorizes as ‘aging,” argues the biomedical researcher.

Since the Th1 pathogens are found nearly everywhere in our environment, everybody picks up the chronic bacterial forms as they grow older; which species one acquires is largely related to one’s unique infectious history. As people accumulate the Th1 pathogens, many of them create substances that dysregulate the Vitamin D Receptor, thus disrupting several of the intricate feedback pathways that keep the levels of the two vitamin D metabolites (25-D and 1,25-D) in the correct range. 1,25-D goes up, and in the process, downregulates the level of 25-D in the body. Thus, a low level of 25-D is not a sign of “deficiency” but rather a strong indication that a person harbors a significant number of the Th1 pathogens.

If you were to graph the population’s 25-D levels on one axis and age on the other, the resulting graph would show that as a whole, the level of 25-D in the population drops steadily after age 40 – a clear indication that increasing age is correlated with a higher Th1 bacterial load. “Something is happening, even during ‘healthy aging’, that we really ought to understand a little more about,” says Marshall.

Not to mention the fact that as people grow older they increasingly succumb to diseases caused by the Th1 pathogens. “Our research points towards Th1 inflammation, the innate immune response to intraphagocytic pathogens, as being the cause of so many “diseases of the aging,” ranging from atherosclerosis, cardiomyopathy and arthritis through to many neurological conditions, and even to dementia,” states Marshall.

Stem cells

Bone marrow stem cells

Many of the cells damaged by cytokines are stem cells – cells that act as a repair system for the body by replenishing other more specialized cells. But as people age, stem cells often lose their ability to repair and heal.

Interestingly, there is a high probability that the Th1 pathogens may be able to infect stem cells. “The key consideration is whether the Th1 bacteria infect stem cells,” says Marshall. Dr Emil Wirostko of Columbia University, one of the foremost experts on chronic bacterial forms, died before he could publish on the subject. But according to his colleagues, Wirostko believed persistent bacterial forms are able to infect stem cells.

This scenario begs the question – do stem cells lose much of their ability to heal and repair due to the increasing load of Th1 pathogens that everybody accumulates over a lifetime?

Indeed, since the Th1 pathogens are intraphgocytic (they are able to survive inside the nuclei of cells) they can likely interfere with the processes of transcription and translation as well as hamper DNA repair mechanisms. “The body has a number of redundant repair mechanisms,” states Marshall. “Actually I should use the word complementary as that is a better description. These defense mechanisms are affected by the pathogens, as evidenced by accelerated aging of folks with Th1 diseases.”

Marshall describes how at a recent conference on Aging at the University of California at San Diego, he heard a presentation by a group of German researchers who had been studying the use of a patient’s own stem cells to repair heart tissue after a heart attack. Interestingly, the team discovered that people who had suffered a heart attack – an event which is most likely caused by certain species of the Th1 pathogens in the heart and blood vessels – possessed stem cells which were only about half as effective at repairing the heart tissue as stem cells transplanted from healthy 20 year-old males. This supports the view that infected stem cells lack many of the healing properties maintained by their healthy counterparts. “It wasn’t a surprise to me,” says Marshall. “Although it was a big surprise for the researchers…”

Telomeres

At both ends of every chromosome are telomeres made up of DNA base pairs, some of which are lost each time the cell divides.

New research suggests that the Th1 pathogens may also affect the aging process in ways not connected to the inflammatory response, namely by affecting sequences of DNA known as telomeres.

Our genes carry inherited blueprints of DNA sequences that determine our characteristics. Inside the center or nucleus of a cell, genes are located on twisted, double-stranded molecules of DNA called chromosomes. At both ends of every chromosome are stretches of DNA called telomeres – regions of highly repetitive DNA that essentially function as disposable buffers. These regions are of great importance because every time a cell divides, a small part of the DNA sequence at both ends of a chromosome is lost in the process – meaning that if telomeres didn’t exist, the main part of the chromosome – the part containing genes essential for life – would get shorter with each division.

Think of telomeres as the plastic tips on both ends of a shoelace. The plastic ends exist so that if the end of a shoelace gets damaged, shortened, or frayed, the soft cloth-like material that makes up the bulk of the shoelace will remain protected.

An enzyme named telomerase is able to add back bases to the ends of telomeres. Thus, in young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, the level of telomerase in the cell decreases, so the telomeres grow shorter and the cells age. When they get too short, the cell no longer can divide and becomes inactive or dies – meaning that the length of a person’s telomeres plays a role in how quickly they will age and eventually die.

Geneticist Richard Cawthon

Geneticist Richard Cawthon and colleagues at the University of Utah found that when people are divided into two groups based on telomere lengths, the half with longer telomeres lives five years longer than those with shorter telomeres – suggesting that if the people with the shorter telomeres could increase their telomere length to that of the people with longer telomeres, they could live five years longer.

In human blood cells, the length of telomeres ranges from 8,000 DNA base pairs at birth to 3,000 DNA base pairs as people age and as low as 1,500 in elderly people. (An entire chromosome has about 150 million base pairs.) Each time a cell divides, the average person loses 30 to 200 base pairs from the ends of that cell’s telomeres.

The fact that different people lose telomere base pairs at different rates suggests that factors other than simple cell division also impact how rapidly telomeres shorten. Increasing evidence is pointing to the fact that the Th1 pathogens may play a significant role in determining the rate at which these sequences of DNA are lost, thus revealing yet another way in which the chronic bacterial forms may impact the aging process.

For one thing, the DNA of pathogens has been found integrated with telomere DNA. And as Marshall describes, if pathogens do directly alter our DNA, then the weakened DNA at the ends of telomeres provides some of the easiest genetic material for them to mutate.

A number of studies have revealed that people who suffer from diseases likely to be caused by the Th1 pathogens often display shorter telomeres. These diseases include cancer, heart disease, and Alzheimer’s

For example, Cawthon’s study found that among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

According to the Genetic Science Learning Center at the University of Utah, “Studies have found shortened telomeres in many cancers, including pancreatic, bone, prostate, bladder, lung, kidney, and head and neck.”

In 2003, researchers at the UCLA School of Medicine found that patients with Alzheimer’s disease had shorter telomeres when compared to control subjects without Alzheimer’s.

Telomere length as people age.

Similarly, the results of a recent study conducted by a team of researchers at the National Institute on Aging at the National Institutes of Health in Baltimore who assessed the telomere length of 41 people caring for loved ones with Alzheimer’s disease and 41 individuals matched by age who weren’t caring for an ill person. Caregivers had been looking after the Alzheimer’s patients for an average of five years. The fact that bacteria almost certainly drive the pathogenesis of Alzheimer’s is supported by a recent issue (May 2008) of Journal of Alzheimer’s Disease which was entirely dedicated to exploring the role of bacteria in causing Alzheimer’s.

The team reported in the Journal of Immunology that the telomeres of the Alzheimer’s caregivers were significantly shorter than those of the control individuals – suggesting that the Th1 pathogens from the Alzheimer’s patients had been transmitted to their caregivers over the course of the 5-year study period, shortening their telomeres in the process.

“So, it appears that in the patients with Alzheimer’s (and in the caregivers who are likely infected with the Th1 pathogens too), the telomeres are shortened,” says Joyce Waterhouse PhD of Autoimmunity Research Foundation. “I guess with our experience with the Marshall Protocol, we could conclude that Th1 disease and its associated inflammation cause this ‘premature aging.’” That view would go along with people seeming to get “younger” on the MP.

The fact that the caregivers displayed shorter telomeres does not necessarily mean that they will develop Alzheimer’s, although they may have a higher risk of developing other Th1 diseases associated with aging. In all cases, they should be comforted by the knowledge that the Marshall Protocol can prevent and reverse these illnesses.

Returning to the subject of shortened telomeres, it’s not surprising that researchers at Cedars-Sinai Research Institute and the University of California at Los Angeles also found shorter telomeres, suggesting premature aging, in patients with Lupus. A team from Homberg Germany came to the same conclusion in patients with T-cell lymphoma.

Futhermore, a variety of premature aging syndromes are associated with short telomeres. These include Werner Syndrome, Ataxia telangiectasia, Bloom syndrome, Nijmegen breakage syndrome and ataxia telangiectasia-like disorder. In all these diseases, genes have been mutated that affect telomere length in a manner yet to be determined.

What causes these genetic mutations? Pathogens are a likely candidate. Over thousands of years, bacteria, viruses, bacteriophages, and the Th1 pathogens have evolved mechanisms that allow them to mutate and alter the expression of the genes inside the cells they infect – meaning that the mutations observed in the above diseases could well be the result of bacterial infection.

Cawthon believes that if the telomere shortening process could be curbed, 10 to 30 years could be added to the average lifespan. Of course, the elimination of the Th1 pathogens won’t completely stop telomeres from shortening with cell division, but since these bacterial forms seem to accelerate the rate at which the telomere base pairs are lost, and everybody acquires significant levels of the Th1 pathogens as they grow older, it’s very possible that killing these bacteria could enhance the average lifespan.

What else does Cawthon implicate in aging? Oxidative stress, or damage to DNA, proteins and lipids (fatty substances) caused by oxidants, which are highly reactive substances containing oxygen. For example, in one study, scientists exposed worms to two substances that neutralize oxidants, and the worms’ lifespan increased an average 44 percent.

But consider this: what generates higher levels of these oxidants? According to Giunta, inflammaging. The inflammaging process generates Reactive Oxygen Species (ROS) – causing both oxidative damage and amplifying the number of cytokines released by the immune system. This perpetuates “a vicious cycle resulting in a….. state where tissue injury and healing mechanisms proceed simultaneously and damage slowly accumulates asymptomatically over decades and is a major determinant both of the aging process and of the development of age-associated diseases,” states Giunta.

But it is likely the Th1 pathogens that cause this “vicious cycle” – stimulating the immune system, which subsequently releases ROS and cytokines in an effort to eliminate them. Thus, when the bacteria causing this immune response are killed, the cycle, and the age-related damage that accompanies it, come to an end.

Nuclear Factor Kappa beta

Yet another way that the Marshall Protocol may affect the aging process is related to a chemical called Nuclear Factor Kappa beta (NF-kb). Just last week, scientists at Stanford University announced that they had successfully genetically altered mice so as to reduce the amount of NF-kB in their skin cells. Why? Because according to the researchers, the protein appears to control various aspects of the aging process.

The team used a lotion that inhibited NF-kB in the mice. After two weeks of treatment with this cosmetic, the skin of older mice displayed the look and genetic profile of younger skin. The skin also became measurably thicker.

Interestingly, the Th1 pathogens greatly contribute to the rise of NF-kB in the body. They are able to activate proteins that increase the activity NF-kB, which subsequently moves to the nucleus or center of an infected cell and stimulates the release of cytokines.

By reducing the level of the Th1 pathogens in the body, patients on the Marshall Protocol should also lower NF-kB and other inflammatory cytokines over time. Furthermore, Benicar, the medication that patients take along with the antibiotics, actually helps block the production of NF-kB.

“We know NF-kappaB is a product of Th1 inflammation, and Benicar is supposed to stop its production by blocking the Angiotensin II receptor,” says Marshall.

Of course the Stanford study was conducted on mice so it’s far too soon to generalize the effects of lowering NK-kB to human beings. Yet the study paves the way for a better understanding of how the proteins affected by the Th1 pathogens may contribute to the aging process.

Taking control of the body’s enzymes, receptors and hormonal systems

It is also becoming increasingly clear that the Th1 pathogens have, over millions of years, evolved the ability to directly alter the activity of the body’s hormones, enzymes and receptors.

A molecular model by Marshall showing a bacterial substance binding, and subsequently deactivating the VDR.

Marshall has isolated one species of bacteria capable of creating a molecule that binds and blocks the Vitamin D Receptor – a fundamental receptor of the body that controls not just the expression of thousands of genes, but the activity of the innate immune system and the production of the antimicrobial peptides. More bacteria with this same capability are likely to be identified in the coming years.

Thus, may be possible that at some point in every person’s life, it is inevitable that the bacteria they have accumulated will start to shut down the VDR, slowing the body’s ability to fight the pathogens responsible for causing the inflammation, oxidative stress, accelerated telomere shortening and perhaps other processes associated with aging.

If this proves to be the case, is the gradual deactivation of the VDR part of a natural process that gradually shifts every human being into the later phases of life, where the body loses its youthful resiliency?

After all, humans and bacteria have evolved side by side. Most of the cells in our bodies are not our own, they are bacterial. In fact, the bacteria in our bodies add up to more than 100 trillion cells. According to mainstream medicine, these cells are limited to our intestinal tract, but increasing evidence points to the fact that many bacteria also parasitize our other cells and live in biofilms within our tissues. Because our bodies are made of only some several trillion human cells, we are somewhat outnumbered by the pathogens.

With this in mind, is it possible that some of the trillions of bacteria are relatively harmless species involved purely in the aging process? According to Marshall, one could construct a hypothesis where relatively harmless species in biofilms have, over the course of millions of years, perfected the ability to gradually shut down the body’s receptors and hormonal systems as it ages.

The fact that an increasing number of people are developing diseases in which symptoms of aging appear earlier in life may simply be a reaction to vitamin D supplementation, immunosuppressive medications and beta-lactam antibiotics – all of which have allowed these bacteria to shut down the body’s hormonal control systems at a younger age.

Indeed, “premature aging” is a good way to describe the effects of increased inflammation, decreased telomere length, and the gradual deactivation of the body’s receptors. Those people who develop a full-fledged Th1 disease at a young age often complain of aches, pains, fatigue, brain fog, osteoporosis – all symptoms that are often considered “normal” in elderly people.

But people who suffer from diseases caused by the Th1 pathogens can now kill the bacteria causing “premature aging” by using the Marshall Protocol. Does this suggest that the elderly, who have accumulated similar forms of bacteria, or who harbor pathogens purely involved in the aging process, can also reverse the symptoms of aging by using the MP? It seems quite possible. Especially since, as described above, many patients who reach the later stages of the MP report feeling younger than when they started.

Consider that an infant not exposed to the Th1 pathogens in the womb begins life with a low pathogen load, no inflammation, little oxidative stress, telomeres that shorten at a slow rate, no VDR blockage, and healthy stem cells capable of efficiently repairing the tissues. Evidence so far suggests that patients who complete the MP regain these same attributes, thus returning to what could be described as a child-like state.

“Experts in the field of immunology are increasingly pointing to the fact that the aging of the immune system is a main factor influencing longevity,” states Dr. Greg Blaney. “As people grow older, their immune systems are forced to deal with higher bacterial loads, which in turn means they have to manage a greater inflammatory response. The MP downregulates this inflammatory response, restoring the agility of the immune system, which significantly affects the aging process.”

The Th1 pathogens may cause telomeres to shorten at a faster rate.

Obviously, it’s much too soon to draw any definite conclusions about the Th1 pathogens and aging as many of the potential roles that these pathogens play in the aging process are still based on speculation. And even if these intraphagocytic metagenomic bacteria are eliminated, who knows what other systems of the body may step in to circumscribe the human lifespan?

Then again, case reports from patients who have reached the late stages of the Marshall Protocol are highly encouraging. Once the Th1 pathogens have been killed, the body is demonstrating a remarkable ability to bounce back.

“We are also observing that the body has an amazing ability to regenerate after inflammatory damage which is currently considered to be ‘permanent’ (eg, fibrosis and peripheral neuropathy),” states Marshall.

In fact, progress reports are revealing that both physical and cognitive abilities are able to heal. “We have seen no sign that the brain doesn’t heal,” says Marshall. “The adults recover all their lost faculties as they heal on the MP, and the several children on the MP, who have had a variety of difficulties, also are recovering fully. So our data (at this point) shows that the body heals as bacteria are killed and immune function is restored.”

In many people who suffer from eye disease, the pigmented middle of the three concentric layers that make up an eye becomes inflamed. This condition is referred to as uveitis. Other parts of the eye can also become inflamed, causing conditions such as scleritis – a disease that affects the white outer coating of the eye. These conditions are both included in the umbrella name ocular inflammatory disease.

Many cases of ocular inflammatory disease are associated with “autoimmune diseases” like Crohn’s disease and rheumatic arthritis, or with illnesses of “unknown cause” such as Chronic Fatigue Syndrome and sarcoidosis – all of which have been linked over the years and most recently by biomedical researcher Trevor Marshall to the Th1 pathogens. Thus, it comes as no surprise that these same cell wall deficient pathogens may also be responsible for causing the many ocular inflammatory diseases. It’s also logical that people who have acquired enough of the Th1 pathogens to develop one form of Th1 disease (and begin to suffer from decreased immune function) find that these same pathogens more easily infect other areas of the body, like the eye.

The Th1 pathogens have also been implicated in “dry eye.” Many people with “dry eye” find that their eyes water but still feel dry. This occurs because the eye has two different tear ducts. Unfortunately, the ducts that produce tears necessary to maintain normal moisture in the eyes are often blocked or reduced by inflammation. Although the tears produced by the eye’s other ducts attempt to make up for loss of moisture, they do not have the same lubricating properties and simply cause the eye to water.

Patients infected with the Th1 pathogens often have inflamed blood vessels in the eye.

Normally, the conjunctiva, a membrane that covers the white part of the eye, is clear and white. Visibly red veins of the eye are a sign of vasculitis – a condition in which the veins of the eye become inflamed. “This condition is common in patients with Th1 disease, especially if Bartonella is involved,” says physician Dr. Greg Blaney. “Because it is in the eye, it is very obvious and disconcerting.”

Presbyopia is another eye condition that affects the proteins in the lens, making the lens harder and less elastic over the years. Changes also take place in the muscle fibers surrounding the lens. The eye has a harder time focusing up close because of the loss in elasticity. Again, it is very likely that inflammation generated by the Th1 pathogens is what causes the lens and surrounding muscle fibers to lose elasticity in patients with the condition.

Cell wall deficient bacteria have been detected on multiple occasions in the eye. Researchers at Columbia under Emil Wirostko detected non-cultivable cell wall-deficient bacterial pathogens in patients with chronic ocular inflammatory disease. In one experiment, they injected these organisms into mouse eyelids, which subsequently caused the mice to develop inflammatory eye disease. They also found that these cell wall deficient pathogens could disseminate and cause similar inflammation in the heart, gut and lungs.

Similarly, Wirostko’s group noted that cataracts developed in the eyes of 14 of the 15 mice who had been exposed to the cell wall deficient forms, whereas no cataracts developed in the eyes of 200 control mice that had not come in contact with the pathogens. This data caused the team to suggest that cell wall deficient organisms can penetrate the lens capsule to produce cataracts, and that these same organisms could cause human cataracts.

L-form bacteria in the eye of a patient with uveitis. Photograph by Emil Wirostko.

Additionally, photographs by Emil Wirostko show a substantial number of L-form bacteria inside the immune system cells present in the vitreous of the eye. Several years later, his son, Dr. William Wirostko, implicated bacteria such as Staphylococcus hominis and Staphylococcus aureus in inflammatory diseases of the eye.

Similarly, researchers at the Massachusetts Eye and Ear Infirmary found Chlamydia pneumoniae present in the diseased eye tissue of five out of nine people with age-related macular degeneration (AMD) – a disease in which the center of the inner lining of the eye, known as the macula area of the retina, suffers thinning, atrophy, and in some cases bleeding. However, the bacterium was not found in the eyes of more than 20 individuals without AMD.

AMD can result in loss of central vision, which entails the inability to see fine details, to read, or to recognize faces. According to the American Academy of Ophthalmology, it is the leading cause of central vision loss (blindness) in the United States today for people over 50 years of age. “The paper showed that C. pneumoniae is capable of modifying the function of important cell types involved in regulating normal eye function,” said lead author Murat Kalayoglu, MD, PhD.

Bacteria in the eye cause the release of cytokines – proteins that cause pain and fatigue. These cytokines, which include TNF-alpha and interferon gamma, cause the tissues to become swollen and inflamed. The active vitamin D metabolite 1,25-D functions as both a hormone and a cytokine, and thus when increased, contributes to a rise in inflammation.

In patients with ocular inflammatory disease, the level of 1,25-D in the eye begins to rise for several reasons, all of which are related to the Vitamin D Receptor – a fundamental receptor of the body that transcribes a wide array of genes and enzymes. In healthy individuals, the Vitamin D Receptor transcribes an enzyme called CYP24. CYP24 breaks down excess 1,25-D, ensuring that the level of 1,25-D in the body stays in the normal range.

Unfortunately, as people accumulate the Th1 pathogens, the Vitamin D Receptor (VDR) is not able to function correctly. Molecular modeling has revealed that some bacteria are capable of creating substances that bind and block the Vitamin D Receptor – decreasing its activity. Vitamin D obtained through diet and excessive sunlight exposure (which is converted into 25-D) also has the same effect – meaning that once individuals have a sufficient load of bacteria in the eye and elsewhere in the body, the receptor can no longer transcribe CYP24. The level of 1,25-D in the body becomes significantly elevated since there is no CYP24 to keep it in check.

Another enzyme called CYP27B1 normally regulates the amount of 25-D converted into 1,25-D. When more CYP27B1 is produced, conversion occurs at a greater rate. In addition, the cytokines released by the immune system in response to the Th1 pathogens activate a protein called Protein Kinase A (PKA). PKA in turn activates CYP27B1, causing more 25-D to be converted to 1,25-D.

1,25-D and the retina

Many patients who suffer from these various forms of eye inflammation experience disturbed vision, which in many cases is due to the effects of elevated 1,25-D on the retina. The retina is a thin layer of cells that line the back of the eyeball.

A molecule of rhodopsin

The primary function of the retina is to act as host for the rhodopsins – cells that belong to the class of receptors that first sense light when it enters the eye. Rhodopsins commonly bind other molecules called retinals. When a molecule of retinal is bound into rhodopsin its shape will change if it is hit by a photon of light. The change in conformation causes a charge called an action potential to be conducted through the retina. When enough action potentials have accumulated so that a certain threshold is reached, a sensory signal is sent along the optic nerve to the brain.

According to molecular modeling research by Marshall, 1,25-D binds into rhodopsin, and will competitively displace retinal. Thus, if the presence of the Th1 pathogens in the eye causes 1,25-D to increase, the excess 1,25-D may directly interfere with the process of vision. “It is the high 1,25-D level due to intra-cellular bacteria which is the cause of abnormal optical phenomena,” says Marshall.

Additionally, the Vitamin D Receptor is involved in the transcription of several key proteins that form the structure of the retina

According to researchers at McGill University these proteins include:

• Epidermal retinal dehydrogenase
• Retinal outer segment membrane protein
• Retinal pigment epithelium-specific protein
• Retinal short chain dehydrogenase reductase
• Retinal outer segment membrane protein 1
• Retinal degeneration slow protein
• Arrestin 3, retinal
• Retinaldehyde binding protein 1

But as bacterial substances and 25-D bind and decrease the activity of the VDR it cannot correctly transcribe the above genes. Vision loss or foggy vision may result. “There are a number of retinal protein genes which are transcribed by the VDR, which is the reason eyesight fails as these Th1 diseases advance, and with advancing age. This provides another pathway for the Th1 bacteria to inhibit the proper operation of the eyes,” says Marshall.

A molecule of 25-D competing with a molecule of retinal. Since 25-D, 1,25-D, and retinal all have very similar structures, it’s easy to see how 1,25-D can displace retinal in the eye.

The Marshall Protocol may help improve vision

Data collected from the Marshall Protocol study site indicates that patients with inflammatory eye disease are able to use the Marshall Protocol to eliminate the Th1 pathogens, which are the ultimate cause of elevated 1,25-D. Patients take pulsed, low-dose antibiotics along with the ARB medication Benicar to activate the innate immune system. With these measures in place, the patient’s own immune system can gradually work away at their bacterial load.

As patients on the Marshall Protocol begin to kill the Th1 pathogens, the substances blocking the VDR decrease, and the inflammatory response of the immune system exacerbated by bacterial death also slows. As the VDR regains the ability to transcribe the genes that form the eye’s retinal proteins, patients may experience improved vision.

It should be noted that some patients experience a drop in eye inflammation as soon as they start the ARB medication Benicar. This is because aside from its ability to stimulate the innate immune system, Benicar also has significant anti-inflammatory properties. Benicar binds and blocks the Angiotensin Receptor, decreasing levels of Nuclear Factor Kappa B, a protein that stimulates the release of inflammatory cytokines – causing a drop in inflammation. When researchers at the Keio University School of Medicine used a bacterial endotoxin to create a condition similar to uveitis in mice, they found that the eye inflammation of the animals decreased significantly after they were administered the ARB Telmisartan.

Of course once on the MP, patients should be prepared for changes in immunopathology – temporary rises in symptoms that result as the immune system deals with the increase in cytokines, 1,25-D, toxins, and cellular debri that are released when the Th1 pathogens die. This means that once on the MP, vision problems can be exacerbated in the short-term. Yet as more bacteria are killed and immunopathology dies down, these issues seem to resolve over time.

Case reports of Marshall Protocol patients noting improvement in vision and eye health are numerous.

“I was completely cured of severe uveitis by the very first stages of the Marshall Protocol,” says MP patient Julia Grier, who also suffered from floaters in the eye and elevated eye pressure. “In fact, I hadn’t even started the full MP with Benicar when my eyes began to heal quite dramatically, just on minocycline.”

Marshall Protocol patient Barbara Proal found that her corneal edema disappeared completely after only three weeks on the treatment. Before this point she had been forced to wear hard contact lenses in an attempt to help her blurred vision. Now her eyesight is clear and she can wear soft contacts again. “When my eye doctor saw that my corneal edema had resolved so quickly he was very impressed. In fact, I think he could hardly believe it,” says Barbara.

68-year-old MP patient Freddy Ash reports that since starting the Marshall Protocol his eye doctor has detected no inflammation, no granulomas, and no macular degeneration in his eyes. At a recent doctor visit he was told that the cataract in his right eye had not gotten any worse than the year before. Furthermore, the pressure in his eyes had decreased. “My eye doctor was well pleased with how the Marshall Protocol had helped my eyes,” says Freddie.

About 3 1/2 years ago, MP patient Leesa Shanahan developed swelling in her eyes. Within months her vision became fuzzy and her eyes painful, until she almost lost vision in one eye. Then, she started the MP. “From that moment on, my eye inflammation improved and I have not experienced a reoccurrence of uveitis in my eyes,” states Leesa. Before the MP Leesa was also forced to use large quantities of steroid eye drops along with oral medicines, steroids and methotrexate. Since starting the MP she has been able to wean off all meds and, at this point, no longer uses any of them.

Retinopathy, a condition in which blood has trouble reaching the eye is a common problem in patients with diabetes, but Marshall Protocol patient Debbie Y, who has suffered from type 1 diabetes for the past 46 years, reports that since starting the treatment, she has shown no signs of retinopathy. “My eye doctor even took photos of my retinas they were so perfect!” says Debbie. She also had psoriasis of both eyelids which after starting the MP is completely gone.

During a recent eye exam, Marie D’s opthamologist found absolutely no sign of cataracts in her eyes. “When asked if cataracts can be reversed, he responded with an unequivocal ‘no’,” states Marie. She found the response interesting because at her previous eye exam two years before (just as she began the MP), another doctor noted the start of cataracts, rating them 1 on a scale of 1 to 10.

L-form bacteria in the vitreous of the eye of a mouse with chronic uveitis. Photograph Emil Wirostko.

“My eyesight is only getting stronger,” says MP patient Sue Andorn. For the last 50 years Sue has worn prescription lenses for farsightedness. She had a script change in May, and her prescription was not nearly as strong as it used to be. In fact, her current prescription is too strong. “My eye doctor can’t believe it. He was so impressed that he asked me for written permission to be able to tell his other customers about my progress on the MP,” says Sue.

“I had to start wearing reading glasses 7 years ago,” says MP patient Nicola deSousa “Every so often, I don’t need them – at all. These spells last about a day, but are fascinating because my vision is completely clear.”

The mother of a child using the MP to treat severe eye inflammation reports that at a recent ophthalmologist visit, her daughter’s right pupil, which had previously been irregular in shape was no longer so distorted. “The doctor says that she never would have expected the change,” says the mother. Furthermore, her daughter, who was previously taking high doses of the medication methotrexate, has been able to stop the drug completely. She has also significantly reduced the number of prednisone eye drops needed to keep her symptoms under control, yet her eye inflammation remains lower than it was pre-MP.

Another MP patient found that after about 8 months on MP, he was able to stop using the reading glasses that he had needed for almost 20 years. “My vision problems started when I got sick, and I had always wondered if the two were connected somehow,” says Sam. In fact he reports that after simply removing vitamin D from their diets, his wife and daughter have been able to stop using glasses. “My wife had reading glasses like I did, but my daughter had a script for distance vision. Pretty amazing stuff,” says Sam.

“I am reading without contacts,” says MP patient Sherry Cook. “I’m not sure my prescription has changed, but I don’t recall doing this for years.”

Similiarly, MP patient Gary Kays notes that about 10 years ago he started using glasses for reading and near-sightedness. However he’s noticed that after 3 1/2 years on the MP, objects in the far distance are actually clearer when he removes his glasses. He still needs correction for indoors and close use, and improvement is coming very slowly. He is quite happy that he no longer needs stronger reading glasses every year.

It should be noted though, that improved near vision may also be due to early cataract formation, which can begin as early as age 40. However, once the MP has brought inflammation under control, it is unlikely that a patient would develop cataracts.

Surgery

The above case reports, combined with molecular modeling data and other research on bacteria in the eye, strongly support the idea that the Marshall Protocol is able to lower eye inflammation in a curative manner – often eliminating the need for many extensive eye surgeries and palliative medications.

In cases where eye surgery is still necessary, the Marshall Protocol can still be used to lower inflammation in the time leading up to the event. “Every on-the-ball ophthalmologist would much prefer the patient to have very little to no eye inflammation at the time of eye surgery,” states the Marshall Protocol study site.

Unfortunately, the corticosteroid medications prednisone and prednisolone – which slow the activity of the immune system – can cause cataracts to form, meaning that the medications should be avoided. However, some patients on the Marshall Protocol have been forced to temporarily use steroid eye drops in order to manage flares in immunopathology. Experience has shown that they are usually able to wean off the drops over time.

MP patients can also use artificial (preferably preservative free) tear drops to manage immunopathology in the eye that temporarily brings back sensations of dryness. But patients should avoid drops that have ingredients for “red eye” or allergies as they may have immunosuppressive properties.

It’s also important for MP patients to understand that what may often feel like an allergic reaction in the eye is, in most cases, actually due to changes in immunopathology, meaning that no additional treatment is required.

Light sensitivity

The excess production of 1,25-D in the eye causes most people with eye inflammation and other Th1 conditions to become sensitive to light. As previously described, the elevated 1,25-D contributes to inflammation, particularly in the brain. As the levels of 1,25-D (which also functions as a hormone) rises, it also directly interferes with the regulation of the thyroid, stress and sex hormones – causing a rise in symptoms.

Consequently, patients with eye inflammation (and other Th1 conditions) must be careful about daylight and other light exposure. Many people find that just a few minutes of daylight aggravates their eye condition. Numerous anecdotal reports confirm the effects of increased and decreased light on the eyes of patients with Th1 inflammation.

According to the Marshall Protocol study site, “If the eyes are not adequately protected, the neurological symptoms can prevent tolerance of the immune system reactions and thus slow the progress of killing the bacteria. Exposure of the eyes to too much light will not prevent recovery but it will delay it and could make it a very rocky road.”

Patients with eye inflammation must be careful to block light correctly.

Thus, MP patients, particularly those with eye inflammation, are advised to wear special sunglasses made by the company NoIR Medical in order to lower the amount of light that enters the eye. These glasses, which have an amber tint, block infrared rays and blue light, and attenuate visible light in a manner that best blocks energy production.

The degree of light sensitivity that patients experience varies greatly from person to person for reasons yet to be fully elucidated – although in many cases, increased photosensitivity seems to be correlated with a higher bacterial load. Light sensitivity decreases as people progress through the MP, meaning once they have killed a substantial amount of bacteria, and the resulting inflammation they cause has decreased, it no longer poses a problem.

With these measures in place healing is possible – and in the end, few things are as valuable as the ability to see clearly. In this day and age, eye issues and blurry vision are considered to be a normal part of the aging process. But perhaps, thanks to the MP, most cases of impaired vision associated with inflammation and aging will prove to be a thing of the past.

Sam’s mother suffers from fibromyalgia, accompanied by insomnia, fatigue, and irritable bowel disorder. His father recently had a stroke, and deals with substantial fatigue and depression. His older brother has debilitating back pain and is hard of hearing. His youngest sister suffers from alopecia, brain fog, depression, excessive fatigue, and mild attention deficit disorder. The youngest brother in the family has a severe case of bipolar disorder, as well as irritable bowel syndrome.

It’s obvious that every member of Sam’s immediate family harbors a substantial load of the Th1 pathogens and that these bacteria have, over time, spread from person to person. Clearly, just like other forms of bacteria, the Th1 pathogens can be passed around. Although Th1 diseases are not obviously contagious, they are communicable – meaning that transmission of chornic bacteria requires close contact and is seen often within the family unit. The pathogens can also be transmitted from person to person through bodily fluids released during coughing, sneezing and other intimate contact.

L-form bacteria can survive in sperm cells.

People whose parents harbor high loads of the Th1 pathogens are much more likely to fall ill with a Th1 disease earlier in life. Research indicates that L-form bacteria are able to survive in sperm, so a father can pass these pathogens to his child at the moment of conception. Evidence is also growing that L-form bacteria and other pathogens are able to cross the placental barrier – meaning they can be passed from a pregnant woman to her fetus.

Researchers at Peking University in Beijing recently discovered that the H5N1 bird flu virus can pass through a pregnant woman’s placenta to infect her fetus. Other studies have revealed that other bacterial species such as Borrelia burgdorferi and Mycobacterium tuberculosis are also capable of crossing the placental barrier during pregnancy. If these pathogens can be passed from mother to child during gestation, then why not other forms of bacteria that are capable of transforming into the L-form?

Successive infection

Infants born into families whose members harbor high loads of the Th1 pathogens are also more likely to pick up these bacteria after birth. As described here, it takes an infant several weeks to develop a fully functional innate immune system, meaning that during the first few weeks of life, infants are particularly vulnerable to bacteria passed around by other members of the family unit. But in order to fully understand what eventually causes an infant to develop a full-fledged Th1 disease, one must understand the concept of successive infection.

Inside every cell in the body are sequences of DNA that make up our genes. Over thousands of years, bacteria, viruses, bacteriophages, and other pathogens have evolved mechanisms that allow them to mutate and alter the expression of the genes inside the cells they infect. Researchers at the Institute of Genetics in China found that when the bacterial species Mycobacterium tuberculosis infects immune cells called macrophages, it causes mutations in about 70 genes and affects the expression of another 366.

The genes affected by pathogens inside a cell are active in regulating the activity of cytokines, coding for receptors on the surface of cells, regulating cell signaling pathways, monitoring cell death (apoptosis), controlling cell mediated immunity, regulating the production of proteins, creating enzymes, and many other essential processes.

Unfortunately, as pathogens gradually gain control over the genes that regulate the above processes, many of the mutations or changes in gene expression they produce can manipulate the host cell in order to aid their survival and reproduction. These changes also create an environment inside the cell that makes it easier for new pathogens to invade and persist. For example, Bukholm and team found that Measles virus infection of cell cultures makes the cells more susceptible to a secondary bacterial invasion. Quite a few species of bacteria have even developed the ability to use the Beta-lactams antibiotics in order to increase the likelihood of DNA sharing as they transform into the L-form.

“When one of the nasty bugs arrives, does it find your DNA intact in the cell it invades, or has the DNA already been altered by a previous pathogen?” asks Marshall. “If it tries to act on an altered gene, then the result will be different from if it acts on a ‘clean’ gene.”

Thus, as each subsequent pathogen that people encounter proceeds to make even more changes to their cellular DNA, eventually these mutations create a snowball effect where, as a person acquires an increasing number of pathogens, it becomes even easier for them to pick up a diverse array of other infectious agents.

In addition to the genetic changes that accumulate as a person encounters an increasing number of pathogens, some bacteria also alter the activity of the immune system by creating substances that bind and block the Vitamin D Receptor (VDR) – a fundamental receptor of the body that controls the activity of the innate immune system and the expression of the antimicrobial peptides (AMPs) – proteins that kill bacteria, viruses, and fungi by a variety of mechanisms including disrupting membranes, interfering with metabolism, and targeting components of the machinery inside the cell. As a person acquires more and more Th1 pathogens, the activity of their innate immune system decreases, and less antimicrobial peptides are produced, making it even easier for these pathogens to survive in the body and continue to alter human cellular DNA.

Inside every cell of the body are sequences of DNA that form genes.

But why do different members of a family develop different forms of Th1 disease? The key is that every person eventually encounters different pathogens and thus develops a unique infectious history. Maybe someone picks up various species of L-form bacteria from a roommate at college. Another person eats a contaminated piece of meat on their trip to Mexico, and on and on. The distinct mix of pathogens that each individual collects is sometimes referred to as their “pea-soup.”

Once a plethora of pathogens find themselves inside the same cell, there is no end to the number of interactions that may allow some species to develop a survival advantage. For example, researchers at the University of Washington found that when the bacterial species P. aeruginosa and S. aureus were incubated together, a protein created by P. aeruginos protected S. aureus from being killed by various forms of antibiotics. When the two pathogens were kept together for a longer period of time, P. aeruginos actually caused S. aureus to develop into small-colony variants, which are more difficult for the immune system to identify and kill.

Bacteria are very competitive, so some species have evolved mechanisms that allow them to gain dominance over other strains of bacteria. The final disease state that a person develops and the population structure of bacterial communities is also influenced by the sequence in which pathogens infect the body and their respective virulence.

It doesn’t help that the world teems with the Th1 pathogens. Because they cannot be killed by pasteurization or chlorination, they are found in food, milk, and water. Since they are too small to be filtered during the “purification” process used in pharmaceutical manufacturing procedures, they can also be found in injectable medicines. Whereas people with little previous exposure to the Th1 pathogens are often able to fend off a greater number of these bacteria in their immediate environment, those whose DNA has been altered since birth and whose innate immune system and AMPs are less active, can pick up chronic disease-causing bacteria much more easily.

It’s worth nothing that people taking high levels of vitamin D are at an even greater disadvantage, since, according to biomedical research Trevor Marshall, the precursor form of vitamin D is actually a secosteroid that also binds and blocks the VDR. “The epidemic of imbalance we are facing now, where the genomes of the microbiota which I call the ‘Th1 pathogens’ have started to gain dominance over the genome of their host, is due to mistakes made during the 20th century, particularly the decision to call “vitamin D” a vitamin,” says Marshall.

Marshall’s insight can also be applied to people who pass their partners the Th1 pathogens. As evidenced by progress reports on the Marshall Protocol study site, there are a substantial number of spouses who both suffer from Th1 disease. There are also entire families on the MP – with each member is using the treatment to eliminate his or her own pea-soup.

Thus, what changes between family members is the mix of species acquired, the sequence in which the pathogens are acquired, the subsequent mutations and changes in gene expression caused by the pathogens, and the profound changes to the body’s proteins, enzymes and metabolites caused by these factors. In most people these alterations develop slowly until they become obvious and diagnosable as a disease.

According to the Marshall Protocol study site, “What disease you develop and how quickly you develop it is determined by factors such as exposure (some species are acquired before birth), route of transmission (health care workers have a higher incidence of sarcoidosis), L-form species, virulence of the species and external stimuli.”

Horizontal DNA transfer also causes bacterial DNA to be passed from generation to generation

Just this month, researchers led by John H. Werren at the University of Rochester in New York elucidated yet another way that bacterial DNA is likely passed from person to person.

Due to horizontal gene transfer – or the reality that once inside the body, organisms swap genetic material with each other, and also with the host – bacterial DNA often ends up integrated into human DNA. This integrated genetic material is then passed from generation to generation, and it is very likely that many of these acquired segments of DNA may help bacteria survive more easily in the body. “Our data are indicating that [DNA transfer] is going on all the time,” says Werren.

“The mechanism therefore provides an alternative to mutation of existing DNA as a way for the species to acquire new genetic traits,” states Patrick Barry of Science News. “The transfer of DNA from bacteria means that an individual could acquire and pass on genes that it had not inherited.”

Warren’s team looked at several species of insects and roundworms infected by a parasitic bacterium called Wolbachia pipientis. The bacterium lives inside the animals’ cells, including their egg cells, giving it ready access to the chromosomes that are passed on to the animals’ offspring.

When the researchers compared the genetic code of the bacterium with the code of 11 other species: four roundworms, four fruit flies, and three wasps, they found that all but three of the fruit fly species had segments of the bacterium’s genetic code embedded in their DNA.

The team also scanned an archive of published genomes for 21 other invertebrate species and found bacterial genes in nine of them – proving that bacterial DNA can indeed be passed from mother to child. Whether this occurs in humans has not yet been demonstrated, but in principle, seems quite possible.

But this process has been taking place for centuries. Why hasn’t it been analyzed sooner?

“Such bacterial genetic code is routinely ignored during the sequencing of animals’ genomes because most scientists have assumed that the foreign DNA is a sign of contamination, Werren says. However, the new research rules out the possibility of contamination, says the scientist.

Moving away from the hypothesis of genetic predisposition

It’s obvious then, that most researchers are making a big mistake in assuming that the correlation between disease symptoms and mutated genes implies that genes (rather than the pathogens creating the genetic mutations) are responsible for the progression of an illness.

Clearly, humans accumulate a plethora of infections during their lifetimes, and it is the genetic mutations which result from active infection that play a major role in what is commonly thought of as “genetic susceptibility.” In the vast majority of diseases, parents do not pass on defective genes to their children. Instead, they often pass on the Th1 pathogens, which are the real underlying factor responsible for causing the symptoms of Th1 disease. Not that inherited genetic variations don’t have an effect in some very rare illnesses, but the vast majority of diseases result from successive infection.

Consider the fact that there is only a 20% chance that identical twins will both develop breast cancer. Geneticists attempt to explain this fact by saying that a person’s environment and upbringing can cause their genes to be expressed differently. These speculations have developed into a prominent “nature vs. nurture” debate.

But an understanding of successive infection should put a damper on these discussions as more researchers start to understand that the main environmental factor affecting the expression of genes is actually the unique mix of pathogens in any given place. Not that nurture won’t play a role – a good upbringing can help ensure that people learn to avoid high levels of vitamin D as well as immunosuppressive drugs that can hamper the activity of the immune system.

It’s true that twins are often more likely to develop the same illness. However it is quite likely that this is not because they share the same genes passed along through generations. Rather, disease correlation may result because twins are in the womb at the same time, and are exposed to the same Th1 pathogens through the mother’s placenta. Identical twins may have the highest risk of developing similar illnesses because they develop from the same sperm and egg, and thus carry the same Th1 pathogens as the sperm and egg. The genes inside the sperm and egg cells have also been mutated and consequently have the same influence on gene expression.

It comes as no surprise then, that after billions of dollars spent on research, not one gene therapy, not even research on the classic genes implicated in causing cystic fibrosis, has proven effective.

In fact, the statistical correlation in most gene studies is very low. “Part of the problem is that the folks computing the statistics are not the physicians who collected the data, and so there is a disconnect, and two disparate sets of knowledge are not quite meeting when discussing the meaning of statistical certainty,” says Marshall.

“The reason for this failure-to-perform is that the hypothesis is incorrect,” he continues. “What the researchers are seeing as changes on genes are indeed changes, but they only correlate at low levels of significance because they are due to pathogens. They are due to mutations from chronic infection. Consequently there is no causal effect – only an associative observation.”

Consider the fact that it takes most patients on the Marshall Protocol study site, who are killing intracellular bacteria at the fastest rate possible, over three years to completely recover their health. This hints at the huge amount of pathogen-altered DNA that many people, even those who are not yet displaying the hallmarks of Th1 disease, are carrying.

Surely this explains why, despite abundant research efforts, researchers have been unable to isolate any specific sequences of DNA that might make a person susceptible to a certain disease. They fail to consider that the predisposition for any Th1 illness is likely not genetic but acquired.

It is quite likely that in the coming years, medicine will move away from the hypothesis of genetic predisposition and towards the concept of successive infection. As this new understanding of the role that bacteria play in chronic disease spreads, the concept of inheritance may no longer refer to parents passing on a defective genes, but may instead be superseded by the notion that bacteria themselves are acquired from the mother during pregnancy, and through a father’s sperm.

Changing the definition of inheritance

No small number of researchers continue to cling to the idea that parents pass their children faulty genes. But if this is so, then why do multiple studies show that spouses – whose genetic backgrounds are not connected – have a higher risk of developing the same Th1 diseases that their partners have?

Pathogens such as Mycobacterium tuberculosis (seen here under electron microscope) can directly alter the expression of genes.

A six-year study of the Th1 disease sarcoidosis, conducted by the National Heart, Lung and Blood Institute at the National Institutes of Health (NIH) in Maryland found that among the 215 study participants who had been diagnosed with sarcoidosis, there were five husband-and-wife couples that both had the disease. Yet sarcoidosis is such a rare disease that based on statistics there should have been none. They also noted that the risk for sarcoidosis increased nearly five-fold in parents and siblings with the disease.

“It seems that the ‘germs’ [L-form bacteria] are passed around families pretty easily,” says biomedical researcher Trevor Marshall of Autoimmunity Research Foundation. “The NIH study found an incidence of sarcoidosis in spouses 1,000 times higher than could be expected.”

There have been other case reports of familial clustering of sarcoidosis. A case-controlled study of residents of the Isle of Man found that 40 percent of people with sarcoidosis had been in contact with a person known to have the disease, compared with 1 to 2 percent of the control subjects. One study reported three cases of sarcoidosis among ten firefighters who apprenticed together.

Dr. Garth Nicholson, a researcher at The Institute of Molecular Medicine in California has also conducted several studies on the communicability of diseases such as Chronic Fatigue Syndrome, autism and Gulf War Syndrome (a disease with symptoms very similar to those of CFS). He noted that among soldiers who developed Gulf War Syndrome during the war in Iraq, 70% or more of family members showed symptoms of the same disease within 10 years after the soldier had returned from the war.

Similarly, researchers at Queens Medical School in England found that men whose spouses had hypertension had a two-fold increased risk of hypertension. Similarly, women whose spouses had hypertension also doubled their risk of developing the disease. The risk for both male and female subjects persisted after adjustment for other variables such as diet.

Further evidence for communicability of Th1 disease among spouses was confirmed by British clinician and Chronic Fatigue Syndrome researcher Dr. Andy Wright, who at the 2006 Marshall Protocol Conference in Chicago, stated that he very rarely sees a family in which the spouses do not both have the L-form bacteria in their blood.

Scientists at the University of Maastricht in the Netherlands also found that relatives of individuals with autism often begin to show mild autistic traits, a phenomenon known as the broader autism phenotype (BAP). In one study conducted by the group, fathers with an autistic child demonstrated a different reaction time pattern and responded slower on the social cues than control fathers.

Spouses can pass each other bacteria.

Since recent research has suggested bacteria are also involved in causing obesity, it’s not surprising that a study recently published in the New England Journal of Medicine found that a person’s risk of becoming obese increases by 57% if they have a friend who becomes obese, and by 37% if their spouse becomes obese. The researchers attributed the results to social factors, but the spread of bacteria is a more logical explanation.

And none of the above studies even take into consideration the fact that spouses and siblings very often develop different forms of Th1 disease. If researchers were to look for the incidence of Th1 disease among family members and take into account all possible Th1 diagnoses, all of the above numbers would be notably higher.

Now think of all the Th1 diseases that are known to “run in families”– heart disease, arthritis, bipolar disorder, breast cancer, inflammatory bowel disease, Alzheimer’s disease – and it becomes increasingly plausible that nearly all inflammatory diseases are communicable, not genetic.

“The spread of Th1 disease in families is undeniable,” says Marshall. “Some members come down with rheumatoid arthritis, some with CFS, as well as a mix of the other Th1 diseases.”

Th1 disease develops as part of a gradual process

Since Th1 diseases result from a gradual accumulation of pathogens who alter the host’s genetic material over the course of decades, each Th1 disease is due to a spectrum of symptoms that gradually accumulate into a recognizable condition.

“I recognize that most people identify a date as the point at which the disease became manifest, but I believe they are mistaken in their understanding of the insidious progression of the Th1 syndromes,” says Marshall.

As they age, some people suffer from aches and pains yet don’t make the connection between these symptoms and exposure to the Th1 pathognes. Others become so used to living with a certain level of symptoms that they are convinced that what they feel everyday is “normal.”

At first, Th1 disease may not be very pronounced. It may manifest as a little arthritic pain in the joints, slow healing of wounds, inability to maintain a healthy weight, added brain fog, or mild fatigue. Some people fail to realize that mental symptoms such as irrational aggression, paranoia, depression, obsession are also signs of Th1 disease. “These symptoms stand out like beacons once one is attuned to them,” says Marshall.

Take, for example, the following case study taken from the Marshall Protocol study site. When the patient was first diagnosed with sarcoidosis, he was convinced that an insect bite he had received during military training – which caused a six-week bout of continuous coughing, was probably what had given him the disease. But, twenty years later, when he reviewed chest X-rays taken well before that incident, the disease was clearly apparent even then. “I was clinically sick, but didn’t know it,” the patient later reported. “Nobody around me noticed, including the person who read those initial X-rays. However, hindsight is 20:20, and nobody could review the early X-rays, knowing what happened to me later, without noting the significance of the adenopathy present on them.”

Similarly, a recent study by researchers at the University of Washington found that children with autism displayed signs of the disease at birth that were not recognized by their parents at the time. The team analyzed coded home videotapes of 11 autistic and 11 normally developing children’s first year birthday parties for social, affective, joint attention, and communicative behaviors and for specific autistic symptoms. Autistic children displayed significantly fewer social and joint attention behaviors and significantly more autistic symptoms, despite the fact that their parents had considered them to be “normal” at the party.

The group went on to show that parents’ recollections of when their child “became autistic” were completely unreliable, and that behavioral traits could instead be accurately recognized by third parties from videos of early life.

The Marshall Protocol can stop the spread of the Th1 pathogens among family members

Fortunately, the Marshall Protocol is finally a way to stop the spread of pathogens among families that has occurred for centuries – giving the next generation a fresh start.

Information gathered from the Marshall Protocol study site suggests that once a person is taking over the minimum inhibitory concentration (MIC) of minocycline, along with Benicar, they will kill any opportunistic blood-borne bacteria that try to leave the body. At this point, there is little chance of them passing L-form bacteria to another person, as the bacteria will be killed within 48 hours of leaving the cells and entering the bloodstream.

Since the Th1 pathogens grow very slowly, it is not very difficult to kill them before they overcome the immune system, as long as a person starts the Marshall Protocol before symptoms become severe. Thus, it is important that people whose parents and siblings suffer from Th1 disease start the Marshall Protocol as soon as possible, in order to kill disease-causing bacteria that have surely been passed among the family. “The less ill a family member is, the less difficulty they will have throwing off the infection,” says Marshall.

Once on minocycline, Marshall Protocol patients usually kill any Th1 pathogens that try to leave the body.

It is also important to remember that when L-form bacteria and other pathogens alter a person’s genetic material, they are only affecting the DNA in the nucleus of infected cells, not the DNA/chromosomes that remain with the person throughout life. This means that every time a cell dies, the genetic mutations in that cell are gone for good. When the immune system has killed all infected cells, the genetic mutations once caused by the Th1 pathogens will no longer be passed from parent to child.

It also seems that once the Th1 pathogens have been killed, and the cells they infected have died, the body is usually able to recover completely. “We are seeing very few signs of permanent damage, except for structural damage (fibrosis, scarring), and the body is showing a remarkable ability to even work around the collagen, in any case,” says Marshall.

The human immune system has two components – the innate immune system and the adaptive immune system. The innate immune system is the body’s first line of defense against invading pathogens. White blood cells of the innate immune system called phagocytes engulf and kill bacteria. The adaptive immune system is primarily made up of white blood cells called lymphocytes. Once lymphocytes encounter a pathogen, they create proteins called antibodies that allow the adaptive immune system to ‘remember’ the infectious agent and prevent it from causing disease at a later time.

A diagram from Rolf Zinkernagel’s paper showing how the group of newborn mice injected with CMV died when exposed to the virus at a later date

While the innate immune system is functioning at birth, it takes several weeks for an infant to develop a working adaptive immune system. Little is known about what happens when a baby encounters pathogens during this early period of life. However, a recent study by 1996 Nobel Laureate Rolf Zinkernagel and team at the Institute of Experimental Immunology in Switzerland illustrates how pathogens may affect infants during the period before their adaptive immune systems are up and running.

Zinkernagel and team injected a virus called Cytomegalovirus (CMV) into the brains of a group of mice that were only a few days old. Their adaptive immune systems had not yet developed and consequently they were not producing lymphocytes. The researchers found that the innate immune systems of the mice were able to eliminate CMV from most of the tissues except for those of the central nervous system. As a result, the virus persisted in the brains of the mice. Later in life, when the same mice were challenged by infection with a similar virus, they developed a condition resembling a type of autoimmune disease and died. The team referred to this concept as viral “deja-vu.”

A second group of mice were not exposed to the CMV virus until they were fully grown and their adaptive immune systems had completely developed. When these mice were exposed to CMV later in life, they were able to successfully fight the virus and lived.

The results of this study reveal what may be one of the main reasons behind why some people seem much more susceptible to the Th1 pathogens (L-from, intracellular and biofilm bacteria) that cause chronic disease and acquire these chronic bacterial forms at higher rates than much of the rest of the population. As Zinkernagel states, “In genetically susceptible individuals, early childhood infections seem to predispose them to [such disease as] multiple sclerosis or type 1 diabetes years even decades before clinical onset.”

According to a study just published in the New England Journal of Medicine, in some infants, the innate immune system may also not be able to clear bacteria from other tissues besides the brain during the first weeks of life. Researchers led by Dr. Hans Bisgaard at Copenhagen University Hospital in Germany found that newborns who harbor certain types of bacteria in their throats, including Streptococcus pneumoniae, a common cause of pneumonia, and Haemophilus influenzae, which causes upper respiratory infections, are at increased risk for developing recurrent wheeze or asthma early in life.

This finding “opens new perspectives for the understanding and prediction of recurrent wheeze and asthma in young children”, says Bisgard. The researchers assessed the development of recurrent wheeze and asthma in 321 newborns who had throat cultures taken at 1 month of age and who were then followed through 5 years of age.

Some infants pick up bacteria in the first weeks of life.

Twenty-one percent of infants were colonized with S. pneumoniae, H. influenzae, another type of bacteria called M. catarrhalis, or a combination of these bugs and this finding more than doubled the risk of persistent wheeze, wheeze flare-up, and hospitalization for wheeze.

The prevalence of asthma at age 5 was significantly increased in the children who harbored these organisms as newborns compared with children who did not (33 percent versus 10 percent).

In a related editorial, Dr. Erika von Mutius, from University Children’s Hospital in Munich, Germany, comments that these findings may be interpreted to suggest that the presence and growth of bacteria in the throat in the first four weeks of life “indicates a defective innate immune response very early in life, which promotes the development of asthma.”

O’Connor and team at the Centers for Disease Control and Prevention agree, stating, “A person’s age at the time of infection—from intrauterine or perinatal (the time period surrounding birth), through childhood and adolescence, to adulthood and the elder years—may further influence the risk for chronic outcome. For example, perinatal herpes virus infection dramatically increases the risk of developing adult or pediatric chronic liver disease. Recurrent infections or perhaps serial infections with certain agents might also determine a person’s risk for chronic outcome.”

If certain human babies are infected at birth with the Th1 pathogens, it is very possible that just like the CMV virus that persisted in the brains of Zinkernagel’s first group of mice, and the bacteria that remained in the throats of the infants in Bisgard’s study, these pathogens could persist in the human brain and other tissues. This could make the same infants more susceptible to the Th1 pathogens they are exposed to later in life – in essence they would develop “bacterial deja-vu.”

This may explain why people react differently to insect bites. Only about 5% of people who are bitten by a tick and fall ill with Lyme disease go on to develop chronic Lyme disease – a condition where the body is simply unable to kill the bacteria responsible for causing the illness. The pathogens may transform into the L-form and persist inside the tissues and the cells of the immune system.

Take, for example Matt Russell, who is currently using the MP to treat his chronic Lyme disease. Matt was born 5 weeks premature. He was breast-fed, but also given formula supplemented with vitamin D through a tube. Ten days later he ended up in the neonatal intensive care unit and tested positive for quite a few forms of bacteria. He stopped breathing on several occasions but was revived each time and put on a cocktail of antibiotics. He responded favorably to the antibiotics and his parents were later told that he had an E. coli urinary tract infection.

Twelve years later, after being bitten by an insect that also carried bacteria, Matt started to suffer from intense headaches and recurrent infections, including bladder infections. Gradually, he developed full-fledged Lyme disease. It is very likely that the pathogens he had acquired at birth had persisted in his tissues, and accompanied by the bacteria introduced by the insect bite, caused him to develop a serious chronic disease later in life.

“We have always wondered why, out of the 1600 boys in Matt’s school, he is the only one in recent memory who has missed a couple of years of schooling due to a chronic disease. We are sure he is not the only one to be bitten by an insect,” says Matt’s mother, Robin Russell.

When assessing Zinkernagel’s study, it must be noted the human adaptive immune system takes even longer to develop than the rat adaptive immune system. While it takes rats only days to fully acquire innate immunity, it takes humans several weeks. Certainly this model hints at why Th1 diseases often run in families. If parents, grandparents and relatives with high loads of the Th1 pathogens hold and care for babies during the first weeks of life, it appears that their bacteria can easily be transmitted to the child and persist in the child’s brain and other tissues. A recent study by Dave Relman and team at Stanford University, which found that infants pick up many of the species that make up their gut flora from family members within a few weeks of birth, further indicates that pathogens are easily transmitted from family to child during the initial periods of life.

“The really important thing to be drawn from [Rolf Zinkernagel's] work is the reminder that the infant is unprotected in the days and weeks following birth, until it starts producing antibodies. The innate immune system is all it has got although many think that antibody transfer from the mother may be present in the breast milk. I am not sure that would be much help, but I just don’t know. Nobody does,” says biomedical researcher Trevor Marshall PhD of Autoimmunity Research Foundation. Unfortunately, the idea of pathogen deja-vu and the presence of the Th1 pathogens are not being considered by the vast majority of other researchers and doctors besides Marshall.

As discussed above, children with a weakened innate immune system will be even more vulnerable to acquiring pathogens early in life, since this branch of the immune system is supposed to kill bacteria before the adaptive response kicks in. Furthermore, the human adaptive and innate immune systems are intertwined, so that a lethargic innate immune system will affect a baby’s ability to develop a working adaptive immune response.

Pregnant women are often told to take prenatal vitamins containing vitamin D (also called cholecalciferal).

Sadly, children who are bottle fed with vitamin D fortified milk and born to mothers given pre-natal vitamins that contain vitamin D are at increased risk of developing compromised innate immune systems. New molecular modeling research has revealed that the precursor form of vitamin D – a steroid called 25-D – binds and inactivates the Vitamin D Receptor (VDR) – a fundamental receptor of the body that controls the activity of the innate immune system and the transcription of thousands of genes. As an infant ingests high levels of vitamin D, the activity of the VDR decreases and the child’s innate immune system becomes less active, making it more difficult for them to kill pathogens. As these infants grow, they are often fed vitamin D fortified baby food that can also negatively affect the activity of the VDR if it reaches high enough levels. Add to this the fact that the Th1 pathogens they harbor also create substances that bind and block the VDR, adding to the level of immunosuppression.

In what has become a public health disaster of massive proportions, the vast majority of doctors and researchers are unaware of the molecular models which show that 25-D is immunosuppressive. They don’t realize that the primary effect of large doses of vitamin D when used in cancer and chronic disease reflects the ability of the steroid to slow the innate immune system and subsequently the cytokine release generated by dying chronic bacteria. They also fail to understand that the low level of 25-D observed in patients with chronic disease is not a cause but a RESULT of the disease process, and is due to the fact that the Th1 pathogens create substances that bind and block the VDR, thus interfering with the intricate feedback pathways that keep 25-D in the correct range.

It is essential that doctors stop thinking of “vitamin” D as a nutrient and recognize that it is a secosteroid, whose active form (1,25-D) functions as a powerful hormone. As Marshall states, “The epidemic of imbalance we are facing now, where the genomes of the microbiota which I call the “Th1 pathogens” have started to gain dominance over the genome of their host, is due to mistakes made during the 20th century, particularly the decision to call ["vitamin" D] a vitamin. More about the effects of “vitamin” D on the immune system here.

In the same vein, many doctors advise pregnant women to supplement with higher than usual levels of vitamin D during pregnancy because the level of 25-D in pregnant women often drops. They fail to realize that the low 25-D observed in pregnant women is a natural part of the hormonal changes that occur during pregnancy. It has long been known that the level of the active vitamin D metabolite 1,25-D rises during pregnancy, meaning that levels of 25-D drop as the precursor form (25-D) is increasingly converted into its active form (1,25-D). There are also feedback pathways in place that naturally cause elevated 1,25-D to downregulate the production of 25-D. Yet, the vast majority of researchers fail to test the level of 1,25-D in their pregnant subjects and therefore misinterpret the low level of 25-D as an indicator of deficiency. Surely this explains why researchers at the University of Pittsburg found that “vitamin D deficiency” was still common in a group of pregnant women, 90% of whom were taking pre-natal vitamins containing vitamin D.

A woman’s level of 25-D is naturally downregulated during pregnancy.

Based on this disastrous misunderstanding, the Canadian Pediatric Society has recently released a statement recommending that during pregnancy and while nursing their babies, women should consider taking 2,000 IU of vitamin D daily – an amount that is 10 times higher than the current Canadian recommendation for adults under 50. Meanwhile, in the United States, two government-sponsored studies are investigating the effects of giving 4,000 IU of “D” daily to pregnant women and 6,000 IU to nursing mothers. These high levels of vitamin D are meant to “stave off” the chronic diseases caused by what doctors misinterpret as vitamin D “deficiency.” In reality, not only do these ridiculously high levels of vitamin D suppress the innate immune systems of newborn children, they also greatly lower the innate immunity of the mother, allowing her to acquire substantially more pathogens which she will subsequently pass to her child.

Besides these excessive amounts of vitamin D, as they age, people are routinely given anti inflammatory drugs, ranging from over the counter anti-pyretics and anti-histamines, to prescription steroids, such as prednisone, in order to suppress what is regarded as pointless inflammatory responses by an immune system that is out of control (e.g autoimmune disease). Unaware that these immune responses are really attempts by the body to eliminate L-form and biofilm bacteria, they try to palliate the symptoms of patients by giving medications that slow the immune system. As the immune system slows down, these persistent pathogens gradually spread to new organs and tissues.

The end result of all of the above – the current epidemic of chronic disease. According to the report comparing U.S. and European health published online in the journal Health Affairs, the treatment of obesity and other chronic diseases adds between $100 billion and $150 billion to the annual health care tab in the United States. But who can deny that the greatest tragedy is the lives that are ruined by these massive and systemic misunderstandings surrounding chronic disease. For babies to begin a life in which they are destined to become chronically ill is one of the greatest tragedies imaginable.

Note: The disease process described above can be reversed with the Marshall Protocol: http://www.autoimmunityresearch.org/

In what is emerging as a new understanding of chronic disease, researchers are increasingly implicating what are often referred to as the Th1 pathogens in a wide array of illnesses previously considered to be of unknown cause or “autoimmune” in nature. “It is our contention that several diseases that are usually regarded as ‘autoimmune’ or ‘idiopathic’, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, sarcoidosis and psoriasis, are caused by infection with related slow-growing bacteria,” states G.A.W. Rook in the journal Immunology Today.

The Th1 pathogens are hypothesized to be an intraphagocytic, metagenomic microbiota of bacteria, meaning that they are able to persist inside the cells of the immune system as well as group into colonies called biofilms. The bacteria inside a biofilm produce a protective matrix that allows them to more effectively evade the immune system and develop resistance to antibiotics administered in a standard manner. Essentially, high-dose antibiotics fail to eliminate all the cells that form a biofilm, leaving what are referred to as persister cells behind. The persister cells are eventually able to re-create the biofilm, allowing it to thrive again. There is a tremendous number of different species of these chronic pathogens.

Many of the bacteria that compose this microbiota are in what is referred to as the L-form. For over a century, scientists have realized that classical bacteria can transform into small forms that lack cell walls. These pathogens are known as L-form bacteria. Researchers have currently identified over 50 different species of bacteria capable of transforming into the L-form, and it is likely many other bacteria also have this ability. Brown et al have found evidence of L-form bacteria in the blood of more than 60% of healthy controls. In fact, the diseases generated by L-form bacteria are far more common than currently realized, and are often only noticed as subtle signs of aging, such as osteoporosis, obesity, fatigue and arthritis.

Unlike other forms of bacteria, L-form bacteria have developed the ability to remain alive and proliferate undetected inside macrophages, the very cells of the immune system that the body uses to kill invading pathogens. Once inside the macrophages, it becomes much more difficult for antibiotics to penetrate the interior of the cell and come in contact with these bacteria.

Beta-lactam antibiotics including penicillin, amoxicillin and the cephalosporins are also designed to attack the bacterial cell wall. These antibiotics are able to kill classical bacteria but are completely ineffective against L-form bacteria, which have lost their cell walls. In fact, in 1934, German scientist Emmy Klieneberger-Nobel first discovered that beta-lactam antibiotics actually promote the formation of L-form bacteria.

However there are other classes of antibiotics, and the sequencing of the human genome has allowed scientists to figure out exactly how these types of antibiotics work at the molecular level. Every antibiotic is different at the molecular level and possesses unique qualities that allow it to effectively target different species of pathogens. Over the past few decades, biomedical researcher Trevor Marshall, PhD, has studied this data and figured out what is believed to be the safest, most effective antibiotics to use against L-form bacteria. He used this data to create a medical treatment known as the Marshall Protocol.

Marshall discovered that a class of antibiotics called bacteriostatic antibiotics have the potential to weaken L-form bacteria if administered in the correct manner. Bacteriostatic, or “Protein Synthesis Inhibitors” are a class of antibiotics that work by disabling bacterial ribosomes – small, dense, structures that allow the pathogens to replicate and survive. This group of antibiotics includes the tetracyclines, such as minocycline and demeclocycline. This class of antibiotics has also been shown to interfere with the ability of bacteria to produce proteins on their surfaces called exoproteins. This makes it easier for the immune system to kill the pathogens.

In the Journal of Postgraduate Medicine, Burke Cunha and team argue that there is an increasing number of “cases emerging of certain infectious diseases against which [bacteriostatic antibiotics] are especially effective, such as ehrlichiosis, Lyme disease, and methicillin-resistant Staphylococcus aureus (MRSA) infection. The researchers argue that another benefit of bacteriostatic antibiotics is that when taken orally, they are just as effective as when administered using intravenous therapy. According to Burke, minocycline is the antibiotic of choice because of its “superior intracellular mechanism of activity and an excellent safety profile.”

A tetracycline antibiotic docked into the 30s ribosomal subunit; taken from riboworld.com

One of the great benefits of minocycline when compared to other tetracyclines is that it has better lipid solubility. This means it can more easily penetrate the central nervous system and the inside of cells. Minocycline is also very effective against the bacterial species Staphylococcus which is one of the most widely implicated pathogens in chronic disease.

Meg Mangin at Autoimmunity Research Foundation states, “All bacteria must create a variety of proteins in order to survive and the Marshall Protocol is designed to make that task progressively harder.” Bacteria have one ribosome, the 70S ribosome, which is divided into two sections – the 30S ribosomal subunit and the 50S ribosomal subunit. Minocycline binds to the 30S ribosomal subunit. Under normal conditions, the 30S ribosomal subunit sends out a helix-like molecule that decodes the sequences of genetic code (RNA) necessary for a bacterium to create proteins necessary for survival. When minocycline binds the 30S ribosome it blocks and prevents this helix-like molecule from initiating the process that results in protein synthesis. One molecule of minocycline will inhibit one 30S bacterial ribosome from manufacturing proteins. This low antibiotic to ribosome ratio proportionately controls the rate of bacterial death.

However, according to the Marshall Protocol guidelines, minocycline must be combined with other antibiotics in order to fully target all the different species of bacteria involved in causing chronic disease. As a result, the Protocol uses other carefully selected antibiotics in conjunction with minocycline, allowing the patient to target the entire spectrum of L-form bacteria.

According to Marshall, “Long term therapy with any single antibiotic will cause the killing of bacteria susceptible to that antibiotic, and the repopulation of the tissues with bacteria resistant to that antibiotic. So your bacterial load may well be increasing while your original symptoms improve.”

Consequently, patients on the treatment begin by taking pulsed, low-dose minocycline. However, they soon add other antibiotics into the mix, until their bacterial load is reduced enough that they are able to tolerate different combinations of three antibiotics at one time.

Minocycline prevents bacteria from decoding sequences of RNA; taken from riboworld.com

“[The Marshall Protocol] uses Minocycline as a base, and adds other symbiotic bacteriostatic antibiotics,” says Marshall, “specifically to make sure that no species can escape. The molecular genomic science is clear and precise. The Marshall Protocol is unique in its avoidance of the mechanisms leading to antibiotic resistance.” He has presented the modes of action of the Marshall Protocol antibiotics at several conferences. At the Chicago conference “Recovering from Chronic Disease,” he presented 3-D models of a bacterial ribosome, and showed where and how each antibiotic docks into the ribosomal RNA in order to prevent protein synthesis, and how the Marshall Protocol antibiotics do this synergistically, without the possibility of interaction.

Note: The antibiotics used by the Marshall Protocol must be very carefully managed so as not to provoke immunopathology that is too strong for the patient to handle. Consequently, I will not reveal the names of the other antibiotics used by the treatment, as I do not want patients to take them without first working closely with a doctor. Both doctor and patient should study and follow the protocol guidelines carefully in order to implement it safely. The Phase One Guidelines describe how to start the treatment correctly.

One of the antibiotics used in conjunction with minocycline is an azolide antibiotic that targets the other subunit of the 70S ribosome – the 50S ribosomal subunit. When this antibiotic binds this section of the ribosome it blocks bacterial proteins from being assembled and exiting through a pore in the bottom of the ribosome. Several other antibiotics are also able to block the 50S ribosome, but the azolide antibiotic used by the Marshall Protocol is unique in that it also forms a bond with a region of bacterial genetic material called 23S RNA – further preventing protein synthesis. This azolide also has superior tissue penetration than other antibiotics in its class, meaning that the drug can persist inside the tissues for weeks. As a result, this antibiotic is not taken as often as the others. In later phases of the treatment this antibiotic is combined with another antibiotic that blocks different regions of the 50S ribosomal subunit, further preventing proteins from being assembled.

Two researchers at the Max Planck Institute in Germany have put together a website that brings together the research of several different scientists who have used molecular modeling software to reveal how minocycline and azolide antibiotics can block the ability of bacteria to synthesize proteins.

Another antibiotic used by the Marshall Protocol works by interfering with the ability of bacteria to create and replicate their DNA. This antibiotic inhibits dihydropteroate synthase, an enzyme that allows bacteria to use folic acid. Since folic acid is an essential precursor in the synthesis of several of the base pairs needed to create DNA, inhibition of the enzyme will stop the pathogen from creating the genetic material it needs to survive.

Because each of the three classes of bacteriostatic antibiotics used by the Marshall Protocol affect different ribosomal subunits and target different mechanisms of protein synthesis, a bacterial species would have to develop three different mutations in order to survive in their presence. Consequently, Marshall argues that when the Marshall Protocol antibiotics are taken in the correct manner, “Statistically, the chance that bacteria will evolve that cannot be killed by the MP is so close to zero it is inconsequential.”

An azolide antibiotic docked into the 50s ribosomal subunit; taken from riboworld.com

Several variables affect how a patient will respond to the antibiotics used by the Marshall Protocol. Marshall argues that these factors include:

1. Patient’s prior exposure to the antibiotics

2. Strength (or weakness) of the patient’s own immune system

3. Species of bacteria present

4. Concomitant health problems – e.g. kidney failure

5. Concomitant infections – e.g. fungal, viral

6. Medications being taken by the patient

One antibiotic that the Marshall Protocol does not use is doxycycline. Doxycycline is not nearly as wide-spectrum an antibiotic as minocycline and does not kill as many L-form bacterial species. It also has effects on the brain that can stimulate feelings of euphoria. Marshall argues “These are both dangerous characteristics because they can make people prematurely think they have ‘conquered’ their infection.”

The Marshall Protocol antibiotics must be taken in conjunction with Benicar

The ribosome blockades initiated by the Marshall Protocol antibiotics greatly weaken L-form bacteria but are unable to actually kill the pathogens. Consequently, patients on the treatment take a medication called Benicar that activates the innate immune system. Molecular modeling has revealed that Benicar binds and activates the Vitamin D Receptor – a fundamental receptor of the body that controls the activity of the innate immune system.

“To us, Benicar is not a “medication.” It is a method of turning-on your body’s VDR (Vitamin D Receptor). This is a key part of the immune system, and transcribes over 1000 genes which affect body processes from calcium homeostasis to cancer metastasis,” states Marshall.

Once on Benicar, the patient’s own immune system has the strength to kill bacteria that have already been greatly weakened by antibiotic therapy. Benicar makes such a difference in activating the immune system that some patients find that once on the medication, they begin to kill bacteria before they have even started the antibiotics. In order for the immune system to function correctly at all times of day, Benicar must be taken every 6-8 hours.

Marshall says that this use of Benicar along with the MP’s unique antibiotic regime “significantly tilts the advantage in favor of the immune system which is actually the most effective ‘antibiotic’.

But Benicar also binds other receptors involved in the immune system response. Recently, Marshall has elucidated additional modes of action of Benicar on the nuclear receptors that control the immune system.

By definition Benicar is an Angiotensin II Receptor Blocking (ARB) drug. When Benicar binds and blocks the Angiotensin Receptor, it decreases levels of Nuclear Factor Kappa B, a protein that stimulates the release of inflammatory cytokines – proteins that generate pain and fatigue. These cytokines include interferon gamma and TNF-alpha. The drop in cytokines results in less inflammation and oxidative stress. As inflammation drops, the antibiotics can also perfuse the tissues more effectively.

The drop in inflammation stimulated by Benicar makes some patients feel better, allowing them to more easily tolerate the increase in symptoms generated by bacterial die-off. In fact, if a patient feels that their immunopathology is too strong, they can take extra Benicar in order to help palliate the inflammatory response.

Benicar was carefully chosen over other ARBs because according to molecular modeling data, it binds the above receptors and the Vitamin D Receptor in a manner that most effectively activates the immune system response. Other ARBs also bind the same receptors as Benicar but fail to activate them at the correct level.

A molecular model showing Benicar activating the vitamin D receptor; created by Trevor Marshall

Although Benicar is a mild antihypertensive agent, even patients who have very low starting blood pressure (80/50) have tolerated it well. The maximum hypertensive effect usually occurs in the 20-40 mg range. Taking higher doses has little, if any, additional effect on blood pressure.

Therefore, taking Benicar more often will not continue to lower blood pressure or deplete sodium more than the usual 40 mg dose. Patients must be sure to get plain Benicar without hydochlorothiazide added (HCT). Adequate sodium and water intake is advised. As noted in The Townsend Letter for Doctors and Patients: “Benicar was well tolerated in safety evaluations (1). Examples of some of the documented protective effects of ARBs include the ability to:

1. prevent migraines

2. inhibit liver fibrosis and aid liver healing

3. protect the kidneys in diabetic nephropathy

4. reduce insulin resistance

5. protect the heart from damage from inflammation in myocarditis

6. protect the mitochondria from age-associated damage from oxidation

Meg Mangin at Autoimmunity Research Foundation states, “The combination of [Benicar] to engage the immune system with the safe, wide-spectrum, symbiotic antibiotics used during the later stages of the Marshall Protocol seem to effectively eliminate all strains of antibiotic-resistant bacteria.”

As noted in the Phase 1 Marshall Protocol guidelines, Benicar is a critical component of the Marshall Protocol. Without it, the immune system is unable to fully utilize antibiotics to kill L-form bacteria. This is evident in patients taking MP antibiotics who do not begin killing bacteria until they take Benicar.

Low-dose pulsed antibiotics are most effective against L-form and biofilm bacteria

Standard methods that use high dose, constant levels of antibiotics are unable to effectively eliminate L-form and biofilm bacteria. The reason lies with the fact that aside from their ability to block bacterial ribosomes, bacteriostatic antibiotics also have effects on the immune system. Unfortunately, some of these effects are immunosuppressive. For instance, the tetracycline antibiotics have been widely recognized as being able to inhibit various functions of phagocytes, the white blood cells that engulf and kill bacteria. These effects seem to be independent of their antibacterial effect.

These immunosuppressive properties decrease the amount of L-form and biofilm bacteria killed by the immune system. This is why some people report feeling better on high-dose antibiotics. The high levels of antibiotic prevents the immune system from killing these forms of bacteria, resulting in a temporary decrease in the toxins the pathogens release as they die and the inflammatory cytokines produced by the immune system. However, in reality, the person’s L-form bacteria remain alive and find it easier to spread to new tissues and organs.

The most effective way to avoid this problem is to use low doses of pulsed antibiotics. Pulsed dosing refers to administering a dose periodically, such as every 48 hours, rather than once or several times daily. When given in this manner, the immunosuppressive effects of the antibiotics are minimized but their ability to weaken bacterial ribosomes remains intact. Patients gradually increase the dosage of the pulsed antibiotic, so that species of bacteria that are susceptible to all different concentration levels will eventually be targeted.

A report in the European Journal of Clinical Microbiology found that treating the bacterial species Staphylococcus aureus with only 1/32 of the minimum inhibitory dose of clindamycin (a very small dose!) resulted in enhanced uptake of the bacteria by white blood cells called polymorphonuclear cells, and enhanced killing of the pathogens by another class of white blood cells called phagocytes. Not surprisingly, the team found that only bacteriostatic antibiotics (the class of antibiotics used by the MP) possess this ability. Antibiotics that work by blocking cell wall production such as penicillin, cefotiam, peperacillin, and vancomycin where unable to elicit such an effect.

Similarly, researchers at the University of Iowa found that subinhibitory concentrations of the bacteriostatic antibiotic azithromycin significantly decreased biomass and maximal thickness in both forming and established biofilms. These extremely low concentrations of azithromycin inhibited biofilms in all but the most highly resistant isolates. In contrast, subinhibitory concentrations of gentamicin, which is not a bacteriostatic antibiotic, had no effect on biofilm formation. In fact, biofilms actually became resistant to gentamicin at concentrations far above the minimum inhibitory concentration.

The advantage of pulsed dosing has been demonstrated in the past. It has long been known that pulsing levels of the hormone GNRH is most effective against infertility. Similarly, intermittent doses of antibiotics seem to disrupt the immune system’s natural state of homeostasis, thus provoking a greater immune response. When antibiotics are taken in low, pulsed, doses, they are also able to effectively eliminate biofilm persister cells in a way that high-dose antibiotics cannot.

Recent research has also demonstrated that pulsing antibiotics can be a superior way of targeting treatment resistant biofilm bacteria. According to researchers at Tulane University who mathematically modeled the action of antibiotics on bacterial biofilms, “exposing a biofilm to low concentration doses of an antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration.” Several studies have shown that even when administered in low, pulsed doses, the bacteriostatic antibiotics are still able to decrease the production of bacterial exoproteins.

The MP antibiotics generate changes in immunopathology

The Th1 pathogens have evolved mechanisms that allow them to live for long periods of time within the cells, and when alive, generally persist without generating too many symptoms. It is when the Th1 pathogens die that they begin to cause a major increase in symptoms for the host, since as they die they release large amounts of toxins and cytokines, proteins that generate pain and fatigue. Additionally, as the Th1 pathogens die, the cell that they have parasitized dies as well, and cellular debris is released into the bloodstream. This means that once patients begin the MP, each dose of antibiotic will cause them to feel bad for the period of time it takes their immune system to deal with the consequences of L-form bacterial die-off.

The severity of the immunopathology reaction differs from person to person depending on bacterial load and the species of bacteria that need to be killed. Patients can adjust their level of antibiotics, and consequently adjust the severity of the immunopathology response. Patients who are severely ill generally experience stronger immunopathology, whereas patients who start the Marshall Protocol during earlier stages of illness often find that they are able to work and manage a high level of activity despite the rise in symptoms.

Since immunopathology must be carefully managed, the Marshall Protocol takes several years to complete. However immunopathology generally decreases as patients progress to later stages of the treatment, allowing them to become more and more active as time goes on.

Because the Marshall Protocol takes a long time to complete and patients are understandably eager to reach a state of wellness, some people try to raise the dose of their antibiotics too quickly. Unfortunately, this can result in symptoms that are so strong that the patient decides to quit the treatment. Consequently, as described on the Marshall Protocol study site, the cliché, “slow and steady wins the race” can certainly be applied to the manner in which patients should correctly ramp their antibiotics. If a patient feels that their immunopathology has reached an intolerable level there are several mechanisms they can use to dampen the reaction which are discussed in this forum on the Marshall Protocol study site.

Before starting the Marshall Protocol, some patients with chronic inflammatory disease report having trouble tolerating many antibiotics. In most cases, it is discovered that these perceived “allergies” are actually due to the antibiotics provoking changes in immunopathology. According to the Townsend Letter for Doctors and Patients, “Experience with the MP indicates that if the antibiotics are started at low enough dosages, they are generally well tolerated, although patients will usually experience immunopathology responses. The pattern of reaction to the antibiotics are not typical of allergies or toxic side effects, in that they usually manifest as exacerbations of the patient’s usual symptoms, and the reactions decline with subsequent doses as the bacterial load is reduced.”

The tetracycline antibiotics may improve bone health

The tetracycline antibiotics also offer patients an advantage when it comes to bone health. Several studies have shown that the tetracycline antibiotics used by the treatment can increase bone mass.

Researchers at the University of Portugal found that just 1 mug/ml of the tetracycline antibiotics “significantly increased proliferation of human bone marrow and osteoblastic cells without altering their functional activity.” In fact they reported that exposure to the antibiotics actually caused a significant increase in the number of bone cells and amount of bone matrix.

Similarly, researchers at the National Institute of Health in Maryland published a study which found that treating mice with minocycline modestly reduced bone reabsorption and substantially stimulated bone formation.

The team concluded that “oral minocycline can effectively prevent decreases in bone mineral density… through its dual effects on bone resorption and formation.”

Activating the Vitamin D Receptor allows the body to effectively create its own antibiotics

Antimicrobial peptides (AMPs) are actually potent, broad-spectrum antibiotics that the body creates naturally. The AMPs have been shown to kill gram-negative and gram-positive bacteria, including strains that are resistant to conventional antibiotics such as Mycobacterium tuberculosis and other cell wall deficient bacteria. They have also been shown to target enveloped viruses, fungi and even transformed or cancerous cells.

The AMPs kill bacteria in a variety of different ways. These include disrupting cell membranes, interfering with metabolism, and targeting machinery inside the cell. In many cases the exact mechanism of killing is not known. In addition to killing bacteria directly, the AMPs have been shown to have a number of immunomodulatory functions that may be involved in the clearance of infection, including the ability to alter host gene expression, inhibit cytokine production, and promote the healing of wounds.

Recent research has revealed that the Vitamin D Receptor controls the activity of numerous AMPs.

Unfortunately, in chronically ill individuals, L-form bacteria create substances that are able to bind and decrease the activity of the Vitamin D Receptor. 25-D, the precursor form of vitamin D (at levels over 20ng/ml) also binds and deactivates the receptor. Patients who avoid vitamin D and use the Marshall Protocol to kill L-form bacteria allow the VDR to regain function. They also take a medication called Benicar that molecular modeling shows is able to further activate the VDR. All these measures return the Vitamin D Receptor to an active state where it can turn on the pathways that create the AMPs.

The Marshall Protocol antibiotics can be used safely and effectively

Minocycline has been used for decades in a variety of medical therapies. Recently, a multicenter double-blind placebo-controlled trial concluded that minocycline was safe and effective in patients with mild to moderate rheumatoid arthritis and supported its use (alone or as adjunctive therapy) in rheumatic diseases. Tetracyclines have been also used effectively in urogenital, gastrointestinal, and lower respiratory tract infections.

There is no evidence that long-term use of the antibiotics used by the Marshall Protocol leads to resistant species forming. In fact, minocycline was introduced in 1968, and since that time, virtually no organisms have developed resistance to the medication. Minocycline is also one of the few antibiotics that remains active against the bacterial species Methicillin-resistant Staphylococcus aureus (MRSA), despite the fact that for decades, it has been widely prescribed in efforts to control teenage acne.

According to the Physicians Protocol for using antibiotics in rheumatic disease, “Minocycline tends not to cause yeast infections. Some infectious disease experts even believe that it has a mild anti-yeast activity. Women can be on this medication for several years and not have any vaginal yeast infections.”

It is important that patients who begin the Marshall Protocol take their antibiotics exactly as directed. Taking the antibiotics when not using Benicar, dosing the antibiotics at higher levels than directed, or not pulsing them, will significantly decrease or completely stop immunopathology from occurring. Patients may feel better temporarily, but they are no longer killing bacteria.

“Please understand that the Marshall Protocol may seem simple, but it has a lifetime of my own research behind it. Anything you change will likely get you into trouble,” says Marshall.

Furthermore, taking medications or supplements that are not part of the Marshall Protocol can impair the body’s ability to correctly put the antibiotics to use.

Marshall argues, “We have to remember that there are many species we are fighting against. Second, the immune system is so finely balanced between not killing them, and killing them, so that small changes to our lifestyle, or to our food, or caused by other drugs we are taking, might stop the immune system from killing the bacteria. If there is no killing the patient will generally feel better.”

But, if taken correctly, the Marshall Protocol antibiotics, in conjunction with Benicar, have great potential to induce improvement and recovery. “There are plenty of people who show that if the treatment is done in the correct manner, healing is possible,” says Belinda Fenter of Autoimmunity Research Foundation.

Bacteria can glean iron from the host and use it to grow

Our bodies require iron in order to function, but numerous studies have shown that bacteria also use iron to grow. In fact, bacteria consume large quantities of iron, leaving little free iron available to the host organism.

This may explain why many people who suffer from certain chronic diseases and obesity, which are now hypotesized to be caused or affected by bacteria, display low levels of iron and are considered to be deficient in the substance. Deficiency reflects the fact that bacteria are using the host’s iron to their own advantage.

Not surprisingly, researchers at the University of Texas found that overweight U.S. children run an alarmingly high risk of iron deficiency. They were able to detect an association between obesity and iron deficiency in children as young as one year old. Dr. Jane Brotanek, the study’s lead author stated, “A key finding of this study is the alarmingly high prevalence of iron deficiency among overweight toddlers.”

Although the researchers hypothesized that the deficiency might be due to “excessive milk or juice intake, prolonged bottle-feeding, snacking and junk food intake”, a more likely explanation is that the obese toddlers had higher loads of bacteria.

The methods that bacteria use to acquire iron have been elucidated by a different team of researchers, also at the University of Texas. According to the researchers, the ability of a particular species of bacteria to glean iron from its host is often a good indicator of its virulence.

The biochemistry of a siderophore.

The team, under the guidance of Professor Shelley M. Payne, has published widely on the genetics and iron acquisition methods of bacteria such as Vibrio and Shigella. Shigella and Vibrio are able to secrete iron binding complexes that have a high affinity for the proteins inside the host. These complexes are called siderophores. Siderophores remove iron from host proteins, making it available for use by the bacteria.

The bacterial species Vibrio produces a variety of siderophores. When deprived of iron, Vibrio bacteria create five proteins on the surface of their bodies. Some of the proteins serve as receptors that allow them to bind and attach siderophores to their bodies. Others serve as receptors for heme, large molecules made up of iron atoms contained in the center of a ring.

The Shigella species of bacteria have at least three different iron transport systems. Two of these, called the aerobactin and the enterobactin systems, consist of siderophores and receptors that will allow the bacteria to bind the siderophores once they have removed iron from the host. The third pathway allows Shigella to transport and utilize iron in the form of heme. By culturing mutated species of Shigella bacteria, Payne and team were able to determine that siderophores provide iron to bacteria in the environment outside the cells of the host, and that the heme transport pathways are used by bacteria when they are growing inside the cells.

The team also discovered that the bacteria S. flexneri create a protein that not only allow it to bind large amounts of heme, but facilitate its attachment to the host cells it will parasitize. The protein is encoded on a large plasmid, a circular molecule of DNA that can replicate independently of a pathogen’s other genetic material.

In order to fully understand the mechanisms of iron acquisition and transport mentioned above, Payne is carefully analyzing the bacterial genes involved in each process. By using cloning techniques to create multiple copies of each gene, Payne has been able to test and measure the expression of various genes under different environmental conditions, such as changes in temperature and pH. According to Payne, “These studies will allow us to determine the molecular mechanisms of iron acquisition and ultimately to assess the roles of these systems in bacterial infection.”

There is no need to remove iron from a healthy, well-balanced diet, but iron supplements should be avoided, as the extra iron will likely be used by bacteria rather than the host. People with chronic disease who are deficient in iron should understand that the low level of the substance is the consequence of bacterial infection.

Sources of dietary iron include red meat, fish, poultry, lentils, beans, leaf vegetables, tofu, chickpeas, black-eyed peas, potatoes with skin, bread made from completely whole-grain flour, molasses, teff and farina. Iron in meat is more easily absorbed than iron in vegetables.

Folic Acid can help bacteria replicate their DNA

Another substance that bacteria use to their own advantage is folic acid. An enzyme called DiHydro-Folate Reductase (DHFR), converts folic acid into a form that the body can use to produce the nucleic acids essential for life. Nucleic acids are building blocks that our bodies use to create DNA. However, if a person consumes too much folic acid, L-form bacteria will use it to generate their own nucleic acids and replicate and create their own DNA.

Enriched white flour products should be avoided.

Folic acid is found naturally in food such as leafy vegetables, dried beans and peas. But it has also been artificially added to “enriched” flour products including white flour, white bread, and a variety of pastas and nutrition bars. Because excess folic acid can be used by L-form bacteria, these enriched products should be avoided.

A conventional treatment for the lung disease sarcoidosis confirms that folic acid does indeed affect the activity of bacteria. Some patients with sarcoidosis are told to take Methotrexate (MTX), a drug that temporarily slows progression of the disease by blocking the activity of folic acid, and subsequently the activity of DHFR. Another drug that blocks the activity of DHFR is the antibiotic Trimethoprim, which is used to create the drug Bactrim.

A team of researchers at the Institute of Food Research in the UK has shown that when people consume foods that are supplemented with folic acid, the liver can easily become saturated with the substance. Writing in the British Journal of Nutrition, the researchers warn this could lead to unmetabolised folic acid entering the blood, which could damage health.

“This can cause problems for people being treated for leukemia and arthritis, women being treated for ectopic pregnancies, men with a family history of bowel cancer, people with blocked arteries being treated with a stent and elderly people with poor vitamin B status,” states british researcher Dr. Sian Astley.

“For women undergoing in-vitro fertilization, it can also increase the likelihood of conceiving multiple embryos, with all the associated risks for the mother and babies.”

Since high levels of folic acid enable chronic bacteria to thrive, it’s also not surprising that two recent commentaries appearing in Nutrition Reviews found that the introduction of flour fortified with folic acid into common foods was followed by an increase in colon cancer diagnoses in the U.S. and Canada. Extra folic acid may also increase the incidence of breast cancer in postmenopausal women.

Some people are told to supplement with folic acid because it lowers levels of homocysteine, a chemical that has been linked to heart disease. However a recent meta analysis on folic acid and cardiovascular disease by researchers at the Tulane University School of Public Health found that folic acid had no beneficial effect on the study subjects, despite the fact that it does lower homocysteine.

The team to concluded, “Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease.”

It should be emphasized that the negative consequences observed in these studies were the result of folic acid supplementation, meaning that these results do not pertain to normal levels of folic acid obtained through a healthy diet.

Carbohydrates provide bacteria with an easy source of energy

A sugar molecule. Both humans and bacteria use sugar as a source of energy.

Our bodies use carbohydrates as a source of energy, but carbohydrates are also a source of fuel for bacteria. The body breaks down both carbohydrates and sugar into the exact same sugar molecules, so a diet high in carbohydrates will produce the same fuel for bacteria as a diet high in refined sugar.

The human body extracts the nutrients in food through a biological process known as the Krebs Cycle. The Krebs Cycle is part of a metabolic pathway that converts carbohydrates, fats and proteins into a form of energy that can be used by the body. The cycle uses sugar to generate molecules of NADPH, which humans are able to use as a source of energy. But bacteria such as Borrelia, Treponema, and possibly other bacteria, do not have proteins in their genomes that allow them to use NADPH as an energy source. Instead, they obtain energy directly from sugar. This means that while humans must wait until sugar is broken down in order to put it to use, some bacteria can use it right away. Consequently, extra sugar inevitably ends up benefiting the pathogen rather than the host.

Furthermore, sugar has been shown to affect the immune system in ways not yet completely understood. Sugars in the body often bind to proteins, a process called glycosylation. Once attached to a protein, sugars adjust the protein’s ability to react with other molecules. T-shaped molecules of the immune system called immunoglobulins have a location at the center of their structure which has a high affinity for sugar. Sugars are attracted to this region and once attached, stay bonded for long periods of time. It is not yet known what changes sugars induce when bound to immunoglobulins, but their ability to bind these molecules does suggest that sugar can modulate the immune response.

Consequently, it’s important that sugar and carbohydrates be eaten in moderation. Depending on metabolism and activity level, some people may want to consider eating a diet low in carbohydrates and sugar, such as the South Beach Diet or Atkins diet.

Some researchers, such as Loren Cordain, who has written several books on diet, argue that humans are meant to eat a diet low in carbohydrates. Cordain argues that the healthiest human diet is that which was eaten during the longest period of our evolution, which was prior to agriculture. Although not all experts agree on exactly what percentage of meat and vegetables were eaten by our ancient ancestors, they all agree that grains, sugar and legumes were not consumed to any significant degree by ancient, pre-agricultural man.

Cordain and others have noted that there was a decline in health, indicated by examination of skeletal evidence, after agriculture took hold. Agriculture permitted large civilizations to develop through grain cultivation, but Cordain argues that the widespread switch to cereals and grains has been a two-edged sword, and he has even linked it to diseases like multiple sclerosis, autism and schizophrenia.

Foods that slow the immune system

Molecular modeling research has shown that the Vitamin D Receptor (VDR), a fundamental receptor of the body, controls the activity of the innate immune system. The medication Benicar binds and activates the Vitamin D Receptor.

Foods high in vitamin D should be avoided.

A wide variety of compounds can also bind the receptor and adjust its level of activity. Some of the substances found in food bind and inactivate the Vitamin D Receptor, causing the activity of the immune system to slow down. These substances are called VDR antagonists. When the immune system slows down, some people report feeling better. These people are most likely infected with chronic disease-causing bacteria.

Chronic bacteria have evolved mechanisms that allow them to live for long periods of time within the cells, and when alive, generally persist without generating too many symptoms. It is when bacteria die that they begin to cause a major increase in symptoms for the host, since as they die they release a large amount of toxins and cytokines, proteins that generate pain and fatigue. Additionally, as bacteria die, the cell that they have parasitized dies as well, and cellular debris is released into the bloodstream.

Many people infected with L-form. biofilm, and other chronic bacterial forms unknowingly eat foods with substances that deactivate the VDR, which temporarily slows the release of cytokines and toxins. Unaware that this reaction is taking place, people often attribute a small boost in “wellness” to the idea that the foods with VDR-blocking substances are somehow beneficial. Often they try to maintain the feeling of “wellness” by eating increased quantities of these foods. But over the long term, eating high amounts of foods with substances that block the VDR only allow the chronic pathogens they harbor to spread and proliferate as the person’s immune system becomes increasingly deactivated.

Some people even find they are addicted to foods with substances that block the VDR. If they stop eating these foods, their immune systems begin to kill more L-form/biofilm bacteria and they feel worse. Unable to tolerate the rise in symptoms, they continue to crave and consume the foods high in VDR-blocking substances.

According to recent molecular models, the steroid 25-D is a VDR antagonist – it binds the Vitamin D Receptor and decreases the activity of the receptor, causing the innate immune system to slow down and shut off. This effect gradually increases with higher concentrations of 25-D, and reaches full blockage of the VDR at around 40 ng/ml.

It is critical that people consume only moderate amounts of vitamin D, so that the level of the steroid does not rise to the point at which it becomes immunosuppressive. People who are infected with chronic disease-causing bacteria should completely remove vitamin D from their diets. This is because certain forms of biofilm bacteria create proteins that bind and deactivate the VDR in a manner similar to 25-D. Extra 25-D only exacerbates the problem by further shutting off the receptor.

Furthermore, the low level of 25-D observed in many people with chronic diseases is not a sign of “deficiency” but a result of hormonal adjustments that occur naturally as part of the disease process.

According to biomedical researcher Trevor Marshall of Autoimmunity Research Foundation, “There is a big problem with the assumption that ‘Food makes the man.’ It doesn’t. In fact, when the body starts down-regulating hormones and metabolites the body is usually doing that for a reason. The whole concept of ‘replacement’ or ‘supplementation’ is fraught with non-sequiturs and risks.

“You should not assume that just because your body is ‘low’ in something that you should be adding a supplement. In the presence of a controlled metabolite, ‘deficiency’ can be a non-sequitur. You have to know more about the underlying metabolite,” says Marshall.

Vitamin D is found in seafood, egg yolks, sunflower seeds, pumpkins seeds, flaxseeds and a variety of other foods. Supplements such as fish oils (Cod liver oil, Omega 3 oil, primrose oil), and mushroom supplements all contain vitamin D. Many herbal supplements may contain vitamin D that is not listed in the ingredients on the bottle. Consequently, it is wise to avoid all supplements unless they are absolutely necessary.

Coffee is high in chlorogenic acid.

According to molecular modeling research, another substance that negatively effects the activity of the VDR is chlorogenic acid. Chlorogenic acid is an antioxidant found in foods such as coffee, tea, apples, pears, tobacco, pomegranate, potatoes and eggplant.

It’s fine to eat these foods in moderation, but eating excessive quantities of any one food high in chlorogenic acid might have an impact on the immune system. In particular, juicing, which greatly concentrates substances in fruits, should be avoided. In order to ensure that the immune system can kill L-form bacteria as effectively as possible, some people on antibiotic therapy to kill L-form bacteria may want to avoid foods high in chlorogenic acid.

Coffee is very high in chlorogenic acid (both caffeinated and decaffeinated). Some people find they are addicted to coffee or require a cup of coffee in the morning in order to function. Although some of this “pick me up” effect may be due to caffeine, it may also be due in part to the action of high levels of chlorogenic acid on the immune system.

Carnosic acid will displace 1,25-D (and Benicar) from the VDR in a concentration-dependent manner.

Some people who suffer from sensitivity reactions to certain foods find that they are sensitive to chlorogenic acid. Researcher Joyce Waterhouse PhD argues that sensitivity to chlorogenic acid might also cause a person to become sensitive to other substances that bind the VDR such as Benicar. This is because all molecules that bind the VDR have very similar structures and the body may confuse one for another. Thus, in the rare case that a patient on the MP becomes sensitive to Benicar, reducing chlorogenic acid in the diet may stop the body from reacting to VDR binding substances, allowing the patient to effectively tolerate the medication.

Molecular modeling research has also revealed that a substance called carnosic acid also binds and deactivates the VDR. In fact, it is a total antagonist of the VDR. Herbs such as rosemary and sage are high in carnosic acid. The calculated affinity of carnosic acid for the Vitamin D Receptor is Ki = 54 nanomolar. In simple terms, that means that only tens of milligrams of the substance can affect the immune system.

It’s okay to enjoy small amounts of carnosic acid in foods seasoned with rosemary and sage, but carnosic acid is also found in a variety of over-the-counter supplements. Consequently, although herbal supplements can seem harmless, they may have unintended effects on the immune system, especially since carnosic acid is only one of the many immunosuppressive substances often found in supplements.

Soy also contains a VDR antagonist. Soy products contain antioxidants called isoflavones. The primary isoflavone found in soy is called Genistein. Molecular models have revealed that Genistein interferes with the operation of the VDR, and also negatively affects two other receptors that control the immune system.

A picture of 1,25-D and Genistein as they dock into the VDR.

A study by researchers at the Rowett Research Institute in Scotland implies that 40mg of isoflavones a day is likely to produce concentrations capable of affecting the VDR (about 500 nanomolar). This amount is equivalent to about 20 grams of roasted soyabeans. It is wise to keep soy content in the diet below this level.

Green tea contains low levels of genistein. According to Marshall, those who choose to drink green tea should allow the tea bag to steep for only 30 seconds or less in order to ensure that the level of genistein in the beverage remains low. Black tea also contains genistein but is processed in a manner that is supposed to remove most of the substance. However, the amount of genistein actually removed by this process is disputed, so black tea should be made weakly as well.

The medication Benicar can counteract the immunosuppresive effects of Vitamin D Receptor blocking substances. Benicar binds and activates the Vitamin D Receptor, reversing to some degree the effects of substances that turn it off. However, even people taking Benicar should limit foods with VDR blocking substances in order to ensure that the immune system works at maximum capacity.

Everything in moderation

At the moment, a large part of the American public seems to feel that maintaining good health involves taking extra supplements. Often people don’t realize all the substances in the supplements they are taking. Taking extra supplements becomes a dangerous habit when many compounds found in these products can affect the activity of the immune system and foster the growth of chronic, disease-causing bacteria.

It seems that the best way to stay healthy is to avoid unnecessary supplements and to eat most foods in moderation. Problems arise when people try to consume an unnaturally high amount of a particular food or substance. It’s also important to have a good understanding of chronic disease and the actions of harmful bacteria when making decisions about diet. Just because a food or supplement makes a person feel better does not necessarily mean that it is improving their health. It may simply be slowing the activity of the immune system. Similarly, just because a person displays a low level of a substance like iron does not necessarily mean that they should supplement with large amounts of the substance. It’s important to realize that the nutrients we consume can also be used by bacteria. Eating a well-rounded and natural diet, while at the same time avoiding supplements unless they are absolutely necessary, will help to ensure that our bodies, and not the pathogens we harbor, get adequate nutrition.