Exploring chronic disease

Category: featured articles

Paul W. Ewald is an evolutionary biologist, specializing in the evolution of infectious disease. He received his Ph.D. from the University of Washington, in Zoology, with specialization in Ecology and Evolution. He is currently director of the program in Evolutionary Medicine at the Biology Department of the University of Louisville.

The first recipient of the George R. Burch Fellowship in Theoretic Medicine and Affiliated Sciences, Ewald’s publication of Evolution of Infectious Disease is widely acknowledged by doctors and scientists as a watershed in the emergence of the new discipline of evolutionary medicine. He has been featured in The Atlantic, Newsweek, Discover, and Forbes.

Professor Ewald is also the author of a groundbreaking book, Plague Time; How Stealth Infections Cause Cancers, Heart Disease and other Deadly Ailments.

How do the concepts of evolutionary biology support the idea that pathogens are to blame for most diseases?

When we consider the possible causes of disease, it’s important to make sure that at our starting point, we put all categories on the table. I believe the most useful way to do this is to think in terms of three main categories:

  • inherited genes
  • parasitic agents (this includes bacteria, viruses, fungi, protozoa
  • non-living environmental factors (too much or too little of a particular substance, radiation, exposure to a chemical etc.)

Once we have this spectrum of categories in mind we ask, “Have all three areas been investigated?

At this point scientists tend to make an error. They decide that if they have found enough evidence for categories 1 or 3, that category 2 is not playing a role. This is a fundamental problem that has led the medical community to misunderstand the cause of most debilitating chronic diseases.

So, which of the three categories is overlooked? Category 1 certainly isn’t – once scientists figured out the structure of DNA and the nature of mutations they were extremely eager to show their relationship to disease. Category 3 hasn’t been overlooked, largely because of the fact that we can sense environmental causes of disease. We suffer from a stomach ache after eating contaminated food or feel the pain from a sunburn.

But, if we look back at every decade, there has been a lack of research on category 2 relative to its actual importance in causing disease. Our track record shows that we have consistently failed to fully understand the role that pathogens play in causing disease and this trend has continued up until 2008.

There are many examples of how we have continually overlooked the category of infectious disease. I’m not talking about acute infection – researchers were essentially able to work out the mechanisms of acute infection from 1880 to about 1920. I’m talking about chronic infection, and thus the role of pathogens in causing chronic disease.

Take the case of peptic ulcers. The idea that bacteria cause peptic ulcers was first solidified in the 1940s, then independently investigated and solidified again by Marshall and Warren in the 1970s. It took over 20 more years before the relationship was finally accepted by mainstream medicine. Now, when people look back on previous theories about the cause of peptic ulcers they think, “Oh, isn’t it surprising that we didn’t understand the cause for so long!” or “We should have known better!” But when they proceed to hypothesize about the cause of other diseases, they go right back to the dogma. They haven’t learned the lessons from the peptic ulcer story.

Instead, they should think in an opposite fashion. If we find that one disease has an infectious cause, we should learn from that information and seriously consider the same possibility in other diseases.

Think about syphilis. In 1913, it was discovered that the disease resulted from infection with the bacterium Treponema pallidum. Soon, the disease was dubbed the “Great Imitator” because its symptoms often resembled those of other diseases, particularly in the later stages. I think syphilis should be called the “Great Illustrator,” because it’s a disease that imitates a whole spectrum of other diseases. This suggests that we should be actively looking for a pathogenic cause in these other diseases as well – especially since so many illnesses are still considered to be of unknown cause. Back in the day, the psychoses associated with syphilis and schizophrenia were grouped together into a single category of illness. But as soon as syphilis was found to have a bacterial cause, we separated syphilitic insanity from what is now called schizophrenia, and assumed that schizophrenia was not caused by infection. Rather than just separating the two diseases we should have actively pursued the hypothesis that schizophrenia also has an infectious cause. The information we can gain from these kinds of relationships is far more enlightening than any genetic data.

That’s one of the realities of medicine – researchers tend to deny associations. Denial plays a major role as scientists love to hold on to the current dogmatic explanation. This suggests that in order for pathogens to be fully tied to chronic disease we will have to wait until the current powerful people pass away and a sufficient number of young people entering the arena without these vested interests mature into positions of influence, to tip the balance of expert opinion. This is something that Charles Darwin, Max Planck, and Thomas Kuhn all agreed with.

That’s because powerful people tend to hang on to the opinions that made them powerful even if there is no longer sufficient evidence to support their views. It’s a social problem that relates to the weakness of the mind. Human beings didn’t evolve to be scientists. Instead they evolved to be competitive – to grab and hold onto what is theirs. Hence the name calling often observed among the medical community and the resistance among scientists to fund or support ideas other than their own, ideas that question the validity of current dogma.

From an evolutionary perspective is it possible that current diseases of unknown cause could all be genetic diseases?

No. Take schizophrenia again. Evolutionary biologists understand that if an allele (a sequence that codes for a gene) were to code for a disease it would slowly get weeded out of the population, particularly since people who are sick are much less likely to reproduce (especially people with a severe disease like schizophrenia). Yet a person’s chances of getting schizophrenia are 1 in 100. The reality is that faulty genes cannot maintain this frequency. If schizophrenia was a genetic disease, then according to the rules of mathematics, it would only occur in about 1 in every 10,000 people. The current frequency of the disease is just far too high.

Some might try to rationalize the 1 in 100 number by saying that schizophrenia is influenced by environmental factors, but if this were the case the environmental factors would have to be widespread and consistent across much of the world which is highly unlikely. Yes, some populations do have a higher incidence of schizophrenia than others, but that variability is much better explained by the idea that some populations harbor more of the pathogens that cause schizophrenia then others.

This highlights another issue. The fact that illnesses tend to run in families does not mean that only faulty genes are at work. Family members could just be passing each other pathogens. If one member of a twin pair has schizophrenia, there is a 35-60% chance that the other member of the twin pair will have it. However, this may be just a reflection of the fact that both twins were exposed to the same pathogens in the womb.

Pathogens also possess the ability to evolve and adapt at rapid rates, meaning that even if the host acquires a defense against them they can often find away around it. As previously mentioned, genetic disease would gradually be weeded out of the population. But as soon as you hypothesize that a disease has an infectious origin, and that the pathogens causing it can adapt and evolve, it is possible to explain how diseases can be perpetuated indefinitely in quite severe forms.

So you support the idea that the genetic mutations picked up on by many scientists may be induced by pathogens?

Yes, it’s possible. We know that some viruses and bacteria mutate and damage DNA. Similarly, the compounds created by the body in order to continually combat pathogens are often potent molecules that can also cause genetic mutations.

Give me some examples of diseases in which an infectious agent is certainly to blame.

Cancer is really a special case of the problems we have discussed. The same dogma has been driving how the disease is viewed for so long. But if people are able to recognize the dogma for what it is, they can take a better look at definitive evidence about the disease. Taking a look at the track record of cancer researchers is a good way to decide whether the consensus view is right or wrong.

Back in 1975, mainstream medicine agreed that about 0.1% of human cancer cases were caused by pathogens. When it came to the rest of cases, their view was that they were probably caused by a combination of inherited predispositions and mutagens. Then in 1985, the percentage of cancer cases they tied to pathogens was 3%, and they continued to make the same argument about the remaining cases. In 1995 the percent of pathogen-induced cancer cases was accepted to be around 10%. Now, we’re at 20%. Still, mainstream medicine contends that the other 80% of cases do not have an infectious cause, but the questions is – do you believe them anymore? In this sense, the clarity of hindsight can help a lot. Between evolutionary instinct and plain common sense we can view the issues of pathogens and cancer much more effectively.

Or, take a disease like atherosclerosis in which noting patterns of infection is unavoidable. There are bacteria in the lesions of people with the disease and all kinds of inflammatory markers. What we need to do is take a step back, divorce ourselves from our predispositions, and look at these ideas together.

Modern medicine has done a poor job looking for clues of continued infection. This may be partly explained by the fact that in many cases, it’s hard to link a pathogen to a disease because the pathogen grows and spreads so gradually. So the time at which a person becomes symptomatic may be years after the onset of infection.

Recognizing these patterns requires thinking broadly and deeply, but medical professionals and researchers have been trained to think narrowly. They’ve tried to follow a model that resembles a NASA undertaking for a great moon mission in which every person brings his or her own particular specialty to the table. But that model doesn’t work for medicine. Instead medical professionals need to work together with a unified theory in mind. But at the moment, they don’t have a unified theory, and without a conceptual model to guide them, researchers are only able to determine risk factors for disease rather than come to an understanding of the overall cause.

Evolutionary biology is the most synthetic area of biology. It asks why things are the way they are, and integrates knowledge of how things work mechanistically. Evolutionary biology promises to be the most synthetic area of medicine for the same reason.

While we’re on the subject of cancer, it and heart disease are now considered to be inflammatory diseases. Wouldn’t the presence of inflammation be a red flag that pathogens are to blame?

Yes. And the immediate questions researchers should be asking is “What causes inflammation?” One thing that we clearly know causes inflammation is the presence of an infection. So, as soon as I hear the word inflammation I think, “What infectious agents are at play?”

That brings us to the concept of autoimmune disease – the idea that the immune system just “goes crazy.” I think the fact that the concept of autoimmunity was developed in the first place is largely related to the fact that our brains have not evolved to think scientifically. People who have studied disease from their own point of view have recognized that the immune system is extremely important. But as we’ve learned more about the immune system, we’ve realized that it is an extremely complicated system – as complicated as the brain. Just like we can’t look at one type of neuron and infer information about the entire brain, we can’t try to understand the characteristics of only some immune cells and think we understand immune function.

So, over the years, as researchers have been daunted by the complexity of the immune system, it has seemed logical that such a complex entity has the potential to go wrong. Because they are limited by the power of their brains, they tend to simplify the issue and view the immune system in the same way they would view a truck that could break down. There are two problems with this type of thinking. For starters, we can’t trust our intuition that something complex is likely to malfunction. The fact is, the immune system functions just fine in a large proportion of the population. The only logical way to explain the immune activation seen in patients with “autoimmune disease” is to suggest that there is some sort of agent pushing the immune system off balance. This argument is only strengthened by the fact that the same evolutionary forces that would cause a serious disease to be weeded from the population would also cause those people whose immune systems are prone to self-destruction to be eliminated from the population.

Ewald with Milo in the boundary waters in Minnesota

The concept of autoimmune disease has progressed to the point that now even researchers who previously dismissed the possibility of infection are accepting the possibility that “autoimmune” disease could be triggered by infection. This is some progress, but it’s not enough. Especially since the concept of autoimmunity encourages doctors to prescribe immunosuppressive steroids to patients. But if persistent infection is involved these steroids may exacerbate the fire by allowing pathogens to spread.

Do you believe that pathogens could be involved in the aging process?

Aging is a super-category. We’ve gradually lumped together more and more symptoms under the category of natural aging. Many of these symptoms are the same as those caused by diseases that surely have an infectious cause. In that sense, you could view much of what we now call aging as an incapacitating illness that leads to a decrease in function. We know that inflammation and the interaction of the immune system with pathogens can destroy tissue. So it’s not surprising that the tissues of a person who harbors a lot of pathogens would age earlier and alter their biological structure earlier in life. I do believe it is inevitable that people will eventually die of old age, but I suspect that this should generally happen when they are 80-100 years old. But we are increasingly seeing signs of aging-related diseases in people who are much younger.

What does evolutionary biology have to say about psychosomatic illness?

Personally, I believe that we label an illness as psychosomatic when we don’t really know what’s going on with the patient. It’s a last resort diagnosis – a black box. If we knew more about what was causing their symptoms we could address the issue more clearly.

Looking at psychosomatic illness from an evolutionary viewpoint, you could say that those people who might exaggerate how sick they feel in order to gain attention and resources could have an evolutionary advantage. But if that’s the truth, it only accounts for an extremely small percentage of cases. It’s also true that often an illness will have both a psychological and physical component. But just because a psychological component is identified doesn’t mean the physical component should be overlooked. Plus, most mental illnesses are probably the result of infection too. Chronic Fatigue Syndrome is a good example of a disease that up until recently has been dismissed as psychosomatic just because researchers couldn’t figure out the cause. On the contrary, it’s quite a serious illness.

What role do you feel the Internet will play in facilitating acceptance of an understanding of pathogens in disease?

I think the Internet plays an incredibly beneficial role as it can provide information to anybody who is willing to put in the time to learn terminology and information presented in the literature available on the Internet. I believe it will, and already is, changing the patient/doctor relationship and also the relationship of the general public with the government mainly because we can now check up on things and check up on them quickly. I can find information in half an hour rather than spending an entire day at the library – and think about the fact that this is happening all around the country.

Of course, now there is so much information on the Internet that it’s too much for an individual mind to keep up with. Sometimes you have to read quite a bit of literature in order to extract the relevant information. That’s why we need people to team up and share information. What we need is small groups of people poring over information together. In this way they can develop a more thoughtful, broad outlook. This is in contrast to the current medical model in which doctors and researchers are trained to specialize in such a narrow area of knowledge. They know very little about issues outside their area of expertise and have trouble seeing the big picture. Thus, what we need is for the NIH to put money into grants that foster interdisciplinary insights.

Do you think that the peer review system and pharmaceutical industry are standing in the way of understanding chronic infectious disease?

I think the peer review system is becoming less important because there are so many other outlets where people can put up information. So I don’t see it as too big of a barrier.

When it comes to pharmaceutical companies, it’s important to recognize that they are very good at some things and very bad at others. What they are good at is product promotion and marketing, and working in innovative ways when the resulting product can bring in lots of money. The problem is the products that make the most money are not necessarily the products that actually help people the most.

Basic economic principles first put forth by Adam Smith show that the free enterprise system does not work well under certain situations. Writing over two hundred years ago, he argued that free enterprise cannot be expected to generate an effective national defense. For modern society, pollution control would be another example. If we want to move in that direction there needs to be a profit driven motive, or we have to get the government to do the things that do not generate sufficient profit. Otherwise, it just won’t happen.

If you think about it, there isn’t very much money to be made off a vaccine because a person uses it once or twice in his or her life and that’s it. Instead, think of the amount of money to be made off a statin when a person is going to take it every day of their life. There’s just not much motive for drug companies to invest in products that are cures or very good preventatives. We don’t have to condemn drug companies, just recognize this role that they are playing in drug development. If we want to develop a drug under a high priority situation that may result in a curative solution we can’t count on the pharmaceutical industry. In cases where the free enterprise system doesn’t result in a situation that may benefit the population the government has to step in and provide funding for the possibility at hand.

What kind of approach to research would best expedite the process of better understanding the role of infectious agents in disease?

Most experts in the health sciences advocate a building-block approach to the problem of causation. They try to understand the workings of disease at the cellular and biochemical levels, in hopes that solutions will eventually emerge. Even among infectious diseases, however, the fundamental achievements have occurred more through the testing of deductive leaps than by building-block induction. What it boils down to is that we need both types of development but we can’t have one without the other. Working incrementally can be great as long as scientists understand the big issues and the larger concepts that need to be guiding their research. But right now we have way too many scientists working in building block mode, missing what’s going on outside the box.

Why do doctors often have such a problem accepting the idea that pathogens are to blame for more diseases then commonly accepted?

Because it’s not in the textbooks. They are trained to look at a patient and try to match them with something in a textbook. These medical texts don’t consider the preponderence of evidence across the entire spectrum of possible causes of most chronic diseases. The evidence implicating infectious causation tends to be a casualty of this restricted perspective, leading to the result that consideration of infectious causation in medical texts is minimal for chronic diseases of uncertain cause.

So until infectious pathogenesis is accepted to the point that it is in the medical texts taught in medical school, they will continue to consult only the standard operating procedure. If they can’t put a label on the patient’s illness it falls into a bin of “unexplained phenomena” which goes back to what I was saying earlier about psychosomatic illness, since they have a tendency to speak dismissively about what’s in the bin.

The problem is that considering a new pathogenesis or a cause that isn’t in a textbook requires thinking hard about unknown problems. They just don’t have the time or training to think logically and deeply about such issues. This is evidenced by the fact that you can go to five different doctors, get five different explanations for your problem and be recommended five different treatment options.

What got you interested in this area of research?

My interest in evolutionary medicine began in grad school around 1977. I came down with a bad case of diarrhea and was thinking about whether I should treat the symptoms or let the illness run its course. At first it seemed like it was most logical to let the illness run its course because that seemed to be my body’s way of eliminating the pathogen. But then I thought about the fact that the pathogens might be manipulating me. If I expelled them, they might be endowed with an evolutionary advantage that would allow them to persist and infect others. I realized that my intuition couldn’t provide me with the answer. That led me on a long web-like series of connections. The more I started to consider medical problems in the light of evolution the more I realized that some diseases simply cannot be caused in a way they are explained by current dogma. So I’ve tried to look at disease in a balanced way, to put all possibilities on the table, and from there to figure out what’s feasible and what’s not.

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  • What do Microsoft and medical research have in common?

    Let’s start with the simple fact that they have both been wildly successful. Microsoft has 79,000 employees, global annual revenue in the year 2007 exceeding $51 billion, and has made more than 12,000 of its employees millionaires simply by increases in stock valuation. Additionally, Microsoft’s market share for the operating systems on desktop computers, by one 2003 estimate, is 90%. Not bad for a garage startup.

    In the United States alone spending on medical research is at or near the $100 billion mark in the year 2007. That’s about $300 for every man, woman, and child and more than doubles what was spent just a decade ago. According to Dan Fox, president of the Milbank Memorial Fund, a philanthropic group that works on health policy issues, the data in a recent JAMA review makes it plain that “we are spending huge amounts of money, more than any other country, to develop new drugs and devices and other treatments.”

    Not bad for a profession that used to do double duty as barbers.

    But perhaps the strongest connection between the multinational and the medical profession may be that both are, in some very key respects, failures.

    Anyone who has ever seen the dreaded “Blue Screen of Death” or had their computer infiltrated by spyware, adware, or other kinds of malware knows the shortcomings of Microsoft software. Maybe Microsoft is an easy target for the technorati, too easy it would seem. But let’s face it– Microsoft has over the past few decades consistently churned out software which costs more, has more bugs, and hogs more memory than comparable software. Right up to the present, new software releases have been slow in coming and devoid of groundbreaking features. Certain releases, namely Windows ME and Vista– some versions of which retail in excess of $350– have inarguably added very little if anything to previous releases. One prominent commentator, John C. Dvorak, in his colorfully titled column, “Vista Death Watch” has argued that the latest operating system, Windows Vista should be completely scrapped.

    Modern medicine, specifically medical research, may be in the same boat. Let’s concede that we all are very pleased that medicine has advanced to the point that a burst appendix can be safely removed, catheters can spring open blood vessels, and that eliminating wrinkles surgically is just a series of injections away– and with a toxin no less!

    When it comes to chronic illness, at least in its traditional form, medicine has largely failed. According to mainstream medicine, what causes Parkinson’s Disease? What causes cardiovascular disease? What about fibromyalgia? Lyme Disease? Crohn’s, cancer, bipolar disease, depression? The consensus among medical researchers has been, “We don’t know.”

    Now, maybe these conditions are all too complicated to unravel over the course of mere decades even for a world that spends hundreds of billions on medical research annually. For that matter, maybe it’s the case that having stable software largely impervious to malware is no less a pipe dream.

    Even if these explanations are mostly true, the absence of real solutions for chronic illness is not good enough– not for the hundreds of millions of patients watching the best part of their lives pass them by. For all the sound and fury of medical discovery we catch wind of these days in breathless press releases (Eureka Alert!), what chronic diseases have been definitively cured in the last few decades? You can count them on one hand: stomach ulcers and cervical cancer.

    Few would argue that medical researchers aren’t highly intelligent and capable or that Microsoft’s software engineers are the same, or that both groups contain people who are quite possibly the most intelligent and the most capable at what they do. If a failure of smartness isn’t the problem, then what is?

    This essay examines the Open Source Software (OSS) movement as a model for a more evolved, more effective system of medical research. We look at four lessons from the OSS movement and try to apply them to medical research. Also, we look at how one treatment protocol for chronic disease, the Marshall Protocol, incorporates many of these lessons and may represent a model for future medical research in more ways than one.

    Lesson #1: Use open review.

    One of the most influential works in the history of open source development is Eric S. Raymond’s, The Cathedral and the Bazaar. In this essay Raymond argues that there are two contrasting software development models– the cathedral and the bazaar. In the cathedral model, represented by Microsoft, software is available for all to use, but the ability to contribute to the code is restricted to an exclusive group of developers– wizards Raymond calls them– who work in “splendid isolation.” In the bazaar model, the code for a project is developed over the Internet in full public view, Linux and Wikipedia being excellent examples. In theory, anyone so inclined can contribute.

    The cathedral model holds that the key to success of a software project is the judgment and experience of a limited group of well-vetted and talented experts. Most proprietary software is necessarily developed using the cathedral model. In contrast, the bazaar model says, “Let’s engage as many developers as are inclined and qualified to participate.” The theory here is that the mistakes and red herrings of inexperienced or confused contributors is more than counterbalanced by an ability to rapidly improve the code given the fact that, as Raymond puts it, “thousands of eager co-developers are pounding on every single new release.”

    Which model is more effective in software development? Raymond explains his thinking: “I worked hard… at trying to understand why the Linux world not only didn’t fly apart in confusion but seemed to go from strength to strength at a speed barely imaginable to cathedral-builders.” For Raymond, the advantage of transparency and openness is simple: “Given enough eyeballs,” he writes, “all bugs are shallow.”

    The track record of a number of large-scale projects like the production of an operating system such as Windows XP seems to support Raymond’s opinion. The day Microsoft released Windows XP, the company posted 18 megabytes of patches on its website: bug fixes, compatibility updates, and enhancements. Two patches fixed important security problems. Or actually, one of them did; the other patch didn’t work. Microsoft suggested that users back up critical files prior to installing the patches. Buyers of the home version of Windows XP, however, discovered that the system provided no way to restore these backup files if things went awry. As Microsoft’s online Knowledge Base blandly explained, the special backup floppy disks created by Windows XP Home “do not work with Windows XP Home.”

    Though it’s certainly not the case with all closed or proprietary software projects, really big systems are forever in danger of the “tar pit” as Fred Brooks called it in his book The Mythical Man-Month. A tar pit– I would argue that that phrase is as apt a description as any to describe the state of research into chronic disease.

    Is medical research a bazaar or a cathedral? At least when it comes to chronic illness, I think it’s pretty clear that it’s the latter– the reason being that the Academy is just not open enough to opposing ideas. The results, or lack thereof, speak for themselves.

    Not only are pulmonologists unwilling to consider infection as the cause of sarcoidosis, but many have actively suppressed publication of articles that are at odds with their points of view.One need look no further than the field of pulmonology. Not only are pulmonologists unwilling to consider infection as the cause of sarcoidosis, but many have actively suppressed publication of articles that are at odds with their points of view. Biomedical researcher Trevor Marshall, PhD, head of Autoimmunity Research Foundation explains, “Dr. Om Sharma from USC Medical Center has kept the lid on bacterial pathogenesis when dozens of researchers have implicated pathogens in the disease.” Marshall says, “Dr. Sharma has discouraged discussion about patients who received organs from people with sarcoidosis also developed the disease – evidence which strongly supports an infectious cause.”

    As is the case with a lot of these “experts,” Dr. Sharma has authored or co-authored over 500 journal articles, some 70 reviews and sits on the editorial board of all the key pulmonology journals. It’s this last line on Dr. Sharma’s resume that has allowed him to effectively act as a gatekeeper for new ideas about sarcoidosis. Yet, even now, there is growing evidence that Dr. Sharma is mistaken in the worst way. What provision does medical research have for reining in the myopia of the Dr. Sharmas of the world? Is it really acceptable for medicine to advance but one funeral at a time?

    Or, take the work of Dr. Alan Cantwell who has photographed L-form bacteria in the cells of people with cancer for decades now. Dr. Cantwell’s research into the so-called “cancer microbe” is strong. He makes a number of claims worth further investigation or, at the very least, outright rebuttal. Yet, the medical community has largely marginalized his work such that it hasn’t even attracted a fraction of the attention it deserves.

    According to Dr. Cantwell, most pathologists who saw his specimens would practically refuse to admit that what they were seeing was bacteria. Few, if any, were willing to co-author a paper to that effect. “For the most part,” Cantwell said, “they didn’t want to get involved.”

    Why the cold shoulder from all corners of medicine? Is it because we have figured out the “true cause” of cancer? Well, that’s not the case. Though we certainly know how diet and heredity can effectively change the odds, we still have only the faintest understanding of what actually causes cancer. Or, is it true that it’s simply impossible that bacteria can exist in the size and shape described by Cantwell? No, there’s no reason to think that it’s not bacteria, specifically L-form bacteria, to blame. Entire textbooks, namely Lida Mattman’s Cell Wall Deficient Forms– Stealth Pathogens, now in its third edition, have been devoted to the culture and life cycle of L-form bacteria.

    Dr. Cantwell was asked to explain his colleagues’ refusal to entertain the idea that bacteria may be involved in cancer. He responded, “I think it’s because finding bacteria in illnesses that are not [thought to be] attributed to infection is highly controversial, and most doctors shy away from controversy.” But if that’s what it takes to open up the dialogue, isn’t controversy exactly what sufferers of chronic disease need?

    If you paid attention to your bulk mail announcing fundraisers, you’d think that the only reason diabetes or sarcoidosis or any number of other diseases have not been cured is a lack of funds for research. This, in spite of the fact that the National Institute of Health alone spends $28 billion annually on medical research.

    You could spend ten times as much money on medical research and without changes to the process of how ideas get considered, that money would be better used as wallpaper.You could spend ten times as much money on medical research and without changes to the process of how ideas get considered, that money would be better used as wallpaper. One of the enduring lessons of open source software development is that the best way to tame complexity is to open up the discussion to as many people and ideas as possible.

    Andrew S. Grove is founder of the computer chip maker Intel. Now Grove is suffering from Parkinson’s Disease and a medical system that continues to test drugs on rats in the laboratory but offers little, if any, medical options for human beings who suffer from Parkinson’s and other chronic diseases. Recently, Grove has been publicly critical of the biomedical establishment, particularly academic researchers, who while successful in getting NIH grants and publishing research papers, seem to have little regard for whether their work leads to ideas or treatments that can actually cure disease.

    “The peer review system in grant making and in academic advancement has the major disadvantage of creating conformity of thoughts and values,” Grove told a correspondent from Newsweek. “It’s a modern equivalent of a Middle Ages guild, where you have to sing a particular way to get grants, promotions and tenure. The pressure to conform [to prevailing ideas of what causes diseases and how best to find treatments for them] means you lose the people who want to get up and go in a different direction. There is no place for the wild ducks. The result is more sameness and less innovation. What we need is a cultural revolution in the research community, academic and non-academic.”

    It should be a no-brainer: medical research, particularly when it comes to chronic disease, ought to be more like a bazaar. You could start with peer review. Peer reviewers are often well-intentioned, but the fact that only two or three anonymous “experts” can act as gatekeepers for what gets published in prestigious journals severely limits the dialogue. Let’s allow increasing numbers of self-selected people– amateurs, volunteers, marginalized scientists– to critique work too. Let’s then publish all reviews, positive and negative, online. To the extent that we can make medical research less like a guild, let’s do that too. Too often grants are awarded on the basis of past success in winning a grant. Do we really want to continue to reward old ideas? Not when those old ideas are failures! Is that any way to foster new ideas and new approaches? After all, until a researcher succeeds in curing a chronic disease, he is neither an authority nor an expert.

    Lesson #2: Write software for yourself.

    In 2005, BMG Music Entertainment started selling CDs that came with copy protection software. Unbeknownst to users, this software contained an evil bit of code called a rootkit. Rootkits are a set of programs or instructions that effectively subvert control of an operating system from its legitimate users. They might allow a third party to install keyloggers monitoring bank account information or turn your computer into a zombie and have it send out thousands of spam email messages. According to security researcher Dan Kaminsky more than half a million machines were infected by the rootkit. Since then, Sony BMG has been the subject of numerous lawsuits and eventually had to settle in a national class action suit.

    What would drive Sony BMG to include rootkits with their CDs to say nothing of notoriously restrictive copy protection software? It all has to do with the bottom line. The rootkit was Sony’s heavy-handed way of preventing users from copying songs they had purchased. For the multinational conglomerate, the bottom line was protecting the profitability of their music artists even if it meant trampling consumers’ rights.

    But, if you’re an open source software developer, your bottom line is straightforward as can be: solving your own technical problems. Eric S. Raymond writes in The Cathedral and the Bazaar, “Every good work of software starts by scratching a developer’s personal itch…. too often software developers spend their days grinding away for pay at programs they neither need nor love.”

    What if everyone researching Crohn’s Disease had Crohn’s Disease? What if all those investigating bipolar had that illness? How would research change?The open source model has been successful time and again.AWStats, the excellent log analysis program, was written by developers who needed to know the makeup and characteristics of visitors to their websites. VLC Media Player was written by programmers who wanted to play back a range of audio and video codecs unrestricted in the way that Windows Media Player or even iTunes is. It’s laughable to think that any open source developer would include anything on par with Sony BMG’s 2005 fiasco.

    So, what if everyone who studied a chronic disease had that chronic disease? What if everyone researching Crohn’s Disease had Crohn’s Disease? What if all those investigating bipolar had that illness? How would research change?

    To paraphrase Samuel Johnson, nothing focuses the mind so much as a trip to the gallows. In sum, I think you would see a greater sense of urgency, a better openness to new ideas, and an increased willingness to do away with ideas that have gone long past their expiration date (more on this last one later).

    The remarkable thing about being a researcher of chronic disease is that you can spend entire careers without actually contributing anything useful to the understanding of it.

    It’s not the fault of researchers, necessarily. It’s the way these professionals are rewarded for their contributions. As it stands, developing and investigating bonafide cures for chronically sick patients can all too easily take a back seat to getting published, getting funded, and getting promoted– “time, tender, and tenure,” Thomas Goetz calls it. As it stands, you are more likely to get funded if you have gotten funded. As it stands, you are encouraged to publish research which has positive results, even with the most tepid, toothless conclusions, because positive results get published.

    If there was the least bit of urgency, you might see the serious reconsideration of a variety of treatments, starting with the use of corticosteroids for sarcoidosis. The 2003 ACCESS study, which was funded by the NIH, shows that two-thirds of sarcoidosis patients do not get better on current treatments and those that do see improvement are in no way correlated to whether or not they received treatment.

    Given all this, you would think researchers would be interested in any broad reconsideration of what causes sarcoidosis. One such idea that sarcoidosis is actually an infection has been posed by Trevor Marshall among others. In fact, since 2002 when the Marshall Protocol treatment was first published– open source style, online– many patients have claimed recovery on the antibiotic-based treatment. Strangely, the response from sarcoidosis doctors, primarily pulmonologists, has been lukewarm at best. “We’re not even on their radar,” Marshall has said of the pulmo doctors.

    You would think that a new idea such as this one, which was backed by molecular data, would receive less of a chilly reception. You would think that this is exactly the kind of big idea sarcoidosis researchers should be looking for. If it was their own skin at stake maybe they would.

    Lesson #3: Openly and honestly size up failure.

    When it comes to chronic disease, there is no failure more categorical, more disastrous than the autoimmune model of illness. Autoimmunity is the idea that– contrary to the forces of natural selection or the dictates of basic common sense– the immune system *somehow* goes haywire and attacks the body.

    One way to measure the worth of a theory in medicine is to gauge how that theory can functionally improve what should be everyone’s ultimate bottom line: patients’ health. In short, all the anti-inflammatory, immunosuppressive, and palliative medications given to those suffering from “autoimmune illnesses” are failures. If I were being paid by the word, I could list hundreds of first line anti-inflammatory, immunosuppressive drugs that don’t cure hundreds of chronic diseases. Corticosteroids do not cure sarcoidosis. Neither hydroxychloroquine nor cyclosporine cures lupus. Prednisone does not cure multiple sclerosis.

    Of this class of drugs meant to treat autoimmune illness, prednisone is typical. Patients taking prednisone complain of weight gain along with any number of other symptoms including itching, increased sweating, irregular or absent menstrual periods, inappropriate happiness, and irregular heartbeat– and that’s just symptoms beginning with the letter I!

    First proposed in more general terms by Paul Ehrlich more than 100 years ago (horror autotoxicus he called it), this theory of autoimmunity has had a lot of time to be tested and refined. Instead, further investigations have only rendered the concept of autoimmunity more flawed and more complicated. Wikipedia lists five theories about what causes autoimmunity: the clonal deletion theory, the clonal anergy theory, the idiotype network theory, the clonal ignorance theory, and the suppressor population theory. What do all these mean?… Does it matter? The point is, as an idea, autoimmunity is a failure.

    A healthy sense of proportion– some would call it succumbing to realism– is much more common in the realm of programming especially of the open source variety. In fact, one of the colorful but enduring proverbs of the programming world, seen in a variety of forms is, “All software sucks.”

    Ron Avitzur has said during the development of his groundbreaking piece of software called Graphing Calculator that if your software was exceptional, fellow engineers would simply say, “This sucks less.”

    Maybe if the medical research community could be a bit more philosophical about failure, certain ideas that have gone long past their expiration, namely autoimmunity, could have been unceremoniously discarded long ago. Some would argue that any kind of operating system Microsoft produces is doomed to be underwhelming given its tens of millions of lines of “legacy code,” and maybe that’s not such a bad analogy for the concept of autoimmunity as they both share any number of fundamental flaws.

    Maybe if the medical research community could be a bit more philosophical about failure, certain ideas that have gone long past their expiration, namely autoimmunity, could have been unceremoniously discarded long ago.The problem for medical research is that it has made little to no provision for failure. With certain notable exceptions (i.e. Journal of Negative Results in Biomedicine) journals tend not to publish negative results, a phenomenon known as publication bias. The media tend not to cover studies showing the absence of a connection.

    If a negative result is based on good science, why confine it to obscurity? Why would we want to, in essence, encourage researchers to produce positive results even if those results make no significant contribution? You get what you ask for, and our system is, in essence, asking for such results.

    One thing medicine might quickly discover if, as a whole, it better embraced failure is just how ineffectual old approaches to chronic disease have been.

    Lesson #4: Seek to rapidly deploy multiple versions of software by iterating incrementally and openly.

    While Andrew S. Grove was at Intel, the number of transistors on a chip has gone from about 1,000 to almost 10 billion. Over that same period, the standard treatment for any number of chronic diseases has remained unchanged: L-dopa is still the standard treatment for Parkinson’s just as it was nearly half a century ago.

    “I picked the semiconductor [transistor] industry because it’s the one I know; I spent 40 years in it, during which it became the foundation for all of electronics. It has done a bunch of unbelievable things, powering computers of increasing power and speed,” says Grove.

    So, twelve years ago, when Grove was diagnosed with prostate cancer he immediately jumped into the advocacy movement, with the expectation that quick, deliberate action could push scientists in the field of cancer research in the same way that a drive for innovation and knowledge had inspired his team at Intel. But nothing happened. “I got disappointed with the lack of real output,” says Grove. “Not much has changed 12 years later.”

    In the last 20 years, there are only two common chronic illnesses for which the cause has been established. I’m thinking here about cervical cancer, caused by the human papillomavirus, and ulcers also found to be caused by bacteria. Is this pace acceptable?

    In January of 2007, Scott Rosenberg wrote a piece about the debacle that is Microsoft Vista. First began in 2002, the development of Vista was beset by a series of problems. Microsoft developers were ultimately unable to execute the original grand vision, which included a complete file system overhaul. As a result, the new operating system came in much later than scheduled and lacked many of the originally promised features. Rosenberg’s analysis: without discipline “too often, software teams get lost in what are known in the field as ‘boil-the-ocean’ projects — vast schemes to improve everything at once.”

    Where did Microsoft go wrong? Some of the failures of process are touched upon elsewhere in this essay, but I would suggest here one of those problems was an inability to iteratively build upon their project by harnessing the power of their natural community, their end users.

    Those who follow software development are familiar with the idea of “perpetual beta,” or that certain software is always being added to and improved upon. Popular examples of software that have had the label of perpetual beta include Gmail, Google Maps, and For many developers, “perpetual beta” is an attitude as much as anything. It starts with the assumption that software should be better. Changes are rapid, but incremental. Testing and assessment are done frequently.

    Even those of us eager for cures to chronic disease recognize that magic bullets do not magically arise as if willed to exist. They need to be worked on, worked over, the subject of productive consideration. Dialogue is the order of the day.

    Jean-Claude Bradley practices something he calls open notebook science, which he describes as making his online laboratory notebook freely available and indexed by common search engines. The underlying philosophy, Bradley says, is as pithy as it is bold: “No inside information.” On his UsefulChem blog he and his collaborators share and discuss chemistry problems and on his UsefulChem wikiobservations from experiments in excess of 150 are described and logged.

    What do third parties do with this data? Maybe nothing. But then again, perhaps a failed experiment or an unanswered question– the programming equivalent of a feature request made before the open source community– could spark progress. It could be the key to new advances and new understanding.

    Bill Hooker on the excellent 3QuarksDaily blog writes that “From our current perspective we cannot predict more than a fraction of the ways in which openness will transform the culture and practice of science.” The advent of collaborative science and the openness that drives it has the potential to help us refine our understanding of medicine at increasing speed.

    We cannot predict more than a fraction of the ways in which openness will transform the culture and practice of science.A prime example of this openness is the world of genomics. Right now, anyone anywhere can search NCBI’s online gateway Entrez and dig into any number of mRNA, genomic DNA and protein sequences using some thirty interconnected and all freely available databases. It’s easy to see how these kinds of resources made freely available can really allow researchers to rapidly and iteratively build knowledge.

    Even in the field of chronic disease, we have seen promising developments where clinical data is posted online and made freely available for inspection. I’m speaking here about the Marshall Protocol site. As of December of 2007, the MP site has 5,000 members and 125,000 posts, the vast majority of which come in the form of self-reported statements of progress. When it comes to the sheer scale of open clinical experiments, the MP may be in a class of its own.

    Patients suffering from a variety of chronic diseases including fibromyalgia, sarcoidosis, multiple sclerosis, even autism are on the Marshall Protocol, a novel antibiotic-based treatment for chronic diseases which is in some respects the original inspiration for this essay. Using instructions that can be downloaded from the web, patients work in conjunction with their prescribing physicians to put the Protocol into practice: avoiding vitamin D and taking low-dose pulsed antibiotics as well as Benicar, a Vitamin D Receptor agonist.

    While the science behind the Protocol hasn’t changed much since 2002 when it was first made available to patients, the site is designed so that each patient reports symptoms and reactions to medications in a weekly progress report entry. Not only are these progress reports open to other patients who can ask questions about data, or on occasion offer advice, but they are also open to analysis by the FDA (who actively monitor the site) or any other health care agency, think tank or organization who wish view the data. Any doctor, scientist, or medical researcher can become a member of a special forum for medical professionals, which not only allows them to view progress reports, but gives them a place to actively engage in discussions about specific cases and share ideas about treatment and research.

    Another indication of this study site’s uniqueness is the chance to get feedback on one’s progress from nurses and researchers including, often enough, from the originator of the Protocol, Trevor Marshall. In fact, this is very similar to the open source software community where end users can be in direct contact with the developers from whom they downloaded the source code.

    This is in marked contrast to most other treatments where a patient’s reactions usually do not go much farther than the doctor’s office. Under such circumstances, each separate case history ends up in a different place, almost always at a metaphorical dead end. Such reports go hidden from the eyes of the public, other researchers, and medical professionals who might under many circumstances offer important feedback or learn something.

    With open clinical data, such as the kind on display, patients can discover a thing or two from researchers themselves but also from each other. How will I react to Benicar? Have patients who share my condition really experienced the telltale reaction to antibiotics? These are all questions that can be effectively and convincingly answered by fellow patients. Such insights make a tough treatment that much more manageable, and it’s the openness that allows it.

    Who can use this study site? The science behind the MP has broad application, so a range of patients with different conditions can participate. Almost no one is turned away. This is quite different from other clinical trials in which participants are required to fit specific inclusion criteria with the aim of accumulating the most homogeneous group possible.

    Had the Marshall Protocol followed that model, how much longer would it have taken to confirm that the Marshall Protocol works to treat other diseases besides sarcoidosis? Surely, since Marshall’s first model was based on sarcoidosis, any other clinical trial model would have carefully excluded patients with other diseases, ailments, and symptoms. But it was by allowing patients with a wide array of symptoms to join his open internet-based site that Marshall soon collected data demonstrating that symptoms other than those related to sarcoidosis respond to Benicar and antibiotic therapy – a reality that would have taken decades for a standard clinical trial to reveal.

    A parting thought

    If the research medicine were anything like the open source software movement, study sites like Marshall would be springing up left and right as other researchers jumped on the possibility that their data might also have a greater impact if freely available on the Internet. You might also see a greater number of bad ideas relegated to historical curiosity.

    Medical research today has all the turning radius of an oil tanker. As a whole, it is too slow to accept and instigate positive change, and any sensible person would be right to lay a good chunk of that blame on the process itself.

    Innovation: how can researchers better innovate in the field of chronic disease? I argue that when it comes to innovation, the open source software community is particularly inspired– and instructive.

    For those of us who truly care to fight chronic disease, what lessons can we learn? Release early and often. Iterate. Practice openness to the point of promiscuity. Collaborate. Embrace failure. No failed or failing system has to be as it is. We can be worlds more productive. Let’s get to work.

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  • Greg Blaney, MD, graduated from the University of Ottawa in 1974. Following internship at Edmonton General he joined a Community Health clinic in Ottawa. From 1987 to 1990 he was a teaching assistant in the College of Osteopathy of the CME program at Michigan State University, having trained in both conventional and manual medicine during the first two decades of his career. He went on to also gain competence in Acupuncture and Homotoxicology, was a medical advisor to the LaLeche league, the Childbirth Education Association, the RCMP and the Bank of Canada. He lectured in the University of Ottawa’s Residency program, and its Masters program in nutrition. Dr. Blaney is currently using Autoimmunity Research Foundation’s Marshall Protocol to save the lives of hundreds of patients with a wide variety of chronic inflammatory diseases.

    How did you become aware of the Marshall Protocol (MP)?

    Before learning about the Marshall Protocol my work had evolved into a chronic pain practice, where I focused on osteopathy and trigger point injections. Despite the fact that some people seemed to benefit somewhat from these therapies, I always had a certain group of patients with chronic symptoms that simply did not respond to anything I tried. I had one patient who was actually aggravated by most of these therapies and displayed multiple symptoms in different areas of her body that did not respond to treatment. At the same time, I was also treating a woman who had been diagnosed with Lyme disease ten years before becoming my patient, however her symptoms had gone into temporary remission. Although she had been told by another doctor that she was “cured”, when she was in a car accident, all of her Lyme symptoms returned. After being tested, she was once again positive for Lyme.

    I started to investigate Lyme disease and it seemed very feasible that bacteria could be persisting in my patients who had tried everything but were not improving. I decided to attend the International Lyme and Associated Disease Society (ILADs) Conference where Dr. Marshall was scheduled to give a small presentation. Before listening to Dr. Marshall speak, I attended a talk about the standard ILADs treatment for chronic Lyme disease. Their advice was to give patients with chronic Lyme disease high-dose intravenous antibiotics. I wasn’t impressed by the approach because it seemed like administering antibiotics in this manner could have numerous toxic side effects. Now, I also realize that many of the antibiotics used by doctors that follow these recommendations actually foster the growth of L-form bacteria (the beta-lactam antibiotics). Furthermore, I wasn’t impressed with the data they had compiled about high-dose antibiotics and Lyme disease. In the long run, no patients actually seemed to be getting better.

    In contrast, Dr. Marshall’s presentation seemed to make a lot more sense. He spoke about L-form bacteria and about how levels of the hormone/secosteroid “vitamin” D become dysregulated in people with inflammatory disease. At the time, I was suffering from quite a few ailments – cardiac arrythmia, low-level psoriasis, restless leg syndrome, general fatigue and some loss of cognitive function. When I came home from Dr. Marshall’s talk I decided to test my own vitamin D levels. My wife was suffering from chronic jaw and sinus problems so I tested her D levels as well.

    Sure enough, both of us displayed dysregulated levels of the two vitamin D metabolites, 25-D and 1,25-D. Consequently, I decided that my wife and I should be guinea pigs and start the MP ourselves, which we did. After that point, I also started to check my patients’ D metabolite levels and test them for tick borne pathogens and Chlamydia. Nearly all of them displayed dysregulated levels of vitamin D and tested positive for different species of bacteria. When I looked at their bloodwork they also showed other markers of inflammation. I decided to start many of these patients on the MP.

    What conditions have you seen respond to the MP?

    I’ve had people with numerous inflammatory conditions do very well on the MP. I’ve had patients with arthritis, fibromyalgia, cardiovascular disorders, hypertension, Raynaud’s syndrome, Chronic Obstructive Pulmonary Disorder (COPD), chronic headaches and migraines, and other diseases respond very well. I’ve also had patients with mental afflictions such as obsessive compulsive disorder, anxiety disorders and depression do very well.

    I’ve noticed that people with CFS are definitely able to recover as well, but it usually takes them a longer time to note signs of improvement – sometimes well into their second year on the treatment. I find that people with psoriatic arthritis also have severe immunopathology reactions. The people I find most challenging to treat with the MP are those with inflammatory bowel disorders. Not that the MP won’t work for them, but sometimes their immunopathology is hard to manage.

    What patients have impressed you most with their recoveries?

    The patients that have the most spectacular initial responses to the MP are often those with severe headaches. I’ve had some patients whose headaches disappeared the moment they started Benicar. I’ve found that many patients with rheumatoid arthritis (RA) also show marked reduction in inflammation after just a few months of MP therapy. It’s easy to see these improvements because they are reflected in the patient’s bloodwork. For example, I can look for drops in C-reactive protein and sedimentation rate. At the moment I have an RA patient who is also being monitored by another rheumatologist. This doctor was initially skeptical of the MP, but I feel that when he sees how this particular patient’s bloodwork has improved, it will be easier for me to cajole him into mentioning this case in some of his papers. Hopefully he may also talk about the treatment with other patients. He just won’t be able to deny the signs of improvement.

    Over the long run, what I’m usually most impressed with is the universal improvement in cognitive function that I see in nearly all my patients as they progress to later stages of the MP. The MP is such a safe way to improve mental function.

    Why do you say the MP is safe?

    For one thing, ARB medications have been used in medicine for a long period of time and have not been shown to cause any significant adverse reactions. It is pretty much universally accepted that these medications are safe to use. In fact, at the moment, ARBs are being administered to some cancer patients at doses that are drastically higher than those used by the MP – around 800-1000 mg daily. The standard MP dose is 240 mg a day. Even at these high doses used in cancer, ARBs have not been shown to have any adverse side effects.

    The MP antibiotics are taken in very low, pulsed, doses. There is no data showing that antibiotics taken in this manner pose any danger to the patient, and clinically no adverse events have been reported among patients taking antibiotics in this fashion. Some people mistakenly interpret changes in immunopathology as adverse events, without understanding that a rise in symptoms is a necessary part of the healing process.

    For more on immunopathology see the Phase 1 Marshall Protocol guidelines.

    Do you put all of your patients on the Marshall Protocol?

    All of them that are willing to do the treatment. It’s pretty amazing how many people out there are walking around with L-form bacteria and could be helped by the MP. When I tell patients about the Marshall Protocol I say, “This treatment is safe and effective, but you also have to be willing to deal with immunopathology and this is not a short-term process.” This makes some people shy away. Some are intent on searching for a quick fix. For example, I have a patient with back symptoms that I know are the result of inflammation, but he’s not interested in the MP because it requires such a commitment.

    But when it comes down to it, I feel that MP will work for anyone who has a chronic condition, unless of course that condition is the result of a catastrophic injury. All chronic symptoms are the result of L-form and biofilm bacteria draining the ability of the immune system to function correctly. These bacteria are always percolating. The science behind the MP is extremely sound. Not that it can’t evolve and improve but I have no doubts about the treatment.

    Why do other doctors often seem skeptical about the MP and how can their concerns be addressed?

    Since Benicar is marketed as a blood pressure lowering medication, many doctors don’t think outside the box and realize that it has other very important effects that allow it to reduce inflammation and stimulate the immune system. They resist the idea that patients can maintain a normal blood pressure while still taking the ARB.

    Many doctors are also afraid that long-term use of antibiotics will lead to resistance. In reality this isn’t an issue. When antibiotics are pulsed, the concentration of the antibiotic in the tissues is always changing and there are different levels of antibiotic in the body at any one point in time. Because the level of antibiotic is never constant, it is impossible for bacteria to develop resistance mechanisms. The effectiveness of pulsing a substance in order to eliminate the ability of a pathogen to develop resistance has been demonstrated with pesticides. It has been found that disseminating pesticides in spurts rather than in a continuous fashion keeps the pathogens in crops from becoming resistant to the chemicals in the pesticide. Plus, we continue to find that when patients take minocycline, it continues to generate strong changes in immunopathology even after they have been taking the drug for many years.

    I find that general practitioners are generally a little more open to the MP, but most of them feel they are too busy to actually sit down and fully read all the literature pertaining to the treatment. The MP is a very complex treatment so there’s a lot of research to be done if one is to understand it correctly. Specialists are difficult to convince because they tend to be rather narrow-minded. If the MP doesn’t invoke or make reference to something they have heard at a recent conference, they tend to ignore the possibility that it might work. It seems that many doctors are just hardwired to resist innovation and change.

    It’s also hard for some doctors to accept the idea that the patient must avoid vitamin D. But I feel these concerns will become less frequent as more doctors realize that we’re telling patients to avoid a hormone/secosteroid, not a vitamin. We need to stop referring to “vitamin D” as a vitamin. I tell my patients, “What would you say if I told you to add testosterone to your food? You would tell me I’m crazy!” Adding “vitamin” D to the food supply is as ridiculous as telling the public to take large amounts of any other hormone. If you ingest massive amounts of any hormone or steroid it’s clearly going to throw off the body’s natural state of homeostasis. I have to say it boggles my mind that when molecular biologists have clearly recognized that vitamin D is not a vitamin doctors are still thinking of it as a nutrient rather than a hormone/secosteroid.

    What is the aspect of the MP that is hardest for patients to understand?

    The hardest concept for people to grasp is that of the immunopathology reaction – the fact that a rise in intensity of symptoms is not a sign that the disease process is advancing, but a reflection that the immune system is active and killing bacteria. We have been hardwired to equate symptoms with disease, but what many people do not realize is that all disease symptoms are the result of an immune system response. If a person gets infected with a virus, the rise in symptoms they display is not caused by the virus, but the response of the immune system to the virus. Once on the MP, some patients report intense exacerbation of symptoms, severe lightheadedness, or profound fatigue, and are convinced that they are getting sicker. I have to assure them that what they are feeling is the natural result of their immune systems dealing with toxins, cellular debris and the remains of dead bacteria. Europeans are usually more open to the idea, but North Americans have really been brainwashed to equate symptoms with disease. In cases where people have trouble grasping this concept, the biggest hurdle is to get them through the first phase of the treatment when the immunopathology is often strongest. If I have any dropouts, they come from this group – the people who can’t intellectually grasp the idea that they need to feel worse before they get better.

    How many people would you say drop out?

    Well, about 20-25 percent, maybe less, all of them during the first phase of the treatment. People with CFS are often impatient because in most cases even after they’ve done the protocol for over a year they feel just as symptomatic as they did at the start. It isn’t until well into the second year that they begin to note improvement. They do improve, but it takes them longer to get better than patients with other diseases. The CFS people also get a lot of slack from other doctors who don’t understand that they need to hang in for longer periods of time before noting improvement. Some patients also lack family support and find it difficult to push forward with the treatment when those around them don’t understand why they are experiencing temporary rises in symptoms. Those who are supported by family and friends do much better. One of the things I believe we should focus on is how to better educate family members about the treatment so that they can provide a better support network.

    Some patients with mental illness also prove to be challenging cases because they need to take quite a few medications in order to manage their symptoms and these medications often interfere with the ability of the immune system to function correctly. Also, many of their family members are not willing to put up with the rise in psychological symptoms that results from the immune system reaction.

    What do you see as the future of medicine?

    I believe that there will finally be recognition of the fact that bacteria do not manifest themselves in the manner in which we are taught in medical school. Doctors will accept that when acute infections are treated, the bacteria causing the disease doesn’t necessary clear, but can mutate into forms that can persist in the body for long periods of time. Then, they will recognize that these persistent bacterial infections are a major medical problem. Perhaps this will lead to further research into how these bacteria will respond to other antibiotics. Maybe new antibiotics will be created to target these pathogens. This reality is already starting to infiltrate mainstream medicine as studies are coming out showing that adult asthma seems to be the result of bacteria that have persisted in the throat since childhood. The same thing can be said for chronic lung infections, chronic bladder infections and well, most chronic conditions.

    I also believe there will be an emphasis on further research into the ways that ARBs can be used to regulate the immune system. Finally, I feel there will be recognition of how bacteria can affect the body’s enzyme systems. This will finally move the focus of medical research away from genetics and towards the reality that bacteria are instead able to directly affect the function of the body’s receptors. Rather than looking at how to turn on and off genes, we can look at how the receptors that control and activate the genome are affected by the presence of L-form bacteria and other substances. Dr. Marshall has already shown that the inflammatory process can dysregulate the thyroid receptors, the glucocorticoid receptors and many of the other nuclear receptors. Armed with a better understanding of how the body achieves homeostasis, we can modify the receptor response in order to restore an organism’s ability to go into normal self-regulatory function. Perhaps we can use this information to develop new therapies.

    There will also be a revolution in concept that will move doctors away from trying to reduce or suppress the end products of an illness. Instead they will learn how to manage the disease process itself. For example, right now it is believed that high blood pressure can damage blood vessels. But high blood pressure is just the end product of an inflammatory response generated by bacteria in the vessels. Rather than trying to use medications to lower the patient’s blood pressure directly (which is what we do now), we can go after the pathogens that are causing a patient’s blood pressure to rise in the first place and actually cure the illness.

    Do you feel that the MP is able to affect the aging process?

    Yes absolutely. My own health has recovered to a point where I see signs of age reversal. My eyesight has improved, my hearing has improved, and my cognitive function is better than ever. After I exercise I feel invigorated – the way I used to feel when I was young, rather than drained. There is no doubt that the MP can have a significant effect on a patient’s longevity. 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. As people grow older, their immune systems are forced to deal with higher bacterial loads, which in turns 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.

    That means that I’m going to be greedy about staying on antibiotics until I’ve reaped every possible benefit of the MP. Come this Christmas I will have been on the MP for three years. All my symptoms are gone and I feel completely healthy. Except for one small issue. I still have occasional tinnitus. Some days it’s completely gone, but other days it’s still at about 20% of where it used to be. I’m staying on antibiotics until this issue is completely gone. I can see myself staying on antibiotics for at least another six months, maybe even a year. I have no concerns about staying on them for a longer period of time. Some of the symptoms that I suffered from before the MP started when I was only 5-6 years old, so I had been sick for over 50 years. I have no intellectual concerns about spending 4-5 years on medications in order to reverse disease symptoms that had manifested over such a longer period of time, especially since I know how slowly L-form bacteria grow and how they can become dormant for periods of time. I also feel there are simply no adverse reactions or negative side effects that I need to worry about while taking the MP medications. It’s an extremely safe approach.

    Is it hard to put patients on a treatment in which they are in control of dosing their antibiotics?

    It’s sometimes problematic when a patient is also being monitored by other doctors and they are being given incorrect advice about managing the MP medications. That’s why I strongly feel that before putting patients on the MP, doctors should do the treatment themselves. That way they get a good idea of what their patients will experience and are later able to reassure and guide them much more effectively. For example, when a patient comes to see me during the early stages of the treatment I’ll ask, “Is your jaw sore?”, “Do you feel…?” And they’ll say, “Yeah!, yeah!, that’s exactly what I feel!” Then I can assure them that I also experienced those symptoms and say, “well, what you’re feeling is completely normal.”

    I think we should continue to work on creating resources that allow the patient to become better at learning how to dose their antibiotics and manage the treatment on their own. Rather than having to ask questions about how to proceed or requiring advice from doctors and the board staff, they can learn to manage and understand their reactions – to be able to say, “Oh, I’ll take an extra Benicar”, or “Oh, I’ll space my antibiotics out to three days rather than two.” The treatment works best when patients are able to intuitively manage their own body responses in this manner.

    What advice to you have for other doctors with patients on the MP

    Doctors should take the time to really understand the science behind the Marshall Protocol. That way they will recognize that 99% of the time the changes observed in their patients, or fluctuations in lab results are the result of immunopathology and not cause for concern. Otherwise they will often incorrectly infer that changes in bloodwork are somehow due to toxicity from the medications. Severe immunopathology reactions are not a sign that something is going wrong, but only a reflection of the fact that the treatment is actually working too effectively. By sitting down and reading about the MP in depth, they will also develop a greater confidence in the safety of the treatment, so that instead of freaking out when a patient’s kidney function temporarily drops, and often blaming Benicar for the situation, they will realize that decreased kidney function is just a result of immunopathology in the kidneys that can be managed. There is simply no evidence that Benicar can affect kidney function – there are even patients on dialysis that take Benicar. It’s also important to learn how to counsel patients during flares in which their immunopathology may kick in very strongly in order to help them manage their antibiotics and keep the reaction under control.

    Another thing doctors should understand is that in the case of nearly every patient, immunopathology occurs in the brain. This means that during much of the treatment, patients are not thinking properly and have psychological issues. These mental reactions should not cause doctors to question the stability of the patient, but instead it should be understood that every patient will experience a certain level of confusion, anxiety and neurological symptoms while on the MP.

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  • Dr. Alan Cantwell has investigated the phenomenon of cancer bacteria for over thirty years. A graduate of New York Medical College, Cantwell completed a residency program in dermatology at Long Beach Veteran’s Administration Hospital in Long Beach, CA and then practiced in the dermatology department of Kaiser-Permanente in Hollywood, California, from 1965 until his retirement in 1994. Dr. Cantwell is the author of more than thirty published papers on breast cancer, lymphoma, Kaposi’s sarcoma, Hodgkin’s Disease, lupus, scleroderma, AIDS, and other immunological diseases. These papers have appeared in many peer-reviewed journals, including Growth, International Journal of Dermatology, Journal of Dermatologic Surgery and Oncology, and the Archives of Dermatology. He has also written The Cancer Microbe and Four Women Against Cancer and several books on AIDS.

    1. How did you become interested in looking for bacteria, first in diseases like scleroderma and later in cancer?

    It all started when I was a second year resident in dermatology. I was in the medical library and I came across a paper in the Southern Medical Journal describing a group of people who had been given allergy injections and who subsequently developed deep skin infection with tuberculosis-like germs. It was thought the allergy injection bottles were contaminated with these bacteria.

    At the time, I had a mentally disturbed patient who had been given multiple injections of medications into her buttocks. She later developed deep painful skin nodules in the same areas. No one knew what was causing these nodules that were diagnosed as “panniculitis,” an inflammation of the fat layers of the skin. I thought, “Let’s culture a skin biopsy from one of these deep nodules and see if I can find any TB-like germs.” I was amazed when Eugenia Craggs, the technician at the TB lab, reported that “acid-fast” bacteria were discovered in the skin tissue. I thought “Hey this is just like the article!”

    We also had three other patients with “panniculitis” of the fatty portion of the skin, all of unknown cause. I took biopsy samples and TB-like bacteria were found in all four. These cases were later reported in the Archives of Dermatologyin 1966. At the time my dermatology professor was J. Walter Wilson, who was also a world famous mycologist, an expert in fungal diseases. He was somewhat skeptical about my findings of acid-fast bacteria in all these four patients and he suggested I use a scleroderma patient as a “control.” Scleroderma is a so-called “collagen disease” where the skin becomes hardened. The disease can affect the internal organs and is sometimes fatal. The cause is unknown, and bacteria were never thought to cause this disease. Dr. Wilson said I should check a scleroderma skin biopsy because that would serve as a negative “control” case. I was astonished when Eugenia Craggs called me from the TB lab and told me the skin tissue grindings of the scleroderma sample were positive for acid-fast bacteria, the kind of bacteria found in tuberculosis. She would try and grow the germ in a TB culture. After much searching I was also able to find a few acid-fast rod forms of bacteria in the scleroderma skin biopsy microscopic sections prepared by the pathologist.

    The scleroderma bacterial took a long time to grow and could not be diagnosed as a TB germ or other definite “atypical” mycobacteria. The microbe was highly pleomorphic (various forms). There were round staphylococccal forms, as well as typical acid-fast rod forms. Eventually this isolate became fungal-like and “actinomycete- like.” Despite expert opinion, it was impossible to classify the microbe into a specific species. This case of scleroderma was reported in The Archives of Dermatology in 1966.

    Some time later, Roy Averill, one of the dermatology residents, told me he heard a woman physician being interviewed on a San Diego radio talk show. She was explaining how she found TB-like bacteria in scleroderma in the late 1940s. That woman was Virginia Livingston M.D. She quickly became a dear friend and mentor in my scleroderma research. She told me that scientists at the Pasteur Institute in Belgium also reported finding acid-fast bacteria in scleroderma in 1953, thus confirming her own research.

    I naturally thought all these reports in the medical journals would be recognized by other dermatologists and scientists, and that scleroderma would be recognized as an infectious disease caused by acid-fast bacteria. But after more than a half-century, I’m sad to say that scleroderma is still considered a disease “of unknown etiology” and the bacteria we found are simply ignored. After discovering acid-fast bacteria in scleroderma, Livingston found similar bacteria in cancer. This made her one of the most controversial physicians in America, as detailed in my book, “The Cancer Microbe.”

    2. How did you identify the bacteria in your samples?

    I began my dermatology practice at Kaiser in Hollywood in 1965. Virginia Livingston introduced me to Dan Kelso, a Los Angeles microbiologist who thereafter cultured my skin biopsy samples from scleroderma, and later from lupus erythematosus and a variety of cancers. Depending on the case, sometimes he cultured Staphylococcus epidermidis, or corynebacteria, more rarely streptococci, and pleomorphic bacteria that appeared sporadically as acid-fast bacteria similar to Mycobacterium tuberculosis.

    Naturally I attempted to find acid-fast rod forms in my specially-stained skin biopsy sections, because these forms are the typical forms signifying infection with Mycobacterium tuberculosis or other species of mycobacteria. “Acid-fast” refers to red-stained mycobacteria that can be observed after staining tissue samples with a special procedure and a special dye. At first, I didn’t see the L-form bacteria since they react differently to acid staining. Instead of rod-forms, they appeared as round forms which were only partially acid-fast, staining purple or magenta with the acid-fast stain. It took me many years to finally realize that these partially acid-fast and round forms were bona fide growth forms of mycobacteria. The typical bright red-stained acid-fast rod forms of mycobacteria are unique and easily recognized by pathologists, but unfortunately the non-acid-fast round forms are not recognized and accepted by pathologists. For a long time I passed over these granular and “dusty” tiny forms as meaningless, not realizing that they were, in actuality, what L-forms look like!

    I knew basically nothing about the microscopic appearance of L-form bacteria (also known as cell wall deficient bacteria and “mycoplasma”) until I carefully read the published papers of microbiologist Lida Mattman. Then I realized all the guises that bacteria can undergo, including transformation into “large bodies.” At that point, I went back and looked at my first case of scleroderma and realized that one skin biopsy sample contained large L-form bodies that appeared as yeast and fungal-like forms! These forms, in 1966, were dismissed as “fat degeneration” by one pathologist; and the biologist thought they looked like yeast cells.

    These large L-forms are compatible with what pathologists recognize as Russell Bodies. William Russell (1852-1940) was a well-known Scottish pathologist who first discovered “the parasite of cancer” in 1890. His view of an infectious agent in cancer was dismissed in the early part of the twentieth century. However, I believe Russell bodies are actually large growth forms of cell wall deficient bacteria — and that Russell was indeed recognizing an infectious agent in cancer. More than a half-century later, Lida Mattman was able to transform mycobacteria into “large bodies” by exposing them to antibiotics. For more information on Russell and pictures of Russell bodies, Google my paper “The Russell Body” in the Journal of Independent Medical Research (

    The fact that L-form bacteria have a “life cycle” and can appear in so many different shapes and sizes (pleomorphism) may be why they are so hard to eradicate and why the immune system cannot cope with them. Maybe the large Russell bodies are harder to kill. Or maybe they are easier to kill. I don’t know.

    3. You found bacteria in the tissues of people who died of certain cancers and AIDS and scleroderma at autopsy. What gave you the idea to look for bacteria in autopsies?

    I got that idea from Florence Seibert, a world famous biochemist who developed the tuberculin skin test for tuberculosis, which is still used worldwide. When Seibert heard about the TB-like bacteria discovered in cancer by Virginia Livingston and her colleagues, which included microbiologist Eleanor Alexander-Jackson and cell cytologist Irene Diller, she decided to come out of retirement and help with the women’s cancer research. Seibert advised me to search for bacteria in autopsy specimens and to determine if I could also find them in the internal organs and connective tissue of people who died of scleroderma. She believed this would make my skin research more credible. For the full story of these four remarkable women scientists, read my book Four Women Against Cancer, published in 2005, and available through Internet book sources.

    Alan Cantwell with Eleanor Alexander-Jackson and Irene Corey Diller

    After I decided to look for bacteria in autopsy material, I contacted colleagues in the Pathology department at Kaiser and asked them to provide me with stored tissue autopsy samples, which they did graciously. I was very fortunate to have them assist me in doing this. One of the great things about Kaiser-Permanente is that everything is under one roof. Few private dermatologists would have the easy access to autopsy material that I did at Kaiser.

    4. When did you begin to look for bacteria in people with cancer?

    Never in my wildest dreams did I think I would ever find bacteria in patients with cancer. Before I started my cancer research (which was totally instigated by my friendship with Livingston), it seemed inconceivable that scientists could have failed to recognize a microscopically visible infectious bacterial agent in cancer.

    For a decade I avoided the cancer controversy because I worked for an HMO and I didn’t want to be regarded as a “quack.” Tragically, Virginia Livingston, because of her outspokenness that cancer was caused by bacteria, was widely regarded as a “quack doctor.” However, in the mid-1970s, I found pleomorphic bacteria in patients with sarcoidosis, and also in a patient with lymphoma. I was amazed at how easy it was to detect bacteria in sarcoidosis and lymphoma when the tissue sections were properly stained with an acid-fast staining technique.

    Once I saw for myself that Virginia Livingston was correct about acid-fast bacteria in cancer, I became very enthusiastic about studying bacteria in other forms of cancer, as well as in immune diseases, like lupus. At that point, I finally had enough conviction in my findings, and had the courage to take a stand along with Virginia.

    5. How did you colleagues react to your research?

    Over the years there were very few doctors interested in seeing the bacteria I found in tissue sections. Some would tentatively acknowledge that there were bacteria present. Most were non-committal. With a little arm twisting I convinced several pathologists, who helped supply the autopsy specimens, to put their name on my published papers. But for the most part they didn’t want to get involved. They would say, “Oh Alan, it’s your research…” “Oh Alan, you’ll win the Nobel Prize someday.” Nobody ever wanted to sit down with me and seriously look at the material. I think it’s because finding bacteria in illnesses that are not attributed to infection is highly controversial, and most doctors shy away from controversy. The finding of bacteria in cancer is like opening Pandora’s Box. Once it’s open, a lot of stuff flies out, and pisses off a lot of people. The bacteria aren’t supposed to be there, they are in closet and not supposed to come out.

    Even after I was retired for almost a decade, I never lost interest in trying to uncover bacteria in cancer. In 2003, my partner was diagnosed with prostate cancer. He underwent a prostatectomy, the total removal of the prostate gland. I decided to see if bacteria could be found in his prostate cancer tissue sections after surgery. Prostate cancer is every older man’s worst nightmare, just as breast cancer is every woman’s worst nightmare. I asked the Kaiser pathologist to cut me a section of my partner’s cancerous prostate and to stain it with an acid-fast stain so that I could study it. Sure enough, there were bacteria in the samples. I had a private microscopist photograph the bacteria. One can view the bacteria in prostate cancer I discovered by reading my paper published at the website.

    6. What’s going on? Why aren’t doctors and researchers taking the idea that bacteria cause cancer seriously?

    As I see it, the identification of simple-to-see cancer microbes would cause havoc in the scientific world and in the cancer treatment industry. It would be the biggest embarrassment to befall modern medicine. Can you imagine the furor resurrecting Russell’s “cancer parasite” — the “parasite” that was thrown out of medical science a century ago?

    It is rare to find a scientist interested in “cancer microbes.” Most physicians are repelled by the idea that bacteria cause cancer. How do you prod scientists to become interested? I’m still not sure.

    A century ago, doctors stopped looking for bacteria in cancer. It’s weird because around that time major diseases like syphilis, tuberculosis, and leprosy were proved to be caused by bacteria. I suppose researchers think, “Well, we looked for bacteria 100 years ago, so there’s no need to look for them now.” But a lot has changed in bacteriology in 100 years. A century ago there was no such thing as an “L-form.” Even now most scientists don’t realize that regular bacteria can change into L-form bacteria, or cell wall bacteria, or mycoplasma, or pleomorphic bacteria, or nanobacteria, or whatever you choose to call these peculiar and little-known growth forms.

    Microbiologists still have a hard time dealing with the fact that bacteria can change so widely in shape and size. How do you get scientists to understand that the tiniest L-forms have the potential to enlarge into a form the size of a red blood cell (or even bigger!). But if you think about it, all human beings were once a microscopic bunch of dividing cells, hardly visible to the naked eye. And we know that these tiny cells can evolve into seven foot tall basketball players. Why then, do we take such a simple view of what bacteria are supposed to do and what they are supposed to look like?

    And the strange part is that using a light microscope you can easily see L-form bacteria. Every scientific paper that I have had published shows pictures of these bacteria. But even when doctors are shown photographs or see these bacteria via a light microscope, they still have a hard time accepting them. It’s bizarre because doctors believe viruses exist, even though most have never seen one. You can’t see viruses. They are too small to be seen with a microscope.

    7. When doctors and researchers claim that there are no bacteria in your samples what explanations do they give?

    When doctors or other researchers try to deny that there are bacteria in scleroderma and cancerous samples their explanations are pretty lame. Maybe something like, “Those aren’t bacteria, those are enlarged red blood cells.” Those “bacteria” are really cell debris, or stain material, or nuclear dust, of mast cell granules, or fat granules— anything but true bacteria. It’s impossible to convince a pathologist, for example, that a “tiny” bacteria can transform into a giant-sized form hundreds of times larger.

    8. Who’s to blame for the fact that bacteria have not been recognized as part of the pathogenesis of cancer?

    Pathologists, dermatologists, infectious disease specialists, oncologists, virologists, microbiologists, and basically all medical scientists who have ignored a century of cancer research pointing to cancer microbes. They have collectively let us down. Unfortunately, pathologists and microbiologists seem to be on two different planets. Pathologists pay little attention to germs in a laboratory, and microbiologists pay little attention to what bacteria do when they infect human tissues that are subsequently examined by pathologists.

    9. What keeps other researchers from finding L-form bacteria in patients with cancer?

    Unfortunately, most microbiologists who have worked with L-form bacteria have not demonstrated how these same forms appear in tissue in human disease when viewed in the light microscope. It’s one thing to describe a microbe in a lab, but what does it look like when it infects the human body? It’s one thing to show these L-forms in pictures taken with an electron microscope that magnifies objects thousands of times. But what do these bacteria look like when view with a “regular” light microscope that magnifies only 1,000 times? As a result, these pleomorphic forms go undetected in diseased tissue. Another reason, of course, is that the pathologist uses a routine stain (the H&E stain) that does not detect these forms. One needs to use an acid-fast stain. This was one of Livingston’s and Eleanor Alexander-Jackson’s most brilliant discovery— the idea that the “cancer microbe” is intermittently “acid-fast” at one or more stages of its growth.

    10. What are some of your concerns about the current medical climate?

    It saddens me greatly that all this great research has been ignored. That is why I wrote The Cancer Microbe (1990), and AIDS: The Mystery and the Solution(1984) and Four Women Against Cancer (2005).

    Every first year med student knows that until you know what’s causing a disease it’s very hard to treat it. In my opinion, hunting for the exact cause of an illness is the most exciting part about being a doctor. The scientists who clued us into the cause of tuberculosis and syphilis, for example, were medical greats because they gave us an idea of what exactly is making the patient ill.

    In my 30 years as a doctor and researcher I’ve never convinced one doctor, not even one, that bacteria cause cancer. My own younger brother is a physician — and I don’t even think he believes me entirely. Two years ago, his daughter-in-law died at age 39 of Hodgkin’s Disease, leaving two small children. I told him, “I wrote about Hodgkin’s Disease!” But he wouldn’t comment. If I can’t convince my own brother — or even interest him in the subject —I feel there is little hope.

    11. What concerns did Kaiser Permanente have about your research?

    A problem with my research was that over a period of years I was finding acid-fast bacteria in patients with a wide array of different illnesses. Some skeptics would say “OK, maybe I can accept that you found bacteria in scleroderma, but come on, in all these diseases?” After several years of productive cancer microbe research, the research committee insisted I be interviewed by a statistician. The committee was concerned because I was discovering bacteria in too many diseases. The statistician insisted that I attempt a statistical study of these bacteria with suitable “controls.” I explained that previous researchers had already determined that all human beings harbor such bacteria, and that these bacteria needed further study as pathogens. It might be impossible to find “negative” controls. At that point I thought, “I’m doomed.” There was no way I could do a statistical analysis of my observations. My research was terminated.

    12. Did anyone try to censor your work?

    In 1984 Virginia Livingston wrote a second book about bacteria in cancer calledThe Conquest of Cancer. She asked me to write a blurb for the back cover of her book. Her publisher took out an ad for her book in the Los Angeles Times Book Review, which included my blurb. Unfortunately, my quote mentioned my association with the Southern California Permanente Medical Group. When the top brass at Kaiser discovered this they were furious. “You can’t do this! You can’t associate our name with a quack like Livingston!”

    At the time I had also discovered that cancer bacteria play a role in the development of Kaposi’s sarcoma, the most common cancer in the newly discovered disease called AIDS. I explained that I had also written a book about AIDS and the bacteria involved in this disease, and that the book was in press and was to be published soon. The Kaiser officials were aghast and told me I was simply not allowed to publish this book. This was at a time shortly before the discovery of HIV and during the period when the precise cause of the immune deficiency was “a mystery.” I had always been well-respected at Kaiser, but I was fearful the Livingston brouhaha and the impending publication of my book might threaten my job.

    Finally my literary lawyer stepped in and worked out a deal with Kaiser whereby I could publish AIDS: The Mystery & The Solution as long as I didn’t mention Kaiser in the book. I had to make sure the printer deleted all references to where I had done my cancer and AIDS research. The thing I had tried to avoid for so long had become a reality: I had inadvertently become a threat to the medical establishment, just like Virginia Livingston.

    13. Tell me about your role model and colleague Virginia Livingston.

    Alan Cantwell with Virginia Livingston

    Virginia was a dear friend whose research formed the foundation of my scleroderma research and subsequent cancer microbe studies. My association with her and Irene Diller and Eleanor Alexander-Jackson and Florence Seibert, changed my life forever. Although she died in 1990 at the age of 84, Virginia still influences me. She is my “scientific soulmate.” These four women are my four greatest heroines in medical science. In Four Women Against Cancer, I describe their amazing cancer research. I knew them all personally, and sadly all of them are now gone.

    14. What do you think about the Marshall Protocol?

    When I heard about the Marshall Protocol I was taken aback. I never thought that a possible cure for chronic disease would happen in my lifetime. I used to tell people that there was no way known to kill L-form bacteria in the body.

    In mid-life Trevor Marshall set out to figure out a good treatment or a cure sarcoidosis because he had the disease himself. That is how — via his own research — that he discovered me and I was made aware of his own admittedly controversial ideas on how chronic diseases might be successfully treated. He certainly, almost single-handedly, revived my scientific career and I am exceedingly grateful to him for his interest and support of the cancer microbe work.

    Having a disease is unfortunate, but it can serve as a great consciousness-raiser. Illness can also bring people together who would have never been brought together otherwise. This interview is a good example of that! From Trevor I am learning about the importance of the “vitamin D receptor” and that Benicar, along with long-term antibiotics can help rev up the immune system and apparently diminish L-form bacteria in patients who are trying his ideas. It’s interesting because Livingston always said that the key to curing chronic disease and cancer is to improve the function of the immune system. In my opinion, the proof is in the pudding. Some people with chronic disease are reporting benefit from the MP.

    Trevor’s not a medical doctor but he obviously is an avid researcher and well-versed and well-trained in biochemistry, pharmacology, molecular biology, subjects that are way beyond my ken. Plus, I went to medical school a half century ago.

    The MP has revealed that the healing process of certain chronic disease needs to go slowly, which in many ways goes against scientific dogma with its “quick cure with a round of antibiotics.” Both Trevor and I believe bacteria are implicated in sarcoid, even though this is still denied by many physicians who consider sarcoid a “disease of unknown etiology” — and all the research pointing to bacteria in sarcoid is ignored. Trevor obviously believes bacterial infection also plays a role in certain other chronic diseases. If you think about it, diseases like tuberculosis, leprosy and cancer all take years to treat. You don’t necessarily expect to get well in one month, one week, or even one year. Similarly, one shouldn’t expect a quick cure in chronic disease, even though bacteria play a big role in these diseases.

    15. What do you feel lies ahead in terms of cancer research?

    I feel that the treatment of cancer will remain dismal until these bacteria are recognized as cancer-causing agents by the scientific and cancer establishments. Only then can better treatment methods be employed that actually are specifically directed against the buildup of these L-forms or are directed towards strengthening the immune system against them, or both.


    Click to enlarge and see descriptions.

    Alan Cantwell is a retired dermatologist. He has written two books on the microbiology of cancer, The Cancer Microbe and Four Women Against Cancer: Bacteria, Cancer and the Origin of Life. A number of Dr. Cantwell’s articles, including those which describe the above images in further detail, are published in Journal of Independent Medical Research. He can be contacted via email

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  • Filed under: conferences and trainings, familial aggregation, featured articles
  • A wide body of research has shown that classical forms of bacteria often transform into tiny variants of the same species, losing their cell walls in the process. They are then referred to as L-form or cell wall deficient (CWD) bacteria. Although researchers have known about L-form bacteria for over a century, up until recently they have not fully understood their connection to chronic disease. It is now known that these bacteria are responsible for causing a wide array of chronic diseases including rheumatoid arthritis, Chronic Fatigue Syndrome, Lyme disease, and sarcoidosis.

    A photo taken by Cantwell showing L-forms of various inside the cells of a patient with breast cancer

    L-forms of various shapes and sizes inside the cells of a patient with breast cancer, photo taken by Alan Cantwell

    Over the past century researchers have identified over 50 different species of bacteria capable of transforming into the L-form and it is likely that even more species will be discovered in the coming years. The vast majority of researchers and doctors are not aware that L-form bacteria are present in their patients because the pathogens will not grow under standard laboratory conditions and must be cultured in a different medium and at a different temperature than classical bacteria.

    In 2005, a team of researchers at the Royal Brompton Hospital in London published a paper that reviewed the clinical significance of the L-form as an infectious agent. The review discussed the work of hundreds of researchers who have cultivated the L-form and implicated it in a wide array of diseases.

    This piece describes several of the doctors and researchers discussed in the review who have perfected the lab methods needed to correctly culture L-form bacteria and have consequently been able to observe and document their behavior. L-forms have also been studied extensively in veterinary literature but those findings are not presented here.

    In 1895 a scientist named Richard Pfeiffer described an altered form of the bacteria Vibrio cholerae that was difficult to see with a light microscope. Other workers in his lab confirmed that the bacteria lacked cell walls and were difficult to grow using standard laboratory techniques.

    Around the same time, Ernest Alnquist, a friend of Louis Pasteur, began to culture the L-form. Alnquist was the first to suggest how extensive and diverse L-forms are. He once commented that “nobody can pretend to know the complete life cycle and all the varieties of even a single bacterial species. It would be an assumption to think so.”

    Emmy Klieneberger-Nobel at a 1965 medical conference

    In 1941, German scientist Emmy Klieneberger-Nobel began to study the L form at the Lister Institute in England. A meticulous lab worker, Klieneberger-Nobel, perfected the method of growing the pathogens on serum (blood) agar.

    After growing colonies of the bacterium Streptobacillus monliforme she confirmed that several of the pathogens in her Petri dish did indeed lack cell walls. She named the wall-less variants L-forms after the Lister Institute where she worked. In the years that followed she studied other species of L-forms and published several papers describing their characteristics and behavior. She once said that “the L-form is an entity of its own as different from bacteria as the tadpole from the frog.”

    Louis Dienes next to incubator used to grow L-form bacteria

    A few years later, Harvard Medical School researcher Louis Dienes began to work with the L-form. He applied penicillin to various species of classical bacteria such as Salmonella typhosacoule and discovered that some of the pathogens transformed into cell wall-less variants of the same species. They also found that exposing the original strains to other antibiotics in the same class as penicillin, chemical injury, high levels of amino acids, lithium, calcium, chromatin and mercuric salts could cause L-form variants to form as well.

    In many of his experiments Dienes noted that the individual L-forms in his samples often swelled into large round bodies. He also found that small colonies of L-form bacteria such as S.moniliformis are able to revert back to the classical form. He published numerous papers detailing his discoveries and was one of the first scientists to warn the medical community that some antibiotics such as penicillin can actually precipitate the formation of L-form bacteria.

    Dienes kept his lab open at all times so that anyone interested could see his L-form cultures and ask questions about how to grow them correctly. Nevertheless, few of the other researchers at Harvard took note of his work. He once remarked that he only became known to the medical staff after a hospital art show displayed some of his watercolors.

    Virginia Livingston

    Virginia Livingston

    Around the same time, a team of doctors under Virginia Wuerthele-Caspe Livingston cultured L-form bacteria from patients with the skin disease scleroderma. Livingston noted that some of the L-forms she observed were as small as viruses. But others were the size of classical bacteria and some were larger forms resembling spores of fungi and yeasts

    Livingston and her colleagues injected the L-form bacteria they collected from patients with scleroderma into chicks and guinea pigs. The chicks died. Some of the guinea pigs developed hardening of the skin like scleroderma, and some developed cancer. In the years that followed Livingston was also able to grow L-forms from various human cancer tumors.

    Her work was published in the American Journal of Medical Sciences and in the years that followed she wrote several books on the subject.

    In 1975, H.M Butler and team wrote a review of L-forms, describing their resistance to penicillin and ability to change form. They concluded that “such organisms may be clinically significant in cases of chronic and recurrent infection.”

    At the same time, Bisset and Barlett identified L-form variants of Bacillus licheniformia during different stages of its life cycle. They hypothesized that the wall-less variants of the bacteria they observed had previously been wrongly classified as other species of pathogens.

    Photograph taken by Wirostko which shows L-form bacteria inside a white blood cell (see arrows)

    Emil Wirostko’s photo of L-form bacteria inside a white blood cell

    A decade later, a doctor working at Columbia University by the name of Emil Wirostko began to culture and photograph L-form. In a series of related experiments, he took white blood cells from the liquid inside the eyes of patients with sarcoidosis, juvenile rheumatoid arthritis and Crohn’s disease and observed them under an electron microscope.

    He detected L-forms in many of the specimens and noticed that the bacteria were grouped into colonies and encased inside tubuoles. He also noted that they were separated from the environment inside the cell by a membrane or exoskeleton that kept them from being digested by the cell.

    Wirostko published three papers that detailed his findings and took many pictures of the L-forms he observed, 20 of which are dispersed throughout his papers.

    Photograph taken by Alan Cantwell showing L-form bacteria inside the tissues of a patient with prostate cancer

    L-form bacteria inside the tissues of a patient with prostate cancer, photo by Cantwell

    Around the same time, researcher Alan Cantwell took great interest in Livingston’s work and proceeded to study the L-form. He applied a technique called acid fast staining to the tissue sections of the skin and lymph nodes of patients with the lung disease sarcoidosis and found L-forms in his samples. Cantwell later isolated the L-form of Streptococcus B from the lymph nodes and blood of patients with HIV. He noted that the L-forms he observed could grow into extremely large forms and determined that they were what are known as “Russell bodies.”

    In the years that followed, Cantwell took samples from the lymph nodes, skin tumors and other organs from the corpses of patients who had died from Hodgkin’s disease and cancer. He found copious amounts of L-form bacteria in his samples, including round forms resembling the bacterial species staphylococci and rod-shaped bacteria known as corynebacteria.

    Over the course of his career Cantwell published over 30 papers and wrote several books that implicate the L-forms in chronic disease, including a book about Livingston and three other women who had worked on her research team.

    Lida Mattman at her microscope

    Lida Mattman at her microscope

    Around the same time, researcher Lida Mattman began to study the L-form. After working as senior bacteriologist at the University of Massachusetts, she became the director of a laboratory that evaluated specimens sent by mail from doctors around the world. Mattman, who would study and photograph the L-from over the course of decades, confirmed that the pathogens could vary widely in size and shape.

    Mattman’s success in growing L-forms was due in part to a relentless drive to perfect the laboratory techniques which allowed her to culture the pathogens. She used fluorescent antibodies and a variety of staining techniques to view the various cell wall deficient forms. She even figured out how to grow them directly on slides.

    Mattman studied patients with Tuberculosis and found that in every patient tested, the blood was saturated with a variety of L-forms.

    She identified two different species of L-form bacteria in patients with Parkinson’s Disease. The L- form species of Borrellia burgdoferi was detected in patients with Lyme disease. She cultured serum from forty patients with multiple sclerosis and found a different species of the borrelia L-form present in her samples. Soon after, she detected Chlamydia pneumonia in the blood of patients who had suffered a pulmonary thrombosis. She also found bacteria that resembled M. tuberculosis in the blood of patients with the lung disease sarcoidosis.

    In the end, Mattman detected dozens of species of L-form bacteria and was able to culture these wall-less forms of bacteria from the blood samples of patients with over 20 incurable illnesses. She published numerous papers throughout her career and in authored an entire medical textbook in which she details her findings.

    In 1997 a team of researchers at Tulane University under Gerald Domingue published an extensive review article on chronic bacterial infection in Clinical Microbiological Reviews. Among their conclusions was the claim that ”the difficult to culture and dormant bacteria are involved in latency of infection and that these persistent bacteria may be pathogenic.”

    The review also detailed how L-form bacteria are able to form electron dense bodies within previously infected cells. Domingue implicated L-form bacteria in several kidney-related diseases including pyelonephritis, glomerulonephritis, idiopathic hematuria, and Interstitial cystitis. He also speculated about their role in other diseases such as rheumatic fever, tuberculosis, syphilis, and rheumatoid arthritis.

    In the review Domingue states “Certainly, any patient with a history of recurrent infection and persistant disability is sending the signal that the phenomenon (infection with L-form bacteria) is occurring. The so called autoimmune diseases in which no organism can be identified by routine testing techniques are particularly suspect.”

    Over the course of his thirty-nine year career Domingue published 65 papers, monographs, and book chapters about L-form bacteria. He was invited to deliver over fifty international and national lectures about atypical forms of bacteria and wrote a book on the subject called Cell Wall-Deficient Bacteria: Basic Principles and Clinical Significance.

    Picture taken by Nilsson showing Rickettsia helvetica inside the cell of a patient with sarcoidosis

    Rickettsia helvetica inside the cell of a patient with sarcoidosis, image from Kenneth Nilsson

    Several years later, Kenneth Nilsson, a researcher at Uppsala University Hospital in Sweden, published photos of the bacteriaRickettsia helvetica living inside the white blood cells of patients with sarcoidosis. The fact that the bacteria was able to persist inside the cells suggested that something was very wrong with the patient’s immune systems. Dozens of other researchers have also implicated other species of L-forms in sarcoidosis.

    A decade later, researchers at the Academy of Science in Bulgaria infected rats with the L-form of Staphylococcus aureus and found that the pathogen were able to “internalize, replicate and persist “ in the lungs of the infected rats. They concluded that “cell wall deficient bacterial forms may be involved in the pathogenesis of chronic and latent lung infections.”

    Long thin L-forms emerging from a cell as shown in a photo taken by Andy Wright

    Long thin L-forms emerging from a cell as shown in a photo taken by Andy Wright

    A team of researchers and doctors in the United Kingdom are currently studying the L-form in patients with Chronic Fatigue Syndrome (CFS). The microbiology team, lead by CFS clinician Dr. Andy Wright has detected L-forms in every single one of the CFS patients they have tested (about 600 to date).

    Wright has developed a method of taking pinprick blood (usually from the ear) and allowing it to degrade for 6-36 hours. The process causes the L-form bacteria to break out of the cells and they can subsequently be observed with a dark field microscope. The bacteria can be stained with fluorescent dye. If the L-forms are alive they will stain green, while dying/dead L-forms stain orange. Wright has created several videos of L-forms under the microscope in which the pathogens can be seen quite clearly.

    In the videos, the bacteria often lengthen into long filamental forms that look thin and snakelike. They can be seen weaving in between infected cells. Sometimes “giant” L-forms, which are more rectangular in shape, begin to grow inside the cells.

    Danish researcher Marie Kroun has also taken several videos of L-form bacteria under a high-resolution microscope.

    Trevor Marshall, creator of the Marshall Protocol

    Trevor Marshall, creator of the Marshall Protocol

    However it’s quite possible that L-form bacteria might have remained in relative obscurity if a scientist from Adelaide Australia by the name of Trevor Marshall hadn’t taken an interest in their ability to persist in the body. Marshall wasn’t a medical doctor – he was an biomedical engineer with an impressive grasp of molecular modeling software. Whereas a doctor can look at a patient and infer a mechanism for disease based only on symptom presentation, a biomedical researcher can take the actual compounds created by L-form bacteria and mathematically determine how they affect the body’s receptors and enzymes.

    Thus, after decades of research, Marshall was able to succeed in two areas where the L-form researchers before him had failed. By combining precise molecular modeling data with previous research on stealth bacteria, he was able to create a model that explained exactly how L-form bacteria are able to dysregulate the immune system and persist in the body. Secondly, he was able to use his model in order to create a treatment that effectively kills L-form bacteria. The Marshall Protocol was born. Patients on the treatment use pulsed, low-dose antibiotics, along with a medication that activates the immune system to eliminate L-form bacteria over a period of several years.

    Patients with a wide array of chronic diseases are using the treatment. Most are reporting symptomatic improvement and a number of patients have claimed complete resolution of symptoms.

    Marshall has since written several papers and given numerous presentations that detail the pathogenesis of chronic disease.


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  • About Amy Proal

    Amy and Zeus

    Amy Proal graduated from Georgetown University in 2005 with a degree in biology. While at Georgetown, she wrote her senior thesis on Chronic Fatigue Syndrome and the Marshall Protocol.