Theoretical Immunology

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Leonard
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On the need for a paradigm change in medicine

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Already back in 1962, Thomas Kuhn in his masterly book The Structure of Scientific Revolutions challenged long-standing linear notions of scientific progress, arguing that transformative ideas don’t arise from the day-to-day, gradual process of experimentation and data accumulation but that the revolutions in science, those breakthrough moments that disrupt accepted thinking and offer unanticipated ideas, occur outside of “normal science”. His ideas on how scientific revolutions bring order to the anomalies that amass over time in research experiments are still instructive in our age. Here we can think of the long path of research into chronic diseases that has not had a real breakthrough even after so many years.

An entirely new look at chronic diseases claims that they are caused by a ubiquitous human pathogen namely the herpes virus. This new view is such a revolution, such a breakthrough moment, a thinking outside the norm, and it offers a whole new perspective on chronic diseases.

This concerns the large majority of chronic diseases: that is cancers (the old theory of somatic mutations is obsolete, most cancers are caused by herpes that transactivates retroviral sequences in the genome), autoimmune diseases (as a reaction to early forms of cancers i.e. paraneoplastic, or even when the immune system just thinks it has to counter a developing neoplasia because of aberrant local viral conditions) and neurodegenerative diseases as Alzheimer’s and Parkinson’s (which are believed to be autoimmune in their origin, most research done there just follows later on when the damage has already been done). We need to look fundamentally different at chronic diseases, through an entirely new lens. We need to look at chronic diseases as a class as much as individual pathologies, with a common herpes viral etiology.

MS falls in this same category as well (this is a forum on MS) and follows the same mechanisms. But in a way MS is also special in that - unlike with diseases as for example Alzheimer's - symptoms become visible very early on in the process. That is when the ATP production of specific cells breaks down with the reversal of the electron transport chain and an immediate relapse of motor functions is seen, when these cells through micro-regulation - previously thought to be a phase of immunological tolerance - make their first moves to control an aberrant internal viral situation. As MS follows the same mechanisms as other chronic diseases, its solution will need to follow an understanding and resolution of the broader picture of chronic diseases, as well as in particular the removal of the many and persistent barriers that stand in the way of their resolution. So back therefore now to the big picture.

The matter concerns a real paradigm change, a paradigm change in the true sense of the word. To say it with the words of Thomas Kuhn, “a paradigm that is one destined to win its fight.” But the medical system is a huge and established system with entrenched interests and control points everywhere and with so many bound to lose so much by change. Hence, there will be barriers seen everywhere. And change may be significantly impeded as researchers would have to step (too) far outside their comfort zone.

Increasingly, we see doctors who want to leave the old world but the new world is not ready so there is nowhere they can go and they are forced to stay where they are. The challenge is to make the world ready for change, to lift the barriers and create the certainties and framework needed for a transition. And to do that as quickly as possible. Here lies a critical role for our governments: to help speed the process. Because of the vast implications and the uncertainties it creates for so many, research can not do its work without a new policy framework providing certainty and clarity to the actors. Our governments have a key role to provide that.

And the sooner the better, and not in 5 to 10 years. If the number of chronic diseases in the EU would increase by more than 24 % by 2035 (from official EU government documents), we are talking here literally about millions of extra new cases of citizens that get diseased, above the number that might be expected with the current percentages of the population. The numbers for the US won’t be very different. And the data for the whole world even point to a doubling of the number of cases by 2035. So this is an impending global crisis that needs urgent action.

Our society has entered a very dangerous path, there is a scourge of chronic diseases that gets ever worse. I just spoke with a professor who had been invited to give the opening speech at a forthcoming international conference on cancers. He told me the number of cancer cases in our societies is increasing dramatically. If you follow the new line of thinking, that is because our immunity is becoming insufficient to contain the herpes viruses and shield retroviral sequences in our cells. And therefore, if there would only be a small chance that the new thinking would point us in the right direction, we should go after it with force. I am sure that if we were to accept the change in perspective, it would spawn an explosion of new discoveries and advances (e.g. in cellular immunity in relation to herpes and retroviral sequences in the genome). And put us on the path towards a healthier society.

With the help of the responsible authorities, we can speed progress. In the meantime, perhaps we should listen more to the Pope and the Bible. No I am not religious but I am dead serious. As I wrote on 24 November 2021 (see above posting), the State could not do what Church has done for thousands of years: to protect us against the smallest species yet our biggest enemies, that is the endogenous herpes viruses that have been with us for hundreds of millions of years and that cause the large majority of chronic diseases. As such, the religious practice of regular fasting strengthens the antiviral properties of our cells through various mechanisms e.g. fasting changes the mitochondrial morphology with cells leaning more towards an (anti-viral) interferon pathway than an (pro-inflammatory) interleukins pathway (see above posting of 31 December 2021), fasting improves gut related epigenetic control of the genomes of our cells and of the virus. Hence, over the centuries, the religious practice has made a very important contribution to contain the herpes viruses and keep our societies healthy. And it will do just that today as well.

There is an urgent need to shift the debate in a new direction to prevent a big systemic failure and a health crisis of unseen proportion. It is incumbent upon the very many health authorities, in the governments and in the medical sector, national or international or global, to leave no stone unturned and launch an investigation into this matter as soon as possible.
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Re: Theoretical Immunology

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I have tried to get my thoughts together on the problem, see the essay below [update September 6, 2022]. It occurs to me that it is probably as much an organisational issue than a medical technical problem.

The challenge now is to translate this into something actionable and identify the stakeholders. I would be very grateful for any comments or suggestions you might have. Thanks.

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Re: Theoretical Immunology

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From the medical literature, I think we can say that the transactivation of and by molecular elements takes place somewhere in the triangle between HERV, herpes EBV and herpes HHV (-6 and -3) and their antigens. But the question of what precisely happens inside our cells is not so simple to answer and will need a lot more research.

There is only one who really 'knows' and that is our immune system. After so many hundreds of millions of years of evolution, perhaps even billions of years (to note the gut microbiome has co-evolved with us for more than 2 billion years), in the core of cellular development and in a very harsh environment, through positive selection the immune system reached a stable healthy situation in our cells that - as some would say - are more retroviral than human.

It may take a lot more time to resolve the what, if ever. But instead of the what, we could also ask ourselves the question why. Why is this happening to us? And there we may be able to find some answers.

Based on my own analysis (see also the above postings), the attached powerpoint [update 17 March 2023] gives 4 main factors for our failing cellular immunity and presents a reconceived immune concept. I invite you to have a look at it.

Without knowing precisely what happens deep inside our cells, by addressing these 4 factors, I am convinced that a lot can be done to improve our health situation, that is by strengthening our immunity by providing the right set of external factors.

It won't be an immediate solution for sick people, but in the medium to long term it will certainly provide healthier people in a healthier society.

If there are any views or comments that you would like to share with me, please send me an email. You find my email address at the first slide. Thanks a lot.

Last edited by Leonard on Sat Apr 08, 2023 3:06 am, edited 5 times in total.
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Re: Theoretical Immunology

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This amplifies your theory Leonard and explains why acyclovir/valacyclovir works so well in some patients!

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Re: Theoretical Immunology

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DIM wrote: Mon Feb 13, 2023 12:07 pm This amplifies your theory Leonard and explains why acyclovir/valacyclovir works so well in some patients!

Lots of information with a very broad point of view. Thanks for posting.
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Re: Theoretical Immunology

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The video calls for a new look at herpes EBV as the cause of MS and also contains a lot of information about existing MS treatments. But HERV is only mentioned in passing, herpes HHV (including Zoster) is not mentioned at all, while the thinking is still far removed from the Annex to my essay and is very much stuck in the old MS world.

I find the video a bit of a struggle between on the one hand the old MS dogma and treatment options and on the other hand new EBV thinking with one-liners as quote we have been barking on the wrong tree, we are missing what MS is, we have to be targeting something else, we have to go back to the drawing board. But the fact that the new look comes from a leading MS neurologist is welcome and hopeful, and adds to all the other news we heard over the last several months about MS and EBV.

I can certainly agree with his call in the video "to look holistically", although what he really means here is to look wider in the field of MS. It is a bit the same as in Ref. B1 of my essay above where rheumatologists struggle with the problem and do not want to step outside the boundaries of their own field: while the article itself is very broad and applicable to many diseases, its title is specific to rheumatology.

I am convinced that the majority of chronic diseases have the same cause (in triangle HERV, EBV, HHV-6 and -3 and their antigens, see the above) and that the solution will only then be found if specialists adopt a much wider approach and, for that, dare to and do step outside the boundaries of their own field and outside their comfort zone. But the consequences will be enormous, as outlined in my essay.

The resulting health crisis will cause huge uncertainties everywhere, where nobody knows anymore who owns what, who does what, who carries responsibility for what. The world does not seem to be ready for that, while attempts to change the paradigm will face enormous barriers. We may expect specialists to remain close to their own values, close to their own beliefs and in their own field of work, perhaps even to protect their own work and their own future. The video of the professor might be also be seen in this latter context.

I think the medical sector has ceased to function adequately in the exploration of chronic diseases. Governing authorities should take the lead to create legal certainty, clarity and predictability for all. For that, new health policies will need to advance in parallel with the new research effort, to prove or disprove the new concept of herpes and HERV causing the majority of chronic diseases. It is only when health policies mature together with new research findings and barriers are effectively removed that we will be able to prevent/unlock a Catch-22 situation and liberate the forces for change.

@DIM, Zyklon: Thank you for posting. I feel encouraged to get response to my thinking.
@all: I would welcome comments from any one reading here. Have I got it all wrong? Or is the thinking spot-on? Where do we go with these ideas? How can we force change? There are tens of thousands of people reading here about the latest views but sometimes I feel like I have to fight this fight alone.
Last edited by Leonard on Mon Apr 10, 2023 4:59 am, edited 3 times in total.
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Re: Theoretical Immunology

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Although this is not the meaning of this discussion, what meds - supplements could someone add to his regimen that will help him with the above virus trio?
AFAIK Valacyclovir is used for EBV/HHV6 (some individuals have adverse neurological reactions), Zidovudine for HERV, while natural treatments are: monolaurin, lemon balm, olive leaf extract, andrographis paniculata, lysine, vit. C, zinc, Inosine (?), artemisinin and berberine (for short periods).
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Re: Theoretical Immunology

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As the world learns more about the role of herpes and EBV in MS, for sure we will see a lot of experimentation with anti-virals. But this comes with a note of caution: the herpes-cellular homeostasis and symbiotic relationship is a lot more complicated than the case of an infection with an exogenous virus. Apparently even latent viral proteins of EBV are able to transactivate HERV. And as mentioned in the video, the experimentation will also include Metformin which, according to recent medical literature, acts as a modulator of anti-viral pathways and as an epigenetic regulator of the cellular DNA methylation machinery. A rather intricate picture of cellular immunity emerges.

The smoldering MS is B-cell centric, and is part of a wider autoimmune mechanism where, as the professor says in his video, meds like mitoxantrone, rituximab (possibly administered intrathecal), repeated light cycles of cyclophosphamide, HSCT, and the new donor T-cells will do their job to deplete faulty EBV B cells and stop progression, albeit at a slightly increased cancer risk. To note here that the primary function of the B cell mechanism, that is made possible by re-engineered T cells, is paraneoplastic.

But the matter under consideration is about a lot more than just MS. This is about the large majority of chronic diseases including cancers, autoimmune diseases (paraneoplastic or anti-tumor) and neurodegenerative diseases (autoimmune in their origin). MS is special and very instructive for what happens in the early phase of cellular anti-viral activity when the electron transport chain (ETC) of the mitochondria stops working and cellular ATP production comes to a halt. When the synapses lack the energy to recharge, we will see a relapse. That process is reversible. When the viral activity is silenced, the ETC starts working again, ATP production resumes and we will see remission. The old theory of demyelination can not explain this RR behavior. The age-old MS model is completely broken!
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Good governance in medicine

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Providing security for its citizens is the primary task of government, any government. Without it, the State has no right to exist. And governments are obliged to pursue an accountability.

Our governments are also involved in vaccination programmes, presumably to secure public health. But now, with the new insights in intra-cellular immunity, where there is not such a thing as a ‘phase of tolerance’ and micro-regulation inside the cells starts very early on and a long time before antibodies trigger external immune interventions from macrophages, the risks of vaccinations for distorting the cellular-herpes viral homeostasis and activating endogenous retroviral elements in the early stages become more apparent and will need to be reviewed and reassessed.

Furthermore, the use of antibiotics will have to be seen in a completely different light now because these 'cluster bombs' may contribute to dysbiosis of the gut microbiome, which can have negative consequences for the methylation state of (retro-)viral elements in the genome and hence increase the propensity to becoming chronically diseased. 

Without knowing precisely what happens deep inside our cells with the cellular-herpes viral homeostasis and possible activation of endogenous retroviral elements, uncovering the new mechanisms of intra-cellular immune regulation will not exactly make it easier for governments to step in and pursue an accountability. But the ghost is out of the bottle, they will never get it back in. Sooner or later, governments will have to crack the hard nut and look into the matter. Because the dramatic growth of chronic diseases in our societies must be stopped and can be stopped!

The health crisis has been mentioned in one breadth with the climate crisis. I think the medical problem is technically and operationally easier to solve than the climate problem. But as a person’s health is so precious and chronic disease carves so deep into one’s life while the climate problem is perhaps seen as a bit more distant, the magnitude of the challenge may feel similar.    

One of the leading principles of good governance is the precautionary principle. In other words, if one does not know the effects, one should take the necessary precautionary measures to avoid or prevent the bad effects. Hence, if there is only a small chance that the new thinking is correct, governments should pursue new initiatives as a precautionary measure until research proves or disproves the new concepts.

I intend to write an open letter to the prime ministers in our countries to sketch the health problem along these lines. It is true that they may get many letters each day and that it won't make much of a difference. But at the very least we can plant a seed in politics and stress that there is an important role for them to prepare a conducive health policy and regulatory certainty as a necessary prerequisite for a transition - a paradigm shift in medicine - to take place.

We could draft the letter together. I prepared a first rough draft which is attached below. If you read here and would like to be involved, please send me a personal message on this forum or an email (you can find my email address on the first page of PowerPoint presentation above). I would be very happy to work with you. Together we can make a difference!

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HERV: friend or foe?

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The story has not quite come to an end, there is something to be added.

We are retroviral in origin, over 70% of the contents of our cells is believed to come from reverse transcription of retroviral sequences while only about 1% is known as human genes. That is why some experts have said: we are more retroviral than human. The insertion of these sequences over several billions of years is believed to have greatly added to cellular build-up and biological diversity and to have started at the very dawn of cellular life. The influx is considered instrumental to evolution of larger and more diverse genomes, where many “traditional” genes are descendants of ancient retroviral genes that after mutations have been repurposed for a new function (exaptation). Most sequences have been domesticated and lost their ability to encode proteins; but more recent HERV loci in our genome retain the capacity to encode fully functional proteins and produce viral particles. Although most sequences are incomplete and silent, several potential pathological roles of HERVs have been observed in numerous diseases, such as multiple sclerosis and rheumatoid arthritis, and especially cancer, including breast cancer and pancreatic carcinoma.

Over the last 500 million years, perhaps even more, these cells have co-evolved with herpes viridae. Herpes is a very successful virus that was never completely eliminated by our immune system and is highly adapted to its host. The arms-race between the virus and our cells has resulted in a delicate equilibrium where both cells and virus have found their place and co-exist alongside each other. Following primary infection, it establishes life-long latent infection, during which there is limited viral gene expression. It is known that some herpes viridae have been incorporated into the human genome where their sequences have integrated in the LTRs of every chromosome and are inherited in a Mendelian fashion. This may explain the mimicry seen in autoimmune disease i.e. by cross-reactivity of herpes antibodies with cellular contents. A very interesting elaboration of the role of herpes viruses in the evolution of our cells can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760548/

It is highly likely the endogenous retroviral sequences (HERVs) and herpes viridae have interacted with each other over this long period of time. As such, something special must have happened: the build-up of the cellular content along with cellular immunity must have picked those HERV-herpes interactions that best ensured the survival of the species. This is what evolution is. We see evidence of such interactions. HERV transactivation induced by herpes infection may regulate viral gene expression. Data show that HERV proteins are able to hijack herpes latent gene products such as EBV EBNA2 to reduce their binding ability to cellular DNA, leading to the down-regulation of the viral promoters. This may represent a protective mechanism which aims at controlling the expression of viral products.
[While there is evidence to suggest that the expression of certain herpesvirus genes or proteins can influence the activity of other herpesviruses, the interactions between different viruses and their molecular mechanisms are complex and not well understood. About mutual interaction of herpes viridae see e.g.
https://pubmed.ncbi.nlm.nih.gov/35060655/ ]


As might be expected from this long period of co-evolution, HERV transactivation thus seems to have a positive side and may be considered to be a normal part of the cellular immune mechanism (part of physiological autoimmunity and cell repair). It is only after a chronic persistent boosting of mutually cooperating herpes strains - a stimulus that cannot be controlled and contained by the cell by the HERV-herpes mechanism or by the ETC/ROS/IFN mechanism or by other intracellular mechanisms - that the situation may become pathological and cause cellular immune instability, malignant HERV transactivation and oncoproteins. This may contribute then to the development of virus-associated tumors (believed to be over 90% of all cancers) but also – a process that must have developed over the 100s of millions of years of evolution - to the onset of autoimmune diseases as a T/B cell driven mechanism to prevent cancers cells from growing (autoimmune disease as a paraneoplastic syndrome).

Over time, HERV sequences undergo many mutations that, in combination with our cellular immunity, lead to a complete domestication of these sequences where pathogenic properties are lost. However, more recently added sequences such as HERV-W and HERV-K (incl. K18), believed to have been added some 8 to 14 million years ago - well before the first human arrived on earth some 6 million years ago, are known to retain their capacity to produce fully functional proteins and viral particles if stimulated by herpes viridae. Hence, on the question is HERV friend or foe, the answer may well be that it is both friend and foe.

I think the very precise mechanism for transactivation can only be found on a highly detailed molecular level. The interactions between herpes viridae themselves and with the HERV boom may be rather complicated and hard to unravel - it's like unravelling many 100s of millions of years of evolution at a molecular level. Therefore, as the PowerPoint suggests, as long as we haven’t found the what, we may have to fall back on the question why. Why is this happening to us? And then the seventh slide with the 4 factors explaining our failing cellular immunity with regard to herpes viral control may be the best answer for us for now and for some time to come.
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Re: Theoretical Immunology

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Chronic disease: joint boosting of herpes viral strains in an immune insufficient host

Herpes virus long-lasting infections stem from, on one hand the virus capacity to cope with the host anti-viral immunity, and on the other, the capacity of the host to tolerate the continuous presence of the virus without appreciable self-infringed damage. A highly complex equilibrium is reached between virus and host, ultimately achieving a stage of homeostatic control in which the viral immunomodulatory capacity intimately influences on general host immune processes.

There is life-long immune control of herpes in the general population. Almost 100% of the world's population is infected with one or more herpes strains, over 98 % of people with the EBV strain. Most infected individuals remain disease-free despite persistent infection and this is likely due to the robustness of the cellular immunity.

It is clear that under certain circumstances the robustness of the immune system against these viruses wanes. That is when the near-perfect life-long immune control of herpes viridae is compromised. The situation may lead to malignancies associated with herpes viruses such as EBV and KSHV. Upon immune system weakening, malignancies emerge at increased frequencies.

Immuno insufficiency

In the medical literature, we often see reference made to immunodeficiencies and immonocompromised hosts caused by immunosuppression e.g. because of disease or medication. This then creates the circumstances that can shift the herpes-host equilibrium toward virus-induced malaise. When the host antiviral cellular immunity is unable to control the situation, the balance turns to the pathological side.

But besides these special cases in the far end of the spectrum, there is believed to be a sliding scale in immune competence of the general population where the cellular immunity gradually degrades, becomes less robust, weakens, and at some point becomes insufficient to keep a persistent boosting of herpes viridae in the cell under control. I call it a situation of immune “insufficiency”.

Chronic persistent boosting

Besides in the more extreme cases of immunodeficiency, chronic boosting of herpes viridae in an immune “insufficient” host can also shift the situation toward pre-tumor and, as reaction to preserve the health of the tissue, to an autoimmune disease (as a paraneoplastic syndrome).

From epidemiological research, the following factors may contribute to an aggravating cellular immune insufficiency and failing cellular immunity to control and/or contain the herpes viruses and therefore to an increased risk for immunopathological conditions such lymphomas/cancers and –conversely – autoimmune diseases:
  • Vaccination: may bring pathogens in the cell with conflicting intra-cellular immune pathways, distorting the host-herpes homeostasis;
  • Bioenergetics: low bioenergetics affects sound mitochondrial workings and therefore its anti-viral regulatory properties. Suspect are a situation of hypoperfusion of the tissue (including e.g. ccsvi) as well as ozone (O3);
  • Methylation: insufficient methylation of the host genome and the viral genome, e.g. because of dysbiosis of gut microbiome, may stimulate the mutual cooperation of herpes viridae and the activation of HERV sequences (open reading frames).
  • Cellular fitness: poor acquired cellular fitness (childhood in the sun protects) and bad instantaneous cellular fitness (fasting changes the mitochondrial morphology and microbiome strengthening the antiviral properties of the cell, Ω3 fatty acids protect by improving the lipophilicity).
Viral cooperation

From the recent medical literature, it is clear that it is the interaction between various herpes viridae that causes malignancies. The viral cooperation between viruses such as EBV and KSHV - a complex interplay among co-infection with oncogenic herpes viral strains - leads to lymphomagenesis. But also the joint reactivation and cooperation of β- and γ–herpes viridae enhances lymphomagenesis. There is clinical evidence that the simultaneous reactivation of these herpes viridae increases the probability of mutual interaction where one virus influences the other. We see two viruses interacting with each other in dually infected hosts and lymphomas.

But it is not exactly clear how. Several conceptual frameworks have been proposed e.g. with mechanisms of indirect communication through immune soluble mediators such as cytokines, chemokines, and IFN molecules. The cocktail of molecules then activates HERV sequences such as HERV K18 through inter-molecular mechanisms that involve various cellular and viral components e.g. through the binding of viral proteins to the HERV promotor regions or through the modulation of host cell transcription factors. The inter-molecular mechanisms work together to control or influence the expression of HERVs. The activity depends on the specific HERV locus where changes in the (alignment of) chromatin structures (related to acquired cellular fitness?) can lead to increased or decreased activity.

In turn, interactions between herpes viridae and HERVs lead to the expression of host genes, promote genomic instability and may lead to the production of oncoproteins. And, as a reaction to the threat of developing a tumor, to the onset of an autoimmune disease or a neurological disorder.

But no one understands the complex and intertwined mechanisms at molecular level. And I guess it may take some time before these mechanisms of high granularity are unraveled, if ever. Therefore, the best shot for now is to strengthen the cellular immunity by addressing the 4 factors mentioned above, as the best assurance for healthy people and a healthy society.

References: Google searches on immune interactions between herpes viruses and suggested literature
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Re: Theoretical Immunology

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Please have a look at these videos from prof. Seyfried.





The central role of mitochondria as a cellular controller stands out. In my thinking (the case of RR-MS), with the electron transport chain (ETC) slowing down, mitochondria regulate cell behavior and correct the viral assault. In the case of prof. Seyfried, the ETC fully breaks down, replacing the process of oxidative phosphorylation by fermentation, an ancient mechanism that characterized our cells for making ATP energy before mitochondria and mitochondrial control kicked in some 2.5B years ago. Lacking mitochondrial control, the cell will be dysregulated in its growth with self division out of control. This will then go on for as long as there is glucose or glutamine. In a dead body, cancer cells will continue to divide as long as there is glucose.  

The genetics come in with the SNPs, and the capacity to reinstate the ETC and mitochondrial function. The herpes EBV and HHV-3/6 and their antigens come into the picture because it is precisely those viruses that via the MAVS/HERVs located in or near the mitochondria incite the ETC to collapse. At which point the cell switches to its ancient fermentation mechanism for ATP energy production. And mitochondria become dysfunctional, the cellular morphology becomes abnormal. Hence, a cancer cell is not a mystery. And not primarily a genetic disease!

Women then are better protected against cancer development than men because autoimmune disease kicks in earlier, i.e. their T/B cell mechanism – a paraneoplastic reaction – is activated faster, and that is because their SNPs which are located in the sex chromosomes are less effective in countering early viral assault. We can see this with RR-MS which is more prevalent in women than in men. In men, we will see a more forceful reaction to initial viral assault by male SNPs, hence less autoimmune disease, lower protection against pre-tumors, and thus more cancers later on. Epidemiologically studies have confirmed such statistics. 

The thinking of prof. Seyfried aligns well with my own thinking. I think we should now merge or amalgamate our thinking. 
Last edited by Leonard on Sat Jul 15, 2023 1:50 am, edited 6 times in total.
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Re: Theoretical Immunology

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But it is not only our ideas on the technicalities of diseases that match (see the previous posting first), it is also his very critical view of the medical system that corresponds with my own ideas and – I guess – that will be shared by many of you. As a professor of a well respected US University College, he does not shy away from using strong words to express his displeasure with what he calls the "cancer industry" and the institutional flaws in the US medical system.

In Europe, the further development of medicine is much a divided responsibility. Medical research is what is called a European competence. The EU has a major research programme on health issues running into billions of Euros annually. But health policies are a national matter where each Member State operates its own system by its own rules. Hence, the status-quo is not only maintained by the Catch-22 situation between medical research and policymaking (where each party waits for the other, as explained by previous postings) but is reinforced by an awkward institutional arrangement.

The letter to the prime ministers that I talked about earlier (see above) has not yet been sent. Instead, I have started to work on creating a favorable climate in political and governmental circles in the Netherlands (I am Dutch) and now also in Belgium (where I live) such that a letter when sent can “land” and will be acted upon.  I hope that “critical mass” will soon develop in these circles and that the “seeds for change” are spread. Faced with overburdened care and spiraling costs - a major concern these days in our little countries over here -  the minds may become more inclined to open up to the need for change.
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A new horizon for thinking about chronic diseases

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This document presents a new horizon for thinking about chronic diseases.
It is based on what we have learned here so far.
I hope it might interest you.

It is still work in progress.
The document needs to be tidied up, references of peer-reviewed papers to be added, acronyms to be spelled out etc.

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Re: Theoretical Immunology

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About the process of collating the above manuscript

The author of this manuscript was trained as an electrical and electronics engineer in the 1970s at the Eindhoven University of Technology in the Netherlands. He worked for more than 3 decades in systems engineering in various positions where he saw that big systems can fail and in fact do fail, sometimes with dire consequences. In 2004, at the age of 47, he was diagnosed with Multiple Sclerosis (MS).

In 2009, the Italian Dr. Zamboni proposed that MS is caused by narrowed veins in the neck after he found a strong correlation between the disease and vascular insufficiencies. The connection had been proposed earlier by the Austrian Dr. Steiner in the 1980s and by the Germans in the 1930s. But although the neurologists and with them the medical sector denied most vigorously the connection, this time social forums on the Internet picked up on the issue and would not let go. Drawing on his background as a systems engineer, the author intuitively felt that this could be a real breakthrough and a big systemic failure in the field of medicine.

The social forums raise new ideas all the time and stimulate thought – they thrive on chaos but at the same time lay the foundations for global colleges. The author had read about a double peak in the graph of age of onset of MS. But the observation was dismissed by neurologists as an error in the statistics. Early 2011 he made the connection between the characteristic behavior and realised that different mechanisms must be underlying MS. His interest as an engineer was aroused and from then on, he delved further into the mechanisms that could underlie MS.

With the help of social forums, in particular patient forums on MS, his own experiences as an MS patient, and the vast amount of medical literature on the Internet with its very powerful search engines that allow one to find the needle in the haystack, he developed a new thinking about MS, its origins and the very important role of cellular fitness in health and disease. Over the last few years, that thinking broadened further to include the majority of chronic diseases and mechanisms explaining how they are interconnected via a common herpes viral etiology. The work then culminated in August 2023 in the present manuscript.

The manuscript is not a typical medical paper with loads of medical jargon and deep references, neither is it the precursor for a new book on the topic. Applicable references however may easily be found using search engines on the Internet. The manuscript should be seen and read as a work in progress from the mind of an engineer who wanted to understand his own disease and, by extrapolation, the majority of chronic diseases. It has evolved from the view of an outsider and newcomer whose mind has not been set and wants to offer a new perspective to the world for looking at these diseases. The author hopes it may provide us not only with a map for new thinking about chronic diseases but also with some direction essential for resolution of these diseases.


A new theory based on facts

As Thomas Kuhn explained in The Structure of Scientific Revolutions, his seminal thesis on paradigm shifts from 1962, the people who invariably do manage to shift scientific paradigms are “either very young or very new to the field whose paradigm they change… for obviously these are the men who, being little committed by prior practice to the traditional rules of normal science, are particularly likely to see that those rules no longer define a playable game and to conceive another set that can replace them.”

Kuhn went on to say that when a shift does happen, it’s almost invariably the case that an outsider or a newcomer, at least, is going to be the one who pulls it off. This is one thing that makes this endeavor of figuring out who’s right or what’s right such a tricky one. Insiders are highly unlikely to shift a paradigm and history tells us they won’t do it. And if outsiders or newcomers take on the task, they not only suffer from the charge that they lack credentials and so credibility, but their work de facto implies that they know something that the insiders don’t – hence, the idiocy implication.

In our modern world with thriving social media, suggestions of idiocy, fake news and conspiracy theories are common place. This is also the first criticism for the manuscript which sets out a new paradigm for thinking about chronic diseases, and challenges many old medical beliefs and dogmas.

But the perspectives put forward in the manuscript are substantiated and verifiable. The narrative is coherent and consistent. The information can withstand rigorous fact checking.

In order to decide what is true and what is truth-like, let’s look a bit deeper. Below, ten facts are summarized where old medical beliefs are DEMONSTRABLY WRONG and need to be replaced by the new views that underlie the manuscript.

1. The cause of MS is unknown. WRONG. The large majority of cases of MS is caused by vascular narrowings in the neck veins. In a cohort of 1200 MS patients and 400 controls, Dr. Zivadinov (Buffalo, US) found a strong correlation between vascular narrowings in the neck and MS where 85% of MS patients had such vascular narrowings vs 20 % of the controls. A long cascade of events follows that ultimately leads to MS.

2. The graph plotting the age of onset of MS has one peak, around 27 years of age. WRONG. The graph of age of onset of MS has two peaks, one around 27 years of age and another one around 42 years of age. These two peaks point to different mechanisms underlying MS onset. The first peak is related to a breach of the BBB due to vascular narrowings and hypoperfusion of the tissue while the latter peak is related to a gut dysbiosis and deficient methylation. In both cases, lack of control of herpes will trigger the intracellular regulatory network and stop the Electron Transport Chain (ETC) of the mitochondria, after which ATP generation comes to a halt and the synapse lacks energy to pass on nervous signals.

3. Relapse Remittance MS is caused by a demyelination of the nerves. WRONG. It is an oversimplification. While there may be seen some demyelination, the recovery is not explained by a remyelination. The relapse is caused by a lack of energy of the synapse in the form of ATP, not by the demyelination. The shortage of ATP is caused by a disruption of the ETC by the intracellular immune mechanism in response to a herpes viral assault. When the ETC starts working again because the viral activity is silenced, new ATP energy is generated and we see remittance.

4. There is a phase of tolerance in our microcellular immunity. WRONG. It may be observed and look as such but in reality there is no phase of tolerance in our microcellular immunity. The cell tries to solve the problems of herpes viral assault first internally and from very early on before calling in the help of the systemic immunity. This explains the ‘immunity hump’, the initial resistance of the cell to call for outside help of the systemic immunity. As explained by the manuscript, microcellular immune regulation decides health and disease.

5. Vaccination is without risk. WRONG. Vaccination may bring pathogens in the cell with conflicting intra-cellular immune pathways, such as Hepatitis B and yellow fever, distorting the delicate host-herpes homeostasis. This may set in motion a cascade of events such as herpes viridae breaking cristae chromosomes, a failure of the ETC and the mitochondria, a loss of cellular control on self-division possibly leading to cancers or, as a protective mechanism, initiating autoimmune disease.

6. Sun exposure is bad for one’s health. WRONG. We are failing to recognize that a lack of sunshine is as bad as sunburn. Epidemiological studies show that a lack of sunshine during childhood is associated with cancers and autoimmune diseases later in life. The most common single factor that may explain the relationship with sun exposure is the amount of Vitamin D during various phases in life. An illustrative example here is the case of identical twins and MS: they have different risks to develop MS if they were separated during childhood and one has moved closer to the equator. From adolescence onwards, there is no difference. During pregnancy and childhood, the cells are built. Vitamin D is not a real vitamin but a crucial component, an essential building block. A high level of Vitamin D is obtained with a high sun exposure and a high level of cholesterol under the skin. That is why the lack of sun exposure during childhood is bad for one’s health, as is the low cholesterol hype for young people. The process of vitamin D generation has been part of vertebral life for hundreds of millions of years. From our analysis, it is believed that a high level of vitamin D ensures a good alignment of chromosomes during cellular build-up. This then contributes to well-performing ETCs and a strong mitochondrial OxPhos function, strong anti-viral properties of the mitochondria and a stable herpes-cell homeostasis. And in turn this ensures good health during life including a lower inclination to develop chronic diseases and indeed MS.

7. Our immune system protects us against all pathogens. WRONG. The immune system developed protection and immunity for the dangerous but is not completely sterilising and does allow foreign elements to invade. Our cells can live in peace with viruses and take genes from them. Our cells have reached a highly complex immune homeostasis with herpes viruses. Retroviruses were and can be reverse transcribed into the genome. We have misconceived the virus in our thinking. Most of them could well be simple inert messages in envelopes carried from cell to cell. The viral mechanisms allowed evolution to occur and even today protect us against diseases.

8. Cancer is caused by somatic mutations in the cell nucleus. The Somatic Mutation Theory is the dominant scientific explanation for the origin of cancer. WRONG. While many mutations have been found in various tumors, numerous inconsistencies have emerged that seriously challenge the credibility of this theory, including the absence of gene mutations and chromosomal abnormalities in some cancers, the identification of numerous driver gene mutations in a broad range of normal tissues, defects of the cytoplasm, and evidence from the nuclear/cytoplasm transfer experiments. Transfer of a tumor cell nucleus into a normal cytoplasm begets normal cells that have regulated growth, despite the presence of the tumor-associated genomic abnormalities. The mitochondrial control of self-division is lost in a cancer cell due to a gradual deterioration of the cell’s energy metabolism pushing the cell from OxPhos (respiration) towards substrate level fermentation. At that point the ancient mechanism of substrate level phosphorylation (outside the mitochondria) to produce ATP energy takes over. The somatic mutations arise as downstream effects rather than as causes of cancer.

9. In case of an autoimmune disease, the immune system mistakenly attacks healthy cells, tissues, and organs. WRONG. An autoimmune disease is not a real disease but a paraneoplastic syndrome, a situation where a set of conditions exist that initiates a form of hyperimmunization to protect the tissue against the growth of cancers. Women have three to four times more risk of developing an autoimmune disease than men. In traditional medicine, sex hormones as estrogens and androgens are believed to have a crucial role explaining the gender differences between males and females, with estrogens being potent stimulators of autoimmunity but also contradictory role for PD where it would offer a strong protective effect on dopaminergic neurons. We believe that, different from the believe in traditional medicine, the main reason for the gender imbalance is in the sex chromosomes. SNPs located in the sex chromosomes cause different reactions to herpes viral disturbance, with much stronger protective reactions in men than women. This is the result of a long path of evolution. What follows is more pre-tumors in women and autoimmune disease that kicks in earlier, i.e. in women the T/B cell mechanism – a paraneoplastic reaction – will be activated faster. While autoimmune disease is more frequent in women, they are better protected against cancer development than men. In men, we will see a more forceful reaction to initial viral assault by male SNPs, hence less autoimmune disease, therefore lower protection against pre-tumors, and thus more cancers later on. Epidemiologically studies have confirmed such statistics.

10. Research into most neurodegenerative disease is highly complex where their etiology is not well understood. WRONG. Most research into neurodegenerative diseases comes too late, after the event. Most neurodegenerative diseases have a common herpes viral etiology. Oxidative stress mechanisms that follow an autoimmune reaction cause specific brain cells to die. What is often researched are the myriad of downstream effects when the damage has already been done.


Ushering in a new era in medicine: a Presidential task

Many things in our traditional medicine are truth-like, but they are not truth. The manuscript is a coherent and consistent narrative for thinking about chronic diseases that brings it all together under a common herpes viral etiology.

When Kuhn wrote his book in 1962, for an outsider there was no easy way to spread new insights and gain traction for new ideas. But now, with the global reach of the Internet and the world-wide accessibility of social forums, this has completely changed. Global colleges unfold with the ease of putting one's finger on a keyboard. This thread on ThisIsMS is an example of that.

The new thinking will turn medicine upside down. The sector now needs to be given the legal certainty and regulatory predictability to enable it to change the paradigm. The new perspective will then spawn an explosion of new research activity and discoveries.

The problem is: Insiders are highly unlikely to shift a paradigm and history tells us they won't do it. Governments wait for the medical sector before approving new developments but that appears frozen by constraints. From my recent correspondence, I can only conclude that governmental departments and agencies as well as authorities in the field of medicine are interlocked with the vast medical system and are seen to be stuck. It is therefore a Presidential task to set a new policy agenda for medicine.
Last edited by Leonard on Sat Jan 13, 2024 1:27 am, edited 1 time in total.
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