Neuroimmune Toxicity of Aluminum Adjuvants 1: Safety studies of aluminum in vaccines lack immunotoxicity analysis of this immunological adjuvant: Ignorance or deception? -Vinu Arumugham

This article is part of a series of guest articles to on the neurological and immunological toxicity of aluminum-containing adjuvants in vaccines.  These articles appear by invitation to the authors.  -JLW

The safety studies most often referred by vaccine regulators when making claims about the safety of aluminum in vaccines, have ignored the immunotoxicity of aluminum.

Vaccinologists admit that they neither understand the general immunological mechanisms involved in vaccination nor do they understand the mechanisms involved in aluminum adjuvant action.

Thus vaccine regulators have no scientific basis to make vaccine safety claims. Given this situation one would expect that vaccine regulators would be very cautious about making vaccine safety claims. Instead, they collude with vaccine makers to actively hide vaccine safety problems and mislead the public.

The dual role of immunotoxicity and neurotoxicity of aluminum in autism is also covered. Cow’s milk contaminated aluminum adjuvanted vaccines cause the synthesis of folate receptor antibodies. These antibodies block folate uptake causing cerebral folate deficiency and autism. The folate deficiency in turn, causes aluminum accumulation in the brain, resulting in neurotoxicity and exacerbation of autism.


Vaccine safety authorities such as the US Food and Drug Administration (FDA) and the Australian National Centre for Immunisation Research & Surveillance (NCIRS) use studies such as Mitkus et al. 1 and Jefferson et al.2 to claim that aluminum adjuvants in vaccines are safe.


Mitkus et al.1 provide the following description of the effect of aluminum adjuvants on the immune system:

“Aluminum adjuvant are important components of vaccines, since they stimulate the immune system to respond more effectively to protein or polysaccharide antigens that have been adsorbed to the surface of insoluble aluminum particles. Specifically, these coated particles are phagocytized by cells of the innate immune system (e.g., macrophages) and activate intracytoplasmic sensors of pathogen-associated molecular patterns located within the cells, such as the nucleotide-binding domain leucine-rich repeat-containing family of sensors ([6]; Schroder and Tschopp [30]). The functional consequence of activation of this intracellular system is the activation of certain enzymatic caspases that cleave pro-interleukin (IL)-1β to interleukin (IL)-1β. The secretion of the mature cytokine, IL-1β, leads to an inflammatory reaction and a downstream Th2-dependent antibody response [7], which amplify the immune response to the antigen. Adjuvanted aluminum, therefore, plays a vital role in facilitating the response that underlies the immunoprotection afforded by vaccines.”


The rest of the Mitkus et al. review focuses on body burden of aluminum after it is absorbed from the muscle into the blood. They completely ignored any negative immunological effects that aluminum can have while it is still in the muscle (following intramuscular vaccine administration).

The quoted paragraph above assumes that the only proteins in the vaccine are viral/bacterial target proteins required for immunoprotection. In that case, as they state, the stimulation by aluminum plays a vital role in generating immunoprotection.

But obviously, vaccines contain numerous other proteins including food proteins (ovalbumin, milk, soy, yeast, oils from sesame, peanut, fish etc.)3,4, culture medium cell proteins (Vero monkey kidney cell proteins, calf serum proteins, WI38/MRC5 fibroblast cell proteins, chick embryo cell culture proteins etc.)3, non-target viral/bacterial proteins5, that are also adsorbed on to the surface of insoluble aluminum particles. As they state then, aluminum adjuvants stimulate the immune system to respond more effectively to ALL these proteins as well. The result is off-target immune responses that includes synthesis of antibodies against any and all of these proteins as well as cell-mediated immune responses.

The result of such a response of course includes food allergy6-9, asthma10, autism11,12 and autoimmune diseases13,14.

How can they perform a safety assessment of aluminum in vaccines while completely ignoring this immunological effect?

Jefferson et al.2 reviewed eight studies (listed in Table 2 of Jefferson et al.) on the effect of aluminum adjuvants. Any vaccine will need about 3-4 weeks to take effect. That’s how long it takes for the immune system to develop the appropriate immune response and antibodies. For this reason, vaccine effectiveness investigators wait at least one month post vaccination to assess effectiveness.15

Aluminum compounds are of course an immunological adjuvant in vaccines.16. So their immunological effect (positive or negative) can only be assessed if the follow-up period is greater than 4 weeks. However, only two out of eight studies in Jefferson et al. had a follow up period of >4 weeks. So rest of the studies they included were useless to assess immunological safety of aluminum adjuvants. Even those two studies ignored immune disorders such as allergies, asthma, autism or autoimmunity. As previously described, each of these immune disorders can be initiated by IgE mediated allergy11 or the Th2 response, which aluminum adjuvants are known to produce.1,17

So not only were the original studies flawed, Jefferson et al. made the mistake of including these flawed studies in their analysis. To really evaluate the safety of aluminum salts in vaccines, one would have to account for all known/potential immunological mechanisms involved with aluminum adjuvants. What are the potential negative outcomes due to that mechanism? What tests are needed to check for those outcomes? Would the outcomes be overt disease or will they be sub-clinical effects for years? This would determine follow-up times and decision on serological examination. For example: to assess if aluminum may be increasing the risk of sensitization to cow’s milk proteins contaminating the vaccine, one would not only have to wait for 4 weeks after vaccination, but also challenge the patient with cow’s milk, pre- and post- vaccination, to assess the impact. Similarly, to check if aluminum induced an autoimmune disease that may only show up years later, one would have to perform autoimmune serology pre- and post-vaccination checking for changes in autoantibody levels, as suggested by Wraith et al.18

These studies have never been performed. Why?  In fact, vaccine makers seem to go out of the way to obscure the adverse effects of aluminum adjuvants by injecting aluminum adjuvant into control subjects during vaccine clinical safety trials.15

Given this situation, the Jefferson et al. conclusion: “Despite a lack of good-quality evidence we do not recommend that any further research on this topic is undertaken.” is inexplicable, and raises serious questions about the manner in which vaccine safety investigations are conducted.

Evidence of aluminum adjuvant dangers

Morris et al.19 have called for the elimination of aluminum adjuvant in vaccines. Prof. Franco Celada, Dept. of Pathology, NYU School of Medicine, called for safety studies of aluminum adjuvant induced innate immune system activation (personal email communication, Oct 2017) in the context of low affinity self reactive (LASR) T cell mediated autoimmune diseases13,14 caused by animal protein contaminated vaccines.

Anders et al.20 have called for the re-evaluation of aluminum adjuvants in vaccines due to its role in boosting IgE mediated responses. In other words, a Th2-dependent antibody response as described by Mitkus et al.1 and Terhune et al.21 Terhune et al.22 further link Treg dysregulation in atopic disease to aluminum adjuvants.  Shoenfeld et al.23 describe aluminum adjuvant-induced autoimmunity.

Aluminum immunotoxicity followed by neurotoxicity in autism

Many vaccines contain casein or casamino acids of bovine milk origin and are thus contaminated with all bovine milk proteins.3,24 One such protein is the bovine folate receptor (FR) protein25. Such aluminum-adjuvanted, bovine FR protein contaminated vaccines can cause IgE mediated sensitization to the FR protein (aluminum adjuvant induced Th2 response1).4,6,10

Since FR concentration in bovine milk is low, the patient can still consume bovine milk without developing an allergic reaction.25,26 It has been shown that consuming milk when sensitized (via an oral immunotherapy protocol, for example) will result in the synthesis of IgG4 antibodies specific to milk proteins.8

In this case, bovine milk consumption causes FR specific IgG4 synthesis. These IgG4 antibodies cross-react with human folate receptors. Human and bovine FR proteins have 90% amino acid sequence homology.27  IgG4 specific to FR is the main antibody involved in binding/blocking folate receptors in the choroid plexus, blocking folate uptake to the brain.27

This results in cerebral folate deficiency and autism.28 Folate deficiency in turn, results in aluminum accumulation in the brain and aluminum-induced neurotoxicity.29-31

The source of the aluminum could of course be the diet, pollutant inhalation and aluminum-adjuvanted vaccines. Mold et al.32 have demonstrated such aluminum accumulation in human autistic brain tissue.


The FDA makes a mockery of science by comparing aluminum in vaccines to dietary aluminum.33 In that case, we should be drinking our aluminum adjuvanted vaccines, instead of intramuscular injection. The FDA’s Mitkus et al. study1 is entitled “Updated aluminum pharmacokinetics following infant exposures through diet and vaccination.”. They studied pharmacokinetics – how aluminum moves through the body. While aluminum pharmacokinetics related safety needs to be understood, they cannot ignore aluminum adjuvant immunotoxicity, if they were really interested in vaccine aluminum adjuvant safety. If the FDA is incapable of even determining the appropriate lines of safety investigations required, how can they be in charge of vaccine safety? How can we expect vaccines approved by the FDA to be safe?

Safety needs engineering not tinkering

For decades, vaccinologists have been reluctant to understand the immunological mechanism of how vaccines work, fail or hurt the body.

Pulendran et al.37 wrote:

“Despite their success, one of the great ironies of vaccinology is that the vast majority of vaccines have been developed empirically, with little or no understanding of the immunological mechanisms by which they induce protective immunity. However, the failure to develop vaccines against global pandemics such as infection with human immunodeficiency virus (HIV) despite decades of effort has underscored the need to understand the immunological mechanisms by which vaccines confer protective immunity.”

Mojsilovic16: “Some of the first adjuvants discovered back then, on empirical basis of trial and error, are still in widespread use today, but only recently some light on the molecular mechanisms of their action has been shed.”

There seems to be little interest among vaccine developers and regulators in understanding the mechanisms of immunoprotection or immunotoxicity of vaccines and adjuvants. This is no way to build a safety critical product, centuries after its invention.

Since the immunological mechanisms of vaccines are not understood, one would expect that vaccine makers and regulators will be extremely cautious about making vaccine safety claims. One would expect that they will thoroughly investigate even the slightest indication of vaccine-induced adverse events.

Instead, we find vaccine makers and regulators collude to hide vaccine safety problems. The ShingrixTM vaccine was recently approved after an inadequate safety evaluation.35 The FDA briefing document (Sep 2017) describes serious adverse events (SAEs) including supraventricular tachycardia following Shingrix vaccination in clinical studies. The Shingrix vaccine package insert (revised 10/2017)36 has no reference to supraventricular tachycardia at all.


Elizabeth Hart, Adelaide, South Australia, suggested this review and provided background material.


1. Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine. 2011 Nov 28;29(51):9538–43.

2. Jefferson T, Rudin M, Di Pietrantonj C. Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence. Lancet Infect Dis. United States; 2004 Feb;4(2):84–90.

3. Vaccine Excipient & Media Summary [Internet]. 2015 [cited 2016 Jan 16]. Available from:

4. Arumugham V. Professional Misconduct by NAM Committee on Food Allergy [Internet]. 2016. Available from:

5. Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2 (ABSTRACT ONLY). Sci Transl Med. 2015;7(294):294ra105–294ra105.

6. Arumugham V. Evidence that Food Proteins in Vaccines Cause the Development of Food Allergies and Its Implications for Vaccine Policy. J Dev Drugs. 2015;4(137):2.

7. Platts-Mills TAE. The allergy epidemics: 1870-2010. Journal of Allergy and Clinical Immunology. 2015. p. 3–13.

8. Hoyt AEW, Schuyler AJ, Heymann PW, Platts-Mills TAE, Commins SP. Alum-Containing Vaccines Increase Total and Food Allergen-Specific IgE, and Cow’s Milk Oral Desensitization Increases Bosd4 IgG4 While Peanut Avoidance Increases Arah2 IgE: The Complexity of Today’s Child with Food Allergy. J Allergy Clin Immunol. Elsevier; 2017 Jul 7;137(2):AB151.

 9. Alice Hoyt, Peter Heymann, Alexander Schuyler, Scott Commins TAEP-M. Changes in IgE Levels Following One-Year Immunizations in Two Children with Food Allergy [Internet]. 2015. Available from:

10. Arumugham V. Medical muddles that maim our children with allergies, asthma and autism [Internet]. Unpublished; 2017. Available from:

11. Arumugham V. Autism Spectrum Disorders: A special case of vaccine-induced cow’s milk allergy? [Internet]. 2017. Available from:

12. Arumugham V. Strong protein sequence alignment between autoantigens involved in maternal autoantibody related autism and vaccine antigens [Internet]. 2017. Available from:

13. Arumugham V. Cancer immunology, bioinformatics and chemokine evidence link vaccines contaminated with animal proteins to autoimmune disease: a detailed look at Crohn’s disease and Vitiligo [Internet]. 2017. Available from:

14. Arumugham V. Bioinformatics analysis links type 1 diabetes to vaccines contaminated with animal proteins and autoreactive T cells express skin homing receptors consistent with injected vaccines as causal agent [Internet]. 2017. Available from:

15. Gardasil Package Insert [Internet]. Available from:

16. Mojsilovic SB. Immunological effects of adjuvants, their mechanisms, and relevance to vaccine safety. Cent Eur J Paediatr Vol 13, No 1 Cent Eur J Paediatr. 2017;

17. Lindblad EB. Aluminium compounds for use in vaccines. Immunology and Cell Biology. 2004. p. 497–505.

18. Wraith DC, Goldman M, Lambert P-H. Vaccination and autoimmune disease: what is the evidence? Lancet (London, England). England; 2003 Nov;362(9396):1659–66.

19. Morris G, Puri BK, Frye RE. The putative role of environmental aluminium in the development of chronic neuropathology in adults and children. How strong is the evidence and what could be the mechanisms involved? Metab Brain Dis. United States; 2017 Oct;32(5):1335–55.

20. Markt A, Björkstén B, Granström M. Immunoglobulin E responses to diphtheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines. Vaccine. 1995;13(7):669–73.

21. Terhune TD, Deth RC. How aluminum adjuvants could promote and enhance non-target IgE synthesis in a genetically-vulnerable sub-population. J Immunotoxicol. England; 2013;10(2):210–22.

22. Terhune TD, Deth RC. A role for impaired regulatory T cell function in adverse responses to aluminum adjuvant-containing vaccines in genetically susceptible individuals. Vaccine. Netherlands; 2014 Sep;32(40):5149–55.

23. Shoenfeld Y, Agmon-Levin N. “ASIA” – autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. England; 2011 Feb;36(1):4–8.

 24. Kattan JD, Cox AL, Nowak-Wegrzyn A, Gimenez G, Bardina L, Sampson HA, et al. Allergic reactions to diphtheria, tetanus, and acellular pertussis vaccines among children with milk allergy. J Allergy Clin Immunol. 2011;Conference(var.pagings):AB238.

25. Nygren-Babol L, Sternesjö , Björck L. Factors influencing levels of folate-binding protein in bovine Å milk. Int Dairy J. 2004;14(9):761–5.

26. USDA Food Composition Databases [Internet]. Available from:

27. Ramaekers VT, Sequeira JM, Blau N, Quadros E V. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. 2008;50(5):346–52.

28. Arumugham V. Epidemiological studies that ignore mechanism of disease causation are flawed and mechanistic evidence demonstrates that vaccines cause autism [Internet]. 2017. Available from:

29. Baydar T, Nagymajtenyi L, Isimer A, Sahin G. Effect of folic acid supplementation on aluminum accumulation in rats. Nutrition. United States; 2005 Mar;21(3):406–10.

30. Yassa HA, George SM, Mohamed HK. Folic acid improve developmental toxicity induced by aluminum sulphates. Environ Toxicol Pharmacol. 2017;50(Supplement C):32–6.

31. Zhu M, Li B, Ma X, Huang C, Wu R, Zhu W, et al. Folic Acid Protected Neural Cells Against Aluminum- Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation. Neurochem Res. 2016;41(8):2110–8.

32. Mold M, Umar D, King A, Exley C. Aluminium in brain tissue in autism. J Trace Elem Med Biol. 2018 Mar;46:76–82.

33. FDA. Study Reports Aluminum in Vaccines Poses Extremely Low Risk to Infants [Internet]. Available from:

34. Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. United States; 2011 Jun;12(6):509–17.

35. Arumugham V. SHINGRIX vaccine is unsafe and its approval must be revoked [Internet]. 2017. Available from:

36. FDA. SHINGRIX vaccine package insert [Internet]. 2017. Available from:


The Evolutionary Arms Race Theory of Autoimmune and Pathogen-Derived Disease

WHEN EVOLUTIONARY EXPLANATIONS are invoked to explain the existence or persistence of specific traits, the normative causal reasoning invokes a benefit to the individuals carrying the genes for those traits, a concept widely understood as individual fitness. Natural selection then results as an outcome of competition for the most limiting resources; nature providing a grand stage upon which all of the theatrical plays of life are worked out, with some characters thriving, and others denied contribution to the next generation: for them, their genetic fate a dismal tragedy.

Tomes of very clever ideas, and deep understanding on how complex evolution could become were worked out in for 90 years in the pages of journals that published theoretic works by such great minds as Sewall Wright, whose ideas on balancing selection explain how two traits, both slightly deleterious, could offset a certain march toward genetic doom, leading to the persistence of apparently deleterious traits in evolving populations over time. He and others worked out ways of thinking about complex genetic interactions, such as epistasis and pleiotropy. All shifts in gene frequencies in most populations, it was thought, could be well understood as a balance between the relative contribution of alleles to benefits in terms of survival and reproduction, and inconsistencies and unlikely or seemingly impossible outcomes could result from shifting balances across adaptive landscapes.

Utterly brilliant, this body of work was confronted with new thinking upon the the arrival of even the earliest modicum of data. Motoo Kimura showed, for example, that most of the changes in gene frequencies over time where not likely to involve a specific genetic contribution to differential survival and contribution, but were rather simply a mathematical necessity, driven by mutation pressure, with most nucleotide substitutions occur simply because there was not enough room in the population to hold all of the alleles at a particular locus.  This is most easily understood in very small populations, in which the smallness of the population makes random factors that influence the survival of specific genetic variants much more important than they would be were those alleles found in a larger population.  Alleles could come into existence by chance, and then, driven by chance, drift to fixation to the exclusion of other alleles, regardless of their relative contribution to survival and reproduction. Under Kimura’s neutral theory of evolution, and its descendant theories, mutation pressure places the limit on the rate of evolution, and most (the largest percentage) of genetic changes over time do not particularly influence survival or reproduction, or if they do, those changes are carried along by chance.

We should understand that evolution is a combination of Darwinian natural selection and neutral drift, both rates limited by the amount of genetic variation in a population, which itself is limited by factors such as mutation rates, and, for a given subpopulation, access to mates from other subpopulations that might contain different alleles and genotypes.

We understood then, and now, that mutations are not restricted to nucleotide substitutions, and that large, deleterious genomic differences can have large impacts on the relative survival and reproduction of individuals, and that many traits observable in a population are impacted by the effects of the environment on specific methylation patterns in parents’ (mostly mothers’) chromosomes, and that changes that occur during gametogenesis both of the nucleotide, genomic and epigenetic levels can be found in offspring.  Most of the important changes in phenotypes over time likely involve traits that are related to differential survival and reproduction, both of which can be measured objectively. In other words, what is important in terms of providing an evolutionary explanation can be consider both in terms of counting shifts in gene frequencies, and in their impact on survival and reproduction.

When I began studying genomic and genetic changes related to disease, I performed most of my studies in the service of others.  I worked hard to try to insure that the data analysis techniques and models we employed were at least empirically reproducible, if not founded upon a solid theoretical basis. When technologies brought the ability to assay entire genomes, transcriptomes, and proteomes, I worked overtime, often deep into the early morning hours, comparing alternative methods for data representation, normalization, finding differences, and interpreting in search of the most empirically justified frameworks to tell, from a single data set, which gene, proteins, or methylation patterns were likely to be truly important to a particular disease. I started in cancer (nearly all types), and from there moved into nearly every other domain in medicine, including immunology, diabetes, pulmonology, neurology, and so on.  In any given week I’d be involved in 4-5 different studies, and when finally tallied, during my 16 years working exclusively on these problems, I contributed results to over 100 studies. Many of the studies were, appropriately, at the pilot level.

I had on several occasions had the opportunity to work with experts in immunology, working on cancer. There was a good reason for that. Part of my attraction to come work at the University of Pittsburgh Cancer Institute was Dr. Ronald Herberman, who had assembled a cracker jack team of immunologists focused on various aspects of cancer. While working as a post-doc under Dr. Masatoshi Nei, I became immersed in his excellent studies on the evolution of the very complex MHC loci, and the amazing adaptive immune system, which uses combinatoric guessing at matching epitopes found in nature.  While at Penn State and at UPCI, it took a while, but over time I became intimately familiar with the roles of the various types of cells, tissues, and signals. It was an amazing time, and I had never been happier in my position.  From breast cancer to melanoma, pancreatic cancer and lung cancer, I had a chance to see some of the world’s foremost researchers working to understand both the causes of and processes of cancer, driven by mutations, and the optimal routes to treatment. Biomarkers were a huge part of the experience, as well as a search for their biological significance (function).

My interests in autoimmune disorders sank in while writing three books: Ebola: An Evolving Story; Cures vs. Profits:Successes in Translational Research, and The Environmental and Genetic Causes of Autism.  The experience of writing those three books allowed me to go into deep study of the primary literature on disease causality specifically on factors that impact our immune systems.  Factors that most profoundly influenced my understanding that leads to this Evolutionary Theory of Autoimmunity of course were threefold:

(1) intensive study on the role of cytokine storms in the pathogenesis caused by Ebola infection, specifically the devastating positive feedback loop caused by our immune systems’ responses to the effects of Ebola on our tissues, with releases of cytokines that activate escalating responses to cellular damage

(2) the theoretical and empirical basis for artificial immunization, and its attendant consequences (most often attempted using vaccines), and

(3) being inundated with information on the fact that dozens and dozens of conditions known as autoimmune disorders defy explanation.

Readers of “Causes” will come to understand that autism can often involve a form of ‘innate’ autoimmunity, in which specialized cells in the brain that play the role of scavenger of cellular debris and killers of intruders, like white blood cells, can become chronically activated in the presence of the persistent activating signal of the excitotoxic amino acid glutamate.  Ironically, I cannot consume monosodium glutamate, because it brings an onset of migraine headaches. This same amino acid, in some kids’ brains, stays at high levels and rather than ceasing their destruction, say, of unhealthy brain tissue, they go on the attack and destroy both dendrites and neural precursor cells, which release cytokines signalling cellular damage, injury, and death, causing sustained microglial activation. The original cause of the high glutamate levels in the brain of autistics may vary from case to case; it may involve a mutation in a glutamate receptor found on astrocytes, or it could be environmental damage to astrocytes via metals, which preferentially bind to astrocytes, and which have been shown to localize both to the nuclear pore and the cell membrane  The literature on traumatic brain injury and stroke is now rapidly filling with how helpful it is to keep microglial cells quiet before they set off a positive feedback of cellular destruction that keeps them chronically activated.

They will also come to understand that many of the adverse events seen in vaccines, and autoimmune disorders, which in most doctor’s minds have root causes that defy explanation, are in fact induced by the presentation of foreign antigens into the human in the presence of an adjuvant. Dr. Yehuda Schoenfeld presented this idea in 2010:

Shoenfeld Y, Agmon-Levin N. 2010. ‘ASIA’ – autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011 Feb;36(1):4-8. doi: 10.1016/j.jaut.2010.07.003.

Other studies by Schoenfeld and colleagues have found that ASIA has been reported from nearly every vaccine on the market, and that we may be able to predict who is at highest risk of developing autoimmunity from after vaccines:

Soriano A, Nesher G, Shoenfeld Y. 2015. Predicting post-vaccination autoimmunity: who might be at risk? Pharmacol Res. 2015 Feb;92:18-22. doi: 10.1016/j.phrs.2014.08.002. Epub 2014 Sep 30.

I suspect that in time most autoimmune disorders, which are known to involve adaptive immune systems attacking healthy human tissue, will be seen to ultimately have an evolutionary explanation. Part of it will seen an resulting from adaptive advantage to pathogens in their ability to effect their hosts in a manner in which transmission to new hosts is made more likely. While none of which could possibly be seen as resulting from adaptive advantage to humans, we will explore that in detail later. It must also be remembered that a part of the explanation could also be come to be seen to be the result of mere chance.

MULTIPLE SCLEROSIS is a devastating progressively degenerative disease that, at its heart, involves stripping of axonal sheaths from victims, leaving their nerve cells in the brain and the spinal cord unable to transmit signal due to a lack of insulation and improper ionic balancing associated with nerve impulses. Clearly, whatever has caused demyelination, and demyelination itself, cannot be seen in Darwinian terms to be adaptive to humans. This is about as far as evolutionary thinking has applied.  The dismissal of an evolutionary explanation based on the ideas that genes that encode ‘for autoimmunity’ would be quickly removed from a population is only halfway thought through. The more rapidly evolving organism on the scene, of course, is the pathogen itself.

From a pathogen’s perspective, for example, making its host immobile, especially if that host is a member of a social species, will increase the duration and frequency of contact between the affected and the unaffected, leading to increased transmission of the pathogen. Thus, from a pathogen’s fitness perspective, injuring its host, without killing it, would be adaptive. The pathogen itself could do the damage, such as infecting specific types of brain cells and impairing movement. Or, it could have the same effect by turning the hosts’ immune system against itself. We could expect that surface epitopes seen on viral proteins would be on adaptive landscape that could lead them, as a result of chance mutation after mutation, to become increasingly similar to key host proteins. In fact, many pathogens that infect humans have been infecting other primates for millenia, and the common, successful ones causing hardly any or no symptoms at all in their native hosts. But many pathogens do cause disease in their native hosts, including paralysis and death.

Within the human population, then, we could see that whichever proteins that are attacked by the immune system as a result of the development of cross-reactive antibodies would be on an adaptive landscape upon which there would be advantage to moving, random mutation by random mutation, further away from the offending pathogen’s epitope sequence.

We can make predictions on the basis of this theory: genes that encode spefic surface epitopes on pathogens that cause autoimmune disorders should show high rates of non-synonymous substitutions that cause increased conformational similarity to that of their hosts’ matching protein sequence, and hosts should be observed to show high rates of non-synonymous substitutions, as the run away from the offending pathogens’ epitope sequence and structure. A third prediction would be that the hosts’ proteins are much more constrained than the pathogens; they are, after all, already serving an essential function in the host, whereas the surface antigens on a pathogen may be more evolutionarily labile, freer to explore a wider area on its evolutionary adaptive landscape. (For more ideas on the importance of individual mutations vs. rates, see this article).

Adaptive Landscape 1 tif to jog

The first step toward testing this evolutionary arms’ race theory of autoimmunity is to determine which pathogens hold the best-matching epitopes.  The second step is to confirm that cross-reactive antibodies exist in autoimmune patients to specific epitopes of interest. This step also happens to be potentially very useful to patients both in terms of helping their doctors understand their disease, and could lead to individualized treatment via immunomodulation therapies. The third step is to measure, whenever possible, the rates of synonymous and non-synonymous substitutions over long enough periods of time to catch the pathogens’ protein racing toward the human sequence, and the matching human protein racing away from the pathogen sequence.

There are attendant logical predictions about variation in the rates of specific autoimmune disorders attributable to specific pathogens across human populations if genetic variation exists within the self-targeted proteins involved in autoimmune disorders.

We have begun these steps, pathogen by pathogen, autoimmune disease by autoimmune disease, at the Institute for Pure and Applied Knowledge, importantly beginning with the proteins that are already known to be targeted by our immune system during autoimmune disease.  Our findings thus far are quite promising, and may lead truly useful information, such as the knowledge of which pathogen’s epitopes should excluded from vaccine, for fear of inducing autoimmunity in a preventable manner.

One realization that we have had is that it is possible that the mechanism of pathogenesis, that is, the ways in which communicable pathogens cause disease in humans (and animals), may be precisely they same way they cause autoimmune disease. From the mildest sniffle, or the most raging fever, it seems likely that pathogen/host protein similarities, driven mostly by adaptive evolution in the pathogen, may explain most – if not all – of the symptoms by which we diagnose communicable diseases.  That would be very good to know.

My next stop in this journey will be the literature – the massive scientific literature on host/pathogen interactions – to see what is already known on this fascinating topic.  You can support our efforts at

-James Lyons-Weiler, PhD

October 31, 2016

I thank Celeste McGovern at Greenmedinfo for her well-written and informative post,

Attacking Ourselves: Top Doctors Reveal Vaccines Turn Our Immune System Against Us