On the origin of 'what immunity is and what it does' Autotoxicus Invictus: Self-Toxicity Unconquered - [ ] The great tools of Pasteur & Jenner - [ ] The great theory of Erlich - [ ] How he is right, GVHD is essentially what he was talking about - it doesn't exist - [ ] It does to some degree in APS-1 patients - but even THEY survive with it - [ ] The flaw in horror autoxicus - [ ] Erlich's tools versus my own - [ ] The proving of autoimmunity - [ ] The implications of autoimmunity - [ ] There is no such thing as a monospecific monoclonal antibody; the 'antibody research reagent problem' is NOT just a reagent problem; it is an expected flaw in immunity itself. Clavis Ex Damnatione: The Key Born from Damnation - [ ] Everything is an autoimmune disease - [ ] When it's not, its still impacted by autoimmune tweaks (just like your genome) - [ ] How ageing and mitochondrial clogging relates to this - [ ] How microplastics and seed oils relate to this - [ ] How viruses and vaccines relate to this - [ ] The window of timing in early childhood - [ ] Imply that these keys can lead to cures, foreshadowing future treatments Codex Corporis et Corruptelae: A Codex of the Body and Its Corruptions - [ ] where we are today; huprot, protoarray, phip-seq, yeast display, etc - [ ] how to build a 'universal human proteome library' - [ ] not just all proteins - all isoforms and genetic polymorphisms - [ ] dark proteome as well, mistranslations, out-of-frame-ome - [ ] multiplied by 'all possible transformations thereof' ie age associated mitochondrial byproducts - [ ] clogged mitochondria byproducts, flooding the engine hypothesis - [ ] microplastics, PFAS, and more oh my! Cartographia Immunis: The Mapping of Immunity - [ ] Tracking how self-recognition manifests across populations. - [ ] What I predict we will find; the cause of autism, als, alzheimers - [ ] the populations to search - [ ] understand where it comes from <bad food? bad vaccine timing early childhood?> - [ ] the weird shit - bees and worm viruses - [ ] what we can get done with the tools we have now, what we will miss <much of it> - [ ] the harder problems: glycosylation, lipids, etc - it gets so much worse folks... Opus Clavium: The Work of the Keys - [ ] by building the atlas we will be able to solve individual problems - [ ] repurposing for drugs - [ ] depletion of bad clones - [ ] imagine a checkup; test your serum - oh you have autoabs against lubricants in your knees transformed by seed oil degredation byproducts - now you have arthritis; let's teach your body to tolerate that; you have autoantibodies against microplastic transformed brain cells - let's teach your body to tolerate that. Let's teach it to cure cancer, to slow ageing. The State of Things - [ ] Multiple Scleroisis - [ ] Long COVID19 - [ ] Alzheimers - [ ] ETC ETC ETC ETC - if there is a regular blog it's right here "this is a recruitment post" Abstract: Autotoxicity is not only common and unavoidable, it likely underlies many of the great unsolved medical mysteries of our age. From Alzheimer's to autism to the obesity epidemic - there is deep and growing evidence for immunity's universal connection across many conditions. The cause of these conditions, and thus the cures, can be found where only scattered pioneers are currently searching. This will be extensively demonstrated across many disparate medical fields. From there, we will discuss why mapping it is so important - for to map an atlas of autoimmunity would be to give us a chart towards curing disease. This will not be easy work - not the building nor the mapping. But from there - there are cures. Ways to personalize and correct these problems on an individual level. It's a challenge worth doing. Who should read this - You or a loved one suffer from an 'uncurable' disease. - You or a loved one suffer from a 'cause unknown' chronic conditions that no doctor seems to be able to diagnose or solve. - You want to understand 'why people seem so sick' these days - You are a scientist who has not yet considered the role of immunity in the disease you study. - You are a technologist who can contribute to upping our methods to the next level. - ghht The article is broken down into the following sections: - The history of autotoxicity - The growing evidence of how pervasive it is - The state of current tools, what needs to be done to improve them - What we are likely to find if we build a 'autotoxome atlas' - How we will then utilize these discoveries to cure conditions Autoimmunity is not an anomaly; it is an **inevitable consequence** of natural immune function. This argument unfolds in multiple layers. First, we will revisit **the origins of the study of autoimmunity**, exposing the blind spot in Erlich's foundational concept of _horror autotoxicus_—the belief that the body utterly prevents self-attack. We now know this is false; autoimmunity is everywhere, woven into **every person’s immunological fingerprint**. From there, we explore **how autoimmunity pervades disease**, from known conditions like lupus and multiple sclerosis to the hidden autoimmune components of Alzheimer’s, ALS, metabolic dysfunction, and cancer. These insights reveal **not just suffering, but opportunity**—for if autoimmunity is the _cause_ of these diseases, it is also the **most precise map we have to solving them**. Thus, we move to **building the grand reference**—the **Codex Corporis et Corruptelae**, a complete molecular atlas of self, including not just native proteins but **every transformation, every post-translational modification, every metabolite, and every damaged byproduct that may become antigenic over time.** Only with this foundation can we begin **Cartographia Immunis**, the systematic mapping of how human immunity interacts with self—how tolerance is maintained, how it fails, and how chronic diseases emerge. Finally, we discuss **Opus Clavium—the Work of the Keys**: how this knowledge leads to actionable cures. With a fully mapped atlas and immune reference, we can personalize medicine in ways never before possible: identifying problematic immune targets, selectively deleting pathogenic clones, inducing tolerance, and **engineering the immune system to repair itself.** The challenge ahead is enormous. **It will require both fundamental biology and industrial-scale biotechnology**, the construction of tools that do not yet exist. But the prize—**the ability to systematically cure, reverse, and prevent molecular-level disease unique to single individuals*—is worth it. The immune system has written its own record of its failures. **If we learn to read it, we will hold the keys to health, longevity, and the greatest medical breakthroughs of our time.** Introduction: Dear reader, **I regret to inform you that you have an autoimmune condition.** Your disease is entirely unique to you, essentially without cure, and likely involved in your eventual death. But fear not, I have one too and am interested in solving this problem for both of us. The purpose of this document is to provide a **grand unified theory** explaining most of the great ailments of our time. Biologists LOVE to refer to problems they haven't solved yet as 'complex diseases' - this is simply a distraction from the fact that they don't know the cause of the disease in question. It is quite simple in fact, especially with modern 'multi-omic tools' to create 'atlases' of data and cells which in fact tell no story at all. Beautiful figures will result, and just to prove I'm not a sore sport here's one of mine. Pretty isn't it? However I do not actually believe in 'complex disease.' There is no such thing. Instead, I ask you to observe biologic systems as a sort of three-body-problem - in which relatively simple pertubations can result in absurdly complex downstream systems as redundancy upon built in evolutionary redundancy kicks in like a series of ancient diesel generators to ameliorate the consequences of said simple problem. Take for example XXXX disease. There is literally one molecule missing, and yet the complexities are legion. On the immune side there is XXXX disease, one antibody against XXXX molecule results in symptoms that have been ignored since XXXXX century. ---historical anecdote of disease--- Biologists love to chase complexity -- for there is in fact no man made system as complex as a cell, let alone an organism made of trillions of cooperating cells -- and it is quite simple to observe intricately fractal patterns in data without actually extracting any insights. IE Our story begins with the discovery of autoimmunity - or rather - the first recognition that *autoimmunity might exist.* This was by [Paul Erlich](https://en.wikipedia.org/wiki/Paul_Ehrlich), famous among other things for "work on immunity" - some of the first ever in fact - which won him the [Nobel Prize in Physiology or Medicine in 1908.](https://www.nobelprize.org/prizes/medicine/1908/ehrlich/facts/). **Erlich did not believe autoimmunity was possible**. This opinion developed following his own attempts to induce autoimmunity by injecting different materials into animals and measuring their antiserum; foreign individuals created antibodies - but self materials did not. - attempts which failed. Erlich was unable to elicit the dramatic antibody responses to 'self' materials he knew were created by 'foreign' materials such as bacteria. Erlich referred to this 'abhorrence of autoimmunity' as *horror autotoxicus* - a principle he believed to be a law of nature. The human body simply could not allow autoimmunity to exist! Today, we of course do know that autoimmunity does exist. You perhaps suffer from arthritis, or have a coworker with lupus. However, what is much less widely known - yet quite well established and the point of this article - *is that the majority of autoimmunity going on in someone with lupus or arthritis has nothing to do with either condition.* In fact - most of the autoimmunity in those 'autoimmune conditions' is no less severe or relevant than your own. All people - including you - bear hundreds of autoantibodies against hundreds of random body components at the molecular level. If we were to zoom in on Erlich's experiments with modern tools - tools that I help build and use everyday - we would see something quite different. Individual small reactions - there before the experiment even begins, that bind to natural components of the human body. Autoimmunity in fact **must exist; it is an inevitable result of how immune systems function.** The amount which it impacts our lives are an inevetiable result of how bodies age. It is not so much he opposite of Erlich's theory - the body does not want or love autoimmunity, there is no *amor autotoxicus.* Howe <Insert image of erlich's experiments; show how his worked 'against cells' -- show where it would FAIL 'against a protein microarray> Erlich's experiments failed because he did not include immune-stimulating adjuvants (as we use in vaccines) to help hyper-stimulate immune responses; nor did he lack the sensitivity and nuance of modern tools millions of times more sensitive than his. But Erlich was not that far off - the body contains very sophisticated mechanisms to avoid, and reduce the harm of, autoimmunity. Exquisitely intricate systems exist to train immunity to recognize 'non-self' infections, and protect the 'self' from immune harm. We immunologists refer to this process as 'tolerance.' Tolerance is currently simplified into two forms: central tolerance and peripheral tolerance. Immunity as a system works on *random shape generation* by the immune receptors in our cell-killing T cells and our antibody-producing B cells. Since it is not possible for the genome to contain 'all possible' immune recognition shapes, it does this by random recombination. In fact, to encode 'all the possible' immune receptors would require a genome larger in size than the known universe. Randomness is thus far more efficient! But randomness is a dangerous way to build a foreign recognition system. What if it recognized the body's own components!? In fact - **this is entirely expected and a key feature of how the immune system works.** Newborn immune cells are compared to a library of the body's protein shapes. If they match? They are eliminated. Thus leaving a the naive young immune system: **a population of random shape recognizing immune cells which do not recognize the body's natural shap**es. This system is of course imperfect. No immune cell can be trusted to have been compared to ALL possible body shapes! Thus if some cells HYPER RECOGNIZE self tissue, they are allowed to become 'regulatory T cells' that head out into the tissues to calm down or delete any aberent autoreactive cells. This 'tolerance,' and the body's very careful assurance that it exists, is what Erlich simplified as *horror autotoxicus*. But it is not near so absolute as he claimed! Systems are inherently imperfect - be they biologic, or made by man. Evolution itself is able to understand this, and I would instead answer Erlich with the law of *autotoxicus invictus* or 'self-toxicity unconquered' – an unavoidable baseline level self-reactivity that is expected to emerge as part of natural immune function. In fact - its likely to lead to your death. Man's eventual conquest and harnessing of autotoxicity will be a key milestone on the road to immortality <one doomed to fail by the physical rules of this universe I am sure - but not the world beyond the veil - read some Andre Cote>. Some level of this has undoubtedly always existed and the body provides redundant safeguards in anticipation of it. Historically these 'expected failures' were mostly naturally corrected or only become relevant in outlier cases - or with extreme age. However, modern Westerners have a LOT of autoantibodies. And it is not at all clear to me that our **current level of autoimmune issues are normal**. In fact, I expect they are not. And the effect and impact of these other than the few outliers you have already heard of? Essentially unknown. But they are important, and they are knowable. The complexities of your own autoimmune disease are legion and entirely unique to you. It is not shared by your mother, your brother, or your identical twin (should you have one). But they are knowable, and they are important. And I think that finding out how to fix them (for both of us) is absolutely essential to our long term survival. Modern medicine is failing to solve the 'chronic disease epidemic' be that ALS, Autism, Alzheimers, or on down the alphabet of named conditions to Obesity, Type II Diabetes, and beyond. Many of these diseases have a 'selectively penetrant genetic or environmental risk factor' (ie weak correlations that typically don't result in the condition). I believe that the keystone to most of these will soon be found to be the errors in our natural '*autotoxicus providens*' - that this might even be improved upon to create therapies to treat cancer and delay ageing. The point of this page is that *if* immunity is the key to these conditions - and it is already known to be the key to some - then better mining 'where it makes mistakes' is the first step in curing or entirely preventing these conditions. Just as DNA sequencing has lead to an understanding of specific sites where 'genetic mistakes cause the biggest problems' early autoantibody analysis is already revealing 'where immune mistakes cause the biggest problems.' The majority of these remain unknown, and it is time to find them. References: A lecture by Erlich, scientist who coined 'horror autotoxica' ie the body's aversion to autotoxicity prevents it occuring. [[Ehrlich-Croonian-Lecture-On-Immunity-With-Special-Reference-To-Cell-Life.pdf]] The great convert to autoimmunity and a disciple of Erlich. Proved once and for all - certainly not the first time, but the moment that converted others - that autoantibodies existed. [[Chronic Thyroiditis and Autoimmunization - Witebsky 1957.pdf]]