Biological Plasticity, Cell Danger Signaling & Symptom Management: Where To Draw the Line?

There’s a fine balance between treatment and non-treatment. Philosophically I verge more on the side of conservative and “less is more treatment” for many reasons. My current philosophy in these regards is based upon the potential adverse effects of pharmaceuticals, and of the assault I believe many drugs have on memory-based physiological processes, also known as biological plasticity. This topic is not extensively studied by any means, but the concept emerges from the process of hormesis.

Hormesis & Biological Plasticity

Pharmacologically, hormesis refers to the bi-phasic dose effect, whereby a low dose has a stimulatory effect, but a higher dose has an inhibitory effect. This phenomenon has been observed since the late 19th century but has failed to gain widespread acceptance due to the close association with homeopathy. Much of the type of toxicity I am referring to with pharmacological agents exists because of medicine’s unwillingness to embrace the reality of the hormetic effect. Hormesis is often equated to the phrase: “what doesn’t kill you makes you stronger”.

Biological plasticity, aka phenotypic plasticity is concerned with the ability of organisms to adapt to heterogenous environments (Calabrese, Mattson, 2011). This involves an organism’s ability to adapt to infectious agents, to stress signals, to drugs, to toxins, to exercise, and essentially to any signal which has the capacity to entrain new phenotypic behaviors. Biological plasticity and its characteristic, quantitative bell curve feature has been observed across all forms of life, from microbe to plant, to animal, to human. Biological plasticity is a fundamental feature of biology, and is an essential defining mechanism of adaptation, survival and health.

The human physiological system can be thought of as containing a neuro memory bank of stored historical information about past traumas and/or illnesses. This memory bank can be likened to an information storage system that gets called upon, whenever the system encounters a problem that needs to be addressed. It is like a type of instruction manual, a memory recall system, part of an intrinsic process that leads to more intelligent intercellular, intracellular, physiological intelligence and understanding of how to better deal with a problem the next time it happens. I freely argue that the Human physiological masterpiece is the most profoundly intelligent system known, more profoundly complex and intelligent than the best machine learning systems or quantum processing computers. Interfering with this system’s ability to learn, by way of symptom management and disease treatments increases the risk of augmentation of the healing cycle, and blunts the system’s intelligence, by interfering too much with the learning process itself.

Entropy and negentropy form an interdependent binary process within physiological systems. We can define physiological entropy and negentropy as disorder and order, respectively. We can study and debate the extraordinary complexity of human immunology through a lens of myopic biology, however the fact remains that entropic and negentropic forces determine the course and direction of the immunological dance. The consequence of the dance of entropy and negentropy is congruence, and learned experience. Otherwise, how else do organisms adapt to danger signals and pathogen vectors? How else does information get passed onward to the new cell, or to the next generation? The process of learning is engrained in biology. It is engrained in survival mechanisms and in evolution. It is the very experience with stressful encounters that induces the process of cellular learning and adaptation.

In this sense, this acquired biological or physiological plasticity is closely related to stress adaptation and hormesis. By regular, continual exposure to a low/moderate stress-inducing agent, the system learns through adaptation. The system learns how to adjust to the vector that has been introduced. The system responds more appropriately over time. The system develops the ability to not overreact, to not overstep boundaries, which may otherwise cause itself harm.

An example of this system adaptation is the regular exposure to helminths. To provide a brief background and context, consider that helminths (hookworms, whipworms and certain types of parasites) are capable of arresting autoimmune disease processes. This is well studied in literature.

Diverse and regular exposure to these macro-pathogens subsequently tempers the immune system response, in part because the system learns to adapt to continued exposure. The beneficial effect of the helminth is rarely immediate. The process requires time, and continual exposure (re-exposure of helminths every several weeks). The interaction between the pathogen vector and the system engages a higher order of intelligence within the physiology. Over time, the physiological system adapts to the vector/signal, and a higher order of intelligence is gained. The system achieves a new type of equilibrium. More importantly, the new adaptation is synonymous with the concept of biological plasticity. The memory of the experience leads to a diffused immunological response, if and when the system is to encounter a similar problem in the future. The system learns. The system calibrates. The system becomes more adapted to the new signal. In this sense we can say that Biological Adaptation = Hormesis + Time.

So many of the symptoms experienced by patients are an exaggerated response that fails to recede. Or in the context of Naviaux’s Cell Danger Response (CDR), the system gets stuck in a certain phase of the healing cycle, and cannot transition back to equilibration. The symptom itself is the result of an ongoing healing cycle. The symptom is the result of an attempt to resolve a perceived problem or threat, even if that threat is no longer present. The symptom is a fragment of an intelligent, living process. The living process has evolved to overcome obstacles, so that life can subsist in spite of whatever threats are present. Adaptation is the result of the new intelligence that the system gains in overcoming the obstacle/danger signal, and perceived threat.

What we’re getting at is the practice of Hormesis. Naviaux talks about this, but it needs elaboration. The concept is so critical for living systems because it’s entirely about adaptation to stress, adaptation to danger and the subsequent learned memory that is imprinted through neural networks through this adaptive response.

I would argue that tonic treatments which attempt to arrest the different stages of the CDR ultimately fail or fall short because the system’s objective is to create a higher order, through the acquisition of adaptation and learned memory. The extension of this learned memory goes on indefinitely through time. In other words, the outer limitations of biological plasticity are unknown, and potentially vast. Attempting to stop or arrest the body’s healing cycle (aka, CDR) inhibits this.

I would argue that the most important thing in terms of the CDR is concerned is Hormesis and learned adaptation. In this sense, unremitting disease, all chronic unrelenting symptoms should be a direct indication that there is something that the system has not yet learned. Tonic treatments that manage the downstream effects of the healing process (i.e. symptoms, disease processes, etc.) have the potential to inhibit the learning process of the system.

The ultimate problem with symptom management, and with linear-based chronic disease treatments are that they completely distort the potential for hormetic adaptation. They do not promote learned, new behaviors. They create dependencies. They dumb down the system’s intelligence, by forcing the system to become dependent on a treatment, in order to manage the effect of healing (i.e. a particular symptom), rather than engaging the innate intelligence and learning-capacity of the system, and it’s complex process of learned new responses and behaviors. Ultimately, the healing system should learn how to resolve the CDR on its own accord.

Under these conditions, the opportunities for the system to learn new behaviors, and physiological responses is arrested at the expense of getting symptom relief. If you rely on steroids to manage your rheumatic flares, you control the symptom, but you do not engage the system to adapt to the disease process. You make the system dependent on the treatment, and you shunt the intelligence of the living system, and it’s ability to adapt.

If you give antibiotics to a 2-year old child to resolve a cold, you are teaching the developing body to become reliant upon this method for resolving its healing cycle, instead of engaging the intelligence of it’s own innate healing cycle. If you give Tylenol to resolve a fever, you are bypassing the system’s thermal process of healing.

Tonic treatments for symptom management may generate signals that the system is incapable of correcting the problem itself, and therefore must become reliant upon the intervention as the means to resolving the issue. But does the pharmaceutical ever resolve a chronic disease process? Medicine’s hangup is always: “well what about antibiotics? Look at how many lives were saved.” For acute infections under life threatening circumstances, antibiotics certainly do possess life-saving properties. But when a condition is chronic, how often do antibiotics resolve the disease? Rarely if ever on their own accord. And what are the longterm effects of a drug on biological plasticity? Has this ever been studied? I frequently am amazed at physicians who tell patients that they need to take a particular drug for the rest of their life. The physician is so confident that the patient’s physiology is incapable of functioning without it, that the patient must become a permanent user of the drug. These arrogant assumptions are the product of a system that simply does not appreciate nor understand the complexity of life, nor the profound intelligence of our body’s highly organized capabilities and potentials. As such the medical system reduces the human to a series of predictable systems, consisting of smaller and smaller separate units. The system of medicine has become so hyper-reductionistic and myopic that it fails to adequately define the living state. As a consequence of this worldview, chronic disease persists, patients are harmed by iatrogenic treatments, and biological plasticity never enters the equation.

Treatments: Where Do We Draw The Line?

Before getting into the discussion of treatments, it’s necessary to discuss hormesis once again. Think of hormesis as the optimal training method for teaching complex systems how to adapt to stress and danger vectors, gain intelligence and plasticity. Hormesis is akin to an optimal preventative therapy, so that you do not need treatments. Fasting, diverse microorganism exposure, exercise, anaerobic training techniques, ingestion of plant glucosinolates, and adequate sun exposure, are modalities, which on some level induce hormesis and biological plasticity.

Some Examples of Hormesis Practices

Broccoli sprout glucosilonates have a net effect of suppressing glutathione in the liver. This forces an adaptive response to mobilize NRF2 to the nucleus, and you have activation of ARE’s (antioxidant response elements), because the initial signal of glutathione suppression is perceived as a mild stress signal.

Controlled hyperventilation as a breathing exercise induces hypoxia, but regular practice of hyperventilation increases the tolerance to hypoxia. Interval exercise training over time increases the anaerobic threshold, and thus the tolerance to lactate and anaerobic glycolysis. High altitude exercise (and related mimetic therapies) improve upon glycolytic pathways. Living at high altitudes forces an adaptive hormesis, because atmospheric oxygen is lower. Mitochondria have to figure out how to survive in spite of the stress of less oxygen availability. Consequently studies demonstrate a lower incidence of obesity, cardiovascular disease and certain cancers at higher altitudes. Moreover, hypoxia induces significant increases in leptin and leptin receptor sensitivity.

The moderate stress signals induced by fasting and caloric restriction activate cell survival gene programs, induce autophagy in cells, increase NAD+ levels, and act to modulate the circadian clock.

Hormesis, biological plasticity and stress adaptation are essential practices for the human organism to create health. I would go so far as to say that the definition of health must include adaptation as a core component, especially in today’s modern world.

The human species has survived up until this point in history, because of the ability to adapt to changing internal and external environments. It is now more important than ever for these biological facts to become widely recognized and studied. When an individual has lost the ability to adapt to various stress signals, disease is inevitable. Without adaptation and biological plasticity, organisms are vulnerable to the destructive effects of the entropic forces of nature. With biological plasticity, adaptation and learned memory, systems can more effectively ride the balance between entropy and negentropy.

Treatments: Supporting Biological Plasticity & The Body’s Ability to Heal Itself

1. Hormesis practices are a prerequisite for health, in order to serve as both a template for biological plasticity, as well as a prophylactic for illnesses, both acute and chronic. Health is a practice that involves work, effort, focus and attention in order to be obtained and maintained.
2. The goal of any treatment should be directed towards enhancing the body’s ability to heal itself and return to homeostasis as quickly as possible.
3. Treatments that involve pharmaceuticals are rife with being iatrogenic, and causing dependencies. Drug dependency not only applies to psychotropic drugs, but to other classes of pharmaceuticals as well. For example, patients diagnosed with Chronic Lyme disease, or related infections, often become dependent on using antibiotics for years and even decades. These types of patients often report that they are “unable to function” without these drugs. It is appealing to consider that these drugs have interfered with certain tolerogenic and immunologic signaling factors, and have abrogated the ability for the system to adapt, learn and adopt biological plasticity.
4. Mismanagement of acute conditions can lead to chronic conditions. To add insult to injury, chronic conditions are often paired with treatments that are incompatible with biological plasticity and cellular learning.
5. A person whose biological system is not primed by hormesis practices (which entrain biological plasticity, adaptations and compensatory survival strategies) are more susceptible to acute and chronic illness. That may sound controversial but it isn’t. Sedentary lifestyles are linked to numerous disease risks, whereas regular cardiovascular exercise (a physiological stressful condition) is strongly linked to reductions in chronic disease risk factors. Intentional acts of caloric restriction, fasting and mimetic fasting diets are now understood to extend lifespan across all forms of life. Continued exposure to helminthic macro-organisms reduces inflammatory signals. Furthermore, various altruistic and large scale de-worming studies in 3rd world countries have been strongly linked to increases in inflammatory diseases, including insulin resistance, diabetes, allergy and atopy (Tahapary, et al; 2017), (Staal, et al; 2018).
6. Nutritional medicine practices tend to have far fewer iatrogenic tendencies. When properly applied within the context of each individual, nutritional medicine can function as the primary type of medicine. We are all dependent on food and nutrients in order to function and to have health. The acquisition of resources from the environment (air, water, food, light) drive interconnected life cycles towards a dynamic state of homeostasis.
7. If certain pharmaceuticals are utilized at lower doses, do not inhibit the healing process, are used for minimal duration intervals, and given with the goal of assisting the body’s return to homeostasis, this approach is more likely to serve the patient well, and not abrogate the process of adaption and biological plasticity.
8. A physician’s ignorance of safer, non-pharmaceutical treatments is not an excuse for iatrogenic-induced disease. In 2021-2022 I was involved in the case of a patient who was sent home to die by a hospital. The attending physician told the family of the patient she was near liver failure and will die within days or weeks. During her stay at the hospital, she was being given regular doses of hepatotoxic drugs to treat her pain. Her preexisting liver damage was made worse by pharmaceutical interventions. When I intervened as she was on death’s door, I trusted that her body had the ability to regenerate and heal itself. Believing this, I initiated a holistic treatment that aimed to restore her body’s many functions. Her own desire to live was the primary factor that became her salvation. Our daily dedication, the constant adjustments to her protocol, and the constant care provided by her immediate family were the ingredients necessary to bring her back to functionality. During this time under my care, I witnessed her body go through many healing crises and pain episodes. These were not dealt with using pharmaceuticals, but rather through manual therapies, acupressure, and protocol adjustments. Within 4 weeks, she stood up for the first time in several months. By week 6 she was walking. By week 8 she was doing regular physical therapy and exercise 6 days per week. To date, she has outlived her medical prognosis by more than 1.5 years.

In summary, biological plasticity is an inherent process of learning, and hormesis is one way of attaining this. Through the recognition that the body is what does the healing, treatments and therapeutics are seen in a different context. Furthermore, by practicing hormesis as a health-promoting method of adaptation to stress, both acute and chronic diseases can become less prevalent.