Overview
The Cell Danger Response (CDR) provides an explanation and framework of understanding for chronic illnesses, including Idiopathic Parkinson’s Disease. According to this framework, the CDR occurs when a cell in the body detects a threat to its existence or that it is in some sort of mortal danger. When a cell thus loses its sense of safety, it moves via the CDR from contributing to the health and vitality of the body towards an “on guard” state of self-perseveration, and then alerts other cells to the danger by releasing chemicals, which can, in turn, set off their CDR, potentially leading to domino or cascade effect. If the threat is maintained long enough, eventually the CDR results in the cell going into a shut-down or hibernatory state, to wait it out until the danger has passed. When enough cells in the body get stuck in a Cell Danger Response, some form of chronic illness ensues.
Introduction
I first came across the idea of the Cell Danger Response (CDR) from Veronique Mead’s website Chronic Illness Trauma Studies. I encourage anyone affected by Parkinson’s Disease to work their way through Veronique’s excellent detailed article ME/CFS and The Cell Danger Response: How Adversity Triggers the Freeze Response and How the CDR Gets Stuck. This is not only immensely helpful, because it provides answers to the perennial questions of "what happened to me" and "why me”, but is also extremely hopeful, because it means the symptoms of many chronic conditions are reversible through the correct choices of long term strategies. In the article, Veronique explains why there is no single "smoking gun" - that we may all have our unique set of personal risk and impact factors, which eventually add up beyond a critical threshold - yet why these very different personal impact factors still result in very similar sets of symptoms.
Indeed, in another article, Veronique says:
“this is how transforming chronic illness into something I can cope with works for me, understanding that my symptoms are real and stem from a nervous system caught in a cell danger response of fight, flight or freeze makes all the difference - it means it’s not in my head, not my fault, nor due to a genetic defect I have no power to change“;
“instead, it means I have options and choices., both in how I view myself and my illness, and also in what I can do about it."
The Cell Danger Response (CDR) is the work of Dr Robert Naviaux MD, PhD and colleagues. Below is a good introduction video to CDR in his own words.
Also, here are some introductory summary notes from Dr Naviaux’s article "Metabolic Features of the Cell Danger Response".:
the Cell Danger Response (CDR) is defined in terms of an ancient metabolic response to threat;
the CDR encompasses inflammation, innate immunity, oxidative stress, and stress response;
the CDR is maintained by extracellular chemical signals of danger from one cell to others;
abnormal persistence of the CDR lies at the heart of many chronic diseases;
drug therapies which block the cell to cell signals have proven effective in many chronic disorders in animal models.
The unifying nature of the CDR
As discussed above, there are many different forms of impacts which can set off the "alarm bells" of the Cell Danger Response. However, too many cumulative insults can cause the CDR to get stuck systemically in the "on" position, blocking healing, and manifesting as a chronic illness. Healing can nevertheless be re-instated by identifying and addressing our personal impact factors. Each of us is likely to have our own highly individual, bespoke set of factors that eventually added up to the CDR getting stuck. which is why there are no "one size fits all" solutions to any of this.
This CDR concept is important as it does seem to me to be an elegant, simple, predictive, and unifying framework which explains similar symptoms resulting from a whole of host of potential triggers, all of which can add up cumulatively. This is why, for example there are various competing, but equally valid, scientific theories which argue that a specific virus, or specific chemical, or specific nutritional deficiency is the root cause of Parkinson's Disease. It is because they are all, in a sense, true, as each can result in the body’s CDR getting stuck on and presenting PD symptoms.
In the CDR framework, then, Idiopathic Parkinson’s Disease is a set of particular symptoms which emerges when the CDR gets stuck. Yet previously, I have described Idiopathic PD as what happens when the Nervous System’s Dorsal Vagus Nerve mediated freeze response gets stuck on, after the person with PD’s danger sense gets so sensitized that it detects threats everywhere. In fact. these are complementary, not contradictory explanations, and indeed the CDR provides a description of what happens at the cellular level when someone gets stuck in freeze. On this, Dr Neil Nathan MD writes:
“It turns out that the major function of the ventral branch of the vagus nerve is to discern safety and it is understanding the importance of safety that is the primary focus of polyvagal theory. The perception of safety is hard-wired into our nervous system. If our nervous system does not perceive us to be safe, no amount of rationalization will change that physiological response. This is another “systems” way of understanding the Cell Danger Response (CDR). We’ve discussed the CDR in previous newsletters, and Dr. Naviaux’s model of how mitochondria respond to a threat dovetails closely with the polyvagal theory. Both models emphasize that the body will continue to operate as if it is under threat until it is convinced that it is safe.”
Risk Factors for CDR activation
Personal impact factors which may cumulatively lead to the CDR switching and getting stuck on include exposures to viruses, bacteria, fungi, pesticides, chemicals, stressors, adverse early life experiences, mental and emotional health issues, developmental and shock traumas, car crashes, accidents, surgeries.
Veronique Mead has usefully developed the following over-arching definitions to categorize the risk factors:
Adverse Multigenerational Experiences (AMEs) - traumatic events our parents and grandparents and other family members experience at times in their lives;
Adverse Babyhood Experiences (ABEs) - events during birth, pregnancy and infancy;
Adverse Childhood Experiences (ACEs) - trauma that is inflicted by other human beings, who are supposed to care for and protect us;
Adverse Childhood Experiences Plus (ACEs+) - other types of adversity before our eighteenth birthdays that also affect long term health;
Adverse Childhood Relationships Experiences (ACREs) - attachment trauma or relationship trauma;
Adverse Adulthood Experiences (AAEs) - stressful and traumatic events that happen after our eighteenth birthdays such as divorce, job loss, accidents, the loss of loved ones;
Adverse Institutional Experiences (AIEs) - effects of trauma from discrimination of all kinds, whether by gender, race, religion, sexual orientation, ability or disability, chronic illness, mental illness;
Adverse Pre-Onset Triggers (APOEs) - stressors that cause exacerbations of or trigger symptoms.
Evolutionary Biology
Here are some further notes from Dr Naviaux’s article:
"...the CDR in its most fundamental and most ancient role is to improve cell and host survival after viral attack; the acute CDR produces at least 8 functional changes.”
These are:
cell stops making the building blocks of proteins so that viruses have little to steal with which to replicate themselves;
stiffening of the membranes of the cell and circumscribing an area of damage to limit pathogen egress;
releasing antiviral and antimicrobial chemicals;
increasing autophagy to remove pathogens;
changing gene expression;;
mobilizing endogenous retroviruses;
warning neighboring and distant cells of the danger;
altering the behavior of the host to prevent the spread of infection to kin and sleep patterns to facilitate healing.
"… any trace of heavy metal in the cell will trigger a response that is similar to that of a viral infection. Likewise, a large number of molecules have been synthesized since the 1850s as dyes, pesticides, drugs, and industrial chemicals... that can also activate the CDR. Mixtures of chemical and biological threats can have synergistic effects, and the total load of danger triggers can influence the magnitude and form of the CDR".
Turning Off the CDR and Healing
Below is a very informative interview with Dr Nathan, who helps people with chronic illness progressively reduce their symptoms by addressing the CDR in their bodies. Dr Nathan covers his significant experience with the modalities, routes and barriers to healing.
In short, we are led once more to all the types of approaches for progressive symptom reduction and quality of life improvements that I have covered in previous articles, and hence the action points arising from the Cell Danger Response framework converges with those now coming from many other scientific and clinical directions and, just as importantly, from real life experiences of those folks who have made full or partial recoveries from chronic illnesses. Indeed, the CDR too points us to the need to doing everything we can to calm our Nervous Systems, Immune Systems, inflammation, stressful emotional states and anxious thoughts, to address unhealthy relationships, to restore a sense of internal and external safety, and to send the message to our biology that “the war is over”. I would currently summarize these as:
identify and remove, or remove ourselves from, as many stressors as possible;
prioritise sleep, rest and relaxation;
minimize use of and exposure to non-natural chemicals and chemical products;
remove inflammatory, highly processed and artificial foods from diet;
restore healthy patterns of breathing from the diaphragm and through the nose;
address, restore and maintain fascia health;
hydrate extremely well;
address constipation;
clear lymph nodes;
cultivate a daily meditative practice, whether meditation, hypnotherapy, art therapy, etc., anything which gives our minds a break from verbose, busy and anxious thoughts;
re-connect body and brain through daily movement and dance;
spend time in nature;
appropriately stimulate the Ventral Vagus Complex and Social Engagement functions of the Nervous System;
synchronise brain hemispheres, rebalance brain by cultivating the right brain’s embodied, connected, big picture, present way of attending;
attend to ruptures in interpersonal relationships, past and present. and identify and avoid toxic people;
practice gratitude, forgiveness, kindness and compassion, seek to let go of chronic anger, hate, despite and try not to engage in judging, blaming and shaming others;
improve relationship with food and mealtimes through how, where and when we eat, not just what we eat;
determine, by trial and error if necessary, our personal responses to food, and find our own personalized optimal health giving foods and food sensitivities;
address trauma with appropriate therapies;
engage in personal development and cultivate a growth mindset;
reject the Medical Institutionalized Narrative, which uses the language of war such as “battling the disease” or “fighting PD”, and instead focus on making peace inside and out;
stay curious and playful, maximise joy and pleasure in life;
focus on what the suffering has to teach us, and not on the suffering itself;
avoid consuming the News Agenda, don’t watch horror films and thrillers, instead cultivate an enjoyment of and appreciation for comedy and romance;
don’t totally abdicate the responsibility for our own health to “experts”, but instead learn as much as possible about how own bodies and minds work;
seek to gain as much agency to act independently and make free choices as possible.
understand that perfectionism and trying control everything comes with great cost;
develop our sense of having a right to be, the knowledge that we are enough as we are, and that we have no points to prove;
cultivate a sense that life is purposeful;
Although this may seem like a tall order, these all support one another and there are many positive feedback loops and virtuous circles. Think of it as a menu of choices to pick from, and that not all need to be pursued simultaneously, so we start with the lowest hanging fruit for us, and this will help open up and make some of the other options easier to incorporate. None of these suggestions are individually particularly onerous or consuming of large amounts of time per day. It is more about taking a long term view of changing the habits of a lifetime, repatterning ingrained, unhealthy behaviours, and removing ourselves from toxic environments, relationships and situations, thereby decreasing our exposures to as many risk factors for CDR activation and worsening PD symptoms as possible.
Helpful books which can support us in making these changes include “Feel Better in Five” by Dr Rangan Chatterjee. “Atomic Habits” by James Clear and “Tiny Habits” by Dr B.J. Fogg.