A New Hypothesis for Viral ME Symptoms

[Wishful]

Many of you know that my ME has been non-standard; I didn't suffer from the physical limitations, and I had some treatments work really well for me that no one else has reported benefits from. In the last few weeks I've been feeling much worse, and getting worse symptoms after eating high-protein meals. I've also returned to an old response of feeling abruptly worse 20 minutes after ingesting quickly-digestable carbs. To top that off, I've developed what seems like the typical physical problems many PWME complain about: using my muscles makes them hurt fairly quickly, though I'm not familiar enough with the 'acid burn' sensation to know if this is that. At one point I was wondering (maybe panicking a bit?) if I'd cured my PEM but switched to a more typical form of ME.

One additional symptom is that my temperature is typically about .3C higher than normal during the day. That suggests some sort of chronic immune system activation. So, it seems reasonable that this is some sort of infection, maybe a new virus, or reactivation of an existing one, or maybe one of those abortive viruses pumping out nasty proteins. What I think is happening is that my immune system is pumping out extra IFN-g, which is keeping IDO high in my brain, which is converting TRP into neurotoxic kynurenines. That seems a logical explanation for my observations.

My hypothesis is that the common muscular symptoms of ME result from this sort of chronic immune activation. I'm presently fairly brainfogged, so this is not a well-thought-out hypothesis. Maybe someone else can point out some supporting or refuting evidence or logic. Maybe it'll trigger some interesting discussion. I do wonder whether the results from patients who tried antivirals fits this hypothesis better than any 'viral infections cause ME' hypotheses.

If this new state hasn't gone away in a week or two, I'll buy some elderberry juice or other product to try, since that seems to be a strong immunostimulant for me. If that makes me feel worse, followed by feeling much better, that would support the hypothesis.

 

[Davsey27]

Many of you know that my ME has been non-standard; I didn't suffer from the physical limitations, and I had some treatments work really well for me that no one else has reported benefits from. In the last few weeks I've been feeling much worse, and getting worse symptoms after eating high-protein meals. I've also returned to an old response of feeling abruptly worse 20 minutes after ingesting quickly-digestable carbs. To top that off, I've developed what seems like the typical physical problems many PWME complain about: using my muscles makes them hurt fairly quickly, though I'm not familiar enough with the 'acid burn' sensation to know if this is that. At one point I was wondering (maybe panicking a bit?) if I'd cured my PEM but switched to a more typical form of ME.

One additional symptom is that my temperature is typically about .3C higher than normal during the day. That suggests some sort of chronic immune system activation. So, it seems reasonable that this is some sort of infection, maybe a new virus, or reactivation of an existing one, or maybe one of those abortive viruses pumping out nasty proteins. What I think is happening is that my immune system is pumping out extra IFN-g, which is keeping IDO high in my brain, which is converting TRP into neurotoxic kynurenines. That seems a logical explanation for my observations.

My hypothesis is that the common muscular symptoms of ME result from this sort of chronic immune activation. I'm presently fairly brainfogged, so this is not a well-thought-out hypothesis. Maybe someone else can point out some supporting or refuting evidence or logic. Maybe it'll trigger some interesting discussion. I do wonder whether the results from patients who tried antivirals fits this hypothesis better than any 'viral infections cause ME' hypotheses.

If this new state hasn't gone away in a week or two, I'll buy some elderberry juice or other product to try, since that seems to be a strong immunostimulant for me. If that makes me feel worse, followed by feeling much better, that would support the hypothesis.

Curious Wishful have you tested for viral/bacterial infections associated with me/cfs like the herpes family viruses ,cocksackie,lyme etc?

 

[Mohawk1995]

Wishful,

Like all who suffer with this, I have immense respect for you in your fight especially in the day to day. I have not suffered from ME/CFS, but I have a son who has and know of others still suffering. So please take what I am saying as another theory or explanation. I think from the perspective of a Physical Therapist, Neuroscience fanatic and Pain Science Education expert, but I by no means have all the answers here.

Our thinking actually intersects where you mention "chronic immune system activation". I tend to lean in the direction of this and other similar disorders as "chronic Neuro-protectective activation" or over-activation including immune, endocrine and inflammatory responses. It does not necessarily mean that there is an active infection however.

If you think of these responses or symptoms as reactions to a threat then it makes more sense to me. A fever is not directly caused by an infection, but is the bodies defense system responding to a threat. Immune responses are the same and they are all regulated by the nervous system (not the conscious). The issue is that sometimes (we cannot explain why very well) the nervous system responds to an "interpreted" threat or a threat that has since diminished or gone away. I use interpreted again not that it is conscious, but that as the nervous system processes input it is then responding to this "threat". Classic examples of this hypervigilant response in other diagnosis are migraines, allergic reactions to peanuts, profuse sweating and more. You can and should have a headache from some highly identifiable problem (toxicity, injury, tumor, etc...) but in migraines there typically is no such severe "threat". You should have an immune response to a virus, bacteria or bee sting, but not really to peanuts. You should sweat profusely if you are exercising in the heat, but not when you are sitting still in a pleasant temperature. In the realm of Pain the best example of hyper-response is Complex Regional Pain Syndrome or CRPS. Severe pain (the worst possible) with no apparent damaging injury or threat.

So why do some forms of treatment help and others don't? I do not know. Antivirals were effective for my son at the time he received them. It still took him 3 years to make a recovery. They work for some and not for others. They are powerful Neural Stimulants so perhaps that is why. Or perhaps the viral load was truly reduced and it gave him the window of opportunity he needed. (more discussion on my post "Did Dr. Lerners patients who improved on high dose Valtrex all have positive EA?")

I hope that added another layer to consider. Honestly I think you are coming to some really good conclusions even with the brain fog

 

[LINE]

My hypothesis is that the common muscular symptoms of ME result from this sort of chronic immune activation. I'm presently fairly brainfogged, so this is not a well-thought-out hypothesis. Maybe someone else can point out some supporting or refuting evidence or logic. Maybe it'll trigger some interesting discussion. I do wonder whether the results from patients who tried antivirals fits this hypothesis better than any 'viral infections cause ME' hypotheses.

Yes, immune activation changes the terrain of the body. It creates quite a bit of oxidative stress which attacks cells.

 

[Rufous McKinney]

I got a pretty big crash several days ago- attributed to standing too long in front of the mirror, combing my rather long and tangled mess of wet hair and then decided to cut some off. I didn;t think I was there very long.

but I crashed pretty hard within 12 hours of that. And my arms were up- quite a bit of the time (I though of you, @Wishful ...). Normally I sit in my chair while trying to get the comb thru this mess. Arm rests, not standing yada yada. Take more time as well- I was rushing before my hair got too dry. And the big difference between this exercise of hair cutting and just doing too many dishes which (does not usually) cause a crash...was Arms Up.

was that temperature 0.3 degrees? (or 3.0 degrees?). I'd somewhat argue your unlikely to have such an accurate thermometer if its 0.3 degrees.

Back when I had mild ME, feeling like I had a low grade fever was a real common symptom when run down. Now its not as much for me. But I"m also not measuring it. What type of thermo do you use for measuring it?

 

[Mohawk1995]

And my arms were up- quite a bit of the time (I though of you, @Wishful ...). Normally I sit in my chair while trying to get the comb thru this mess. Arm rests, not standing yada yada. Take more time as well- I was rushing before my hair got too dry. And the big difference between this exercise of hair cutting and just doing too many dishes which (does not usually) cause a crash...was Arms Up.

Definitely arms above head has a much higher exertional level than arms down or even using legs to a degree. When I am working with patients who do Upper Extremity Cardio, I always like to get a little Leg Cardio in first to warm up. The arm work cold turkey can create stress issues. Probably the reason why the highest percentage of people who die during a triathlon are during the 1st phase which is swimming.

 

[Rufous McKinney]

Definitely arms above head has a much higher exertional level than arms down or even using legs to a degree.

interesting...

so sometimes I just have , as we all do, My Reality. So related to arms- movement- lifting, any of this is the lymphatic problem.

In addition to all the various theories I feel frequently Poisoned.

..by something the body stores...seems to be the case- this is how I often think of it. Is it the LPS from the leaky gut? Is it the Kynerinnies...not enough or too much (still confused there, but I do like the IDO trap theory..as a factor..not a cause..just of many I suspect). Is it the metals?

So: my arm explanation would be not so much as it was something about muscles, or running out of something in the muscles: no its whatever has been stored up in the lymph in my arms: some of that was released and dumped into my system. ANd maybe the poisons are in muscle tissue as well- so it comes out when- the muscles are moved. A combined muscle/lymph effect- released- it entered circulation and now I'm still processing the poison.

Last winter i developed bursitis in both elbows. One swells up with liquid...(in the bursa) and the other hurts way worse...but is not swollen at all. This goes on for quite a while, I'm wondering Why This , Now?

Suddenly elbows are out of business. And I don't believe I had injured them (the dr.s theory of buristis). This was a problem for a number of weeks. So then one day- I just stretched my arms as hard as i could up above my head and stretched and stretched and made sure the joints were really stretched : the swollen bursa cleared 2 days later. It left. (that all felt real good at that moment this huge stretch).

The bursa itself- was incredibly sore and sensitive for many more months. 10 months later- I think my elbows are now OK. But I decided- somethign about all this is tied to: some type of lack of flow in the lymph...

The funny part of all this is I did go to my herbalist, I got herbs to soak the elbows, but it didn't work well. (or wasn't ready to leave, yet). I came back some weeks later- I still have this elbow problem...I was saying how it hurts (it does..the bursa is somehow hyper sensitive to- the slightest touch).

He announced- Well thats arthritis.

NOOOOO. Its not: inside my elbow, not in the joint- the point being when you tell another person something hurts- they make huge assumptions. They aren't asking- questions. They project...

My doctor kept insisting I'd slammed my elbows- No. So that point being- they don't know. They pretend they know the cause, the why, but they dont.

 

[Mohawk1995]

In addition to all the various theories I feel frequently Poisoned.

So interesting thoughts and description. So if every system in our bodies runs on energy and the energy producers (mitochondria) are in really bad shape, then everything is impacted. Metabolic processes are impeded creating inefficiencies and chemical/hormonal issues. Fluid movements (lymph, blood, interstitial, axoplasmic) are reduced due to decreased energy and activity. Not to mention you have increased production of neuroinflammatory agents like cytokines. So you have what could be described as a chemical/hormonal "soup", that is stagnating in the body and likely creating the feeling of having "poison" in your system. But more importantly this then compounds and creates a vicious cycle of the soup limiting function, creating inflammation and making more soup. No answers, although possibly some very gentle full range movements performed regularly during the day but that do not overwhelm you might help?

Yes although medical providers most often intend to help, they rarely understand these issues. Furthermore, medicine has moved more toward reliance on Diagnostic Tests and less on exam and history. ME/CFS is very complex and really difficult to understand even for those of us who are willing to think outside the box. I would not see anyone for ME/CFS who did not perform a full history and a hands on exam. Made even tougher now with COVID

 

[Wishful]

Immune responses are the same and they are all regulated by the nervous system (not the conscious).

I accept that the nervous system affects the immune systems, but don't immune cells react to proteins all on their own, and then send alerts to call other immune cells into the battle? If you put some t-cells in a petri dish with suitable medium, won't they react to the allergens that they are programmed for, even though there's no nervous system connected?

As I (with no medical background) see it, if a virus infects me, or a hidden one reactivates, it will trigger the t-cells, resulting in IFN-g and other cytokines travelling around my body, and setting my glial cells on high alert, and producing more IDO and nasty KYN's. I don't see it as some sort of subprogram in my nervous system that accepts a threat notice from immune cells and then gives the orders for the other immune cells to alter their activity. I think of it as collective response, such as seen in ants: each ant has only a few possible responses to inputs, but collectively they accomplish amazing things. Even if the nest is attacked, there's no supreme general accepting scout reports and issuing commands.

 

[Wishful]

Curious Wishful have you tested for viral/bacterial infections associated with me/cfs like the herpes family viruses ,cocksackie,lyme etc?

I had some standard tests done, but I don't remember the details other than not having any active infections.

 

[Wishful]

was that temperature 0.3 degrees? (or 3.0 degrees?). I'd somewhat argue your unlikely to have such an accurate thermometer if its 0.3 degrees.

It was .3C. My thermometer may not be accurate to .1C, but as a digital one, it does have that precision. It seems to be stable, so when it reads .3C higher than usual, it's probably correct. I had mercury thermometers before, and I could read them to tenths too, and they seemed equally stable. My temperature on waking has been 36.4C for the last few times I've checked.

 

[Wishful]

NOOOOO. Its not: inside my elbow, not in the joint- the point being when you tell another person something hurts- they make huge assumptions. They aren't asking- questions. They project...

Yes, some doctors see/hear only what they want to see/hear. They also seem to be oblivous to the fact that you want to smash their face into something hard a few times for refusing to listen properly.

 

[ljimbo423]

Yes, some doctors see/hear only what they want to see/hear. They also seem to be oblivous to the fact that you want to smash their face into something hard a few times for refusing to listen properly.

This made me laugh out loud! A good belly laugh.

 

[Mohawk1995]

I accept that the nervous system affects the immune systems, but don't immune cells react to proteins all on their own, and then send alerts to call other immune cells into the battle? If you put some t-cells in a petri dish with suitable medium, won't they react to the allergens that they are programmed for, even though there's no nervous system connected?

As I (with no medical background) see it, if a virus infects me, or a hidden one reactivates, it will trigger the t-cells, resulting in IFN-g and other cytokines travelling around my body, and setting my glial cells on high alert, and producing more IDO and nasty KYN's. I don't see it as some sort of subprogram in my nervous system that accepts a threat notice from immune cells and then gives the orders for the other immune cells to alter their activity. I think of it as collective response, such as seen in ants: each ant has only a few possible responses to inputs, but collectively they accomplish amazing things. Even if the nest is attacked, there's no supreme general accepting scout reports and issuing commands.

The best way I can explain what I am postulating is from the world of pain. If you will go with me down this path, I think it might give an additional explanation of what is going on in people's bodies.

In pain, scientist have been discovering that there is both a "bottom up" AND a "top down" component to the response. Neither is wrong, just incomplete without the other. So when a bundle of pain or nociceptive nerves is stimulated in an ankle sprain(bottom up), that is immediately sensed by the nervous system and depending on the severity of the injury (from minor tweak to grade 3 ankle sprain) pain will be experienced in the ankle. Truth be told, the experience/expression of pain to the injury would not be felt unless the nerves in the ankle are connected to the brain (top down). That is why in the case of spinal cord injuries and nerve disease (diabetes, leprosy) there may be no perception of pain to an injury in the ankle. One could argue that the experience or expression of pain need only have the central nervous components (ie brain) in order to express pain. Most significant case would be phantom limb pain in a "leg" that is no longer present. So you can have injury without pain.

To make this more interesting, the application of the "Bayesian" nervous system model comes into play. It's hypothesis is that the nervous system is not just reactive, but really more predictive. This is owing to the complexity of the nervous system and in particular the brain. There are somewhere between 85 and 100 Billion nerve cells in the brain. They each have from 1000 to 200,000 connections (synapses) to other nerve cells. In addition there are by some estimates 8-10 times as many glial cells that have connections the neurons use like jumper cables. So it is mathematically impossible to measure the complexity of the brain based on all of the variables this presents. Scientist a few years attempted to estimate how long it would take the most advanced supercomputer in the world to calculate what the brain and nervous system can do in 1 second. The estimation came out to 40 minutes! So yes I am a firm believer that there is one dominant or supreme if you will system in our body that manages, regulates and responds to anything that occurs in our body.

So relating it back to the immune system, there are as you say responses (immune, inflammatory) in the immediate (albeit collective in the case of a virus) area to foreign invaders and messages then sent to the nervous system (bottom up) AND there is the brain and nervous system's immediate and predictive response (immune, inflammatory, endocrine, hormonal, protective) to this invasion. I would argue that because the brain and nervous system respond systemically it is able to bring far more ammunition to bear. In exponential degrees. The question is can the local area responses slow way down or even shut down because the threat is lessened or eliminated and yet the top down process continue on and continue to reek havoc on the entire body. Yes I am confident it can. In the world of pain, this is what we think happens in CRPS (Complex Regional Pain Syndrome) which can be just as disabling as ME/CFS and actually has some of the same features including brain fog.

So your logic is definitely not wrong in my thinking, but I would say it is incomplete. As with most things related to ME/CFS very little has been proven. Certainly we are making improvements in our understanding, but far more out there to learn. My experience (studying, treating and observing the human body) of 10s of thousands of hours with patients and 10s of thousands of hours spent with my son when he was suffering seem to confirm (at least in my eyes) that this disease is very much driven by neurophysiology. Neuro-pathophysiology to be more accurate. I am confident that is why the original definers of ME/CFS termed it Myalgic Encephalomyelitis or "Muscle Pain and Weakness with Brain and Central Nervous System Inflammation"

 

[Davsey27]

Many of you know that my ME has been non-standard; I didn't suffer from the physical limitations, and I had some treatments work really well for me that no one else has reported benefits from. In the last few weeks I've been feeling much worse, and getting worse symptoms after eating high-protein meals. I've also returned to an old response of feeling abruptly worse 20 minutes after ingesting quickly-digestable carbs. To top that off, I've developed what seems like the typical physical problems many PWME complain about: using my muscles makes them hurt fairly quickly, though I'm not familiar enough with the 'acid burn' sensation to know if this is that. At one point I was wondering (maybe panicking a bit?) if I'd cured my PEM but switched to a more typical form of ME.

One additional symptom is that my temperature is typically about .3C higher than normal during the day. That suggests some sort of chronic immune system activation. So, it seems reasonable that this is some sort of infection, maybe a new virus, or reactivation of an existing one, or maybe one of those abortive viruses pumping out nasty proteins. What I think is happening is that my immune system is pumping out extra IFN-g, which is keeping IDO high in my brain, which is converting TRP into neurotoxic kynurenines. That seems a logical explanation for my observations.

My hypothesis is that the common muscular symptoms of ME result from this sort of chronic immune activation. I'm presently fairly brainfogged, so this is not a well-thought-out hypothesis. Maybe someone else can point out some supporting or refuting evidence or logic. Maybe it'll trigger some interesting discussion. I do wonder whether the results from patients who tried antivirals fits this hypothesis better than any 'viral infections cause ME' hypotheses.

If this new state hasn't gone away in a week or two, I'll buy some elderberry juice or other product to try, since that seems to be a strong immunostimulant for me. If that makes me feel worse, followed by feeling much better, that would support the hypothesis.

The best way I can explain what I am postulating is from the world of pain. If you will go with me down this path, I think it might give an additional explanation of what is going on in people's bodies.

In pain, scientist have been discovering that there is both a "bottom up" AND a "top down" component to the response. Neither is wrong, just incomplete without the other. So when a bundle of pain or nociceptive nerves is stimulated in an ankle sprain(bottom up), that is immediately sensed by the nervous system and depending on the severity of the injury (from minor tweak to grade 3 ankle sprain) pain will be experienced in the ankle. Truth be told, the experience/expression of pain to the injury would not be felt unless the nerves in the ankle are connected to the brain (top down). That is why in the case of spinal cord injuries and nerve disease (diabetes, leprosy) there may be no perception of pain to an injury in the ankle. One could argue that the experience or expression of pain need only have the central nervous components (ie brain) in order to express pain. Most significant case would be phantom limb pain in a "leg" that is no longer present. So you can have injury without pain.

To make this more interesting, the application of the "Bayesian" nervous system model comes into play. It's hypothesis is that the nervous system is not just reactive, but really more predictive. This is owing to the complexity of the nervous system and in particular the brain. There are somewhere between 85 and 100 Billion nerve cells in the brain. They each have from 1000 to 200,000 connections (synapses) to other nerve cells. In addition there are by some estimates 8-10 times as many glial cells that have connections the neurons use like jumper cables. So it is mathematically impossible to measure the complexity of the brain based on all of the variables this presents. Scientist a few years attempted to estimate how long it would take the most advanced supercomputer in the world to calculate what the brain and nervous system can do in 1 second. The estimation came out to 40 minutes! So yes I am a firm believer that there is one dominant or supreme if you will system in our body that manages, regulates and responds to anything that occurs in our body.

So relating it back to the immune system, there are as you say responses (immune, inflammatory) in the immediate (albeit collective in the case of a virus) area to foreign invaders and messages then sent to the nervous system (bottom up) AND there is the brain and nervous system's immediate and predictive response (immune, inflammatory, endocrine, hormonal, protective) to this invasion. I would argue that because the brain and nervous system respond systemically it is able to bring far more ammunition to bear. In exponential degrees. The question is can the local area responses slow way down or even shut down because the threat is lessened or eliminated and yet the top down process continue on and continue to reek havoc on the entire body. Yes I am confident it can. In the world of pain, this is what we think happens in CRPS (Complex Regional Pain Syndrome) which can be just as disabling as ME/CFS and actually has some of the same features including brain fog.

So your logic is definitely not wrong in my thinking, but I would say it is incomplete. As with most things related to ME/CFS very little has been proven. Certainly we are making improvements in our understanding, but far more out there to learn. My experience (studying, treating and observing the human body) of 10s of thousands of hours with patients and 10s of thousands of hours spent with my son when he was suffering seem to confirm (at least in my eyes) that this disease is very much driven by neurophysiology. Neuro-pathophysiology to be more accurate. I am confident that is why the original definers of ME/CFS termed it Myalgic Encephalomyelitis or "Muscle Pain and Weakness with Brain and Central Nervous System Inflammation"

Unique PT perspective.

 

[Mohawk1995]

Davsey,

I will take that as a compliment . I have actually been asked "are you sure you are a PT?". My answer is "yes I am, but I don't like being boxed in". I am not the only PT who thinks this way though. I have been fortunate to be able to learn from some really great minds in the PT world.

I only hope what I offer is helpful to those (almost all of people who suffer with ME/CFS) who are continually frustrated by the world of medicine. I think there are some new things on the horizon and honestly I am working to move medicine that way in one area (the world of pain). Long way to go and I am only a small part of the movement.

Paul

 

[Wishful]

So yes I am a firm believer that there is one dominant or supreme if you will system in our body that manages, regulates and responds to anything that occurs in our body.

Hmmm, I think I'm fairly convinced that that's an illusion, the way that insect colonies appear to have a guiding intelligence, but actually it's just a whole bunch of individual reactions that end up improving survival. If an anthill is ripped open by a bear, the individual worker ants don't get commands to rebuild based on a master blueprint; they just do their regular actions to push sand grains around in a way that results in a tunnel, and the soldier ants are probably just following a basic 'move towards something that's moving and bite it' response. I don't think the brain tells antigen-presenting cells to present a viral protein to a t-cell; it just does it due to basic physics. The t-cell does it's functions, producing proteins, opening microtubules or whatever it does also due to basic physics. When certain cytokines enter the brain, certain cells will react, maybe some neurons will fire, and maybe a signal will get sent that alters the function of t-cells or other parts of the immune systems. However, I don't see it as the brain looking up a table and deciding that EBV has entered the left foot, and then sends out a whole set of commands for fighting EBV.

As for immune responses being controlled by the nervous system, what about organisms before the nervous system first evolved? They would have had to have a functional immune response, since their world was filled with potential invaders. I wouldn't be surprised if t-cells and b-cells and various other immune cells existed before neurons evolved. Neural responses may have added some more functions to the overall immune response, but the basics are still from before neurons evolved.

 

[Wishful]

Something I remembered about my mercury thermometers: all three were graduated in tenths, and they all agreed that when my ME symptoms weren't flaring, my temperature during the day was 36.65C. Yes, it quite reliably rested in between those two tenth division marks. They might have been a couple of tenths off compared to a scientific standard for temperature, but they were consistent at a precision of .05C, at least for that part of their range. My cheap digital one only reads to tenths, so it's less precise.

 

[Wishful]

This morning my worsened symptoms seem to have faded. My symptoms didn't flare up 20 minutes after breakfast (as it had the previous mornings) and I managed a much brisker walk than the previous morning's painful trudge, and still had energy, so I handsawed firewood for an hour or so, and still felt okay. Hopefully this represents my immune system winning the war on whatever it was, and not just some temporary effect. I think it fits the worsened symptoms being due to an activated immune system.

 

[Mohawk1995]

Hmmm, I think I'm fairly convinced that that's an illusion, the way that insect colonies appear to have a guiding intelligence, but actually it's just a whole bunch of individual reactions that end up improving survival.

Wishful,

I admire your tenacity in sticking with your ant colony hypothesis. More than that, I am glad you were and hopefully still are having a better day!

A couple of gaps in comparing an ant hill to the human body and specifically the human nervous system:

• The shear number of nerve cells in one human nervous system as compared to an entire ant colony (50,000 ants). The math adds up to around a 7000:1 ratio. This does not include the added complexity of there being far more synapses per neuron in humans, the addition of 10 x 100 billion Glial Cells in a single human and much more complex chemical and hormonal signaling occurring in the human body.
• The individual ants are not immediately and permanently connected or integrated into the colony or mound and certainly not connected to the queen directly.
• The concept of a fully integrated human nervous system should then be included. One that is not only reactive, but also predictive. This includes the millions of receptors in the area of an injury and billions of receptors in play when you are considering a systemic infection.
• Even though ants are note directly connected to each other there are still subject some communication controls or pheromones secreted by the queen that control them. And of course the colony will die without the queen but that could be considered simple reproductive math.

It also important to note that I am not refuting that there are local cellular responses in the cellular and molecular structure, but I am absolutely not confident that this alone explains the complexity of an immunological, chemical, hormonal, thermal, circulatory, lymphatic and metabolic response that occurs to an infection. It is just not complete enough.

The discussion about what may have existed prior to the evolution of neurons is interesting to consider, but that brings up many more questions including complex mathematical explanations and probabilities required to explain a neurons existence and yet still it is not fully explainable. So I can only truly consider what we do know and what I have personally seen/experienced.

I also think there is room for both disagreement and respect. That is what I am intending. I hope that comes across.