Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment, Robert K Naviaux, 2018

Yes for all of the reasons stated earlier in this thread.
It doesn't help that the reporting is perfunctory.

 

The human body has a huge number of negative feedback loops to deal with any oscillations or setpoint changes. So for example when blood sugar raises following a meal, the insulin concentration starts to rise, and there is actually some oscillation going on around this setpoint, which would be a healthy response. In diabetes you would have larger oscillations and inability for this control system to work properly. A similar thing would be with high blood pressure and autonomic system remodeling. So once the system goes wrong, I can see the point that the body no longer can return back to a state of homeostasis.

But I don't see how oscillations over millions of years would be relevant in this model. As long as the healing response works correctly, I don't see a reason why the body would not be capable of dealing with oscillations of variables. The human body can endure tremendous stress and pain and still recover in most of the cases.

 

Most of the cases

 

Fair question, deserves a considered answer.

"... a hitch in cell danger response, natural cellular reaction to harm" sounds to me very nonspecific. Would it ever be possible to pin down this claim so that we could test it? Is there any opposing possibility? Or does it boil down to a vague truism?

"The healing process is a dynamic circle that starts with injury and ends with recovery." That one's circular. Yes, healing ends in recovery. The idea is implicit in the word "healing". And yes, its obviously a dynamic process, because your health status changes.

I would like to know what a "cell danger response" is. It could mean anything at all. Is he referring to the immune response? If so, which aspect? If not the immune response, what does he mean?

Then there is some study with 10 autistic kids. Which is obviously not enough to say anything, and also they didn't seem to show any sustained improvement.

Here, we might be getting a bit closer to an actual hypothesis. But right now its all a bit, er hand-wavy.

Is this man really claiming he has a way of treating and preventing 'chronic disease' in general? Extraordinary claims require extraordinary evidence. I don't see any.

 

I did not in any way mean to give the impression I thought oscillation periods of millions of years are relevant. I was simply illustrating that oscillations can occur in nature from the extremely high frequency to the extremely low, according to process.

Yes, I have begun to realise since joining PR and then S4ME, just how amazingly complex biology is. I suspect that if a control engineer sought to model the control behaviour of the human body, it would be a significant undertaking.

And yes, negative feedback loops are typically there to keep a process variable close to or on its setpoint, without undue oscillation. But the premise is that the healing response is not working properly, and so maybe not all control loops are functioning effectively. Maybe something has affected the characteristics of the process being controlled, such that the controller can no longer cope? Or maybe something has damaged the regulation mechanism itself? Negative feedback loops have a nasty habit of turning into positive feedback loops when some component of the feedback loop changes, potentially including unintended cross-talk with other feedback loops.

Am I saying this is what I think is happening? No, of course not, as I said at the start of my earlier post. I have no medical expertise at all. Just conjecture.

 

Many thanks. Yes, my medical knowledge is virtually zilch, so would not know the rights and wrongs. And of course if Naviaux is not backing up what he says with solid evidence then scepticism is right and proper. I suppose I just like the sort of thinking that turns a problem on its head sometimes, and looks at a problem in a different way; lateral thinking. The idea that some ongoing health problems might be due to repair mechanisms being obstructed and still ongoing, to me seems very worthy of further investigation - it just may be valid. It may not of course, but isn't that what good science is about? Being prepared to fail, and to accept failing, so as to pursue a line of investigation that nonetheless might succeed, and if it does could even be a game changer? I don't think it is always right to criticise scientists who have the courage to set themselves up for a possible fall, in pursuance of discoveries that just might improve the lives of everyone.

 

The trouble is though ..science has a way of taking that spark of imagination and luck and processing it to check that it’s not bullshit.

in terms of scientific method this proposal is extremely sloppy and quite rightly should be treated with skepticism

It’s a case of putting his cock on the block and saying what he means specifically ....otherwise it’s just a load of hot air ..might be good for the lancet?

 

Yes! I'm with you on that one @Barry. Not only is it fascinating to follow somebody else's out-of-the-box train of thought but it's in fact necessary to stop one's own thinking from getting stuck in a rut.

Also agree with the numerous skeptics here: a somewhat vague and general hypothesis by itself is not worth all that much until it's been refined and thoroughly challenged and tested, and there's some way to go is this case.

However, the very process of testing something out-of-the-box can lead to unexpected and valuable insights, even if along the way it destroys the original hypothesis. Given that this particular hypothesis is about the stages of healing and what might go wrong with them it's worth giving some thought to it and figuring out ways to test it, or elements of it.

 

The issue for me here is that, for the disease we're interested in, whatever the pathology is it notably causes no disrepair/damage to be healed in any typical sense. It makes more sense when he talks about specific signaling abnormalities. But to me that's not some novel conception - I think that describes what people have done (or are trying to do) to figure out what's going on in and devise treatments for all sorts of chronic acquired diseases.

Maybe we will need some truly out-of-the-box thinking to make a breakthrough but it seems unhelpful to try to work off of some vague panacean theory that is actually at odds with the facts of ME if the premises are to be meaningful in any way.

To me it looks like there are some novel and interesting specific elements in what he calls Cell Danger Response. What I recall of it is the idea that chronically excessive levels of extracellular ATP is signaling cells to continuously operate under some sort of threat mode, so if we can block the extracellular receptors (called antipurinergic therapy) we can return cells to more normal function. I don't know enough to comment on if this makes any sense, but at least it looks like a specific, testable hypothesis.

 

[My bold]

But surely the suggestion is that something atypical may be going on, at least insofar as something possibly not yet understood?

 

For me this theory, if applied to ME, is trying to explain it in terms of already familiar processes - tissue damage and healing - that look to be irrelevant.

For this theory to be relevant, it would have to use some expanded meaning of 'healing'; but without specifics, you could sort of fit any condition into the theory without actually knowing any more about said condition. That's what I meant by 'any typical sense', which could also be 'any meaningful sense'.

And then if you have the specifics for a disease, you no longer have any reason to care about this theory.

Something atypical is definitely going on. I just worry that this is an ornamental theory that potentially distracts from digging into 'the specifics'.

 

I found Naviaux’s long paper well worth reading, as hard as it was without an education in medical science. I could only tackle it on a good day, skimming what I couldn’t understand and diving in after every single point and pattern I could pick up. I will not try to summarize any of it here, but would recommend more here try to tackle it. He is only presenting a model, a proposed model as a guide for research, what I believe may be called a “heuristic model”. It is backed up by some research, which he notes frequently when applicable, but as a hypothesis or model, it doesn’t have to be totally proven yet. There is enough good research to support it, however, as a guiding structure/model for future research is his point. My guess is that he is “going big” with this paper to attract and make the case for research funding for both the projects he wants to do, and that other scientists might be attracted to do.

As far as I know, Naviaux is an excellent research scientist, not wooly minded in terms of scientific facts and valid ways of proceeding, but he is also the kind of thinker who can expand beyond this into the field of scientific and medical knowledge to hypothesize and propose new ways of understanding. And this can guide research, potentially bringing results far more quickly than research that can only inch ahead one minuscule fact at a time or else gets stuck going around in circles, maybe hitting the same dead ends. I feel we need some “higher order” thinkers, along with those who can construct good experiments—and sometimes these will even be in the same body as in this case, if not on a team as the Open Medicine Institute puts into action.

But back to Naviaux’s paper on the healing process, ME is such a systemic condition affecting so many different organs and aspects of physiology that the large idea of unblocking a stuck healing process, like escaping a metabolic trap, could be a much more direct path to effective treatments than the absurdly complex task of correcting every imbalance and abnormal finding. All the time, energy, money, and hope that I and so many have spent researching, buying and taking supplements and medications or following abstruse and difficult diets, etc., all in the Sisyphean attempt to change our bodies back to normal, can’t be claimed as a success. Naviaux’s model is a kind of meta-model that suggests a simpler more direct route to treatment, like the model of the metabolic trap that Dr. Phair and Dr. Ron Davis are using to try to see what the levers might be to spring it.