Professor Ron Davis's response to Naviaux study, including Q and A with Dr Naviaux

[msf]

Ron and Bob have extensive "chats" almost daily. You are assuming things not in evidence. I will try to get Ron to clarify this point as soon as I can.

I´m not assuming anything, apart from that their differing conclusions reflect differing views on whether the study argues against persistent infection in ME.

 

[BurnA]

Of course, the guy is incredibly overworked and this was just his first reaction to it, so perhaps he will change his mind on this.

Wow. Ron Davis, one of the most respected scientists in the US, one of the most knowledgeable people on ME / CFS suggests something that you dont agree with, so you state he is overworked and might change his mind in due course. Are you for real ?

 

[msf]

Yes, I am for real, and if you considered things for a second, you would see I am saying that I prefer Naviaux´s conclusions (or lack of them). So it´s not a question of me claiming to be smarter than Prof. Davis, it´s me saying that Prof. Davis seems to disagree with another professor, who may be just as qualified for all I know.

Of course, I may have misread the situation, but others (Halycon for instance) also seem to think that the conclusions reached by the two professors are different. If they are not different, then I will be happy to have helped to clear the situation up for other people as stupid as me.

Oh, and I had forgotten that Davis had edited the paper when I made that remark. I was operating under the mistaken assumption that he had just read the article (whilst probably being in the middle of doing something else) and had been asked to give his first impressions of it. I apologise a thousand times for my faulty memory.

 

[alex3619]

Something very convenient that can fill nearly any gap?

It clothes emperors too.

 

[alex3619]

If they are not different, then I will be happy to have helped to clear the situation up for other people as stupid as me.

Personally, I love to see differences. They are at the core of good science. Differences lead to questions which lead to new hypotheses and differently designed experiments. I would love to be a fly on the wall listening to the debates. If you don't think they debate stuff ... well, without debates I doubt they would be good scientists. Debates and disagreements prove nothing, but they can pave the way to better hypotheses and experiments.

 

[Ben H]

Personally, I love to see differences. They are at the core of good science. Differences lead to questions which lead to new hypotheses and differently designed experiments. I would love to be a fly on the wall listening to the debates. If you don't think they debate stuff ... well, without debates I doubt they would be good scientists. Debates and disagreements prove nothing, but they can pave the way to better hypotheses and experiments.

Agreed. As was mentioned recently(and we all know) good science needs no protection. Ron can handle this quite easily, he is a consummate professional scientist.

But it's assumptions that are made that can get taken out of context that are an issue. That's all. Dialogue and conversation is good-that's why this is posted here!



B

 

[hixxy]

I appreciate Prof Davis´s efforts on behalf of the ME community (before anyone accuses me of being ungrateful), but I have to disagree with his comments here:

´Another important finding from this study is that the metabolomic response observed in ME/CFS is opposite to the pattern seen in acute infection and metabolic syndrome. This result supports the controversial idea that while infection is often the initiating event for ME/CFS, it does not contribute to the ongoing illness. What is important to note is that in the absence of evidence of an active infection, it is plausible that the long-term antimicrobial treatments often used for ME/CFS patients are doing more harm than good.´

I disagree as well. I don't see how this study can be used to rule out any role of persistent infection. If it's not able to differentiate between the dauer process being "stuck" on erroneously and being active for a reason, then it seems it can't differentiate between no on going infection and persistent infection.

 

[alex3619]

then it seems it can't differentiate between no on going infection and persistent infection.

Everyone has persistent infections, unless they are very young, live in a bubble, or are super lucky. So if you have enough such infections, at critical locations, its possible, though not proven, that they can keep sending signals that reinforce a dauer state. We are still a long way from finding all the answers, but at the start of this road it looks that we can finally see our destination in the distance.

For example, let me point out that an infection of the brain or nervous system, even latent infections, might alter neurological signals. They might also alter immune and eicosanoid signals. We just don't know enough. What is clear is that large numbers of patients do not have acute infections. Acute. This does not apply to absolutely everyone though. I know two patients who have recurring infections of things which are not supposed to recur.

 

[Research 1st]

CFS can never be one disease in its present state, because of how it's diagnosed. We can all agree on that.

We can also all agree, as of today, there is no accurate way to say that CFS is or is not associated to Chronic infection, because the diagnostic criteria for CFS are poor and don't screen out chronic infection robustly (patients generally have FBC, LFT, U+E, Glucose, Thyroid tested). If all comes back neg, they're diagnosed with CFS - that's terribly bad medical practice.

I've met people, sick for decades, who get so ill, they haven't seen a doctor for 10 years!!! They have no idea, at all, about their body, what's making them sick now, and never searched (too ill, no money, can't work, doctor won't speak to them). This disturbs me as a human, other humans are left to rot, totally clueless, how sick they are.

This is the problem we face today: millions of patients diagnosed with CFS who:

1)Don't get tested for every infection under the sun and believe they are infected with no evidence!
2)Do get tested,blow the bank, and find nothing - convinced they aren't infected.
3)Do get tested, blow the bank and find multiple pathogens - know they're infected. Minority.
4)Denied tests- unsure either way.

Question: Who has CFS in groups 1-4?

Question: Who will test positive using the new Mito technology from Dr Davis + Navieux?

Point to consider: Without more honest biomedical research in well described cohorts who at the very least meet CCC CFS criteria, we have no idea the percentage of CFS patients with Chronic Infections who test positive for the Mito defect found, Vs those who test positive but don't have Chronic Infections.

Additionally, no commercial tests exist for multiple HERV infections (increasingly found in Autoimmune diseases), so none of us, can test for these even if we wanted to, so no one, not even researchers on our side can say at his point in time that CFS is NOT associated to HERV's as patients haven't been tested.

 

[Research 1st]

I disagree as well. I don't see how this study can be used to rule out any role of persistent infection. If it's not able to differentiate between the dauer process being "stuck" on erroneously and being active for a reason, then it seems it can't differentiate between no on going infection and persistent infection.

I wouldn't worry about infections being ignored, as the findings would actually make sense of an infectious agent doing what has been discovered.

Mitochondrial Disease signs,are often found in ME and severe grade CFS.

*Dysautonomia
*Seizures
*Chest pain, shortness of breath
*Visual defects
*Balance problems
*Cognitive dysfunction/short term memory impairment
*Muscle weakness
*Increase incidence of infection
*Chronic pain

But ME CFS is ''acquired'', that is what is unique about it and often (not always) why our Muscle Biopsies are normal.

Now we have preliminary evidence for Mito Dysfunction in CFS, it actually helps not hinders the 'issue' that patients have (inc myself) of having multiple infections at once, but some researchers saying they can't find infection, which to be fair, is the case in many patients who meet Fukuda CFS criteria only, or, are not severely affected for decades.

It's just a problem of subsets, and researchers not knowing who donated the blood, so they don't know what signs of ME the donor had, if any. (Simply meet Fukuda CFS criteria and you become a 'patient with CFS'). Meaningless in terms of deciphering who is who.

With a test, we can change the game and really see what's going on, but until then, we can't say either way. So to conclude regarding infection and this specific finding, no one can say with confidence what is going on at this point in time with regards to a heterogeneous disorder such as CFS.

 

[halcyon]

Oh no, someone mentioned Lyme. I purposefully kept my objections as general as possible, because I didn´t want it turning into another Lyme thread.

Given the exclusions present in the criteria used to select patients for this study, there should have been no lyme disease patients in this cohort. The authors on this paper from Gordon Medical are well known LLMDs, so we can guess these patients have all had extensive lyme testing.

 

[duncan]

Given the exclusions present in the criteria used to select patients for this study, there should have been no lyme disease patients in this cohort.

Not deliberately at least.

 

[Nielk]

From Dr. Davis:

"Another important finding from this study is that the metabolomic response observed in ME/CFS is opposite to the pattern seen in acute infection and metabolic syndrome. This result supports the controversial idea that while infection is often the initiating event for ME/CFS, it does not contribute to the ongoing illness. What is important to note is that in the absence of evidence of an active infection, it is plausible that the long-term antimicrobial treatments often used for ME/CFS patients are doing more harm than good."

What about all the ME patients who suffer from consistent chronic high viral loads - like EBV, CMV, etc.?

 

[hixxy]

From Dr. Davis:



What about all the ME patients who suffer from consistent chronic high viral loads - like EBV, CMV, etc.?

I guess he's excluding viral reactivation as likely being only a symptom.

 

[Gingergrrl]

This is an amazing thread and I am responding to a bunch of quotes in one post below to not clog up the thread.

Heck, how many of us have taken abx or AV's and got permanently worse

The very first trigger or "injury" that I had was a neurotoxic reaction to the antibiotic, Levaquin, in 2010. I was healthy at that time and did not have ME/CFS or any other illness. I had a systemic neurotoxic reaction and was hospitalized and it permanently injured a tendon in my right arm. I was able to make a very solid recovery until the second trigger (Mono/EBV) approx two years after the first trigger. But I do believe that people can be made permanently worse by both A/V's and ABX (while of course in others it can lead to improvements).

You cant close the possibility of active infection out, but there is no good reason to strongly assume that it`s probable at this point.

That is my feeling, too. I believe that EBV and other viral triggers are what initiated my illness, in addition to severe mold exposure, but what perpetuates the illness is now an autoimmune response. I took Famvir for eight months at a pretty high dose with zero improvement and then attempted Valcyte but did not tolerate it. I have had bad reactions to just about everything I have tried. The first thing that is helping me is IVIG to target an autoimmune antibody and it has virtually eliminated my mast cell/allergic reactions. To me, this implies it is tamping down an autoimmune response (in my case- this may not be relevant to anyone else) vs. fighting an infection.

OK, mental note: don't trust my own memory... In this case I have no idea what PTSD has to do with us. But I'm still pretty sure he talked about mitochondria shutting down - I guess it was after physical trauma then? (burn victims?)

I had never associated PTSD with this illness but to use the example above, if someone was a severe burn victim (a physical injury) they could also have PTSD from the event and the aftermath of the event. So it seems like many physical injuries or events could lead to PTSD. If you lose your leg in a war, it is not only the psychological impact but also the physical impact of the body losing a leg. So in many instances, I can see how PTSD does relate.

Some of this fits the theory/treatment model being used by Dr. Ty Vincent--the on button being stuck after some kind of a pathogenic assault. He is using low dose immune therapy. It does seem to "un-stick" the button, after finding the most appropriate antigens (to the original assaults), and giving them at low doses.

This is very interesting too, b/c I wonder in my case if the button that was stuck in the "on" position is starting to become unstuck from me trying IVIG in a similar way to what Dr. Vincent is doing (but at a lower micro type dose)?

Now that a collective understanding is being reached on the forum that the issue is a signaling problem that is stuck, I want to bring to attention the occurrence of spontaneous remission and relapse that repeats itself in some cases.

But what about someone who has never experienced a spontaneous remission or has never had a relapsing/remitting form. I feel like this does describe one group of patients but certainly does not apply to all (and I know you said "in some cases" so you might be agreeing that it does not apply to all)?

Prof. Davis is extremely meticulous, and does not say things without good reason. Certainly not due to being overworked, or any other reason. He is a man of science. I won't wax lyrical, just take a look at his career thus far.

I think it best we wait for his possible response before assumptions are made on behalf of Prof. Davis

Agreed 100% and I don't think anyone should be making assumptions on behalf of Dr. Davis or statements that he is publishing or agreeing to having has name on articles that he did not agree with b/c he is overworked. From day one, I felt if anyone is going to solve this illness it is him and I now feel that even stronger.

People also have different onsets. Many have sudden onset. Some have gradual onset, and some like me have a bit of both. Mine was gradual over many years, perhaps more than a decade, up and down, and then, at the end leading up to my diagnosis, a very sudden onset that left me permanently sick.

Mine is sort of similar although the entire course was much shorter than a decade. I had first trigger in 2010, second in 2012, and then final trigger in 2013. I count 2013 as the official start of my illness b/c it was this final trigger that I could not recover from and led to severe POTS/dysautonomia and the entire downward cascade to where I am now.

The authors on this paper from Gordon Medical are well known LLMDs, so we can guess these patients have all had extensive lyme testing.

Now I am even more confused! Was Dr. Navaiux's study conducted with subjects from Gordon Medical Group (meaning if I had the Metabolon test at OMI then I absolutely was not a part of the study) or were the subjects from both GMG and OMI? I have read so many different things, I am unclear on this now!

 

[Janet Dafoe]

I'd say that just because this state doesn't look like acute infection doesn't preclude it being a chronic one. His interpretation of this seems to differ from Naviaux's:

I just spoke with Bob Naviaux and Ron. They do not disagree one bit. I read that paragraph to Bob and he said, "Ron is SPOT ON". He said the trigger can be an infection and the process gets triggered, but then keeps going long after the infection agent is gone. He said a lot more too but I am not capable of repeating it. I sent him the two quotes and he said he would write down his explanation for me to post here for you.

Also, keep in mind, evidence of infection is not necessarily ANTIBODIES to an infectious agent. You can have high antibody titres way after the agent is gone. This has been an area of confusion for a long time. When Ron looks extensively for any infectious agent he doesn't find any that are not normally there in healthy people. Doesn't rule it out completely, but maybe this is the wrong thing to focus on at this point. Not my call though.

There are many things coming up in these threads that he and Ron can answer; their knowledge is SO DEEP. It couldn't all fit in the paper. I am going to try, with Ben's help, to compile a list of things that are questions or misconceptions and Bob is going to add to the Q and A paper for everyone to see. This may take a while. I have had a death in my family and have to go to Portland for a few days. Lucky I now have a new great caregiver who can do my night job while I'm gone. I'll get back to this as soon as I can because I think it is important to clear up things and get people all the info possible so they can be focussing on the right things. Bottom line: there may be a diagnosis soon, and they are working actively on how to get the process unstuck! My answer would be: Tell your body it's springtime! LOL How to do that is the million dollar question. We will get there!

 

[halcyon]

Now I am even more confused! Was Dr. Navaiux's study conducted with subjects from Gordon Medical Group (meaning if I had the Metabolon test at OMI then I absolutely was not a part of the study) or were the subjects from both GMG and OMI? I have read so many different things, I am unclear on this now!

I assume they would have put someone from OMI on as an author if they used any samples from their patients. I don't believe Metabolon had anything to do with testing these samples. I think it was all Naviaux's lab with Gordon Medical Group's patients.

 

[Janet Dafoe]

This is an amazing thread and I am responding to a bunch of quotes in one post below to not clog up the thread.

Now I am even more confused! Was Dr. Navaiux's study conducted with subjects from Gordon Medical Group (meaning if I had the Metabolon test at OMI then I absolutely was not a part of the study) or were the subjects from both GMG and OMI? I have read so many different things, I am unclear on this now!

Subjects in Naviaux/Gordon study were from Gordon Medical Associates practice, NOT OMI.
The OMF Big Data Study patients were from OMI. Ron's results are from Metabolon. Bob Naviaux's are from his own Mass Spectrometers at UCSD.

 

[halcyon]

Also, keep in mind, evidence of infection is not necessarily ANTIBODIES to an infectious agent. You can have high antibody titres way after the agent is gone.

Right, but many of us have serology in addition to histopathology both showing viral presence and there are several lines of research that back this finding up.

When Ron looks extensively for any infectious agent he doesn't find any that are not normally there in healthy people.

I don't expect ME to be caused by a novel pathogen at all. Poliovirus was commonly found in healthy people as well.

 

[halcyon]

I have had a death in my family and have to go to Portland for a few days. Lucky I now have a new great caregiver who can do my night job while I'm gone. I'll get back to this as soon as I can because I think it is important to clear up things and get people all the info possible so they can be focussing on the right things.

Really sorry to hear this by the way. Safe travels.

We very much appreciate you spending your time filling us in on things!