Davis speech from Millions Missing. Some new info on metabolic trap hypothesis

[ebethc]

I just did some searching and couldn't find any connection of big pharma to Jackson Labs. The NIH is funding their ME/CFS research.

Jim

I have nothing against a drug that could work, but so many immune drugs fix one problem then create another AND that's only if you can afford them... Of the top 5 drugs (by revenue), FOUR are immune drugs.. Annual Recurring Revenue = $32+ billion... They have terrible side effects... Lots of examples, but check out the link re Glenn Frey below... His wikipedia page used to explicitly say the name of the drug he took (Enbrel?) but it was taken off the page.. No doubt due to litigation threats.. Fixed his RA, and triggered serious gut problems that lead to his death...ugh.. First do no harm, a-holes..

https://en.wikipedia.org/wiki/List_of_largest_selling_pharmaceutical_products

https://en.wikipedia.org/wiki/Glenn_Frey#Illness_and_death

 

[Pink]

Is there any way for us to access these drs and resarch centers for treatment, or are they only for research?

 

[alex3619]

Is there any way for us to access these drs and resarch centers for treatment, or are they only for research?

Stanford does clinical treatment. However there are no highly effective treatments just now, though some patients seem to do very well. This is less a promise of treatment than of research, and these grants are not for clinical treatment. Its about research. If you live close by then it might pay to keep an eye on what the local centre is doing. You might be able to sign up for a study. In time those studies may become clinical studies, instead of investigative studies. That means you might be able to sign up for clinical trials. In those trials everyone might get a treatment, or they might be divided into placebo and treatment, which means a fifty-fifty chance of an experimental treatment in a lot of cases.

If in an investigative study however you might well learn things that are wrong that most doctors would never guess, and can then take that information to your more regular treating doctors. They may not know what to do with that information though.

 

[Murph]

Is jackson lab a private lab, funded by big pharma?

Jackson Lab is one of the four research centres that got big NIH money in the recent round.

https://www.jax.org/news-and-insights/2017/september/new-chronic-fatigue-center-grant

It has not yet published anything and is not well-known in the me/cfs community but I follow the leader of the lab, Derya Unutmaz, on Twitter and his statements certainly inspire confidence.

 

[Murph]

It's not even a hypothesis as there are no specific testable ideas yet. At best they're holding back their specific ideas, but I don't think that is helpful for the field (unless they want to take all the credit for a discovery...)

Ron Davis says they have the hypothesis, the money and materials to test it, and a plan to have results "by the end of summer" so I think this skepticism is uninformed.

Furthermore it is clear they are thinking hard about the limits of the hypothesis test they are doing, which will involve attempting to generate the metabolic trap in peripheral blood mononuclear cells. The question of whether those cells are representative enough to conclusively prove the presence or absence of the trap is something weighing heavily on the mind of Robert Phair. It is possible that they will also have to test muscle cells, which will involve biopsying some people.

 

[Neunistiva]

Jackson Lab is one of the four research centres th

Just a little note, there are 3 research centers, the fourth one will just be for collecting their data, they won't do any research.

 

[ebethc]

Jackson Lab is one of the four research centres that got big NIH money in the recent round.

https://www.jax.org/news-and-insights/2017/september/new-chronic-fatigue-center-grant

It has not yet published anything and is not well-known in the me/cfs community but I follow the leader of the lab, Derya Unutmaz, on Twitter and his statements certainly inspire confidence.

One of the scientists working w Dr Unutmaz @ Jax worked w Ron Davis, and she's a microbiome expert:

"Dr. Oh's main research interests focus on the human microbiome—the diverse bacteria, fungi, and viruses that inhabit our bodies—for its potential to deliver treatments for infectious and other diseases. Dr. Oh comes to the microbiome world by way of fungal chemogenomics with technologist and geneticist Dr. Ronald Davis at Stanford and comparative genomics of wild wine yeast at the FAS Center for Systems Biology at Harvard. Prior to joining the Jackson Laboratory, she was a postdoctoral fellow at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health. Dr. Oh's research, exploring the complex interactions between the host and its microbes has lead to important implications for the contribution of the microbiome to disease."

 

[ljimbo423]

Just a little note, there are 3 research centers, the fourth one will just be for collecting their data, they won't do any research.

There are actually 4 research centers plus the data management center, I think.

Jim

 

[Hip]

If you look at the right hand side of this picture. You see the "incidence of immune disorders" starts to increase dramatically around 1950. The first widely used antibiotics came out in the late 1940's. I don't think that's a coincidence.

There are other things that happened in the 1950s that could also help explain the rise of autoimmune diseases:

Poliovirus vaccine was introduced in the late 1950s, and it is speculated that because this eradicated poliovirus infection in Western countries, that allowed coxsackievirus B infections to become more fierce (because natural infection with poliovirus early in life may offer some immunological cross protection against other enteroviruses such as coxsackievirus B and echovirus).

In particular, the poliovirus vaccine is speculated to be responsible for the rise in type 1 diabetes, which is linked to coxsackievirus B1 and B4. And it's possible the poliovirus vaccine might have caused the massive rise in ME/CFS incidence that apparently occurred in the 1980s. ME/CFS is linked to coxsackievirus B and echovirus.

See this thread: Did the introduction of the polio vaccine cause the massive rise in ME/CFS incidence in the 1980s?

So this underlines the urgent need to introduce a coxsackievirus B vaccine.



And pesticide usage increased dramatically in the Western world from the 1960s onwards (the graph on this webpage). Pesticide exposure has been linked to various autoimmune diseases. So that could also help explain the rise in autoimmunity.



Also, if we assume that bacteria and antibiotics do play some role in the increased prevalence of autoimmune disease, it may be the bacterial infections themselves rather than the antibiotics used to treat them that are the culprits. Prior to antibiotics, a lot more people with bacterial infections would have just died of the infection, and therefore even if the bacterium they caught were to trigger autoimmunity, no one would know, because the person may not have survived the infection.

25% of OCD cases are thought to be due to an autoimmune condition triggered by Streptococcus bacteria, via molecular mimicry So that's one example of how bacteria might be triggering autoimmunity.



I came across this article explaining a theory that the aminoglycoside class of antibiotics might play a role in triggering autoimmune disease due to the way they alter gene expression in human cells. Apparently aminoglycosides will cause human cells to read through stop codons in the human genetic code, producing a longer protein product, which it is speculated may then help trigger autoimmunity.

 

[TreePerson]

@Hip yes I have sometimes wondered if some of it's to do with survival of the fittest. How many of us would have survived our childhoods without antibiotics or with the protection provided by vaccinations against polio diphtheria whooping cough etc?

 

[alex3619]

Poliovirus vaccine was introduced in the late 1950s

If I recall correctly, and maybe someone can comment on this further, the 1934 LA County Hospital outbreak was associated with an early polio vaccine that never made it to market. Or am I misremembering?This hospital was using animals to study pathogens, and working on early vaccines from what I recollect.

 

[nryanh94]

So does Ron think that CFS is multiple illnesses that all course the same metabolic trap and can be fixed by the same thing, or multiple illnesses that require multiple different treatments.


If it’s the latter then that’s depressing

 

[ljimbo423]

I think there are many things that have and are contributing to the high increases in autoimmunity and immune system diseases in the last 50-60 years.

As you said, pesticides are probably one. I think antibiotics are probably the biggest though.......

25% of OCD cases are thought to be due to an autoimmune condition triggered by Streptococcus bacteria, via molecular mimicry So that's one example of bacteria triggering autoimmunity.

I think this paper explains how OCD gets triggered by streptococcal infections very well-

Abstract
Obsessive-compulsive disorder (OCD) is a debilitating disorder for which the cause is not known and treatment options are modestly beneficial.

A hypothesis is presented wherein the root cause of OCD is proposed to be a dysfunction of the gut microbiome constituency resulting in a susceptibility to obsessional thinking.

Both stress and antibiotics are proposed as mechanisms by which gut microbiota are altered preceding the onset of OCD symptomology.

In this light, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) leading to episodic OCD is explained not by group A beta-hemolytic streptococcal infections, but rather by prophylactic antibiotics that are administered as treatment.


Further, stressful life events known to trigger OCD, such as pregnancy, are recast to show the possibility of altering gut microbiota prior to onset of OCD symptoms.

Suggested treatment for OCD would be the directed, specie-specific (re)introduction of beneficial bacteria modifying the gut microbiome, thereby ameliorating OCD symptoms.

Special considerations should be contemplated when considering efficacy of treatment, particularly the unhealthy coping strategies often observed in patients with chronic OCD that may need addressing in conjunction with microbiome remediation.

LINK

I think the same thing happens in some cases of lyme disease. People are treated with weeks or months of antibiotics.

Creating significant dysbiosis and increased intestinal permeability, causing post treatment lyme disease syndrome.

EDIT-

Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years.

We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases.

LINK

Jim

 

[Hip]

I think this paper explains how OCD gets triggered by streptococcal infections very well-

That paper is from the journal Medical Hypotheses, which presents hypotheses about the causes of a disease, rather than evidence for the cause. So the ideas in the Medical Hypotheses journal are not considered fact, just theories to consider.

The idea that OCD can in some cases be caused by autoimmunity triggered by Streptococcus infection is also a hypothesis at this stage, although there is supporting evidence for this particular theory.

 

[Neunistiva]

There are actually 4 research centers plus the data management center, I think.

No, as you can see from the article @Murph linked

This Center will be one of three ME/CFS Collaborative Research Centers (CRCs) that will be awarded, together with a Data Management and Coordinating Center (DMCC).
​

Same was said by NIH itself:

The grants will support the creation of a consortium made up of three Collaborative Research Centers (CRC) and a Data Management Coordinating Center (DMCC). ​

If you look at the map you will see the "fourth" research center is actually Dr. Ron Davis at Stanford.

NIH still hasn't given them a single dollar, it's all financed from our donations. We are just lucky that Pineapple Fund gave $5 million and that Dr. Davis is sharing data freely with any researcher in the world who requests it, otherwise it would be impossible.

But that center is not part of the NIH's collaborative, although I am sure Dr. Davis will give them any data they want. It's a great pity though, we need a lot more than just 3 centers.

What might become a fourth center is actually a Canadian center which will join forces with NIH. The maximum amount for the grant is $280,000 per year, so that's not much either.

 

[ljimbo423]

If you look at the map you will see the "fourth" research center is actually Dr. Ron Davis at Stanford.

NIH still hasn't given them a single dollar, it's all financed from our donations.

Thanks for the clarification. So that map I posted is wrong in saying Stanford and Ron Davis are part of the collaborative? I didn't make that map by the way.

EDIT- Ron Davis and Stanford are part of the collaborative just not being funded by the NIH is how I understand it?

In September last year, the National Institutes of Health (NIH) announced $35 million of funding to establish three new ME/CFS research collaboratives and a supporting data centre. Since then, the Open Medicine Foundation (OMF) has helped to establish a fourth research collaborative, at Stanford, committing $2.4 million for the first two years. It aims to fund the collaborative at similar levels until the work is complete.

LINK

Jim

 

[Neunistiva]

Ron Davis and Stanford are part of the collaborative just not being funded by the NIH is how I under

I don't think it's just about the funding

These new centres also bring researchers together to form a critical mass, and the three NIH centres are themselves working together, with plans to collaborate on at least one joint project. ​

 

[ljimbo423]

with plans to collaborate on at least one joint project.

Are they giving any hints as to what that one joint project might be?

Jim

 

[ebethc]

@Hip

my understanding of the hygiene hypothesis is that a confluence of factors creates the problem; so, agreed that it's more than antibiotics

 

[FMMM1]

Thank you @Murph

I believe that the interesting bit starts at the 46:00 minutes mark. I've never looked at the work of Chris Armstrong which sounds very interesting.

If i understand well, AMPK may be the switch that Ron talks about (?). However it is more interesting to focus on why as Chris Armstrong puts it "less and less nutrients are being absorbed". This is where a key piece of the puzzle probably exists, it is this trap that needs to be found.

I haven't read the above in detail. It's been some time since I looked at Chris Armstrong's research. At one stage he was looking at low gut pH (acidity closer to neutral than it should be). He demonstrated high levels of volatile fatty acids in your blood which indicated that food was being processed lower down in the digestive tract. Interestingly he proposed that once you had this problem then you were stuck with it (negative feedback loop). Lower gut acidity leads to lower stomach acid production, which leads to altered metabolism, which results in lower acid production. He did a webinar possibly December 2016 and published a number of papers all readily available (and reviewed on Cort Johnson I guess).