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Comment by Smaug123 | Hacker News Reader

Paper at https://www.pnas.org/content/pnas/early/2019/04/24/190127411...

Pleasantly surprised to discover that it was legally available!

The test appears to be ridiculously good. Perfect separation of 40 subjects into those who have been diagnosed with CFS and those who are known to be healthy, from blood samples.

I want to see this replicated, by people who are not the original authors; but if this test is anything like as good as it looks, it's revolutionary.

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Keep in mind that CFS is a currently a diagnosis of exclusion - many people labelled with CFS may in fact have another, undiagnosed illness.

For example, it's been found that a lot of CFS (and fibromyalgia) patients turn out to have small fiber neuropathy (damage to he nerve fibers that signal pain), and neurotoxins have been shown to cause general fatigue (I'm in mobile, so no references for now I'm afraid).

The skin biopsy test for small fiber neuropathy isn't routinely done because there aren't that many labs capable of testing the sample, and it's relatively expensive. Of course, for all we know neuropathy could be a symptom of CFS... but the point is there is a lot of cross-over, and there is no diagnostic test specifically for CFS.

I found out last year the root cause of my CFS is life-long mercury toxicity (a well understood neurotoxin). I am responding very positively to treatment.

I rarely talk about it because people get very upset when I tell them about the evidence of where the mercury came from.

Nice curiosity gap there. Where did the mercury come from?

Going to assume given the way this is phrased that the poster means a vaccination.

IMO he is clearly implying it came from a vaccine(s) but he is trying to do it without being seen as an anti-vaxxer.

Surely you'd have to have a lot of vaccines for it to compare to the amount you get from other sources (mostly seafood afaik?)

Yes. One vaccine contains less mercury than one (average) serving of fish, and the mercury is in a less toxic form.

Not even just a "form". Thimerisol is a compound. I like to compare it to saying we shouldn't eat table salt because it contains chlorine.

Now, as to the safety of Thimerisol, obviously that has to be judged on its own merits, but just because a compound "contains" a certain kind of atom, by itself means nothing.

Why would I be an anti-vaxxer? Mercury is not in any childhood vaccines.

Because mercury toxicity is a common claim of anti-vaxxers and because you implied the alleged source of the mercury which caused your CFS is something that upsets most people. Doesn't seem like that much of a stretch to think that you're referring to vaccines.

If you were less weirdly cryptic about it, we could just have a normal exchange and perhaps I'd learn something new. Perhaps you instead believe it's from seafood and people don't like hearing that they shouldn't be eating fish, IDK.

What exactly is the source of the mercury that you're referring to? You accuse others of not being able to have rational/intelligent conversation in this thread, yet you haven't even stated your basic premise, just trolled and then acted like a victim when people got annoyed with your coyness.

Where did the mercury come from?

I don't get angry like some people about "anti-vaxxers", but the reason I am not one, is because I think that if low levels of mercury were a major health issue, then it would be apparent in large populations that consume a relatively large amount of mercury-containing seafood. e.g. Japan. And in Japan, there have also, as it happens, been incidents of acute mercury poisoning with significant numbers of people, so the difference between toxic and non-toxic levels is clear.

Yes, data on mercury toxicity is quite clear that vaccines as safe.

However it's unfortunately easy to find sham "doctors" that will diagnose whatever the patient requests - mercury poisoning, EBV, chronic lyme disease, just pay in full and all your beliefs will be confirmed! Just don't look too closely at the placebo, er, cure...

Well, there are lots of rare diseases, and mercury could be a factor in some of them. That doesn't mean they are imaginary. It's more of a definitional/philosophical issue, that some other factor is essential as well, so it's not right to attribute the problem only to mercury.

The distinction I'm making is that I am pretty sure low level mercury is not an issue like lead from gasoline, although I can imagine evidence that would change my mind. If it was, we should be able to see blatant differences in large populations, just like we see with lead and violent crime.

I'm also pretty sure that peanut butter is not an issue, but it does kill some people. Maybe there are people out there who are ultra-sensitive to mercury.

True, but people with deadly peanut allergies are still completely fine when peanuts aren't around... I can't imagine why vaccine mercury would explain life-long CFS.

There is a compelling theory that when a child is simultaneously exposed to injected mercury along with another stressor, the mercury is not excreted as it normally would be.

It's all kind of moot though because mercury is no longer in child-hood vaccines. I really don't see the point in bringing the discussion of vaccinations into this since almost no one can have a rational discussion about them.

Do tell please, it would be educating for all of us. Hopefully you’ll find a less negative reception in this thread.

I'm already being down voted and I've said nothing but what has been rigorously verified as the root cause of my illness. It's impossible to discuss this intelligently on public forums.

just spit it out, please

You're being down voted because you're being unnecessarily vague. I dug through your comment history and you haven't mentioned it before, so it's not this community that you've had a bad response from before. (Unless you made a new account?).

I made a new account and I am trying to avoid absolutely destroying the karma on this one.

I have confirmed mercury toxicity through hair analysis, which is controversial and difficult to interpret. It is described in depth by an Princeton trained biochemist, Andrew Cutler, in his book, Hair Test Interpretation: Finding Hidden Toxicities.

This diagnosis has been confirmed by a dramatic improvement of symptoms upon treating specifically for mercury toxicity with low-dose chelation therapy.

My symptoms began when I was a baby. Before I ever ate any tuna. Before I was anywhere near a mercury thermometer. I've never had amalgam fillings. I've never been exposed to a mercury spill to my knowledge.

These are the facts that I am 100% certain on.

Do you eat 20 cans of tuna a day? When I was much younger I ate 1-2 cans of tuna pretty much every day for few years and I didn’t have any ill effect at all.

Did you just like the taste?

He's a tigershark, of course he likes the taste of tuna. Duh.

TIL that HN people like tuna less than no-vax. Probably you should taste a proper one, not that awful mess that sell in 90% of the world.

yeah you have to be careful with the amount of fish you eat these days, the long living predatory ones tend to accumulate a lot over the time in tissues

Just wanted to add that I made this post to throw life-lines out to those who are suffering with the same illness as I am. This was not meant to be an invitation to healthy people to debate the merits of my diagnosis. I don't think healthy people can really understand this illness. It takes an immense amount of research and dedication to wrap your head around what's really going on. I gave up everything in my life to focus on studying my illness for over a decade. I'm talking 80-100 hour weeks for years and years. It just doesn't make sense to argue with people who haven't put in a similar amount of time and effort.

wavepruner, what exactly are you using for chealation? Please mention things like where you are getting your treatment, and how many sessions did it take to show positive results.

I specifically follow Andrew Hall Cutler's frequent low-dose chelation protocol.

This is all done in 3-10 day rounds. I started with 1mg DMPS every 8 hours and saw rapid improvement of many symptoms within a few rounds. I worked my way up to 10mg DMPS and added ALA every 3 hours currently at 1mg.

I take many supplements which facilitate healing. It is unlikely that one would see rapid improvement without a proper supplement regimen.

I'm currently using 3mg DMSA only due to DMPS supply issues. I get many side-effects from DMSA so progress has slowed recently.

I've completed 37 rounds and have been chelating for just over a year. I know several people who are claiming near 100% remission of their symptoms after 2-6 years of chelation.

ALA is easy to obtain as it is regulated as a supplement. It is very dangerous to take in the doses normally sold if you are mercury toxic. DMPS/DMSA are prescription only, but is easy to get.

There is another product that I am going to try soon. They make dramatic marketing claims which makes me suspicious, but the science behind it is compelling once you dig past all the bullshit. It is called TRS annd is manufactured by Coseva.

Feel free to write me at jbob286 (aat) gmail if you have questions. I can point you to a bunch of free resources.

Belatedly, FWIW, I guessed dental fillings.

I had mine replaced ages ago. Haven't considered testing my mercury levels. Maybe I should.

I had aplastic anemia as a kid, cause unknown, treated with a bone marrow transplant (before they had means to isolate stem cells).

Yea I've talked to hundreds of people who have had success with removing amalgam fillings. This was not my issue though.

I posted above about a test you can do. Feel free to write me at jbob286 (aat) gmail if you'd like more info. I can point you to a bunch of free resources that can help guide you through the process.

I'd love to know what the source was! It might help my kids someday.

Thanks for the paper link. I read the paper and it's really a semiconductor sensor engineering paper, not a biology paper. The paper seems very preliminary; it shows that CFS and non-CFS sample have widely different impedances under osmotic stress, but the mechanism behind this is entirely hand-waving.

If I'm reading the paper correctly, the samples were peripheral blood mononuclear cells (i.e. lots of different cell types) in their own plasma. It would be nice to have samples that weren't so heterogeneous, since it's unclear what type of cell is causing the effect, or if it is something in the plasma.

It would be nice if the paper gave the actual measured resistances, rather than % deviation from normalized impedance which is an unusual unit. The paper's use of machine learning seems entirely pointless, basically drawing the obvious line between the two sets of points.

The discussion section didn't seem to have anything concrete. It reminded me of a patent application where you try to list everything that might possibly turn out to be vaguely related.

I apologize for the negativity; the paper's result is very exciting so I hope it pans out, but I found the paper itself disappointing.

The use of machine learning needs to be explained. I’m half expecting it to boil down to “we evolved the neural nets until it perfectly separated the two groups” — overfitting “learning”.

Why does it need to be explained if the test can be proven to be extensible? Asprin worked for nearly 100 years before anyone had any clue how (ditto with many, many more modern drugs).

I also had that impression at first but it seems that they are just using Support Vector Machines to draw the separating boundary between the two group of points.

If you look at the graphs by eye, there is an extremely obvious divide. SVM just let them find it automatically, but if you gave a human those graphs, they could instantly point out where the line is.

> samples were peripheral blood mononuclear cells

Yeah, I was expecting to see flow cytometric cell sorting (1) for monocytes on CD14 and CD64 (2), which I would believe to be monocytes.

The "sample preparation" procedure they describe (3) is ... somewhat lacking in specificity. They pelletized the sample three times. I'm not even sure those cells are intact, and, mechanistically, the sample no doubts includes granulocytes, lymphocytes, and monos, so who knows what's going on there.

(1) https://www.labome.com/method/Flow-Cytometry-and-Cell-Sortin...

(2) https://www.ncbi.nlm.nih.gov/pubmed/9844593

(3) https://www.pnas.org/content/pnas/suppl/2019/04/25/190127411...

This is less a criticism of the paper than it is a statement of misaligned expectations.

> but the mechanism behind this is entirely hand-waving.

The objective of this paper was not to specify, or even attempt to specify, the mechanism.

> The paper's use of machine learning seems entirely pointless, basically drawing the obvious line between the two sets of points.

Yeah, that is pretty much the entire objective of SVMs.

> Yeah, that is pretty much the entire objective of SVMs.

Which is hard to do by hand in many dimensions but almost trivial in 2. I haven't read the paper but maybe the OP is complaining about something like that?

Yes, the data is essentially 1-dimensional and looks like "CCC MMMMMMMM". (Seriously, look at Figure 2 graph H in the paper.) It seems entirely gratuitous to use machine learning to build a SVM classifier to separate the C's from the M's, when it's obvious that the C's are on the left and the M's on the right.

Perhaps the use of machine learning helped to acquire funding, or enabled the researchers to acquire skills for future projects.

To me different impedances implies different electrolyte concentrations. That's my EE perspective, at least.

I’m also very interested in seeing how strong the effect is when tested on mild and moderately ill patients. I hope they follow up with that. (The study group OMF have been using has been 20 severely sick patients, which is a good plate to start.)

From the paper:

Of the 20 ME/CFS patients studied, 5 were severely ill and 15 were moderately affected by their condition

Oh! That’s good news. (I’ve been following the OMFs work for a while now and somewhere along the way I got it into my head they were all severely ill.)

I have to agree with you here - the separation is too good. You just never get anything in the real world that works this well with complex diseases.

This is true, but everything is complex only up to the point when you begin to understand it. Scurvy was a complex disease until the discovery that it was cured and prevented by citrus fruit(1). Now we have the technology to skip right to the discovery of vitamin C, a miraculous 100% accurate test for scurvy.

I know I'm oversimplifying, but I think the point is valid. This is why discovery of a biomarker is so crucial -- it begins to "decomplexify" the disease so we can properly define it and start to find treatments for it.

(1) Ok, it's never really that simple: http://mentalfloss.com/article/24149/how-scurvy-was-cured-th...

Maybe link to the original blog article [1], your link is just a summary.

[1] http://idlewords.com/2010/03/scott_and_scurvy.htm

Thanks -- I just copied the first link I found in a search engine.

It is suspicious but look at the scatterplots: https://www.pnas.org/content/pnas/early/2019/04/24/190127411... It really is pretty much perfect separation on their metric. When the effect size is that large...

One thing that would be interesting to investigate in the future would be to see how the test behaves for CFS patients who are not as severely ill, or for non-CFS patients that are currently ill from a different disease.

Exacly, just sorting it would show it better, it feels like it should just output percentage with (arbitrary/based on population %age/whatever) threshold that is outside of the test.

AIDS was once considered a very complex disease, but it has a very accurate (HIV) test today. My big concern would be if, like cancer, there are really many diseases and Chronic Fatigue symptoms are common, not differentiating.

That could still be very interesting. Eg. There are some other illnesses like MS where patients can get fatigued in a similar way to CFS, but not always. If we find a similar response between the fatigued and non fatigued MS patients for example, that could still point to something that is going on causing the fatigue in both cases. Ron Davis’s line on this was to point out having one disease doesn’t mean you can’t have any others.

There are a lot of other interesting overlaps showing up. One of the more interesting to me (because I have it) is that about 40% of CFS patients are testing positive for small fiber polyneuropathy on punch biopsies that appear to be autoimmune in origin. Is that itself an underlying cause of some 40% of CFS cases or is it just a common comorbid condition that whatever triggers CFS also triggers?

I've done a lot of reading on CFS and fibromyalgia, and this has been my opinion too.

For starters, these are both diagnosis of exclusion; these labels are also used by lazy doctors who lack a deeper understanding of their field (anecdotally, both personal and otherwise), or who are reluctant to run expensive tests for rarer conditions; and many people with these conditions have been found to have small fiber neuropathy.

AIDS, like CFS, was never considered a disease in the medical sense. They both are called “syndrome”, which is medical short-hand for “interesting enough to study further, but frankly, we don’t know shit about what’s causing this”.

https://en.wikipedia.org/wiki/Syndrome: ”A syndrome is a set of medical signs and symptoms that are correlated with each other and, often, with a particular disease or disorder.”

That’s why AIDS became “HIV infection” when medical science discovered what caused AIDS.

If this research gets confirmed, and a mechanism is found, that will happen here, too.

However, as you say, if that happens, there’s a good chance there are people currently diagnosed with CFS who don’t show this biomarker.

If so, those people run the risk of getting stigmatized even more than current CFS sufferers do.

The real solution to that problem, I think, would be for the world to accept that, if you have a mental problem, a) that doesn’t imply you put it there, and b) it doesn’t imply you should be able to get it out without outside help.

Only a few centuries ago, people were being blamed of being “unfaithful to god” when they got sick, be it due to a bacterial infection or due to mental illness. I see blaming people for their mental problems as a remnant of that.

On the other hand, there are times when blaming people for their misfortune is appropriate, and serves a social purpose. The hard part is telling when it is appropriate. It does seem pretty clear though that we tend to both give ourselves too much credit for our successes, and too much blame for our failures, overall.

My impression is that people give themselves the credit for their successes, and blame somebody else for their failures.

My successes are due to my moral worth, and others' failures are due to their moral failings.

Who care is the separation is "too good." It's a lead. This is what science is. You find leads and followup on them. Lots of dead ends in the process.

You should care if it “too good” because it could be a sign of overfitting or tampering with data during analysis to reach a desired conclusion. Replication should shed some light here.

Of course skepticism is warranted however an important distinction to make is that they are measuring a whole cell phenotype, rather than some surrogate such as gene expression or a circulating molecule. I work on cancer biomarkers, and phenotypic readouts work much better than you might expect.

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