Outsourcing the "Something in the Blood?"

[sebaaa]

In light of the recent observations from Ron Davis and Dr. Prusty about "something in the blood," which causes excess mitochondrial fission, I was thinking if there's a way to outsource the work of isolating this substance, which could be a lot faster and cheaper than waiting for him to publish the research.

@nandixon had an idea on how to do this since she worked as a medicinal chemist, and she also had a hypothesis on what the "something in the blood" could be. I tried to contact her about it, but she hasn't been on the forums since last October now. Here's the quote:

They're not extremely difficult to isolate [EVs]. Note that there's no need to have a pure exosome isolate initially. A crude isolate (e.g., from ultracentrifugation) is good enough for the initial purposes of (1) simply seeing if a generic isolation procedure for exosomes yields a positive result for the "something in the blood" in the nanoneedle - they should have this information already(!), and (2) fractionating the crude exosome contents using liquid chromatography methods to see if the "something in the blood" happens to be in the cargo of the exosome.

. . . I think I understand the challenge pretty well. I probably spent at least 20% of my time as a research medicinal chemist using very similar or identical chromatographic techniques to what they'll need to use.

It may be best just to farm the isolation out to some other group that has experience doing that. (The pdf file that I attached earlier for the especially fast and simple exosome isolation procedure was from a group who was doing the same thing for sarcoidosis.)

Does anyone, especially someone from a research background, know if it's possible to outsource finding the "something in the blood" to researchers that have experience in isolating natural substances or maybe an undergraduate, and do it cheaply? Is this possible at all? Are there independent labs that take this kind of commission work assuming that they have have the right equipment?

 

[godlovesatrier]

But without a study that backs up the evidence of even a handful of samples, that are done outside (potentially) of rigirous laboratory processes and procedures, how would that help us all?

There could also be issues with outsourcing around the problem of controlling the work done. So even though you might trust a group renowned for doing it to do it "correctly", that lab group might do it differently to another lab group.

I like your thinking though assuming it returned good results.

 

[sebaaa]

It's not about being a replacement for actual science. It's about finding what that "factor" is, and then inhibiting the "factor." This is a fast way to test the hypothesis that this is what's causing the symptoms in ME/CFS. If mitochondrial fission is what's causing the symptoms, and the "something in the blood" causes mitochondrial fission then inhibiting that could lead to a cure.

The thing is... it's already been found. According to Prusty, he's already found what it is so unless he lied, other researchers should be able to find it with the techniques I outlined. We also know the size of it. It's the size of an exosome, which narrows it down a bit.

 

[wigglethemouse]

@sebaaa This is what I found before in relation to Stanford.
https://forums.phoenixrising.me/threads/research-re-exosomes-and-me-csf.75840/page-2#post-2195837

 

[godlovesatrier]

You can't blame me for being sceptical. Everyone on this forum wants a biomarker and a cure. Me no less than anyone else.

I missed the bit where he said he had detected it. If so that's really fascinating. So when you say outsourcing do you mean outside the study work or outsource the testing so anyone can access It? I assume you mean the former?

 

[Wishful]

I'm surprised that the 'something' hasn't been identified yet. It seems simple in principle: use filters and fractionation to separate the components in the sample, then test them to see which fraction triggers the cell change, until you focus down to the specific molecule. If these techniques aren't common to most labs, then send it to a specialist. I hope that it's not just politics (who gets credit) slowing the process down.

Once the molecule (or several candidates) has been identified, then the more rigorous process of proving it can begin. You can't start the lengthy proof process until you know what you are trying to prove.

 

[wigglethemouse]

Once the molecule (or several candidates) has been identified, then the more rigorous process of proving it can begin. You can't start the lengthy proof process until you know what you are trying to prove.

Well said. One spanner in the works with the Stanford nanoneedle test is that the nanoneedle paper described needing fresh blood.

 

[wigglethemouse]

Come to think of it, at the Stanford Symposium last year they presented the red blood cell diagnostic work. The paper they published used fresh blood + plasma and found some differences, the follow-up work removed the plasma and stored the red blood cells for later measurement and could not find a difference.

This is another example of when you remove things from the samples, other effects can come into play.

 

[percyval577]

Does anyone, especially someone from a research background, know if it's possible to outsource finding the "something in the blood" to researchers that have experience in isolating natural substances or maybe an undergraduate, and do it cheaply? Is this possible at all? Are there independent labs that take this kind of commission work assuming that they have have the right equipment?

This is a nice idea. I would think though that you need good luck to find a lab or other researcher who were especially firm in this.

I think the particular problem is that you need to make the molecule visible, so you need a procedure to identify it. And here I think - but I am not an expert - that the success depends also on good luck, and no lab or no other researcher has automatically the right approach. And therefore an outsourcing will be very difficult to appear with much sense.

 

[Wishful]

And therefore an outsourcing will be very difficult to appear with much sense.

To me it seems like this technique--isolating components via fractionation--is something that depends on experience and talent. It's somewhat of an art form, and there are amateurs and there are great masters. I wouldn't be surprised if there was a lab that specialized in this work, which could do it far faster with far greater chances of success than a lab that just bought a new fractionation tool and is just starting to read through the instruction manual.

 

[sebaaa]

I missed the bit where he said he had detected it. If so that's really fascinating. So when you say outsourcing do you mean outside the study work or outsource the testing so anyone can access It? I assume you mean the former?

Yeah, I think he mentioned it in a tweet about "transferable factors." He also told me that in an email. I'm not sure what you mean with your question. Essentially, just pay someone, e.g. undergraduate or lab, to find the "factor," and then release the information to everyone.

I hope that it's not just politics (who gets credit) slowing the process down.

Unfortunately, I think that's exactly what the problem is, and probably the coronavirus too. Prusty wants to be the one that finds it, which is fine I guess but it's definitely not the fastest approach due to research taking such a long time.

Well said. One spanner in the works with the Stanford nanoneedle test is that the nanoneedle paper described needing fresh blood.

I don't think that's necessarily a problem in regards to finding what the "factor" is. All you need is 1 patient to get the plasma from them, and they should have an abundance of patients.

I wouldn't be surprised if there was a lab that specialized in this work, which could do it far faster with far greater chances of success than a lab that just bought a new fractionation tool and is just starting to read through the instruction manual.

Then, the problem is finding this lab and knowing how much this costs. Depending on what it costs there's possibly a lot that can be done.

 

[junkcrap50]

Unfortunately, I think that's exactly what the problem is, and probably the coronavirus too. Prusty wants to be the one that finds it, which is fine I guess but it's definitely not the fastest approach due to research taking such a long time.

Researchers like Prusty have such a strong incentive to do so. I mean, him finding it could make his entire career: tenure, American university job, huge funding, own lab/institute, world recognition & credibility, etc. Someone like Ron Davis who has nothing left to prove and at the end of his career should be more willing to let other get credit.

 

[wigglethemouse]

Unfortunately, I think that's exactly what the problem is, and probably the coronavirus too. Prusty wants to be the one that finds it, which is fine I guess but it's definitely not the fastest approach due to research taking such a long time.

Well he is collaborating with Naviaux who has access to some pretty good metabolomics equipment, and the collaboration allows them to submit a grant application to NIH which he couldn't do on his own. Naviaux is also an experienced mitochondria researcher who has some background in virus work so would seem to be a good fit.

 

[raghav]

Vast majority of the researchers are using ME/CFS as a platform for their career growth. We cant blame them. They dont know what it is like to have the fatigue and pain of this disease. Why would they want to kill the goose that lays the golden egg ?

 

[Rufous McKinney]

Vast majority of the researchers are using ME/CFS as a platform for their career growth. We cant blame them. They dont know what it is like to have the fatigue and pain of this disease. Why would they want to kill the goose that lays the golden egg ?

Money makes the world go round. Repeat.

We should be so lucky as to have a whole PILE of outstanding researchers using ME CFS to grow a career.

Wonder how many cardio, and cancer doctors, there are?

There are so many complex autoimmune or neurological type issues- if somebody solves ME, well feel free to work on the next mess out there.

 

[raghav]

Money makes the world go round. Repeat.

We should be so lucky as to have a whole PILE of outstanding researchers using ME CFS to grow a career.

Wonder how many cardio, and cancer doctors, there are?

There are so many complex autoimmune or neurological type issues- if somebody solves ME, well feel free to work on the next mess out there.

The only problem is they dont want it to end at least till their careers are over and the loop loops.

 

[Rufous McKinney]

Vast majority of the researchers are using ME/CFS as a platform for their career growth.

Like example- here is just one random Oncology center in the state of Ohio:

This high-tech cancer center employs more than 200 oncologists, each of whom specializes in just one type of cancer.

Imagine it! That WE HAD 200 specialists in just one hospital in just one state that each specialised in- our lifetime Sentence.

 

[Rufous McKinney]

The only problem is they dont want it to end at least till their careers are over and the loop loops.

Its also pretty common that each thing one discoveres leads to yet another thing...and there is not end to it.

Cancer- has lots of treatments. AIDs has lots of treatments. There are still: many specialzing in it. Maybe just to collect a check.

My husbands life was saved by a surgeon. Sign on His Wall: Cut and Cure.

Our problem- we don't know what to cut out.

 

[sebaaa]

Vast majority of the researchers are using ME/CFS as a platform for their career growth. We cant blame them. They dont know what it is like to have the fatigue and pain of this disease. Why would they want to kill the goose that lays the golden egg ?

You could say that about every disease that hasn't been solved yet. It's also not as easy as just getting the golden egg immediately. We know what happened with Dr. Lipkin. But I generally agree. Urgency is sorely lacking in this field. It's not like HIV/AIDS or cancer where the patient will die so you MUST find a cure as fast as possible.

 

[godlovesatrier]

Urgency is severely lacking. Don't forget Ron Davis' 5 funding applications all got refused last week. He's trying to get money from every angle but it isn't working. We should all start a lottery syndicate so we can give 90% of the pot to OMF or like researchers. I do wish there was a way to fundraise more money for people like Prusty and OMF though, if there was a way we would start getting somewhere I think.