Video Update with Prof. Ron Davis April 2019

[Ben H]

Hi guys,

It's been a long time coming but I very recently did a video with Ron that talks about a number of things, hopefully you'll find it interesting.

Huge thanks to @Janet Dafoe (Rose49) and Ashley for helping with this and making it possible, and Ron himself. It was so last minute but I think we did okay.

Here is the video for you,

Hopefully you can watch it or listen to it,


B

 

[Hopeful1976]

Thank you. So much. Ron, you are an amazing hero to me. I know, despite my moments of hopelessness and fear, that you are doing everything you possibly can for us. I hope all your efforts come to fruition soon. You are truly an angel.

 

[Moof]

Thanks you, @Ben H, and thanks to Dr Davis for taking the time to do this. Some really interesting thoughts and news here.

The sweating thing really made me laugh, though...if they need sweaty ME people, women over 50 can produce gallons of it with no effort whatsoever!!

 

[MEPatient345]

Thanks @Ben H.. v interesting.
Ron didn’t mention any work being started at the Harvard center.. am really interested in hearing if they are up and running yet. Maybe during your next chat you can ask that.

 

[bertiedog]

Thanks to Ben and Ron plus Janet for keeping us updated and giving us all some much needed hope.

Pam

 

[Ben H]

Thanks @Ben H.. v interesting.
Ron didn’t mention any work being started at the Harvard center.. am really interested in hearing if they are up and running yet. Maybe during your next chat you can ask that.

Hey @Silencio

Yeah, afaik it is up and running for sure, but regarding current projects I am not so sure. Perhaps @Janet Dafoe (Rose49) could get an answer from Ron on this if possible.


B

 

[sb4]

@Ben H Really enjoyed this, would be great to see more, if Ron is willing of course.

I will say this about sweating. I think it is mostly due to autonomic dsyfunction so I am not so sure about low activity levels being the cause. I previously tried getting as much sun as possible which meant being all day outside in summer. My body was baking, all my symptoms flared, I felt like I was cooking, yet no sweat. This is reported with others with autonomic dysfunction as well.

 

[TreePerson]

Anyone know what “a particle” is? What would be examples of particles in the blood? Is this the exosome?

 

[msf]

Anyone know what “a particle” is? What would be examples of particles in the blood? Is this the exosome?

Spoiler alert:

It is LPS.

 

[Murph]

One way to handle long videos is to get the transcript, which youtube provides. First open the video in a separate window or tab. Then click on the gear-wheel at the bottom right of the video and select subtitles.

Then click on the three dots below the video and select open transcript. It is computer generated so it makes mistakes and it fails to differentiate between the speakers, but it is still useful. It looks like this:

Spoiler: transcript: warning. Long.

00:00

I probably should preface this but

00:02

everyone this is this is about the most

00:05

ad-hoc random Skype I think we both have

00:10

ever had isn't it and you've been

00:13

incredibly gracious to let me have some

00:15

time with you to talk about various

00:18

things so thank you for doing that

00:23

so yeah

00:25

basically it was just a catch it really

00:27

has been a long time since we've spoken

00:30

like this in terms of giving some people

00:35

and the community an update so I was

00:38

hoping if I could ask you to a few

00:40

questions and you can just go wild with

00:44

them wrong whatever comes to your mind

00:46

you say so one of the western front of

00:51

the the the biggest pieces of news that

00:54

I know that people are kind of stoked

00:56

about is the new CER see the

00:59

collaborative research center with Jonas

01:02

Bergquist that I think is at Uppsala

01:04

University I probably pronounced that

01:06

wrong I don't know if you could just

01:10

give a little overview of that for

01:13

people in terms of how that will

01:15

integrate with Stanford and Harvard and

01:19

various things well he has a very nice

01:23

facility with a lot of high-end

01:25

equipment and one of the particular

01:30

values of using him is that he does a

01:34

lot of spinal tap on patients and he's

01:36

very good at it that's that's a concern

01:43

with some of the patients with how you

01:44

do a spinal tap because sometimes they

01:47

have a lot of pain with that and he says

01:50

that he if he does it in a good way that

01:52

doesn't have much pain in fact he said

01:56

the patients would have it brother have

01:58

a spinal tap than a standard blood draw

02:01

and turned a level of pain so puts into

02:04

perspective and and he does have access

02:09

to MA CFS patients he's done a number of

02:12

experiments

02:13

sort of funded by the open medicine

02:17

foundation looking for antibodies but I

02:21

think it would be a good collaboration

02:23

especially when we wouldn't like to do

02:25

something with the spine of blood right

02:29

now that's sort of his area we can

02:32

certainly expand that and also it's

02:36

useful to have a validation sometimes

02:41

when you find something you think is

02:43

really very important you want to make

02:46

sure that it's reproducible in a

02:48

different laboratory so that's another

02:50

place that we will use him as facilities

02:54

are pretty much alike what we have so

02:58

really really top-end essentially yes

03:02

and we've been talking about maybe doing

03:04

some kinds of trials with canary Neen

03:08

injected into the spinal hood

03:17

they're doing similar experiments like

03:19

that with in a clinical trial for a

03:23

different disease which I don't think I

03:26

should talk about because it may be

03:27

confidential

03:29

but things of that type with what we

03:33

would like him to work on and we may

03:38

have been trying to validate what we

03:39

find in the metabolic trap and see if he

03:44

finds the same thing with his patients

03:47

always worried about different artifacts

03:50

or equipment malfunctions or all sorts

03:52

of problems and you don't want to get

03:57

led onto the wrong in the wrong

03:59

direction because of the instrumentation

04:03

problems yeah yeah I remember you

04:07

mentioning that before I think in our

04:09

last chart or in our update about the

04:11

the issues with I think it was mass

04:14

spectrometry yeah well it's a the amount

04:19

of tryptophan in generating in the cells

04:22

is not very high and the other major

04:26

problem is

04:28

there aren't very many cells that

04:30

actually have the Canadian pathway on

04:34

helpfully about 1% so that all reduces

04:39

the signal and I don't know if he has

04:44

the state-of-the-art mass spectrometers

04:46

there that have a high sensitivity or

04:47

not but that would be what we would

04:51

explore and also tell him what we have

04:54

concluded him how to do the experiment

04:57

and see if he concurs where he may

04:59

decide to try it in a different way yes

05:03

that's really interesting actually

05:05

because I think a lot of people have or

05:08

maybe it's just me but have associated

05:11

Jonas with kind of immunology and and

05:20

and the spinal tap stuff before just

05:26

from from what he's been talking about

05:27

at the conferences right now but that's

05:32

really interesting actually to know that

05:36

he may be testing or it may be a plan to

05:39

test kind of any injected injected into

05:44

the spinal fluid I know these ideas all

05:48

kind of integrate you know metabolic in

05:51

not immunological and stuff but yeah

05:55

that's I think that's probably something

05:58

a lot of people didn't know so that's

06:02

really yeah really good to know well

06:06

it's all focused on trying to understand

06:08

what's really happening in this disease

06:11

and and also how we might launch elate

06:15

it in some way or other yes what you'd

06:18

like to have is the primary cause and of

06:21

course that's always very difficult to

06:22

be sure that you're you're actually in

06:24

the primary cause there are you on a

06:26

side track about some effect of the

06:28

disease

06:33

now that's us really good um really

06:36

interesting I think a lot of people will

06:40

be very interested enough sure that kind

06:44

of kind of brings me on to just another

06:48

point which was the metabolic trap

06:51

itself whether there was any news I know

06:54

obviously there's some news that you've

06:56

just spoken about we've Jonas but

07:00

whether there's any update to the mass

07:05

spectrometry problems that you can give

07:08

out all well we've been looking at the

07:11

error analysis you know what is this

07:13

what is the standard error and our

07:16

measurements and it's pretty high and

07:19

that's making us a little bit concerned

07:22

and I think we need to have a more

07:26

accurate determination and problems are

07:29

the sensitivity the mass spectrometer

07:31

the number of cells that have the

07:34

pathway and then another problem that we

07:37

are we realized is that the we have to

07:40

do an incubation in media we use equals

07:43

media that's classic and we didn't

07:47

realize at the time but eagles media has

07:49

25 milligrams per minute Tripta thing

07:53

and that dilutes our label and plasma

08:01

only has 5 milligrams per mil so I don't

08:05

exactly trip Eagles media was made

08:08

developed back in the 1950s so they

08:11

probably even didn't even know how much

08:13

tryptophane was in the plasma but it

08:16

worries us that we're putting in pretty

08:18

high trip today so we have found some

08:22

eagles media without tryptophane and so

08:27

we're now using that so that we can

08:30

control the amount of tryptophan that's

08:32

cells are incubated in and we can

08:35

increase the amount of label percent of

08:38

the label and that should give us

08:40

something about an increase in signal

08:44

but most unlike Schneider has let us use

08:46

his very high-end mass spectrometer he

08:51

has actually three of them and so and

08:56

the postdoc that's running it is excited

08:59

about this project so he will pitch in

09:01

and helping us now then that's good

09:04

that's more work force and he's very

09:07

experienced in it so now we have two

09:10

very experienced mass spectrometers

09:12

people so we carried out that experiment

09:18

all the way through with it changed in

09:20

the media we enriched for the dendritic

09:24

cells by pulling out the T cells and B

09:27

cells and not including them we still

09:31

use the same number of cells so that

09:33

enriches for the antigen presenting

09:36

cells that are in the wet sample and

09:40

then that went into the higher

09:42

sensitivity mass spectrometer so all

09:45

combined that increases the signal about

09:48

a hundredfold I think it's a lot learner

09:52

that's going to be a lot more accurate

09:54

and but we run one patient so far under

09:58

these conditions and that we get the

10:00

same kind of increase in tryptophane and

10:03

reduction and contain over healthy

10:05

control okay so but now but we have

10:10

samples already collected from patients

10:13

and I think enough that we can run I

10:16

think on Friday they were four samples

10:20

ready to go into the mass spectrometer

10:23

[Music]

10:25

Julie has set aside as the cells are

10:27

frozen and then we can pull them out and

10:29

and use them so hopefully that will go

10:33

quickly we're hopeful to get quite a few

10:36

cells and healthy control a patient and

10:38

healthy control samples in the next

10:40

couple of weeks and that's be a much

10:44

more rigorous test of the hypothesis one

10:49

of the considerations and complexities

10:51

of this is that this trap is presumably

10:55

a cellular based process

10:57

so it could happen in one cell and or

11:00

not in another

11:02

and once it's trapped it that cell is

11:05

trapped it's also possible to curse you

11:08

the stem cells that are producing the

11:10

immune cells could be trapped and then

11:12

all cells generated from that stem cell

11:14

would be continued to be trapped

11:17

these are these of this whole thing that

11:20

we don't totally understand and so those

11:24

are also have to get some some

11:26

explorations of that we would like to

11:30

try to start some cell culture

11:35

experiments and that may be done by

11:38

making stem cells and then generating

11:42

the right side sub cells from those stem

11:44

cells but that requires an expert in

11:47

that field we have to find one and there

11:50

is a collaboration on this project over

11:53

recruit somebody that you do to the

11:56

center to do that I think that's it

11:59

that's a really important no actually

12:01

isn't it that that comes up time and

12:03

time again is that so much of this is

12:06

cutting-edge research and it requires

12:10

almost new tests to be made or tests

12:13

that haven't been run before correct and

12:16

people in very specialist fields to be

12:21

brought along onto the team which isn't

12:23

a particularly necessarily a quick

12:25

process yeah and it seems like

12:27

everything that we do has never been

12:28

done before so it's always yeah but no

12:35

that's fascinating and yeah give some

12:40

cell culture and we can reproduce them

12:42

we can actually create you know

12:45

effectively create the disease that good

12:48

cells that aren't trapped and get them

12:49

trapped that when maybe allow us to set

12:54

up a sample of you know a modeling

12:56

system that would allow us to see how we

12:59

could get them out of the trap yes

13:02

because all the ideas that we have

13:06

currently and the modeling all comes

13:08

from measurements that were made years

13:10

ago

13:11

and it's always a possibility it's

13:13

something isn't quite correct and all

13:16

that it's always important to check

13:19

everything yeah yeah so yeah that makes

13:25

a lot of sense I think that's um yeah

13:29

there's a lot of clarity with that one

13:33

one thing that gets mentioned obviously

13:36

being on the forums and and talking to

13:41

patients and seeing things that are

13:44

brought up one thing that I do know gets

13:45

a lot of attention is the impedance

13:49

device so obviously the the fact that

13:54

healthy cells cells from healthy

13:58

controls or as healthy as controls as

14:01

one can get with Emmy Bloods show a

14:06

certain impedance signal similar to Emmy

14:10

cells with Emmy patients serum hopefully

14:16

I've got that right and my brain fog

14:17

isn't confused but um and yeah I don't

14:23

know if you can kind of ELISA date on

14:27

how how that's going if there's any

14:31

progress in terms of filtration if

14:34

there's molecule or molecules that have

14:37

been found or basically just what just

14:41

what the progress is on that really if

14:43

there has been any since because it's so

14:47

it's such a dramatic thing isn't it went

14:49

to see that you know healthy healthy

14:52

patients cells get seem to be having a

14:58

very severe response to any patients

15:01

blood it's quite a yes

15:02

rounding really and gets a lot of people

15:06

excited so I don't know if you can talk

15:09

a little bit about that if there's if

15:11

that you know the current state well one

15:13

thing is that we've written up the

15:15

current status of it simply because we

15:18

had a very good statistic

15:21

the probability that it's this this

15:26

difference could occur by chance was one

15:30

chance in a million so that's was

15:33

sufficient to try to do a publication

15:37

and that has been renewed by an engineer

15:41

about the circuitry and the design and

15:44

it's reviewed by a medical person that

15:48

does diagnostic testing so they made

15:51

some suggestions we made those

15:53

Corrections the paper is going to

15:55

Proceedings of the National Academy of

15:56

Science

15:58

I think it's passed the review it's now

16:01

at the editor but we think it's all good

16:07

to go and it will be out soon so we have

16:15

done quite a few experiments trying to

16:17

figure out what it is

16:19

we've done some filtrations

16:22

and it's large but now it appears that

16:27

it's quite large and it's it's possible

16:30

in some kind of particle and of course

16:34

this could be mixed with you know some

16:36

all small molecules contributing and and

16:39

so forth it's what we're looking for is

16:44

the thing that causes the biggest effect

16:47

yeah it could be a particle and so

16:50

that's necessarily where that is

16:52

the moment trying to figure what that

16:54

particle might be we might take the try

17:00

to purify that particle better and then

17:04

break it apart and and either do a mass

17:09

spec analysis of it or some other kind

17:12

of analysis you see what's it what what

17:14

is in the particle and that might give

17:15

us a good clue yes but an the biggest

17:20

interest is really to try to see if we

17:22

can find some drugs that might abolish

17:26

the that signal it's not necessarily a

17:30

cure or even a treatment but it's

17:32

possible and it would be worthwhile

17:35

what kind of compounds can kind of

17:37

reduce the signal yeah so that's an

17:42

effort that we all make and but to do

17:46

that we really need to change the

17:48

circuitry so that we can screen the

17:51

amount of blood that we require for this

17:54

is about one drop so a blood drop can do

17:58

many many essays independent circuits

18:02

before that and there isn't a there

18:05

isn't a commercial device that will do

18:07

that so we have to design it and build

18:10

it and so that's sort of where that's ad

18:13

and the a research associate that was

18:17

working with me Rahim has accepted a job

18:21

at University of California at Irvine

18:23

and they opened electrical engineering

18:26

so that will allow him to bring in new

18:30

students to help him work on the project

18:34

so it represents a bit of an expansion

18:36

of the efforts a lot of stuff will still

18:39

be around here at Stanford because we we

18:42

collect the patient's blood and stuff so

18:45

the the device development and other

18:47

parts of that will happen in Irvine it's

18:50

not that far away she sorts like that

18:55

the biological assays will probably

18:58

continue to run in Stanford yeah I just

19:02

have saved the cost because if he does

19:04

the biological stuff too then he has to

19:05

have a yes this has a set up for

19:08

collecting the blood and a global

19:11

phlebotomist and someone to take charge

19:13

of the patients and it would represent a

19:16

duplication of effort since we do that

19:20

had Stanford in any way yes okay I think

19:24

just maybe one yeah just to make sure

19:26

and I think you already have made made

19:29

it very clear but I think it's it it's

19:32

easy I kind of get pulled into the fore

19:35

as well that it's this whole filtration

19:37

thing is a lot it almost comes across a

19:40

lot more a lot more simpler than it

19:43

actually is it's actually a very complex

19:44

thing to find this molecule or molecules

19:49

I kind of think of it as a kind of

19:52

fishing net and then trying to scoop out

19:54

things but it really isn't quite like

19:56

that right it it's a bit more

19:59

complicated

20:00

but yeah I do know people are very

20:03

interested in in that in particular so

20:07

that's really good to hear some

20:08

clarification on that and the blood flow

20:15

device only been doing a lot of modeling

20:21

of the device to try to help in its

20:24

design I've made a new fabrication

20:27

design this is the red red blood red

20:32

blood cell all right that should maybe

20:36

give us a what we're hoping for is

20:38

something that gives us a bigger a

20:40

bigger distinction if this is going to

20:42

be a diagnostic test then it has this it

20:47

has to separate out all of the patients

20:49

from healthy controls and then of course

20:53

we're setting that up so that when we

20:55

start running other diseases which we

20:58

are getting samples for that now we want

21:03

to look at the different technologies

21:05

and how they differentiate between

21:08

chronic fatigue syndrome and the the

21:11

other diseases but the problem we have

21:15

is that chronic fatigue syndrome is

21:17

initiated by a stressor and having

21:20

another disease is a stressor so it

21:24

raises a problem in the sense that if

21:26

you have MS which is a pretty bad

21:28

disease is it possible that you also

21:31

have chronic fatigue syndrome and that's

21:35

pretty much dismissed by the physicians

21:37

because they even dismiss chronic

21:40

fatigue syndrome from a healthy person

21:42

yes you know but so when I've talked

21:45

with them it's kind of they say well you

21:47

know it's very unlikely they have two

21:49

different diseases at the same time but

21:52

they're kind of similar in many ways and

21:55

and certainly the MS patients had

21:58

fatigue and they say well it's the

22:01

fatigue caused by the MS

22:03

yes so it trying to do this experiment

22:07

and see how other patients behave is a

22:11

little complicated

22:12

yes it's not so complicated if they MS

22:17

patients don't show a signal but it is

22:20

complicated if they do yeah no that

22:24

makes sense because I think a lot of

22:27

people know already but obviously we rub

22:29

red blood cell deform ability isn't

22:32

something found just in you know mecfs

22:36

so far it's being found in you know lots

22:42

of lots of diseases so yeah so they

22:49

they're working simultaneously obviously

22:53

on this device but are they are the team

22:55

looking into ways to possibly with the

23:00

data they've got so far any any drug

23:02

targets or is this a little bit too

23:04

preliminary yeah we haven't sent that up

23:07

we want to we want to change the device

23:09

so that we get a bigger effect on the

23:11

deformability so that the new device is

23:14

smaller the channels are smaller it

23:19

causes the red cells to be stretched out

23:22

a lot more and we need to improve the

23:25

imaging analysis so because we want to

23:30

be the problem is that as your cells

23:32

move through this channel they got there

23:34

pretty fast it if it sort of snares out

23:40

because of the picture isn't taken fast

23:44

enough

23:46

it makes it makes our accuracy low so we

23:50

really have to greatly improve on the on

23:55

the imaging and then we have to make

23:56

sure that that imaging analysis is

23:58

automated in the past it wasn't

24:02

automated and it took hours of effort on

24:04

each sample to get the numbers we also

24:10

wouldn't want to decrease the variance

24:12

and

24:14

one way to do that is to have the seller

24:17

go through multiple constructions then

24:21

measure it multiple times and then take

24:23

the average and then that may taken up

24:27

the distribution and therefore the

24:28

accuracy yeah okay that makes makes a

24:34

lot of sense it's it's coming back to

24:38

this constant theme of being on the

24:42

razor's edge of science again creating

24:44

the I mean I can't really imagine how

24:48

complex the device on that is but yeah

24:52

just to be able to do that it's not

24:53

exactly it's not an established medical

24:56

tool is it so no it's a again kind of

25:02

creating creating all of these things

25:06

for biomarkers which is fascinating but

25:10

um yeah it would be nice if they existed

25:13

already in some ways yeah one of the

25:22

other things that it's very recent is

25:25

the board members so obviously there's

25:27

been a few new board members I think

25:30

there's hopefully pronounce their names

25:33

right there's Jennifer Frankovich Daniel

25:36

Peterson who's an MD I think Jennifer

25:40

Frank which is an MD as well and then

25:42

yeah she is and then Michael Schneider

25:47

who I think he's obviously a PhD but I

25:50

think people will recognize his name

25:52

somewhat from prior talks you know big

25:59

data analysis and other and looking at

26:01

other diseases he does a fair amount

26:02

with similar kinds of diseases he's also

26:09

interested in chronic fatigue syndrome

26:11

he's thing about and he's been coming to

26:13

our working group meetings and he shows

26:15

a lot of interest and we're using some

26:18

of his facilities so he's in the same

26:20

building that's another advantage so

26:22

we're on the first floor he's on the

26:24

second floor yeah and so and we agreed

26:27

when we moved in

26:28

which air facilities so that we didn't

26:30

have a lot of duplication yes

26:35

sounds sensible I don't know how it

26:38

works but that that sounds very sensible

26:40

I mean in terms of them joining the

26:45

scientific advisory board the reasons

26:48

for them joining it is it obviously it's

26:51

different for each person but I don't

26:53

know if you can

26:53

well the Dan Peterson is a lot of

26:58

experience with the disease you know

27:01

he's not he's in Incline Village area

27:05

yeah

27:07

that's not too far it's a drive and you

27:10

can you don't have to comply if you

27:12

don't want to so it's useful to have him

27:20

because if he's a lot of experience for

27:23

the disease and in fact we've talked

27:25

about a number of projects that we might

27:26

do in collaboration a lot of that is

27:29

with his samples and he's been trying

27:31

lots of things as well so there's a lot

27:35

of opportunity there and also giving his

27:38

vast experience and making suggestions

27:41

of what to try yeah he's quite a

27:45

well-established well very established

27:48

name I would say in the AME community

27:50

from and we had David Bell and that we

27:53

can still connect today of a Bell by

27:55

phone but he's really too frail to

27:58

travel anymore so he really can't come

28:01

to our meetings we can't keep him posted

28:04

but we don't really give him any work to

28:06

do yes so he's sort of a replacement for

28:10

David Bell

28:10

but David bells not off I mean just that

28:13

he really can't help us as much that's a

28:17

shame because yeah yeah David Bell is is

28:21

quite hero and there and very

28:25

knowledgeable and also experienced yeah

28:29

and Jennifer is at Stanford and picked

28:33

her because she knows a lot about

28:35

chronic fatigue syndrome but she also

28:38

works on pans

28:40

there's a lot of similarities and tried

28:44

lots of things and it's also my feeling

28:47

is that we really need to learn from

28:50

other very closely related of the

28:52

diseases and and it may give us an idea

28:56

of how to other types of experimentation

28:58

to do or also possible treatments that

29:03

in the case of pans I think they they

29:07

they discovered it a little bit earlier

29:09

and so she's tried a number of

29:13

treatments that had been successful when

29:16

when the patient hasn't been sick for

29:19

very long okay so they mostly and she

29:23

runs a fan's clinic she has two patients

29:29

we will probably plan to evaluate some

29:33

of those patients but some are

29:34

techniques that we've used done I'm

29:37

gonna miss you first see what the

29:39

similarities and differences are yes it

29:43

s that's kind of similar to ms perhaps I

29:48

may be well off base with that but in

29:50

terms of looking at the similarities

29:51

between fatigue between conditions and

29:54

seeing if there's you know that there

29:58

could be one central player for fatigue

30:00

or you know a certain number of similar

30:03

or the same mechanisms between different

30:06

diseases so we we do plan now to do some

30:13

collecting data on patients with

30:15

fibromyalgia and chronic Lyme and

30:21

but we have to raise money from those

30:23

communities we do not want to use money

30:27

donated by from chronic fatigue syndrome

30:31

patients and caregivers and so forth

30:36

there do research on our different

30:39

disease yes so the financial stuff will

30:44

get compartmentalized

30:47

we do have some donations from chronic

30:50

Lyme so we will do

30:54

we're setting up a collaboration with

30:57

bill Robinson who's also he's an

31:00

otologist so that adds another person

31:02

yeah it's an MD and he gets samples from

31:06

the East Coast there are organisms and

31:10

on the west coast but they're slightly

31:11

different yeah and so we will be using

31:15

samples flowing in from the East Coast

31:18

for chronic Lyme okay and see how that

31:22

compares to the mecfs Duga yeah that's

31:26

very interesting that's pretty good yeah

31:32

very interesting I think it's um I I

31:36

think I'm correct in saying that the

31:39

just to talk about funding very very

31:42

briefly that the CRC the new Research

31:45

Center

31:46

well that was fully funded by our MuRF

31:49

by patient donations I'll tell you which

31:53

one would like that the we've Jonas

31:56

Bergquist a top seller with that funded

31:59

by patient donations for I've gotten

32:02

some patient donations and from Sweden

32:06

and that's all go to him yeah we'll try

32:10

to get more that will then go to him

32:12

yeah but Linda is really Lauren charge

32:19

of all the how much we have been wearing

32:23

we should we we should put it and what's

32:25

gonna come with the Advisory Board

32:27

talking about it yeah yeah that makes

32:32

sense okay I guess this is the last

32:38

question I've taken Mike Schneider so

32:41

although we have shared facility yeah we

32:44

ain't problem should do something

32:46

together so one of the projects we've

32:48

been discussing is trying to develop a

32:51

wearable device like a watch yeah that

32:55

collects data from the patient and we've

32:58

had we both have quite a bit of

33:01

experience in that field with some

33:02

different points of view

33:05

and the goal is really to have a

33:10

measurement so that we know when

33:12

patients have gone to their their limit

33:16

and before they crash tries to try to

33:20

make that make it so they don't crash

33:24

yes so incredibly helpful yes so is that

33:30

something that would measure potentially

33:32

something like lactate or so we could go

33:36

with biochemical that's or kind of

33:38

things that we have done it also be a

33:41

very sensitive vise measuring heart rate

33:43

variability and there probably is a

33:48

signal in in that as well they'd like to

33:52

tell you that there's a there's at a

33:55

level where they're starting to get

33:57

physiological change Mike has had some

34:01

success with that with some other

34:03

diseases and predicting before there's a

34:09

damage it's been done in terms of this

34:13

is just me being really nosey now but is

34:16

that in terms of heart rate variability

34:18

you were talking about then or just

34:19

generally heart rate and a number of

34:25

things you made your temperature and you

34:28

get a change in temperature it's very

34:30

subtle but you have 10 a high accuracy

34:33

for this so most of the devices are not

34:36

attic adequate the Fitbit the Apple

34:40

watch those are not adequate the

34:42

accuracies are not high enough so you

34:45

need much more complex device that

34:48

measures how high accuracy we're going

34:50

to look into the the lock a possibility

34:54

okay that's another possible way to do

34:57

this that would probably be done from

35:01

sweat that's the simplest thing to do we

35:08

could problem there are ways to which

35:09

you can do continuous blood monitoring

35:12

putting a needle most tiny tiny nano

35:15

needle into this under the skin

35:18

yeah but sweat is also very very

35:23

sensitive hasn't been looked at in in

35:26

the patients yet when we can induce

35:30

sweat electrically and so we the part of

35:35

the patient does not have to be

35:36

physically active just to cause the

35:39

sweating this can be done from someone

35:41

who's you know even in bed yes it's not

35:47

painful or anything of that type it's

35:49

just it's a little bulge that can induce

35:52

we've worked out the methods for doing

35:54

them because uh yeah I was gonna say not

36:01

necessarily that relevant but I know

36:03

that a lot of any patients don't seem to

36:05

sweat right like they used to

36:08

don't exercise them well either yes the

36:11

other correlation appears that if you're

36:14

you're in very very good shape you sweat

36:17

one so they not sweating is actually a

36:20

sign that you're not in good physical

36:22

shape yes I did I don't know that that

36:26

is but then we've seen that in are

36:28

trying to do this wedding people sweat a

36:31

very different in the amount of sweat

36:34

which is what made us focused on trying

36:36

to figure out how to electrically

36:38

stimulate the sweating so that they

36:41

didn't require our activity yes

36:44

yeah I think I read a paper very

36:46

recently actually if something about

36:48

some people can very healthy fit people

36:53

can sweat up to two liters a day which

36:55

seems in the obscene amount yes so we're

36:59

we have a device that has been being

37:03

tested out now is to measure their you

37:05

have malice worth is that the amount of

37:08

sweat that could very well be a good

37:11

indicator of physical fitness

37:14

yes yeah I know for myself being being

37:21

bed bound I don't think I've sweated

37:23

properly in about five years

37:26

it's a very very likely yes yeah which

37:30

has its

37:32

and cons I guess but I'd rather be more

37:36

healthy and sweat more okay I won't take

37:41

of it hardly any more of your time I

37:44

hope I just wanted to talk about the

37:47

focus over the next few months so we've

37:49

got the London boy we've got millions

37:52

missing and we've got the London

37:54

conference yes right and then there's a

37:58

conference next week well this week in

38:02

the end of this week at NIH okay that's

38:08

I don't know how broadly that's attended

38:13

by international people but they're

38:14

certainly welcome it's only a two-day

38:17

conference so it's a little bit small

38:20

okay I think it's I think the

38:23

participants is around 300 okay and is

38:27

that for it's that for kind of I mean

38:29

that's that's passed me by that one

38:31

unfortunately I don't know anything

38:33

about Barbara is that basically faked

38:36

for input in terms of just just

38:42

gathering people's input for their own

38:46

studies or is that supposedly they're

38:49

going to do a little bit of their own

38:51

study but I think it's gonna be pretty

38:53

small I thought they were gonna do more

38:56

and that's why I was excited about

38:58

seeing what they were doing but I think

39:00

it's a I think it's a fairly small

39:03

amount okay okay I felt less interesting

39:08

and obviously you you'll be a invest in

39:11

any conference yes the plane - yes

39:16

speaking again like as per usual well

39:20

hopefully we'll have more data on the

39:21

metabolic travel

39:23

yeah which will be exciting okay I guess

39:29

that's about about it really well I

39:34

should probably leave you be and stop

39:38

interrupting your Sunday evening

39:41

afternoon evening thank you for being so

39:45

gracious

39:47

and Janet as well I know this was

39:49

extremely short notice so yeah I'm very

39:54

grateful that you you took the time to

39:57

do it for us well there is one other

39:59

area I could just briefly mention and

40:02

it's it's kind of a new area and that's

40:07

more from looking at sort of an

40:09

environmental engineering perspective

40:11

and we now have a professor that's

40:16

retired at Stanford and environmental

40:19

engineering and he would like to come

40:24

and I think join us just to be part of

40:28

an activity okay and because we're

40:32

seeing things like mercury toxicity and

40:37

the patient's about a third we're also

40:40

seeing uranium and in the patients and

40:44

mostly from California

40:46

we don't know where that's coming from

40:47

or the consequence of that and that

40:53

person will help us maybe with some of

40:55

the mold experiments somebody may be

40:57

wanting to do for some time there's just

40:59

a lot of complexity and exactly what to

41:01

do so the things that we're thinking of

41:05

looking at is of developing DNA probes

41:10

for all the molds if they're in in the

41:15

body similar yeah and then the other one

41:19

is looking for a collaboration where

41:21

they can detect the the mold toxins that

41:25

was something that we wanted to do for

41:28

the severely Arab patients that never

41:33

happened because of the the company that

41:36

was going to do it's just went on a

41:40

business and it's ideal replacement for

41:45

them yeah and there are a number of

41:48

people that are trying to do that and I

41:50

don't we don't have to reinvent the

41:51

wheel if they can find someone who can

41:54

looked over the presence of the taxes

41:56

and the patients

41:58

yeah so just quit just very quickly that

42:01

the I know mercury is quite a big thing

42:03

in the CFS community and so is obviously

42:06

mold but for mercury I presume again the

42:10

this is hair testing isn't it this is

42:13

all hair testing percent we worry about

42:17

the validity of that the value of the

42:18

hair testing is it's pretty painless on

42:22

the patients and patient anywhere in the

42:25

world can send us a hair sample and it

42:28

doesn't have to get refrigerated and put

42:31

it in an envelope and mail it right so

42:34

and it's very simple what we don't know

42:38

for sure is the validity of the hair you

42:42

have to worry about contamination of the

42:45

hair but it's out there and getting

42:47

interest so if you guys something high

42:50

you have to worry about contamination if

42:54

there's contamination with mercury I

42:55

think that's still a problem that means

42:57

a person was exposed to mercury so that

43:00

one doesn't bother us so much but if you

43:01

look at things like copper and tin zinc

43:05

and other metals that might be in the

43:07

environment then we have to be careful

43:11

yeah okay well I believe you be to go

43:18

and hopefully enjoy your afternoon so

43:21

we've had some meetings with Eric with

43:23

Eric Johnson about that and we've

43:25

actually visited him and he's a person

43:28

that will help us the mold I don't want

43:33

to call in the mold guy but the Sun

43:37

comes select appearance and we always

43:40

like to gain the experience from the

43:42

patients sometimes they don't use the

43:45

rain scientific terms sometimes they get

43:47

this understand some of the scientific

43:50

background but you've you listen to them

43:54

and you try to figure out what it is

43:57

that they're experiencing and they take

44:04

them seriously enough that you need to

44:06

if you're going to dismiss it you should

44:08

dismiss it because you can't find any

44:10

evidence scientific it

44:12

and testing that it's there so until you

44:16

do that you have to listen as and there

44:19

very well could be the the the the mold

44:22

toxins the mic effects is that they

44:26

produce are unbelievably powerful and

44:28

very scary

44:29

so the aflatoxin is the most mutagenic

44:36

compound no one and so that there's an

44:41

incredibly powerful and there's a reason

44:43

 

[Murph]

here's the rest:

Spoiler

that they they make these things for

44:45

their own defense yes and they're

44:49

capable making very large numbers of

44:51

things under different circumstances yes

44:54

it's something that I think needs to be

44:57

explored and so far I don't see anybody

44:59

really exploring the molds no I know

45:04

that was Richie shoemaker

45:05

I don't know much about him but I know

45:08

he was one of them old people an MD or

45:14

something like that but I know from from

45:17

reading Julie Remo and various first

45:22

peoples accounts of mold that it's not a

45:24

particularly easy thing at all to get

45:28

rid of no it is not easy to get rid of

45:31

and she's another person that we'd like

45:33

to work with she's been helpful as well

45:34

we just figure out when it's the right

45:37

strategy and what is the right what are

45:39

the right people to do the study and

45:42

it's taken us a while on her knee and

45:44

it's also it's also a financial problem

45:50

all right everything we do if we start

45:52

any project where's the money coming

45:53

from

45:54

yeah find NIH grants because they will

45:58

be awarded until you've actually almost

46:00

finished the project because then then

46:04

they'll know it will work it has to do

46:06

with it isn't the problem with NIH

46:08

particularly it has a problem it's the

46:10

fact that the amount of money that they

46:12

have to fund research is so inadequate

46:15

compared to the research capacity that

46:18

is present in this country and

46:21

[Music]

46:23

when I looked at the research grants I

46:26

would say that probably 90% should be

46:28

funded but their funding at the 10 to

46:30

15% level yeah and they like to say

46:34

their grants said don't get funded

46:36

weren't good grants but I don't think

46:37

that's correct they're all good grants

46:39

yeah that the review committee found

46:42

being in that were tasked with finding

46:45

the best 10 15 percent so it's more of a

46:48

personal choice for the review code then

46:51

it is really hard core of best grants so

46:56

that just makes it difficult to to get

47:02

research funding and be like good ideas

47:05

don't get funded very fertile I know any

47:08

places obviously places the kind of

47:13

emphasis on patient donations and people

47:17

donating to OMF for various

47:19

organizations to help fund this research

47:21

because again like you say na check so I

47:27

we will get the funding at NIH I realize

47:33

it's gonna take a very long time because

47:34

you have a lot already accomplished so

47:39

if we show that that a metabolic trap is

47:41

real then we can probably get grant

47:45

funds to to work on it which but you've

47:49

already done most of the work yeah yeah

47:53

that in fact when you get a grant

47:55

because they will surely be productive

47:58

which is pretty right and so that's one

48:01

of the problems that they're having

48:03

because of the the really lack of

48:05

adequate research dollars at the

48:08

National Institutes of Health overall I

48:10

think it's a problem it will say yeah

48:15

also it appears to me from from when we

48:18

talked before and various things that

48:20

they're not so much interested in

48:23

exploratory research I don't know if

48:27

that's because of funding I don't know

48:29

if that's political or a kind of mixture

48:32

of both but they they don't seem to be

48:34

interested in observational

48:36

kind of studies it's kind of like you

48:39

said it's almost in once something's

48:42

almost kind of proven or well in the

48:45

levels get that low it makes the review

48:48

committees very conservative yeah so you

48:51

have an exploratory grant that hey this

48:53

might make might discover something

48:55

really important or then it won't again

48:59

if this hypothesis testing when they

49:02

have a track record they've you know

49:03

it's been a renewed many many times we

49:06

know they're gonna be productive we have

49:08

to give them the money because we can

49:11

take the chance of funding something

49:12

that doesn't work and it's the

49:15

conservative us of not taking chances or

49:18

doing something new and it happens with

49:20

everybody when you start doing these

49:22

reviews so yeah but it makes research

49:27

progress slow you want to take the big

49:30

leaps yeah and they're very difficult to

49:32

get something big leaps funding anyway

49:35

that's why we are focusing on donations

49:37

because that can come in fast and move

49:40

the research faster yes in the last

49:44

round we put a grant in we're putting a

49:46

grant in in June effect will be two

49:50

grants going in June we're gonna try to

49:53

every every every round we'll try to get

49:56

a grant in yeah and then that that adds

50:01

to the funding that from the from the

50:03

patients but it has to be something that

50:05

we know for sure is actually working so

50:07

the grant that went in the last grant

50:10

Lannon is on the mercury good we know

50:12

that that's that's right it's not a lot

50:14

of patients and we'll focus on on

50:16

collecting more patients and then

50:18

setting up their aspects of that yeah we

50:23

will do some analysis of looking at the

50:25

hair and the blood and then we're also

50:27

wanting to do cellular level because

50:31

it's what is in the cell that makes the

50:33

different how much you know like for

50:34

example Mercury's in the cell makes its

50:37

and if it doesn't get from the blood to

50:40

the cell it doesn't matter that much and

50:45

the hair comes from cells so it has it

50:48

might reflect what's in the cell better

50:50

then the villain does so we have to sort

50:53

all this out and I think the way to do

50:54

that is to look at the hair the cells

50:56

and the blood the same person at the

50:59

same time yeah be the new area that

51:03

we're gonna be exploring yeah

51:06

that's really interesting mercury is

51:09

quite something I've looked into quite a

51:11

lot and it's kind of fraught with

51:14

difficulties especially when you come to

51:17

trying to get the mercury out in someone

51:19

who is quite ill to start with so any

51:25

better any diagnostic better diagnostic

51:29

methods and anything like that will be

51:31

really helpful well that and the Marcus

51:34

could be coming some of it coming from

51:36

old fillings I have all my old fillings

51:39

removed

51:42

you know nothing a lot comes from that

51:45

can my mercury is not very high but it

51:47

sounds from eating fish yes there are

51:50

other other environmental things that

51:52

you can expect get exposed to mercury I

51:54

mean a lot we used to have mercury

51:56

thermometers and yes we have one patient

52:02

I think they're in Europe that broke a

52:06

thermometer in its backpack and took out

52:11

the most of the mercury but continued to

52:12

use the backpack he's very high in

52:17

mercury again this probably came from

52:18

that because yeah suddenly being exposed

52:21

to a little bit of mercury yeah so it's

52:28

interesting with the fish as well

52:29

because obviously fish contains selenium

52:31

and I know that's a compound of it sure

52:34

is sorry a trace mineral which is I

52:38

think quite often found quite low in in

52:41

in patients and I know that it it came

52:44

somewhat combat the oxidant effect of

52:48

the pro rocks is an effect of mercury

52:50

well it's probably that the selenium

52:52

binds the mercury well yeah he's

52:55

actually taking the selenium out yes

52:58

that's probably good that it's about

53:00

binding it helps to sequester the

53:02

mercury yeah

53:04

the low selenium because the selenium is

53:07

used for lots of things and one of them

53:10

is the conversion of t4 to t3 and we

53:12

know that one of the patients are low in

53:14

t3 what we don't know is we don't have a

53:17

connection between the t3 and the

53:20

mercury they're not measured there my

53:22

pendant like so we don't know that the

53:25

patients that have a low t3 at mercury

53:27

and we don't know that the patients and

53:29

that working have low t3 that's

53:31

something to actually try to look at

53:35

yeah I don't know I think I've mentioned

53:38

this to you before probably a little bit

53:41

too much but I think I mentioned about

53:44

measuring

53:45

cellular t3 mercury sorry cellular t3

53:48

levels because that doesn't seem to I

53:51

mean obviously t3 impacts ox AMPK and

53:55

oxygen and where is a metabolic switch

53:59

of some sort so right love but I

54:02

personally love to see that at some

54:03

point in in a study but it's obviously

54:07

these cellular measures are pretty

54:09

difficult to do from what I understand

54:11

yes it's it's hard to do any of these

54:14

cellular things because it's sensitivity

54:15

your methods the methods just for most

54:20

things are not sensitive enough and

54:22

that's what we need new technology to

54:25

increase the sensitivity and why is that

54:27

hard to get grant funds for yeah very

54:32

willing to fund you if you've already

54:33

developed it yes having an idea of what

54:38

would increase sensitivity which would

54:40

have some risk it doesn't it isn't

54:43

getting funded it kind of makes the

54:48

blood measurements we have now seem all

54:50

the more archaic in many ways that's

54:54

correct one cell yeah yeah and when you

54:59

do a medical test you take ten melts in

55:04

one cell the content and 10 mils just a

55:07

tremendous difference and so that's

55:11

where we would really like to be able to

55:13

measure than one cell we would like to

55:15

do the metabolic trap in one so that

55:18

there is no none no method a sense you

55:22

do not do that at the moment that we can

55:24

find but no but that's what we like to

55:27

think about and try to achieve you come

55:29

up with some idea about how to do that

55:31

okay

55:32

anyway that's that's our long-term sort

55:36

of things I didn't everything that we're

55:38

gonna try to do in the future that a lot

55:41

of this depends on the men a funding

55:43

that we get and also the problems and

55:47

the funding is that sometimes we get

55:51

donors that like to start a project but

55:54

you often don't finish the project the

55:56

project leads to they get another idea

55:59

but it's not quite a new project so it's

56:02

how you sustain some of these efforts

56:04

like the metabolic trap we've been

56:06

funding to to look at that but now

56:11

there's many other things that we have

56:13

to explore in terms of it looks like

56:16

it's correct in terms of you know how do

56:18

we get people out of it well it's still

56:20

the metabolic trap it's already funded

56:23

so how do you get new funding that's a

56:25

it's a problem which NIH grants are

56:27

great at because in fact that's exactly

56:29

where you have if you if you establish

56:32

something like the metabolic traffic

56:34

then it's easy to get renewals after

56:36

renewal after renewal so that's what we

56:40

have to get NIH grants and when we have

56:41

some what looks like a potential

56:44

breakthrough and then get it supported

56:46

by NIH because that they will sustain

56:48

funding yeah so in the meantime we just

56:52

carry on as best we can and as advocates

56:58

and people fundraising and hopefully and

57:01

the NIH will step up to the plate and

57:03

give us a nice fat grin I hope so many

57:07

fat grounds so ok ok I will leave you

57:13

this because then some evening just to

57:17

say thank you to Janet as well I know

57:19

she might be there for helping arrange

57:23

all of this at ridiculously short notice

57:25

yes my benefit now is not bad

57:31

yeah you've got to seize the day haven't

57:36

you yeah hopefully people can see you

57:40

again soon I guess for most people that

57:42

will be millions missing first as

57:48

opposed to France

57:51

yeah well probably being aged I think

57:53

that's gonna be live-streamed okay okay

57:57

so hopefully people continuing I'm sure

58:00

OMF will put something out about that

58:03

okay thank you so much I think those

58:06

Thursday and Friday first time Friday a

58:09

young investigators meeting on Wednesday

58:12

I believe I don't know what that I don't

58:14

know anything about that I'm not

58:15

attending that I'm not a Young

58:17

Investigator I'm not saying anything

58:24

yeah okay thank you both so much it's

58:29

been great to speak to you and I hope

58:30

you have a really nice evening we'll

58:34

speak too soon again okay all right take

58:38

care get rest yeah I will do yeah I'm

58:45

sure it is yes all right take care

 

[Rufous McKinney]

Spoiler alert:

It is LPS.

I required translation: Wiki served this up: certainly sounds capable of gumming up the works.

Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, are large molecules consisting of a lipid and a polysaccharide composed of O-antigen, outer core and inner core joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria.

Wiki indicates exosomes are considered small in size. "exosomes are generally thought to be smaller than most other EVs, from about 30 to several hundred nm in diameter: around the same size as many lipoproteins but much smaller than cells."

Unable to determine how to compare Large LPS with small exosomes. Noting LPS may be involved in toxicity....and/or is affiliated with cyanobacteria (blue green algae).

Once upon a time I was an algae expert: now I am NOT an expert!! If algae moved into my blood via diffusion and osmosis: that would be ironic.

 

[TreePerson]

So if exosomes are small then why has Ron considered them as a possibility? As he knows he is looking for something large? I would love to know more what his thinking is on the particle. And how likely they are to be able to isolate it. He seemed more interested in finding a drug but I would’ve thought identifying the particle would be a massive clue to understanding what’s going on.

 

[Cam Newton]

Great to here the trp trap still is possible. Ron mentions the new measurements are 100x more accurate. Also they are 1/1 so far (which means nothing but gives hope), and will be measuring plenty before the invest in ME conference.

 

[Rufous McKinney]

I would love to know more what his thinking is on the particle

Its possible BOTH a large particle and small exosomes could occur simulatenously. We needed a followup question from our interviewer.