“This proposal aims to uncover the immunological basis of ME/CFS”. Ron Davis – grant application
Sometimes the third time is the charm. Ron Davis has gotten (and been turned down for) many NIH grants but even he was shocked by the response to his first couple of attempts to get an NIH grant for chronic fatigue syndrome (ME/CFS).
This time, though, the NIH came through. Davis’s first try at a NINDS review panel was rejected by reviewers who refused to even assess the grant. His second try for an NIH ME/CFS research center was met with such a weird response that he went before an NIH committee to protest. His third try, the first apparently through the grant review panel for ME/CFS (Special Emphasis Panel [ZRG1-CFS-M (80)S]), thankfully, met with success.
The big multi-year, multi-million dollar RO1 grant to the Stanford Genome Center titled “Molecular and Single Cell Immunology of ME/CFS” lasts for five years and pays out a cool $745,000 this year.
Remarkably, Davis, at 76, was the first and is still the only ME/CFS research center grant applicant to flip his big, NIH Center’s grant application into a smaller – but still quite hefty – grant application since the Research Centers were announced in the fall of last year.
This was a grant application, in truth, that one would have expected to succeed. It ticked all the boxes; it features cutting-edge technologies featuring two highly respected researchers from a top academic institution. It’s the kind of application the NIH has said it’s wanted from ME/CFS researchers for years.
A rejection would have raised a big red flag about bias, but this time the grant review panel came through giving Davis’s application extremely high scores and the NIAID funded it.
The grant combines Stanford immunologist Mark Davis’s work on T-cells with Ron Davis’s work on HLA genes. Mark Davis is a T-cell expert – he’s spent 35 years studying these prime movers of the immune system. T-cell and B-cells are the big guns of the adaptive immune response which swoop in later in an infection to clear it out. T-cells are unique in their refined approach to pathogens; while other immune cells react to whole antigens, T-cells need only a fragment of an antigen to respond. Their job is a staggeringly complex one; to produce literally billions of potential binding sites that are able to capture small bits of pathogenic proteins and then lift them to the surface of the cell so that the immune system can respond to them.
Once a pathogen is found, T-cells create specially designed copies (clones) of themselves that swarm through the body targeting infected cells or the actual pathogen itself. As Mark Davis explains in the video below, that process is occurring in ME/CFS; ME/CFS patients’ T-cells are busily churning out identical copies of themselves; they’ve responded to something with a fury.
The best candidate is a pathogen – a virus, bacteria, fungus, etc. – which may be gone, but which has ticked off an overactive immune response that is now attacking the body, producing an autoimmune disease.
In this study, Mark Davis will look at an array of T-cells to determine the breadth and extent of the T-cell activation in ME/CFS. He’ll pair that with new technology developed by Ron Davis which gives researchers a better handle on the genes used to capture those pathogenic antigens. They’re found in the most mysterious part of our genome in the HLA locus.
Because the HLA genes also help the immune system differentiate “self” from “non-self” cells, they also play a major role in autoimmunity. Studies indicate that people with certain HLA types are more at risk for autoimmune diseases such as type I diabetes, lupus, myasthenia gravis, Sjögren’s syndrome, narcolepsy, and others. This study will assess the HLA locus of a large number of ME/CFS patients.
Finally, the study will use new techniques developed at Stanford to try and determine what those activated T cells in ME/CFS are targeting.
By the time the study is done, we could know if ME/CFS is an autoimmune disease or is caused by a pathogen (or both!); plus, we could know what specifically has tweaked our immune systems. Plus, Ron Davis, in a section of the grant, and which shows his predilection for long-term thinking, envisions the study as the opportunity to build a new (and precise) molecular framework for understanding, diagnosing and treating ME/CFS.
“This project will build a precise framework for ME/CFS as a molecular and immunological disease, opening up broad new possibilities for research, diagnosis, and treatment.”
Davis is all about getting at the molecular nature – the very basic building blocks – of ME/CFS – a pursuit he believes will illuminate other diseases.
“Moreover, the similarity of ME/CFS to other medically challenging diseases like Lyme disease, multiple sclerosis, Gulf War Illness, fibromyalgia, and more means that the insights derived here could be relevant to many millions of patients.”
Mark Davis on his T-Cell Research in ME/CFS
A Remarkable Six Months
The NIH grant tops off a remarkable first half of the year for Ron Davis, the Stanford ME/CFS Collaborative Research Center and Open Medicine Foundation. First came the $5 million Pineapple Fund donation, then the $1 million donation to support work into Robert Phair’s Metabolic Trap hypothesis, and now the multi-million dollar NIH grant to Davis’s Stanford ME/CFS Research Center.
Ron Davis Speaking From His Lab on the New NIH Grant
The Stanford ME/CFS Collaborative Research Center is a research center in the best sense of the word. From the Severe ME/CFS study, to the nanoneedle work, to the big omics study in Mike Snyder’s Stanford lab, to Robert Phair’s metabolic trap hypothesis, the red blood cell deformation studies, Mark Davis’s five year exploration of T-cells, and Ron Tompkins’s muscle cell work, the OMF is now funding a staggering amount of research.
Three years ago, I was at a fundraiser Ron Davis held at his house trying to raise some money for ME/CFS. The future did not look promising. Persistence, however, has paid off and three years later he, Linda Tannenbaum and their ever increasing cohort of workers and volunteers are on a research roll the likes of which we have never seen before.
Huge congratulations and thank you so much for not giving up , so pleased for you and all us me/CFS sufferers. Joy of joys, hope is in the air. thanks a million for all your hard work .
This is very hopeful news!
So thankful for all who advocate and continue to communicate the latest news on ME/CFS!
I think this is incorrectly phrased, “The Open Medicine Foundation’s Stanford centers is a Research Center in the best sense of the word.” If I understand right, OMF is a funding organization, it is not actually conducting research. Just to clarify, it appears this grant is outside of OMF and directly granted to Ron Davis via his affiliation with the Stanford Genome Technology Center and other labs he’s collaborating with within Stanford.
Yes, thanks for pointing that out. I altered the blog to make that clear.
I am overwhelmed with hope and excitement about this grant! I have been feeling that I do not want to go on, that 17 years is enough. This news could not have come at a better time for me personally. This has to be the answer. I can now put my toe in the pool of a normal life. Soon I hope. Thank you so much Dr. Davis, Linda, Marilyn, and all who are working so hard for people like me. You all are a beam of light for me.
I feel the same Michelle. Hang on!
I have been ill for 20 years , so I understand exactly what you mean.
I am convinced however that we will see the end of this!
Hallelujah for you all!!
Why do warriors fight? They fight for those who can’t fight for themselves.
You have our gratitude and ?
Ditto Colette. I can’t speak for all my ME/CFS brothers and sisters. But thank you Cort for sharing all the latest information as it becomes available. It’s a godsend. And please continue to share any findings they uncover (no matter how seemingly small and whether or not they have anything at present to treat us). Information is power…and HOPE!!
Thank you on behalf of myself myself, and others I know personally, whose lives have been devastated by ME/CFS. Praying for great success in this new research!
Great News there is Hope on the Horizon for everyone & thanks NIH for finally coming through
This gives me so much hope! Thank you for everything you all do
This is such great news! I am especially excited because, in addition to ME/CFS, I also have Fibromyalgia and Chronic Lyme Disease. Hopefully, this will finally bring the answers needed for all three of these horrendous diseases, along with the much needed cures! Thank you for all that you have been and will be doing to give us our lives back!
THANK YOU SO MUCH for the thing that keeps most of us going – HOPE!
Congratulations for your well deserved grant, Ron and Mark Davis and all who work silently in the background! Thanks also for being a light in this darkness.
And thanks to people like Cort hitting the road (with a van) to spread the word!
Hooray! Such good news and HOPE for all of us! Thank you for keeping us informed and updated.
This is great, great news! Thanks Cort. Very curious what will be found!
That is such fantastic news. These researchers have been amazing especially Ron Davis in perusing the potential cause of this mystifying illness and never giving up. Also his persistence to get funding despite so many setbacks is amazing. Good luck with this. After 40 years it would be wonderful to have this illness designated as REAL in the medical world.
Wonderful heartenening news! Gratitude to all fighting for ME/CFS health equity. Thank you for lifting the blanket of neglect & bringing HOPE ??
I am so thankful that Ron Davis finally received his grant. If you can contribute please do. I know it is challenging when so many of us subsist with so little. It seems like a tide is turning. Let’s hope that results happen quickly and treatment around the corner.
Thank you for sharing such wonderful news! I hope this is just the beginning of millions more NIH funds flowing into ME/CFS research. A huge thanks to Ron Davis, Mark Davis and their team!
This is wonderful news! I’ve been feeling like I can’t continue on like this any longer…..this gives me great hope that we all might get our lives back again, especially Dr. Davis’s poor son. Thank you to Dr. Davis and his team for working so hard to try to figure out this devastating illness!
Keep going Larissa! Like dr. Klimas once said: This is not a good time to give up.
There is real hope now and we will get there.
Notti it was so sweet and thoughtful of you to reply to me! It means the world to me. Thank you so much for your kind words! I wish you all the best!
Check the link in this sentence: “His third try, the first apparently through the grant review panel for ME/CFS (Special Emphasis Panel [ZRG1-CFS-M (80)S]), thankfully, met with success.” It leads to “Page Not Found.”
Did you mean https://public.csr.nih.gov/studysections/SpecialEmphasis/Pages/default.aspx OR https://internet.csr.nih.gov/Roster_proto1/meeting_roster.asp?stdate=06/28/2018&enddate=06/28/2018&grcode=80&srg=CFSJ&SRGDISPLAY=CFS-J&agsqnum=341962
I had the same problem. I went to the link on the NIH to the CFS review section and it led to page not found. I assumed it was a temporary glitch. Thanks for providing a good URL yeah
Why did this article say it was written by Dan Neuffer this morning?
I wondered if anybody noticed that. Thankfully my partner pointed it out and I republished it under my name. It was written by me not Dan. I am about to publish a Blog by Dan; something went awry. I kind of wrote it on the Run; they’re actually quite a few different Boo Boos in the original draft
This is very good. Now we just need to see Dr Robert Naviaux draw in some funds to extend his Suramin and cell danger response work.
Great news! I particularly like that the HLA issues will be addressed, that could help people with so many related autoimmune conditions. Often in the same families.
A big thank you to all those who donated their own money over the past few years as without that I doubt Ron Davis would have been able to study and collect the massive amount of research data to present to the NIH. Data that couldn’t be ignored anymore.
I know some of you gave as much as you possibly could over that time. So you are the heroines and heroes of this story too!!!
How do the T-cells respond differently with people with Gulf War Illness who have been exposed to chemical toxins? Also, do different types of toxins determine different T-cell responses? I still wonder if the author of The Canary and Chronic Fatigue was on to something.
Hi. Thanks to all whom are persevering. I am always amazed at how complex our species is. I studied zoology with an almost Masters in species habitat interactions. I included 24 variables in semi random selection gathering thosands of connected mosaics which crashed the computer in 1985 86 87 88 89, long before biologists were replaced by algorithms and AI. I was hit by 5 cars, giardia, mononuleosis with high fever and vestibular neuronitis before diagnoses with MECFS FMS CES PTSD COPD NMH POTS plus. Complex issues all hitting my system. Maybe T cells met this and overloaded my system like my multivariate analysis crashed a computer. It is perhaps an outlier that caused the final break?
I too am an almost Master’s biologist with so many diagnoses that I get exhausted just listing them – 20 years of trying to figure out the primary issue. Yes, I always had an “over active” immune system ( allergies, asthma after viral illness, etc) but underneath all of this are structural differences, including a possible connective tissue difference – EDS with no noticeable hypermobility? Remembering that the dura meningeal system is composed of connective tissue and is a basic construct of the blood/ brain barrier.
Anyway if you see some of these physical characteristics check out my forum comments: mild scoliosis, one leg shorter, straightening of neck curve, spina bifida occulta ( just a missing section of L-5), large bunions and funny toes, rotated fingers, high arched palate with TMJ issues, chronic pain in hip and sacrum, one shoulder a little lower, and more.
Maybe immune system differences are just one aspect of a bigger picture, and perhaps a compensation for ???
Thank you. Your endless enthusiasm and drive to keep us up-to-date, hopeful and not forgotten is ‘medicine for the sole’. A big shout out to Ron Davis; that man is INCREDIBLE. What a big win for us all…..
From the bottom of my heart, I thank you, Mr.Davis for persevering and finally getting a grant which will help thousands of sufferers, It is a dream come true for all of us, thank you.
Great news! I wonder if the activation of T cells can be caused by persistent herpes virus like i.e. EBV… My feeling is that there is an autoimmune problem.
I’d like him to look into the role our Microbiome has on this condition. As it is our safety net. And when you have it wiped out, every part of your body becomes open to chemicals, toxins, bacterias etc,WHY IS NOBODY LOOKING AT THIS. My MCS/CFS, was brought on after being given an antibiotic, for a Giardia infection, we lived where a lot of chemicals are used, and 20yrs later,worse than ever. And his son’s case sounds similar. Gets sick from a bacteria, lots of antibiotics, and WAM, everything snow balls.
Ian Lipkin at Columbia, among others, is looking at the microbiome, Donna. He is a lead investigator of a study right now that will measure changes in gut microbiota, serum metabolites, and immune cell function post-exercise tolerance test, comparing pre- and post-samples of both patients and controls. (I was a study participant as a patient early last month and still have not quite recovered from the bike stress test). Maureen Hanson and Susan Levine have also published a study on this topic.
While disturbances in the microbiome might lead to the onset of ME/CFS, it may be much easier to ruin the microbiome than to repair it. ME/CFS patients who have had a fecal microbiota transplant seem in general to recover only briefly before reverting to baseline.
You are right Marco. I am in Australia, and have been under Prof. Borody and had a FMT, a yr ago, yes, it has fixed my 20yrs of constipation, but, the CFS/MCS has not changed.
Whatever happened to the Norwegian gut study (faecal transplants) which Maureen Hanson was involved in? It was due to completed late 2017.
I tried probiotics before to no avail. Recently I started to eat papaya with protein rich meals. It resulted in a remarkable and quick improvement, but it’s far from a cure. Possible methods of action I see in order of likeliness:
* I have an undiagnosed problem digesting protein
* I had an undiagnosed problem with gut parasites; having low immunity makes even minor infections hard to fight off
* the enzymes kill off bacteria in stomach or gut or killed off bacterial or fungal overgrowth in the bowels
The results is improvement on many areas, including my digestion feels so much lighter then before. A few months ago I wouldn’t have bet 50 to 1 I even had a major gut problem. It feels like my gut is now restoring naturally.
Relation to your comment: if fecal microbiota transplant delivers only brief recovery then it seems to have been abundant enough to colonize the gut, but a “constant onslaught” like poorly digested proteins/food, parasite infection or immunity problems in the gut itself or a severe problem of the gut extracting food cause an enduring attack on beneficial gut microbes. For those interested I posted a post about my results in the diet and gut section.
Donna, if you are the one who did FMT under Barody, may I ask you some questions about your experience?
As I sit here on my couch too fatigued to do much of anything this brings me immense hope. Just having someone acknowledge ME\CFS is so uplifting. If we ever get to a cure please let me come over and clean up your office.
LOL! Cynthia, I wanted you to know this really gave me a much appreciated chuckle. Both Ron and Mark Davis’s. I’ll come help you!
Thank you so much for keeping going with this. Hopefully something will soon explain why 4 of our family have this illness!
Fantastic news! I will share it on our Facebook groups!
Congrats to Dr. Davis! We are so blessed to have this great mind working in ME/CFS.
When the day looks the darkest the sun shines through! Thank you Cort for the wonderful news. God bless Dr. Davis , his Son and all who are working so hard.
WOW! Finally! Congrats to Dr Ron. I don’t think there will be any help for me in my lifetime but there are so many younger PwME that wii benefit. Exciting news for sure. Thanks Cort for keeping us up to date
Interesting! Since being DX with CIRS and having the worst HLA genetics one can have with it and inability to throw off mold or biotoxins – this for sure makes sense. I’m of the opinion that the issues are Autoimmune and Inflammation. They found a type of mold/fungus in my blood and thyroid biopsy that was once thought to be a protozoa. Also having Lyme and that being chronic with other co-infections. Again, if my immune system were working properly it would detect and kill. Instead it defends and protects. Forming protective biofilms and tumors. Working on breaking down those biofilms and using things to attack what’s in them – be it mold, fungus or bacteria or even protozoa and parasites …..now this is making a difference.
Happy to say I’ve gone from 7 thyroid tumors down to 3. My menigioma is shrinking. My swollen brain and compression on two essential areas in it is normal. My energy is improved and I’m doing better with POTS and MCAS. Not needing as many meds or supplements. Still not all the way, and probably will be a lifetime fight. But I’m on the right track.
Hi Issie Im glad your doing better. I have whole list of me/cfs issues with ebv dyautonimya ect ect. I have had two cancers last which spread to lymphs. Wondering what your taking now as protocol??? thanks hope for your continued improvements
So grateful after decades of so much disappointment.
Thank you, Cort, for relaying this wonderful news!
This is very exciting! Thank you, Cort,for continuing with your great work and inspiring us all.
Apparently this research will look at CFS as an autoimmune disease. I had not looked at my illness as being an autoimmune disease. However at my last visit to the Stanford Clinic I was given a prescription of leflunomide or Avara. This is an autoimmune drug often given for rheumatoid arthritis. The side effects are frightening to me. Also the drug stays in your system for a year after you stop it unless you take two additional drugs to help get it out of your system. I am hesitant to try this medication.
I was just wondering if anyone out there is taking autoimmune or rheumatoid arthritis drugs for their CFS /ME? And if so how is that going for them?
Hello Cort Johnson I am from South America my young adult children and I are sick with ME/CFS, I would like to know if you know if there are more sick families like us? Thanks for all the information and your work.
Hi Diana, I am in Australia, and I have myself and 2 adult children with CFS/MCS
I know what brought mine and my childrens CFS/MCS on. My 2 1/2yr old was never sick, a really healthy baby, could eat anything. Then we moved from Toowoomba QLD to Mackay QLD a tropical town. I was 7mths pregnant, and she was 2 1/2yrs old, and she got a GIARDIA infection, and the doctor in his wisdom, gave her the drug FLAGYLL, told me to take it too. Within a month she developed a UTI , developed kidney problems, health just went down hill from there. My son was then, born a sickly baby. When she was 9yrs, we moved to Hervey Bay, which had alot of chemical in the air, and within 1yr, she was bed bound, I just got sicker and sicker, and so did our son. It wasn’t until someone gave us some fruit (was suppose to be chemical free) that had been sprayed around the base of it, with ROUNDUP. That our son got as sick as our daughter, and was housebound too. All came down to having the Microbiome destroyed, which would have protected us from the chemicals in the air. And Prof. BORODY, explained all that, he understood it all. The problem now is that our bodies absorded to many chemicals, and we justaren’t strong enough to detox.
Have you all been tested for the ALPHA-GAL test? Meat Allergy Alpha-Gal, it is not only in all Meats it is in medicine,
vitamins/minerals, food additives the list is long even Sugar processed on Bone Spurs in Factories…If Positive one needs to
carry at all times 2 Epi-Pens
My understanding is that ME/CFS and FM sometimes do run in families. Ron Davis is actually engaged in a familial study right now to explore just that idea. Plus a recent paper suggested that fatigue itself does run in families presumably because of a genetic connection. So while it doesn’t always sometimes it does appear to run in families.
Twin Res Hum Genet. 2017 Jun;20(3):208-215. doi: 10.1017/thg.2017.22. Epub 2017 Apr 24.
Familiality and Heritability of Fatigue in an Australian Twin Sample. Corfield EC1, Martin NG2, Nyholt DR1.
Familial factors have previously been implicated in the etiology of fatigue, of which a significant proportion is likely attributable to genetic influences. However, family studies have primarily focused on chronic fatigue syndrome, while univariate twin studies have investigated broader fatigue phenotypes. The results for similar fatigue phenotypes vary between studies, particularly with regard to sex-specific contributions to the heritability of the traits. Therefore, the current study aims to investigate the familiality and sex-specific effects of fatigue experienced over the past few weeks in an older Australian population of 660 monozygotic (MZ) twin pairs, 190 MZ singleton twins, 593 dizygotic (DZ) twin pairs, and 365 DZ singleton twins. Higher risks for fatigue were observed in MZ compared to DZ co-twins of probands with fatigue. Univariate heritability analyses indicated fatigue has a significant genetic component, with a heritability (h 2) estimate of 40%. Sex-specific effects did not significantly contribute to the heritability of fatigue, with similar estimates for males (h 2 = 41%, 95% CI [18, 62]) and females (h 2 = 40%, 95% CI [27, 52]).
These results indicate that fatigue experienced over the past few weeks has a familial contribution, with additive genetic factors playing an important role in its etiology.
So glad that the funding has finally come through for Dr. Davis. But how can we little individual people who have been suffering so long and with doctors who understand almost nothing about ME/CFS and don’t seem to care or even ask questions, how can we become part of the study to solve this terrible painful conundrum? More than thirty years of this chronic misery, 30 years of study of biochemistry, 365 plus supplements I’ve tried, and finally I just give up. But, you know, hope springs eternal. I would so like to understand what has brought about such a medical horror.
What know one tells you is, that ROUNDUP, is an ANTIBIOTIC, that kills insects by killing off there bacteria.. And guess what , it works the same on us. And when you don’t have much, due to antibioitc use, or not enough from the mother, diet causes a big problem. You know they spray most grains (wheat, rye, barely, sorgum, legumes etc) with roundup, before they harvest it. Know wonder it is such a sick world, what hope have we got!!!
you highlighted that several ME/CFS cytokine studies had shown a positive correlation for one cytokine; was it TNF alpha?
See below a study of the relationship between mutations (SNIPs) in the HLA and TNF alpha gene, and an autoimmune disease.
Polymorphisms at the human leukocyte antigens (HLA‐C) and tumor necrosis factor (TNF) genes have been associated with susceptibility to psoriasis in several worldwide populations. In this study, HLA‐C and TNF (–238/–308) polymorphisms were performed in 125 Brazilian patients and 202 healthy controls.
The strong association of HLA‐C*06 allele with disease susceptibility, particularly in early onset psoriasis, indicates that younger ages could be considered to stratify psoriasis into early and late types. TNF –308 polymorphisms can be associated with psoriasis susceptibility and severity. Potential genetic markers of psoriasis in populations with a complex mixture of ethnicities should be investigated.
Your article highlighted that TGF-B was elevated in ME/CFS cytokine studies i.e. not TNF. Still it would be interesting to see if SNIPs on HLA and TGF-B are related to ME/CFS.
Displaying an unusual level of consistency for ME/CFS, TGF-B has now been found elevated in about six out of the ten studies it’s been tested in.
I hope they look at testing for ALPHA GAL Meat Allergy in all their samples & it is not only Meat it is in everything as additives from
medicine, vitamins, food additives, Sugar processed on Bone Spurs use Vegan unrefined white Sugar do not use Brown Sugar. One example is
magnesium stearate in countless products made from animals & there is another type called Cat Pork Allergy…2 Epi-Pens to be carried at all times…
Also, Alpha-Gal is in Whey protein even in all household cleaning items from dish soap hand soap toothpaste shampoo detergent. Candles, colognes,
house sprays, body sprays…Cipro, Doxy have magnesium stearate, Gel Caps have alpha-gal contents…Condoms dental floss the list is
enormous…Gelatine is out
Please look at TNF2 Rs1800629 G>A
I know 6 veterans personally with Gulf War Illness that carries this polymorphism.
I’ve struggled with GWI for 26 years. My symptoms are now Amyotrophic Lateral Sclerosis.
I had a cytokine storm in 2015 that was triggered by bactrim. Bactrim is cytotoxic.
After the storm, the ALS symptoms started. Recently my arm and leg are twitching, getting heavy and hard to lift. Swallowing problems are more pronounced now too.
I know it’s too late for me, but please save others.
I’ve had CFS for so long that I may have been born with it and I’m 72 now, I’m wondering if I will find out what normal feels like in my lifetime. Better late than never, I guess.
THANK YOU FOR FIGHTING FOR US AND NEVER GIVING UP! I HAVE HOPE AGAIN . MAYBE I WILL GET TO SEE MY DAUGHTER GROW UP. THANK YOU SO MUCH