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At age 75, Ian Lipkin is excited about where we are with ME/CFS.
Who would have thought the world’s greatest virus hunter would ever have taken an interest in chronic fatigue syndrome (ME/CFS)? There are lots of nasty bugs out there, after all, and Ian Lipkin’s lab has been hunting them for decades.
Lipkin has developed numerous methods (MassTag-PCR, GreeneChip diagnostic, High Throughput Sequencing) to track down emerging pathogens. The list of pathogens he’s played a key role in is long, and includes West Nile Virus, the first SARS virus, Arenavirus, hemorrhagic fever virus, MERS, Zika, and Bornavirus.
Closer to home, the Tick-Borne Disease Serochip (TBD Serochip) he and his lab developed, significantly improved diagnostic accuracy by enabling the quick and accurate detection of eight different tick-borne diseases. Lipkin’s group has identified at least 20 new viruses ticks carry in the northeastern U.S.
We could go on and on about the number of pathogen detectives he’s trained and the hundreds of viruses he and his teams have discovered. Lipkin’s ability to speed up the detection of pathogens has saved countless lives. Given all that, the question that begs to be answered is, what is this paragon of pathogen detection doing, spending most of his time now working on a neglected, controversial, and often overlooked disease like ME/CFS?
The Gist
At age 75, Ian Lipkin is excited about where the ME/CFS field is at.
Who would have thought the world’s greatest virus hunter would ever have taken an interest in chronic fatigue syndrome (ME/CFS) – let alone devote much of his time to it?
Ian Lipkin, the leader of the NIH-funded ME/CFS research center at Columbia University, is doing just that. In our “What’s Up Doc?” video, he explained that he’s been interested in ME/CFS for 25 years, but over the past 15 years or so, he’s been devoting more and more of his time to neglected, chronic diseases like ME/CFS and autism.
His personal connections to people with this disease run deep. He knows three formerly young and healthy people who committed suicide.
The Best of Times – Despite using supersensitive techniques, Lipkin’s never found a pathogen that’s responsible for ME/CFS. Instead, through a series of studies employing metabolomics, genomics, proteomics, and the microbiome, among other approaches, he has been exploring the “hit and run” hypothesis, whereby a pathogen hits the body so hard that it leaves a lasting impact.
Lipkin’s been studying ME/CFS for a while, but now believes the field is on the cusp of something exciting indeed. Lipkin believes his and others’ work on the molecular underpinnings of ME/CFS have produced “some very plausible models that suggest that we can start clinical trials very soon.” He said, “There’s so much hope right now. We can finally get somewhere with this.”
Lipkin’s three NIH-funded projects involve a “Good Day, Bad Day” study, which utilizes wearables and a comprehensive battery of molecular tests to determine the drivers of the illness. Another study complements and expands the UK’s extensive DeCode ME genomic study, and the third utilizes millions of stored samples to assess the characteristics of people with ME/CFS before they become ill, the changes that occur when they become ill, and how they change biologically over time.
A new technique allows Lipkin to assess not just the antibodies produced in response to an infection but specific antibodies that are reacting to specific parts of a pathogen that are – and this is the key part – triggering an immune reactivation in that person.
He found, during a small study, a group of ME/CFS patients for whom viral reactivation to specific parts of the virus appeared to be driving their illness and who might respond to antiviral therapy. That presents the possibility, for the first time, of a clinical trial of antiviral therapy specifically focused on that group of patients who would likely benefit.
Another study suggested that a subset of people with ME/CFS have a reduced threshold for triggering an innate immune response – something that could make them, he said, very sick when faced with the slightest stressor.
Another group of patients has reduced gut butyrate levels. The upshot of all this is that Lipkin believes we are getting close to being able to precisely identify subsets in ME/CFS. He said, “I think we’re very, very close to being able to have precise treatment for people with ME CFS, at least for a large number of people”.
Lipkin also implored people with these diseases not to give up, saying, “I am so, I am so encouraged. I am so eager. And anybody watching this podcast, don’t give up hope. I really think we’re almost there. You know, it just, you know, I, I get these notes sometimes from people who say, you know, I want to donate my, my body for your research. And I say, please don’t… just hang in there”.
The Worst of Times – The Trump administration’s battle with Columbia University has, for now, at least, upended Ian Lipkin’s work with ME/CFS. (The Trump administration has suspended or terminated approximately $700 million in NIH grants to Columbia).
In a kind of Kafkaesque situation, Lipkin has never been told who turned the spigot off, why it was turned off, who to contact to turn it back on, or if his ME/CFS has been terminated or is simply on hold. A few weeks ago, he received a notice that the ME/CFS spigot had been turned on, only to get another one a couple of hours later stating that it had been shut off again.
The Wall Street Journal reported yesterday, though, that Columbia was in talks with the Trump administration to restore some of its federal funding.
The good news is that it appears the ME/CFS grant could be reinstated. The WSJ reported yesterday that Columbia might be near a settlement to restore some of the federal funds.
The bad news is that Lipkin’s program is being kept alive by money provided by a generous donor, Jeff Ansell and his daughter, and Lipkin and his family, but the funds have all but run out. He now needs support to keep his ME/CFS research center going.
Ian Lipkin’s work is currently hanging on by its fingernails. You can support his work via a fundraising page his team created to keep it going during these uncertain times.
Health Rising is also in the midst to its quickie summer donation drive. We’re about 35% of the way to our goal.
HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT
As Lipkin explained in our “What’s Up, Doc?” interview, about 15 years ago, he transitioned to helping people with chronic neglected illnesses like ME/CFS and autism. Lipkin has heart disease, but there are lots of people working on heart disease. Not so with ME/CFS. Lipkin’s personal connections to people with this disease run deep. He knows of three formerly young and healthy people who committed suicide.
Please excuse my blurry image! (Unexpected WiFi problems occurred. Ian Lipkin’s image is fine.)
Oddly enough, the great pathogen detective has never had much success in directly finding pathogens in ME/CFS. The bornavirus, with its central nervous system-altering capabilities, seemed like a promising fit for ME/CFS, but Lipkin’s attempt in 1999 to link it to ME/CFS was unsuccessful. Its failure left behind a telling clue, though. Likewise, Lipkin’s later use of techniques 1000xs more sensitive than had been tried before failed to find evidence of an unusual pathogen at work in ME/CFS.
Lipkin failed to find evidence of bornavirus in ME/CFS but did find that most ME/CFS patients’ B-cells were spitting out odd antibodies like there was no tomorrow.
In retrospect, it turned out that the headline,”No bornavirus for in ME/CFS”, might have better read “Substantial B-cell dysregulation found in ME/CFS”. Lipkin’s bornavirus work found evidence of ‘non-specific polyclonal B-activation’ – a sign that B-cells were pumping out scads of odd antibodies in almost 80% of ME/CFS patients. B-cells, of course, have become of great interest in ME/CFS recently.
Likewise, Lipkin’s autism work in the Autism Birth Cohort suggests that pathogen-triggered immune dysregulation in the mother during pregnancy increases the risk of autism. (It has also been found that folic acid supplementation during pregnancy reduces the risk of ASD by 40%.)
Over the past fifteen years, Lipkin has turned his attention to exploring, through microbiome, proteomic, metabolomic, and immune studies, the hit-and-run hypothesis, whereby a pathogen is vanquished but leaves behind a lasting impact. He’s been studying ME/CFS for a while but now believes the field is on the threshold of something very exciting.
The Best of Times…
“There’s so much hope right now. We can finally get somewhere with this.” Ian Lipkin
Lipkin believes his and others’ work on molecular underpinnings of ME/CFS has produced “some very plausible models that suggest that we can start clinical trials very soon.” He is not alone. Avindra Nath and Nancy Klimas have also asserted this. All think the key will be identifying subsets, which he stated we now have the tools to do and is “just around the corner”.
Lipkin said, “There’s so much hope right now. We can finally get somewhere with this.” On a personal level (Lipkin knows many people with these diseases), he called the progress “gratifying.”
One of Lipkin’s blocked studies involved a genomic collaboration with Decode ME.
His NIH-funded ME/CFS research center has been involved in three projects. One was a Good Day/Bad Day project to scour multiple tissues (saliva, blood, urine, and more) for clues to what’s happening when people with ME/CFS feel better and feel worse.
Another was a genome-wide study that aimed to do for the US what Chris Ponting’s UK Biobank study is doing for the UK. Combining the two would result in a much larger, more powerful GWAS study, which could pinpoint the genetic risks of coming down with ME/CFS, potentially pointing to causes and treatments.
The last, and perhaps the most interesting, was to take advantage of millions of blood samples gathered by the Department of Defense, using an AI program to identify samples taken before and after people developed ME/CFS, to pinpoint triggers, such as immune or metabolic issues, assess the effects of duration, etc.
After Lipkin failed to find direct evidence of a pathogen in ME/CFS, he switched gears and developed a new method to assess the body’s reaction to a pathogen. This method allows Lipkin to assess not just the antibodies produced in response to an infection but specific antibodies to specific parts of a pathogen that are – and this is the key part – triggering an immune reactivation in that person. Nobody has been able to assess antibody levels/pathogen reactivity in this kind of detail in this disease. (Lipkin used this technique to break the code on acute flaccid myelitis a couple of years ago.)
Using this unique technique, Lipkin found, during a small study, a group of ME/CFS patients for whom viral reactivation to specific parts of the virus appeared to be driving their illness, and who might respond to antiviral therapy. That presents the possibility, for the first time, of a clinical trial of antiviral therapy specifically focused on that group of patients who would likely benefit. He compared it to treating high blood pressure: if the marker is there, you treat it.
He noted that Ampligen, which boosts the innate immune system to eliminate viruses, clearly works for some patients. A kind of paralyzing question for ME/CFS doctors has been what to do with the immune system: suppress it or enhance it, and if you enhance it, which part of it? Lipkin’s subsets provide a roadmap for them.
Lipkin believes the ME/CFS field is on the edge of achieving a kind of holy grail – identifying biologically based subsets.
Lipkin’s presently moribund Good Day/Bad Day study clearly presents an immense opportunity to pluck out this group of patients. In this study, patients wear wearables to provide a baseline. Once a threshold is reached—the patient is either doing much better or much worse— the investigator reaches out to the patient and collects a sample. The sample is then tested for metabolites, proteins, nucleic acids, antibodies, and gene expression, among other biomarkers, and compared to samples taken when the participant is performing better. The beauty of it is that patient never needs to drag themselves into the lab when they’re feeling really bad – the investigator comes to them.
Lipkin referenced a study where he took immune cells and exposed them to triggers of the innate immune system. Using metabolomics, immunological measures, cytokines, gene expression and others, he found that people with ME/CFS – in particular, women with ME/CFS – had a much greater response to immune stimuli – a finding that tracks with the ideas of immune exhaustion. Metabolically, they identified abnormalities in metabolites associated with mitochondrial damage.
That suggested to Lipkin that many people with these diseases have a reduced threshold for triggering an innate immune response. (This fits in well with Nath’s and others’ work, which suggests that defects in B and T-cells in the adaptive immune response are putting the innate immune response on a hair trigger.)
Lipkin said that when something like that is happening, the smallest stressors will throw you off, and “you’re going to feel sick all the time.” In contrast to the other group, you might want to suppress innate immunity (and enhance the adaptive immune system?) in this group, and some drugs can do that.
Lipkin’s goal is to develop a diagnostic panel for ME/CFS subsets that will inform targeted treatments. He believes we’re closer than we think.
Ditto with Lipkin’s gut flora work, which shows that some people with ME/CFS have very low levels of butyrate-producing bacteria while others don’t. While gut flora may not be the answer, its effect on the immune system suggests that rebalancing it should be helpful. Ultimately, Lipkin’s goal is to create an efficient diagnostic panel that doctors can use to rapidly decide which category a patient fits into and which treatment to pursue.
Lipkin believes we are closer to developing effective treatments than figuring out ME/CFS. In fact, he believes those treatments may not be far off. “I think we’re very, very close to being able to have precise treatment for people with ME CFS, at least for a large number of people”. He noted that recently, a group of leading clinical and basic researchers had been trying to prioritize the first efforts in establishing a clinical trials program.
Lipkin is more optimistic about the future for people with these diseases than I’ve ever heard him. He said:
“I am so, I am so encouraged. I am so eager. And anybody watching this podcast, (and there’s one person in particular, Ron) don’t give up hope. I really think we’re almost there. You know, it just, you know, I, I get these notes sometimes from people who say, you know, I want to donate my, my body for your research.
And I say, please don’t… just hang in there”. He rued the young, formerly healthy people he’d known who’d committed suicide, and said, “We’re almost there. It does seem like so many things are tying together.”
Of course, more funding is needed. For years, Lipkin has felt that given the right funding, progress will be rapid. We’ve never received that kind of funding, but Lipkin is clearly encouraged by what the field has accomplished with the limited funding it has had. If a wealthy person came to him and said I want to do a Manhattan Project in ME/CFS, though, he predicted, “We could get this thing done in two years.”
That’s how close he thinks we are.
The Worst of Times
With its funding locked up, Lipkin’s ME/CFS research center is being kept afloat by private donations. A recent WSJ piece stated that Columbia may be getting close to restoring some federal funding.
The field is progressing, but Lipkin’s work is currently on hold, and has been for a while. In what Lipkin called a “painful” situation, his NIH-funded ME/CFS research center funding at Columbia was cut during the Trump administration’s kerfuffle with Columbia University.
(First, the administration terminated $250 million in NIH grants, and later froze $700 million in NIH grants at Columbia. Columbia is not alone. As of June, the Trump administration has ended or delayed nearly 2,500 grants across the NIH, effectively reducing funding by $2.3 billion. The vast majority do not involve DEI projects.)
In a Kafkaesque situation, Lipkin has never been told who turned the spigot off, why it was turned off, or who to contact to turn it back on. Lipkin was informed by one source (Sponsor Projects) that his grant had been terminated, but the NIH website indicates it’s on hold, and he has never received a termination letter.
He agonized over a Gulf War Illness/ME/CFS study that has been terminated. All the samples had been collected, and much of the data had been analyzed, but the project was suddenly terminated because the powers that be didn’t understand that he also needed to analyze the data, perform the biostatistics, create the models, and write up the paper.
A few weeks ago, he got a notice that the ME/CFS spigot had been turned on, only to get another one a couple of hours later that it was shut off again. (Science reported that the NIH initially told its program officers that they could resume funding to Columbia. Six hours later, the grants were back on hold, with the NIH communications officer reporting, “There is no funding for unvetted woke ‘research’ at Columbia”. The Wall Street Journal reported yesterday, though, that Columbia was in talks with the Trump administration to restore some of its federal funding.)
The good news is that it appears the ME/CFS grant could be reinstated if a way to do so can be found. The bad news is that Lipkin has no idea how to do that. He said, “If anybody listening has any influence, you know, on how these decisions are made, please get that turned back on.”
The program has been kept alive by money provided by a generous donor, Jeff Ansell and his daughter, and Lipkin, but the funds have all but run out. He now needs support to keep his ME/CFS research center going.
Lipkin is now 75 and is not in the greatest health, but he’s clearly excited and eager to move forward in the field. Let’s hope he’s able to fully bring his decades of experience to bear on this work. Maybe now is the time for a Manhattan project for ME/CFS.
Supporting Ian Lipkin’s work
Ian Lipkin’s work is currently hanging on by its fingernails. You can support his work via a fundraising page or by using the QR code below that his team created to keep it going during these uncertain times.
Health Rising’s Quickie Summer Donation Drive Update
Thanks to everyone who have quickly brought Health Rising to about a third of its goal.
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