#15 Monoclonal Antibodies and the Future of Complex Illness Treatment with Dr Nancy Klimas

[MUSIC PLAYING] Welcome to Make Visible, the podcast shining a light on complex chronic illness. I am your host, Emily Cape Stevens, and I've been living with an energy limiting condition since 2020. Here, I will speak to the world's leading experts to bring you the latest science research and insights into invisible illnesses, including MCFS, EDS, fibromyalgia, POTS, long COVID, and more. [MUSIC PLAYING] Welcome. Well, it has taken a while and quite some effort, but a new study looking at monoclonal antibodies for the treatment of long COVID is finally underway. And I had the pleasure of discussing it along with her decades of research into MCFS and other complex conditions with Dr. Nancy Klimas at the Institute for Neuroimmune Medicine at Nova, Southeastern University, along with the deep investigative science that they undertake. We discuss existing ways to manage and treat patients, helping move the body back to homeostasis. What an absolute pleasure to be in the same room as this inspirational Dr. Scientist, researcher, and thought leader. And I hope that you enjoy this interview as much as I enjoyed speaking with her. [MUSIC PLAYING] Dr. Klimas, I am very excited to be here in person. What we're trying to do at Makevisible is try and bring some of the research that people like you have been doing for decades, into illnesses that have not got necessarily that much attention in terms of the actual global attention. And pull those strands together. So I came to this from having long COVID, but what has become to have parents to me is that emphasis on long COVID and the funding that has gone into long COVID has enabled us to actually start looking and start piecing together pieces in conditions like MCFS, which has been much underrepresented historically, not underrepresented by people like you or Lisa the Bayman, or these people that I have spoken to who have been working extensively and tirelessly for decades out there in the world. It has been underrepresented. Your focus is research and clinical efforts Yes, we do. Into multi-symptom disorders. Is that how you would describe it? I never like the word multi-symptom disorders. But no, what we have going here is really exciting. We have a group of scientists in a group of clinicians sort of in a mind meld. It's pretty cool doing translational research. So we have this amazing computational modeling team and biomarker discovery group and in vitro testing and all the laboratory, bells and whistles, similar exciting stuff going on in lab. That leads to these kind of models for the complexity of these illnesses that give us new ways to think about it but also to potentially treat it. So on the science side, we have all this preclinical work that's incredible. I mean, it's just like, wow, and it's all got to do not just with all the skill set of these people, but the fact that they're working together, talking to each other, communicating, improving the way as a group or even able to conceptualize these illnesses. But then what we have in the clinic or the clinical team is the ability to translate that into clinical trials, which is nice. We also have a really outstanding clinical team doing treatment. And they inform us as our patients inform us every single day on things that we might not have conceptualized using all that fancy science, we're sometimes just listening to people and hearing what's going on with them is the way you find your direction and discover important things. And as the director here, do you bridge actually each of those to me part of the team? I'm a very odd person because I have a pretty strong laboratory science background, not a computational scientist at all. I have to go look up their words and then come back to the meeting later and go, OK, now I get it. But I am good at the biomarker piece, but I'm also a doctor, a physician that takes care of patients and I'm an immunologist. I've been taking care of them through the lens of immunology for quite some time. How recent is it to have that computational piece as part of the work that you're doing? You're talking previously about bench research that you're doing. But this must revolutionize the speeds. You were speaking about Suzanne Vernon, when before we started talking. When Suzanne was at the CDC, she organized this amazing meeting with her colleagues at the CDC. They put clinicians, scientists, and computational scientists together at a table and created a competition between four or five groups to try to model ME/CFS. So they handed them this big data set that the CDC had. So I was in one of these teams. And that's how I came to know about the strength of computational biology, Gordon Brotter, who's on my team. And we had designs on napkins sketched out in the evening of what we'd like to do. And it turned out to be a very great way to start down that path. Wow. So that's what worked with that 2005, which was-- Yeah, easily that. And then I moved to Nova Southeastern University when they offered us the opportunity to develop our own institute. And so you got that decision then to bring in all of those elements. You came with the whole thing, the whole shebang. That was our vision when we came here. So we would have a team that could move from the lab to models to patient care. Wow. Yeah. I look at your website and see how often it has to be updated with your latest errors. It's probably editing it. I think we've been doing a big job with fans anyway. So why don't we start with your latest projects that you're working on? You and I did actually speak a year or so ago about some work that you had been doing into monoclonal antibodies. And it was just off the back of-- Oh, well, I'm just kidding. This has been so. So what happened is you were looking at potentially doing a trial into monoclonal antibodies. But tell me what happened. So yeah, what happened? We got funded, which is amazing to do that in January of last year. So a little more than a year ago. And the longest shelf life product at the time would have expired in July. So I tried to race the July expiration date with the things you need to submit an FDA, I&D. Yeah. It's not a short or an easy process. I will say the FDA was very efficient, but the getting to the point of the application's hard. Anyway, one of the things you need for the application is the commitment of the company with a product that you can link your application to their file at the FDA. Well, that never happened. I think four or five companies, and we went through them, knocked at the door, used powerful people to knock at the door from other directions. The district didn't work. We couldn't get them to work. But about that time, a British company, AstraZeneca, had created a second generation product to protect people against COVID that were medically vulnerable. And that product was in trial, but not approved yet. At the time when we found each other last summer, which was very good timing, we were there to help from some amazing people to put us together and all the right people that could make decisions in the room. And AstraZeneca committed to providing us with product for this trial. And tell me what that trial is, or is looking at, or is looking to a draw. There's so much more data since you and I talked before, because now it's even more exciting. So the idea is that some people may be not all of them, but some, now what do you mean by some, maybe 40% have this circulating spike protein from COVID long after they've had COVID? And are we talking about people who have long COVID or is that people in general? Long COVID. So it's not 40% of the population. It's 40% of the population. Definitely not. And that people that are well. OK. Which is a good point, because some people-- There is a signature that chases recovered people. Yeah. These are the proteome studies. They're saying that every one of us that I COVID has a signature you can see years later. Yeah. So that's true. But it's not spike protein. Because spike protein is actually made-- it's a piece of the virus, right? It's a chunk of the virus that's on the outside. It's the thing that binds on your receptors in your blood vessels to something called the ACE-2 receptor, the binding site for this virus. It's actually a lot of other tissues too, [BLANK_AUDIO] But on the blood vessels, it's particularly troublesome because starting an inflammatory reaction in the blood vessels is going to give you trouble. And as you know, the people with lung COVID have trouble that sounds like they're blood vessel walls are part of the problem. They have microclots, perfusion problems, the work of Dr. Vist, and the Netherlands with the muscle biopsy, pre-phosed exercise that showed, you know, a scheming and lack of perfusion in lung COVID after an exercise challenge. These are all really important features of an illness that's affecting the capillaries, the tiniest blood vessels, and not letting the blood get through. So on one hand, you got this pathophysiology that makes you think, man, this happens really messing up the blood supply here. Why can't the microvascular to open up and let the blood come through? And then on the other hand, you've got this data now supporting that there's this thing that binds to blood vessel walls that calls the immune system over and creates inflammatory reactions, which is the first step of clotting. So the microclots could be coming from the. So it just starts tying together, right? And you're going, "Oh, okay." Then there was some studies out of Japan that biopsy organs, when people were having surgery for this or that, they did like liver and kidney biopsies, that kind of thing. And found more evidence that COVID was in the cell at tissues than that was even in the blood vessels. So, I mean, their numbers weren't arranged up there. I'm just pulling this out of the area. I don't remember exactly, but it was really high, 60, 70% of the tissues that they biopsy. So there's this evidence of the virus is persisting or despite protein is persisting without the whole virus attached. Yeah. How had you talking about this before? It's a really important concept, because when you have a bug, a bacteria virus, whatever, it can actually lend the code for something to other cells and leave that behind, and the cells can then start manufacturing things. Like HIV can make GP 120 the energy and that little piece of the cell wall that binds to the T cells. In huge quantities compared to the amount of actual HIV that's circular. And it's not what's causing the problem in something like this? Yeah. Well, in HIV, it causes a different problem. But in this one, you've got this protein that can be measured that is really a big problem in itself. All by itself can cause reasonably, you can understand that having something that causes the immune system over to these two receptors is going to result in some serious stuff. That's the concept, the theory behind it in the year since year and I talked, the data to support that is very, very much stronger. Dr. Ware, Harvard's lab has got this ultra-sensory data. He'll be a part of his study and he's but published some papers now with the big numbers of subjects not a handful that are pretty compelling. That's the argument behind why would you want to mop up spike protein? That's what the AstraZeneca drug is. That's the target. It comes in and swipes the spike protein. Yeah, it's just spike protein. Monoclonal antibody. If there's a living virus, it's replicating it should grab it and bring the immune system over to kill it. But if it's just bits and pieces of spike protein, it should still suck that up into an immune complex and remove it. The liver removes immune complexes in a single path. So if you just sort of like a sponge pop it up and then these cells in your liver called the coop for cells. It's like you're just literally giving it a bit of a clean out. Yeah, yeah. And the other advantage of this AstraZeneca product is that it lasts six months after infusion. So you only need one shot for six months, which is the length of our study. So we'll be able to know if, you know, with some of the other products you didn't, they just didn't last very long. And you might have had to go back and get repeated injections. But that's when you have like six months of coverage. And then we'll follow another six months to see whether that was good enough or if a breakthrough broke through. And how many people will you 100 people in the study? Okay. So it's 50, placebo 50 drug. And then at the end of six months, anyone who has symptoms can get open label drug. So there's the opportunity for anyone to study that actually get treated without being entirely impossible the whole time. Okay. And the, you said that they have child this. But that's trialing it in active COVID. Is that right? That when you said AstraZeneca, I mean, looking at it. Now actually the way this drug is to prevent COVID, right? Okay. So you give it to people with immune system. Oh, that's right. And you try to prevent COVID. And very nice. More than 400 people in that trial and went on for six months. It's on their webpage. You can read it. It was protective. It was as protective as the first version of every shield, which was released as, you know, a few years back. Yeah. So, the other good news about this product is that it covers all the old variants, alpha-bedded Delta. And right up to, not the current, up to the time when they made it. Because these variants change like tomorrow. You've got a new variant. You don't know until she tested it. It's okay. But it's definitely good for the variants of up about a year ago. Okay. So, another thing that I noticed about this particular project is that you've got private investment haven't you? And it's funded by the state. It's come. It's a combination. It's really wonderful. That there was so much enthusiasm for this project at this state level. And Dr. Shepke in particular, he could keep making these amazing introductions to people that could help. And there's a foundation, Cova Schmidt Family Foundation, which is the initiative for Long COVID Silk Initiative. The initiative for Long COVID. They're doing global studies. Doing studies that have matched funds from somewhere else so that they're not carrying the whole burden. Are you finding that that is a sort of model that you're having to rely on more and more is that private benefit? Yes. Are you asking me today? Yes. Short answer. Is that even here in the United States for us to fully moly? That's going to have to be more of your reliance on that kind of thing. We so need philanthropic support and private foundation support and little startup support, all the non-federal ways of finding support to take projects like this for. But in this instance, this particular study, it's been a joy to work with the Schmidt Foundation because they not only funded it. They put their investigators together of all the things they fund and brainstorm together and network together and grow things that are even bigger than what the initial ideas were. That's amazing. And to be just do that because they want to be philanthropic. Or are they doing it ultimately? I'm assuming that they are really philanthropic, but perhaps they have someone they care about that's got long COVID. It's amazing. They wouldn't have spun up this one. The Schmidt Family is very generous in many ways, but actually they probably love our modeling work because they do a lot of supporting young technology and young people going into tech stuff. They have a lot of different ways that they use their wealth to do good in this world. We will have to talk about it once you've actually gone through that. So that we stand for a Mrs. Zalger News, so compared to last year, it's slower than we hoped. There was a process and then included an FDA, I&D. So we successfully have an FDA, I&D, which is a multi-month process. So yes, they required a fair number of changes to everything that we submitted to them, so you can go back a bunch of times. But it's all good. We're good to go and we're ready to shoot out the gates. We'll be recording and going. So that is finding news for people who have had long COVID for multiple years. But it is exciting. I'm going to caution a little bit because I'm in this field of horribly ill people who haven't had cures in the horizon. And I'll say this, I think it's this very exciting study. And it could be a curative study, which is super, super exciting. I love that whole concept of curative. And I will say in chronic illnesses like these illnesses are, there's a lot of things that make your life better that aren't necessarily the cure. And they're equally important. But when you go into a study that may be curative and you don't get cured because it's all a gamble, it's a study. You know, research, it's a hypothesis, we're testing it. I've seen people get so discouraged, they're suicidal. Okay. So I'm always trying to warn people who are so invested in it. But I appreciate that. But I don't want you to be hopeless if this trick doesn't work because we're working on lots of tricks. This is just a trick. And there will be more tricks. And the science is so strong in long COVID. That's every day the amount of new knowledge is coming out. It's growing, growing, growing. You know, and it just gives us a new and better way to come at it. So the patients I know are impatient because they're sick right now and science takes time. But that the recovery initiative is at 15,000 plus people, longitudinal follow-up, digging deep into the biomarkers, coming up with models and doing an extraordinary investment. But it's really hitting the ground with, I'm really getting some decent science coming out of that. It's changing the way we think about this illness. Have you found that from the record specifically from recover? I knew that baby was on censor and I think I was told was it a Beth Angle someone who was to whom to? There seemed to be people who really really rate the work that is coming out of recover. I think it's really great. And I went to the NIH meeting with last fall. They had a meeting that they're investigators and was open with the public. And I mean I didn't want to leave the room. Every single talk was like, "Oh man, when did they learn that? It's not out yet." It was really, really exciting. Do you feel like, obviously horrendous for the people right now who have long COVID or any other of the conditions? But do you feel that this has actually just made leaps and bounds in terms of, I'm talking about the attention and funding that has gone ahead of life? The ME/CFS patients are still kind of the poor cousin very much so because even in the recovery network, we applied to be a site and we were turned down because we wanted to compare to ME/CFS and they didn't want to do it. They kicked CFS comparisons when they were starting the funding, now the girl I studied a little bit, that they couldn't get. It was interesting because it's like 2022 or 3 whenever that was first happening, right? I swear to God it was just like the beginning of a acute COVID when people said, "Well, if we just study it, it'll fix it and it'll go away." Then how are you going to compare it to this long-term chronic illness? I'm like, "Because this is going to be a long-term chronic illness if you don't come up with big answers fast." I think perhaps some people regret that they didn't grab the ME/CFS cohorts quite early because they're a part of the comparative group to understand the kind of chronic disease as well as acute changes. It fix people where they are in the course of their illness. If you have somebody that had COVID six months ago and they're still sick, they're going to be mostly inflammatory, there's going to be the microclodding, there's going to be a lot of systemic inflammation and decided to know me, the autonomic nervous system is going to go cup-her-y all because of the very acute things that are happening in that window. But as you develop a chronicity, all these other systems that lean on each other, lean into that illness. There's going to be the immune system becomes exhausted, immune exhaustion, it has immune somatocytes, it tells us that the virus is reactivating, now you're dealing with all the other viruses that are reactivated, on and on and on. If I have patients in a trial, and they've been six, six months, they've been sick three years, so they've been sick. And then the ME/CFS case 10, 20 years, those are important to understand the differences of how having an illness for a long time can. where are your points of intervention? Did they change? And can you expect what you designed from these people with short-term illness to work on long-term illness? You know, that's a good, great question. Great question. They need to be answered, you know? Yeah. One of the areas that you have been looking into historically, but I think you've got a couple of studies that you are looking at right now, is the sex differences in ME/CFS, in Gulf War syndrome. So there's that idea in your mind, obviously, or your team's mind, that we need to look slightly differently at the way that we. is it the way that these things have developed differently between mal and female or is it just the therapeutic target that we need to. Again, we think of this whole thing as homieostatic networks being screwed up, so that when you're healthy, everything's in the balance. Your endocrine system, your immune system's all in this little balance, and if you listen to the monolers talk, they would talk about a well, like a little valley between two mountains. And if you got the flu, you'd get out of balance. You'd crawl up this mountain a little bit, but when you're better, you'd drop back, you'd back down into your healthy well, right? And the idea that a chronic homieostasis thing is going on, a chronic illness, is that you climb the mountain, you drop the ball down into the next well. And now you've got a chronic, unwell person, but very stably sick. The things that are wrong are going to be the same things, what hormones are wrong, whatever. This is unwell, but stable, and this is well and stable. And now I got to find a mountain way to climb up the mountain and drop the ball back into the other well. That's sort of the theory to turn our computational modeling group, and I think it makes good sense. And then you can deal with all the complexity. When you talk about gender differences, men and women are different in some very significant ways. Women are far more inflammatory. The immune system is more reactive. Women get all the autoimmune diseases far more frequently than men do, right? Men are swimming in this anti-inflammatory thing called testosterone that really quite stuffed out, so they have a biologic advantage on inflammation. So when we look at our models of these diseases, actually, they model differently from men and women. They model differently for postmenopausal, paramanopausal, and premenopausal women. And actually, the models predict different interventions for each of those stages of life. And that's because they're interactive, that the endocrine system is a play in a role in your estrogen and testosterone levels are in the model. And they drive a bunch of imbalance that's involved in the illness. Is it predominantly the whole main differences that you know? No, it's what the hormones do to everything else. If it was just hormones, every guy would just start testosterone and we have a low T syndrome, they have their TV ads here, because they advertise drugs here. I don't know. We're not allowed to. Remember when I made that, they advertise drugs and they're this guy looking kind of wiped out and go, I got low T. That's a great one. And then it gets testosterone. I'm like playing golf and doing football again. So if it was just testosterone, we wouldn't have those bulky little football dudes running around, but it's not because it's one of the easiest things to fix is hormone levels. So if all you do is fix that one thing, you know, make people better. But it puts the stage in place to be able to bump the other things that were completely out of balance and leaning into the wrong levels of all these hormones to stay out of balance. So in our models, we have to kind of fix the hormones and fix the immune system and fix the adrenal, the cortisol system. It's very complex. Yeah, it is. But it's got, because if you don't think in a complex way with such a complex illness, I don't think we have a chance to make people better than have been ill for a long time. So if you take those sort of three sections of the system, what therapeutics or interventions are you currently able to use that target each of those that enable returning to some kind of homeostasis or coming back into that in style? So if you walked into clinic without the benefit of having evidence-based medicine in ME/CFS saying, do XYZ, and you just walked into a clinic, the first question is, what clinic should you walk into, right? Because you're going to get a different treatment depending on who's door you walk through. So it's kind of important when you know all these different systems are whacked out to walk through the door of someone who's looking at the whole thing and not on the end of the chronologist and I'm the immunologist and I'm the cardiologist. But you are an immunologist, but you do seem to approach this from a very, very integrative medicine. When I moved from my other university where I ran the immunologic clinic and that's what I saw was nothing but immunologic problems. And I came here, we re-envisioned the whole clinical thing to be initially, it was going to be multidisciplinary. So you can see an immunologist, cardiologist, and all this at the same time. Yeah. Realized, you know, actually, no. Because most of the cardiologists really don't know what to do with this, you know? And neither do the neurologists or all these other specialists that see these folks who was doing the best job were people that were in the integrative or functional medicine. Okay. So we ended up with eight clinicians, I think we have eight right now. And I'm the only one that's not bordered in integrative or functional medicine. I'm the sole subspecialist left. Although actually we have a hematologist in the group too. So she's also bordered in integrative medicine. She did start in the knee. I went back to those board exams. So that's quite interesting. It's not actually something that I have actually speaking. That integrative medicine, which means combining, is that what you call it? Yeah, it's like binding specialty. It is. It's so interesting because look at my gray hair, I trained in medicine before you triaged anybody anywhere. You just took care of them. You know, I'm a boarded in internal medicine and immunology. So the internal medicine training would have been, I got training cardiology, hematology, I got training and all those things. And you only push someone after a subspecialist if you were over your head. Right. But now it's like triage and just everybody gets consult with every kind of specialist. But for long COVID and for MECFS, it's a tough situation because somebody has, even if you do that, who's taking all those consults and knitting it back into a management plan. Instead, you see people stepping on each other, prescribing drugs that shouldn't be put together because two different doctors ordered two different things or whatever. I just like integrative medicine conceptually because it's a whole body way of thinking. We do complex medical disease. these integrated medicine, most integrated medicines all about wellness, diet, nutrition, and do this and do that, and exercise exercises. I'm very bad at myself. I should do more. It's true confession. But anyway, we do something differently because we are starting from people that are pretty darn sick and trying to help them get up to better and better levels. I think with our treatment style in our group and other integrated medicine type folks, you just kind of a layered approach. Get them up a little notch and then get them up the next little notch until you bring someone out of the well into a much more functional space. So that's a really interesting approach that you're talking about just taking small steps because people can't do big steps. I'm definitely far, far away from my own conversation about trying to find cures, but I'm trying to say someone who's been stuck for a long, long time in a chronic illness is not a magic one that puts them better. Instead, you have to figure out the layers of their illness. What is autonomic? Can I fix that? What is nutrition? It's amazing how many people don't have the energy to put a meal together. And you start looking at their nutrients. And this person can never get better. She's not even feeding her mitochondria. So how is she going to make energy? Yeah. And that goes back to what you were saying about the all of the different time points and you can't treat the person who's had something for six months. Yeah. The only ones who did easy ones. You know? What's the layers in that one? The later ones are the harder ones. But treatable, very treatable and respond to treatments. So that's where they've so discouraged because they haven't gotten effective. No treatment has been sick for a long time. Interestingly, when they are more functional, you have to be careful that they don't fly back into making themselves sick. As I was actually mentioned, Dr. Unger. I was just on the phone with her right before this. And we were talking about cure rates. And I was remembering Kathy Row, R-O-W-E, she's an Australian pediatrician with the most amazing personal touch. And she saw every child on the head, M-E-C-F-S, in the South end of Australia. And then she followed them until they were well under their adulthood. So unlike just seeing them for until they got to be 18 and passed them on, they kept up. And she surveyed her kids in their 20s and early 30s to see that the recovery rate was, and the recovery rate was phenomenal. But when you really looked at it, it was adaptive behavior that made them feel completely normal and healthy. So even when they felt healthy, they were still being careful not to overexert. They were keeping their stress levels down. They were doing internal centered wellness kinds of daily activities. And they felt great. So, and so is that recovered? Or is that someone who's adapted to an illness to make it to the point where they're not currently symptomatic? I think that's a really interesting question. And I also wonder, obviously there is an illness and an adaptation that's gone on. But do you also have to look at whether the previous lifestyle of hard living, perhaps not sleeping enough, those kind of things were actually unsustainable in the first place. So perhaps the new lifestyle of pacing and nutrients is a more natural or an easier place for the body to find home status. But this may be a little bit of science to justify that hypothesis because in ME/CFS, there are some papers that look at just that type A, type whatever personalities. And there is more of what they call type A and type C, the cancer prone personalities. If you looked across the population versus people with ME/CFS, the pre-mortrific state was more hard driving or more keeping everything in. Right. Yeah. I think it's interesting because perhaps this idea of the way you were living previously was not normal. This is the more normal way to live. This taking it slightly easier. Yeah. It's not necessarily that easy to come to terms with. So because I have that feeling now, I actually operate. I'm five years I've had long COVID. And my life, the way I live now is very different. I'm not able to live in the same way that I used to live. But for the past two months, I've been on a relatively even kill with hugely adapted lifestyle measure. But because I mean, every Christmas we send out a newsletter that says happy holidays, the following things you will not do. And we try to keep them from us. Everyone goes out shopping until they drop and they cook for the house up. And they try to cook for dozens of people. And even the relapse rate during the holiday season is extremely very, very high. And I know what it is. It's just pure physical exhaustion on top of an illness that can't deal with that kind of trigger. But having the illness, you're slightly able to go, I can't do this. So it exonerates you from. So that takes you time, right? But you didn't do that in the first year. But you made yourself pretty much sicker than you would have otherwise been. Yeah, very definitely. Yeah. I wonder if this culture to that. One time I was hanging out with some French doctors and they said there was no such thing as chronic fatigue syndrome in their country. And I said, "Oh, that's just bullshit." Really? I mean, there's just no way. And you guys, "No, no, they really won't be." Because if you got mono in our country and you were still sick after six weeks, we would send you to the medical retreat. You'd be paid for by the. By the government. Beautiful place on the river and you'd get walking the woods and massage and stuff until you were better. And you could come home. And I wonder if that's really true. I didn't know the French way of practicing medicine, but what a lovely way to practice medicine. Yeah. Openstreet. I don't have it. I think they just don't recognize it. But the. A pretty cool answer, I thought that was neat. You've recently been part of quite a few papers. We came more bit pain condition papers with the CDC, where you've looked. Nice to see. Yeah. Where you've looked at back pain, migraine, various other conditions that are come more bit. You've done a study looking at joint pain. That's in Long Hover, a study looking at cognitive dysfunction in MCFS. In terms of research, where in our bodies or what is being affected and impacted, all of those things? Are they coming together in some kind of cohesive. Are we now understanding with all of these disparate symptoms or disparate parts of the illnesses, is something becoming clearer in terms of them coming together? Yes. I mean, just in the research that we've been doing in the last five years, is it guessing? Definitely. I mean, I'm going to say that we did the first 30 years, we were also telling us these things, and no one listened. So. Interesting point. Very interesting point. When I was in the Institute of Medicine Panel for MCFS, this case definition, and they were doing this intense review of every paper ever written on MCFS, very critically, very evidence-based, very carefully done the way they do at the National Academy of Science. It's really an amazing process to be a part of. But they were dismissing so much of the stuff in our field, almost offhand, not because it wasn't important, but because it was never validated, that you would do the first study with 30 or 40 people and you make the observation. And there was no one to pass the torch to to validate that. We're such a small field. You know, there's quite a hundred of us, maybe in the whole. 150, maybe, in the whole field doing science. And when you try to get funded to do validation, it's not original. You don't get funded for that, right? So it's cool about this long COVID study, the recovery one, even though I'm not in it, I can be really pleased with having 15,000 people because they can look into 5,000 and then they can go find a different 5,000 and validate their own work with a different chunk of the cohort, right? And it's like, "Kook, kick us. Indisputable. You proved it. No one's going to argue with you. That's evidence, right?" So we've never had a sample size close to this long COVID sample size that they have there and some other countries. The other thing they're doing, which is amazing, is with AI, data digging through medical records, right? Yeah. Which used to be pretty crummy because you had to do word recognition, text recognition, try to figure out what that means and build in some programming to try to make sense out of that. And now, there's just AI as much clever, it actually could read almost contextually the way I read. It's very close to being able to pull out of text, really meaningful phrases. So they're able to do more than simply search for codes and look at numbers. They actually can look at recovery rates and look at what medications people are on that influenced what. Yeah. So that's amazing, isn't it? Yeah. That's the sense you can pull out data that you almost didn't know that you were looking for. Exactly. Yeah. I mean, you've seen the VA does this now. The system called Vinci. I forget what it stands for. Anyway. - I think they have more than, I don't know, crazy number of veterans, I think 40 million veterans in the healthcare system. - Wow. - So you can look at 40 million medical records for codes or buzzwords or something. It's pretty cool. - Yeah. - And then they've been publishing one paper after another that was really important early in the pandemic. They were publishing the rapid release important observations from clinical interventions and changed the way we were treating the acute COVID. That was pretty cool when this goes, they could do it with a computer, which is doing, yeah, really cool, some cool stuff. So I have these new tools and those are, I guess, a big end studies when you look at 40 million records up, no one's gonna argue that you didn't find something. So it's pretty neat. And those things find stuff. So this study, and again, I'll use Francis, an example, just 'cause I remember this one. They did one of those big reviews before COVID for risk factors for Parkinson's disease. So, disease I'm very interested in studying. They discovered that people with asthma had a lower risk for Parkinson's disease. Well, that didn't click, but there was a definite association. So then you could dig back in a little deeper and you could discover that the puffer you take for asthma, which is essentially adrenaline, was neuroprotective. And these people that were asthma meds for many years had been taking unbeknownst of them and neuroprotective agents and their puffer. Well, it kind of changed the way we thought about the whole brain thing, right? Because we didn't know that that should be neuroprotective. Someone had to postulate, why would this asthma do that? Shouldn't it's inflammatory, should make everything worse? But I'm taking puffers and they have one of them's got adrenaline type things in them and not those God. Stereoid type things in them. What would that do? And that started making some sense. It was kind of cool. So that's digging into a massive data set, looking at the entire population of France literally, 'cause it's a healthcare system. And then finding these patterns that actually help you discover the biology of an illness that you didn't know. It's kind of cool. - So that's what our technology is really stepping forward. And AI, that is one of the positive developments coming out of the AI. - AI is not all positive, but that is positive. We used it appropriately in understanding where its limits are. - Yeah, I was actually saying this to someone the other day that there are amazing things within the medical field that can be achieved with AI, the advancement. It's pretty cool. - So in terms of MECFS, you were part of the directive in 2017 with your whole crew, this whole, these people who have been working in MECFS for decades, the next day. - And you have come up on all of you, all seem to work together. - And that's for that, 'cause you can't review a paper. If you've been on a paper with somebody else in the last five years, you can't review their grant. If there's about five years there, we're not, this we're real. - No, no. There's no expert left in the country, because we're all on the, the extra paper. - So you were part of the team that created the standardization of how you evaluate and treat MECFS. And now in 2025, you're actually, I think, you're doing another project. I don't know if you'd call us a study. That looks at the clinical assessment. - I think you talked about our CDC study, the COVID-up study. So what you say? - It was about MECFS and the clinical assessment and creating a biorepositive tree. - Yes, that's exactly right. - Is that an MECFS or is that an object? - That one's long COVID. - Oh, is it? - But it's been compared to the MECFS one. - Okay. - So right before the pandemic, we just finished a five year study of MECFS with the CDC design of the study, contracted seven sites to recruit. - Yeah, yeah. - So there were seven sites with the who's who? - Yeah. - That was a sort of longitudinal study. - It was a longitudinal study. It was very comprehensive. It was kind of a deep phenotyping study. They had lots and lots of components to it. And a lot of assessment in its pre-pandemic, clean pre-pandemic cohort of MECFS. So the problem post-pandemic is we don't pick out the MECFSs that aren't long COVID. - Yeah. - Because how do you know? It's getting trickier. So that's the comparative group is this nice 750 patients that were in that study. And now in this study, the long COVID study, we repeated essentially the same assessment with a few more biomarkers that were in available then. And we are digging into their, the biopository from that old study. - Right. - To be able to do comparisons with MECFS. So it's a very exciting study. We're just sending samples after the O-Link assessment, which is a big proteome link assessment that they underbuilt for both those cohorts. - And is there hope with that that you create that slightly more standardization in terms of long COVID? Or is it just to develop your understanding at large in terms of MECFS and long COVID? - Probably deliberately we're comparing the two to see where they're the same and where they're different. Okay, with a large enough group to be understanding gender differences and whatnot. We're particularly pleased with our, the code was called COVID up, the COVID, understand the post-fire all phase, COVID up. And we are in the final year. We have about 900 people in a longitudinal sample. And about, we're bringing in 200, we've got 150 complete ish, maybe a little more, to bring them in for the phenotyping part and have all the samples and things. And batching those up and sending them after the best labs in the country, Dr. Wears Lab. And it's going to do the spike protein assay for us, for instance. And the link thing's going in our own laboratory here, which is doing cytokines and hormones. - And that's very exciting. That can sort of sit alongside the study that I, based on Vernon about which was looking at the prevalence of MECFS, which was actually done based on the data of self reported symptoms and how people were feeling. And you're suggesting here that what you're doing is you're taking samples and you're doing assays to actually look. - In addition to all that self reporting. So, I mean, the poor patients are doing, you know, a couple of hours worth of self reporting every time they assess them. So they're really being very generous with their time and their dedication to the study. And I'm grateful. And the M-CAM study, the original CCC study was also equally time consuming for the patients. - Yeah. - And so, but anyway, there are great studies to try to answer that question where they're the same, where they're different. What's nice about the one that we're doing now for along COVID is that it's here in South Florida. We're doing this great CCC study and an incredibly diverse community, which is South Florida, where we're just a tremendously diverse community. And we recruited this study using hospital systems so that we send emails and links to everybody in the whole hospital system begging them to be in our study. So what we ended up with is a demographically representative cohort that very much looks like South Florida, 55% Hispanic, 19% African American, which is a little bit different than the M-CAM study because that was a clinic based. And you will always find, particularly in expert clinics, that you have to have advocates and resources to get into expert clinics. It's just overwhelmed and too many patients to see and somehow those most diligent people get in. So I look into this group that we have coming in from the county hospitals and things. And I'm like so happy to see them getting in a proper assessment. And the data that we're learning from is truly the data that's in our community. We're not just the people that can find us. - Fit the South demographic. Yeah. - Amazing. - Yeah, I'm good. - Are you talking to Dr. Thierry? - I speak to him already. - He's great. He's our most popular podcast. And he gets the most downloads of anybody. (laughing) He really does. - He's so lovely. - He's great, but he has all these connections that decide on how to make a community knows him, that they're the mass cell activation. - But this is so interesting about so many of these cross-avers is that people will put into boxes, but they're actually-- - And they're not. He's a great guy. I love his career because he's a doctor who saw something, pursued it, had his own laboratory, gave us most of what we understand about mass cells coming out of his laboratory and his career trajectory, developed interventions that treat those abnormalities and then saw them all the way to market. Good for him. You know, it's so many people that do science. They do these amazing discoveries. I mean, I've had PhDs that were retiring, come and hand me boxes of step and say, please take this and move it to the next milestone, right? I'm like, oh man, how awful would it feel if you're retiring knowing that you hadn't taken your discoveries all the way through their patient care? That's how privilege as a group is that we have this amazing group that can take a discovery and get it all the way through. - And get it to page. - Yeah, exciting. - Yeah, it's very exciting. Is there another study that you would like to talk about? We're doing the reboot study which is trying to reboot systems. That one's kept a long stall for the pandemic. We're about to do it right before the pandemic and we got stalled because some of the medications are in suppressor that we kept use them during a pandemic. So it took us a lot to get that one going back again, but now that's finally off the ground. And we have a study on the mic. biome using probiotic types of treatments to try to get a less inflammatory. Because those are the kind of things that you actually advocate for aren't they? We use the proteins and probiotics. Using food is a therapy. It's really important. And if you've looked at the diet of people who are too ill to stand in the kitchen, you'd be shocked with their eating. They're just not getting the nutrients. They're not getting the nutrients. They can't get better if they don't get the nutrients. But also nutrients are anti-inflammatory, nutrients are the things to know about your diet that can help your immune system recover. And that's really important. So if there was one thing that I asked you for people with chronic illness to consider or just to think about, if there was one piece of advice that you could give them, would that be? Yeah, I know. Would that be nutrition today or would that be? That's a thing. But I say it's a layered approach and they're all important. Restortive sleep, how important is that? I mean, it's not an easy thing to achieve, but that's when you heal, that's when you mend. There's actually a flow of something called glymphatics in your brain that reverses its direction when you're asleep and detoxifies your brain. You need sleep to detoxify your brain. That's way important. You wouldn't even think this two things are connected, but boy, are they connected? So it's just anti-inflammatory foods and nutritious foods. Never putting anything in your mouth, it's not going to actually help your body, that makes good sense. And you can get restorative sleep and have a family that loves and supports you. Keep your networks together and love them back for it and support them. Be a part of the love circle. There's so many parts to this, what do you say? And then yeah, the immunologist says, take good care of your T-cells, but that's trickier. And yes, your microbiome matters because it really messes up your whole body if it's wrong. That matters, yeah, that's true. I'm out of our within immunologist and we haven't talked about the T-cells. That's okay. That's for another time. And in terms of this going forwards, outside of what you are all your team is doing here, which is incredibly exciting and talking to Dr. Thierry-Duz as well, it just seems that you are all so involved in interesting areas, who is doing exciting work or what is exciting outside of the work that you're specifically involved in. Because every time we talk about the T-cells, so many people. But there are so many people. I mean, I don't really know about that. This network, about the way that you all collaborate, it's absolutely amazing. And it's not just within your country, the collaborations that you seem to have outside as well. No, it's going to be international. In fact, I love, if you look at our group, our clinician group, we have Somers born in Russia, Somers born in Poland, Somers born in Israel, Somers born in, I mean, everyone's from somewhere else, right? And when you talk, and they learn medicine there, so when they come to me with my US, not just Western, but US Western medicine, and I realize, man, am I in a little box? These guys know things I've never heard of. And so I long ago committed to go to international conferences and learning from everybody because they bring so much to the table. And I've learned a lot that way. It's been really helped us and helped us develop our ideas and our thoughts. I continue to be blown away by the people operating in this field, the level of dedication from people like Dr. Climus and her entire team there. And I have to tell you that the facility at the Institute for Neuromy Medicine is phenomenal. The people that I met were so dedicated to rigorous robust science and compassionate care. And as Dr. Thierryde said in episode 13, they are truly thinking outside the box and look at these conditions in a multifaceted way. I feel that people are in safe progressive hands under their care. I am genuinely humbled by the people that I meet working in this field. So whilst I wouldn't wish chronic illness on anyone, I am so grateful for the path that my life has taken that enables me to have these conversations. Thank you to each and every one of you who contribute to this research, to this care, and to making progress for patients and our medical understanding at large. Thank you for listening to Make Visible. Please do like, follow or subscribe to listen to our next episode where we'll be uncovering more insights into complex chronic illness. This was brought to you by the team at Visible, a group of scientists and engineers whose lives have been affected by energy limiting health conditions. We're building wearable technology that's helping a hundred thousand people measure and manage their complex chronic illness. To find out more about what we're working on and how visible could help you, visit our website at makevisible.com.