Episode #205: GENIE Testing in CIRS with Dr. Ritchie Shoemaker, MD

Why You Should Listen

In this episode, you will learn about the use of GENIE testing in Chronic Inflammatory Response Syndrome.

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About My Guest

My guest for this episode is Dr. Ritchie Shoemaker.  Ritchie Shoemaker, MD is a recognized leader in patient care, research, and an education pioneer in the field of biotoxin related illness.  While illness acquired following exposure to the interior environment of water-damaged buildings (WDB) comprises the bulk of Dr. Shoemaker’s daily practice, other illnesses caused by exposure to biologically-produced toxins are quite similar in their “final common pathway.”  What this means is that while the illness might begin acutely with exposure to fungi, spirochetes, apicomplexans, dinoflagellates and cyanobacteria, for example, in its chronic form, each of these illnesses has similar symptoms, lab findings, and Visual Contrast Sensitivity (VCS) findings.  Taken together the inflammatory illness from each of these diverse sources is known as  Chronic Inflammatory Response Syndrome.

Key Takeaways

• What is GENIE?
• Is HLA-DR still relevant?
• What are the common triggers of CIRS?  Actinobacteria?  Endotoxins?  Mold and mycotoxins?
• What is hypometabolism?
• How does CIRS impact insulin and blood sugar?
• What is apoptosis?
• What is the role of coagulation in CIRS?
• Are upregulated cytokines seen in CIRS?
• Can GENIE identify those that may have Lyme?
• What are defensins?
• What is Ikaros?
• What is the role of MAP kinases in CIRS?
• What do Toll receptors tell us?
• How are B and T cells involved in CIRS?
• How many CIRS markers are needed in GENIE to suggest CIRS?
• What is the PTSD gene?
• How often is histamine involved?
• What are the cytoskeleton and microtubules?
• What can be determined around the function of Treg cells?
• What are the recent additions to GENIE in the realm of Parkinson's disease?
• What has GENIE told us about MARCoNS?

Connect With My Guest

http://SurvivingMold.com

Interview Date

September 11, 2024

Transcript

Transcript Disclaimer: Transcripts are intended to provide optimized access to information contained in the podcast.  They are not a full replacement for the discussion.  Timestamps are provided to facilitate finding portions of the conversation.  Errors and omissions may be present as the transcript is not created by someone familiar with the topics being discussed.  Please Contact Me with any corrections.  

[INTRODUCTION]                                               

[00:00:00] ANNOUNCER: Welcome to BetterHealthGuy Blogcasts, empowering your better health. And now, here's Scott, your BetterHealthGuy.

The content of this show is for informational purposes only and is not intended to diagnose treat or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.

[00:00:35] SCOTT: Hello, everyone. And welcome to Episode 205 of the BetterHealthGuy Blogcasts series. Today's guest is Dr. Ritchie Shoemaker, and the topic of the show is GENIE Testing in CIRS. Dr. Ritchie Shoemaker is a recognized leader in patient care, research, and an education pioneer in the field of biotoxin-related illness.

While illness-acquired following exposure to the interior environment of water-damaged buildings comprises the bulk of Dr. Shoemaker's daily practice, other illnesses caused by exposure to biologically-produced toxins are quite similar in their final common pathway.

What this means is that while the illness might begin acutely with exposure to fungi, spirochetes, apicomplexans, dinoflagellates, and cyanobacteria. In its chronic form, each of these illnesses has similar symptoms, lab findings, and Visual Contrast Sensitivity results. Taken together, the inflammatory illness from each of these diverse sources is known as Chronic Inflammatory Response Syndrome, or CIRS.

And now, my interview with Dr. Ritchie Shoemaker.

[INTERVIEW]

[00:01:48] SCOTT: The topic of biotoxin illness or CIRS, which is Chronic Inflammatory Response Syndrome, has been a key factor in my personal health and recovery and a top issue impacting many with various chronic conditions. I first learned about this work around 2006 from reading Dr. Shoemaker's book Mold Warriors, which came out in late 2005. At that time, I was living in an apartment with visible mold but had no concept of mold being a potential contributor to chronic illness. Fortunately, for me and for many, Dr. Shoemaker brought these concepts to our attention and has changed many lives for the better. Thanks so much for being here, Dr. Shoemaker.

[00:02:25] DR. SHOEMAKER: Well, good morning. Thank you for having me on your show. I look forward to it.

[00:02:29] SCOTT: At a high level, what is the GENIE test? I know it stands for Genomic Expression: Inflammation Explained. We know that inflammation is at the core of CIRS.

Many people are familiar with SNP testing, or single nucleotide polymorphism testing, which really is more the potential than actual gene expression. And as I understand, GENIE is looking at how certain genes are expressing in the moment and not just the potential of a gene to express one way or another in the future.

And then adding on that, can we potentially use GENIE over time as an indication of treatment effectiveness by exploring how treatment has impacted or changed our genetic expression?

[00:03:13] DR. SHOEMAKER: All true and well-stated. The one thing I would add is it also gives us a chance to recognize relapse. And the etiology of the relapse is sometimes very hard to figure out. But GENIE provides mechanisms to identify recurrence of illness abnormalities even before symptoms become dominant.

[00:03:33] SCOTT: And so, as I understand, the fingerprint essentially of the different genes that are either overexpressed or under-expressed, that can give you some insights into the potential contributors to someone's Chronic Inflammatory Response Syndrome. Correct?

[00:03:49] DR. SHOEMAKER: Absolutely.

[00:03:50] SCOTT: Talk to us about how you now use HLA-DR testing compared to the GENIE transcriptomics testing. Is HLA-DR testing still as helpful today as it was many years ago? Or are we now looking more at GENIE to bring insights around why someone may be having a health challenge? Do you still use both? And how are they different in terms of their clinical value and application?

[00:04:15] DR. SHOEMAKER: Use of HLA goes back to the year 2000. By that time, I had been looking at Pfiesteria patients for three years, and cyanobacteria patients for two years, and mold patients for a year and a half. And it was quite clear that there were similarities in clinical presentation. Visual Contrast Sensitivity was our only tool for a while. Started recognizing that symptoms were the same of these different illnesses.

There was exposure situations where people could be exposed and get sick. And people sitting and standing beside them would not get sick. People would be exposed to Pfiesteria blooms in the Pocomoke River or the …. Chesapeake Bay. And why did three people get sick and seven people didn't?

And we looked at lifestyle and little questions of medication, and diabetes, and heart failure, and renal failure, and cardiovascular disease, nothing stood out until HLA came out. At least to my knowledge, it came out in 2000. I think the book was “HLA for Dummies”, which is appropriate. I thought, "Oh, look at this. We can now point to an objective, and that was key, an “objective” parameter that would tell us who is sick and who wasn't when they had their illness grouping coming forward.” We knew we had to establish exposure. We knew we had symptoms. And some labs were just getting started. But in order to get people better, we need to help start out with what's wrong with them separate from one to another.

As HLA became clear, that when we looked at the HLAs, we identified Lyme disease. Two triplets, 15-6-51 and a 16-5-51 jumped off the page. They were in the post-Lyme syndrome. That was it. If you had 15-6-51 and you had symptoms and you've been treated for Lyme, this was going to be something that was not an infection but it was inflammation. And that was fun to find.

Less commonly initially was 4-3-53 and 11-3-52B. These were found in 3% of the controlled population and 1% of the controlled population respectively. And, boy, were these people worse off. I would see the lab report and I would dread seeing it. I started calling these the “dreaded genotypes”. And sure enough, HLA would pick out the worst ones with great accuracy.

Then we had subtypes that would pick out illnesses from water-damaged buildings and low MSH. And there were a few others. But, basically, there are 54 different haplotypes that we could stratify and look to see with a disease incidence of found in cases versus controls of a relative risk about 1.5. And that was a way, that was one of the first diagnostic tests that really helped me find what's going on.

It wasn't until 2006 that we found the mechanism of this differential susceptibility. And it turns out that HLA-DR or human leukocyte antigen or histocompatibility locus A is coding for exposure to proteins. And there will be a protein-based structure, a cleft if you will. And then the offending antigens will fit into the cleft. And if there is the sequence of amino acids that was not known very widely before 2006 that we could then say that this is the mechanism of protein identification, which is important in host versus graph for transplant testing and all that.

But beyond that, it didn't really tell us what was making the illness come forward. But it was the first step. And MSH was the next step in 2001. And there we found lack of the regulatory neuropeptide called melanocyte-stimulating hormone. And it controls cytokines. It controls circadian rhythms. It controls a whole lot of things. But most importantly people, who are deficient in MSH would have problems with fatigue. And chronic fatigue became kind of synonymous with low MSH.

MSH is made with endorphins when it is being manufactured. Chronic pain accompanies deficiency of MSH. And then we also had people who had leptin resistance. And leptin would be turned on by a cytokine which would turn on an area in the brain, a gp130 cytokine receptor. And that would then regulate diet. If you didn't have MSH, and cytokines were too much, and leptin got too high, people will be heavy.

We could come up now with a construct that, under the influence of HLA, we can tell who's going to be tired, who's going to be in pain, and who's going to be overweight. And that was the lead-off into cytokines. And cytokines got their big start probably about 1995. And before that, with TNF. But by that time, there was 10,000 papers that were written on cytokines.

And sure enough, if the MSH was deficient and HLA showed susceptibility because of the kind found in a given illness, we could start to stratify who had inflammation due to an exposure. And inflammation was driven by cytokines. We could identify who is going to be having that with an objective parameter called the Heidelberg retinal flow meter. And that led us to see velocity of red cells in the retina and the neuro rim of the optic nerve head.

By 2002, we had a pretty good idea of what was going to be involved with what was later we called CIRS. We called it chronic biotoxin illness-associated illness the first time. But HLA has maintained its role as the best way about finding proteins that are abnormal and it still holds true. But it only tells us probably 95% of patients. And 5% will have no known HLA if they're still sick. And that's where MSH deficiency comes in.

It just showed that HLA was a static measurement. You need to do one HLA test in your life. Because genes won't change. But we needed something better. And that's something better, which we'll get to directly, is GENIE.

[00:11:04] SCOTT: Just to keep some hope out there for people listening to this podcast, I am a 4-3-53. And I've done very well with treatment over the years. Just because you may have one of those HLA-DR types that Dr. Shoemaker suggested are more difficult, I don't think that he's suggesting that those patients cannot improve with treatment.

[00:11:24] DR. SHOEMAKER: One of the fascinating issues is 4-3-53 is also found in rheumatoid arthritis is a leading cause. Found in mitochondrial diseases. The autoimmune types. And so, it's not just CIRS, which we now know HLA is important. Multiple Sclerosis will show up more frequently with 15-6-51. And there's a whole series of new advances being made. But the key issue is that your HLA is not going to change as you get older. My HLA won't change as I've gotten older. But it still carries the same susceptibilities. And that means that the risk for us is avoidance of relapse. HLA won't tell us with relapse. Cytokines will of a certain kind. We really found that defining the gene basis for relapse led us into the gene basis of illness paralleling HLA. It's good but it's not the same as GENIE.

[00:12:25] SCOTT: While we're on the topic of HLA-DR, given some of the more recently understood CIRS triggers such as Actinos, endotoxins, beta-glucans, have we yet made any correlations to which HLA-DR types are more susceptible to those triggers? Is that a work in progress? Do you anticipate someday that there will be an HLA-DR type that might serve as a clue for Actino or endotoxin exposure as a potential for a CIRS trigger?

[00:12:54] DR. SHOEMAKER: One of the difficulties with a good answer to your reasonable question is what are the structure of the antigens that we're thinking about? Is it a protein? HLA will give us a result there. If it's not a protein, we're not going to be expecting HLA will be looking at it. And that's where we ran into the definition of CIRS from years ago was looking at an acute and chronic illness characterized by exposure to biologically-produced toxins, including those from mold and Lyme, what have you.

But we also made room for Actinos. They were known to be a problem back in 2000. Endotoxins are very – many different kinds of bacteria make endotoxins. They're all gram-negative rods to this day. But the issue is that if we find HLA in them, that is reflecting a protein that they're reacting to.

Now, we're going to get to I think probably the difference between Actinos. And just for sake of argument, it's Actinobacteria. Not Actinomyces. We'll call it Actinobacteria for today. You made me happy. Actinos are associated with HLA. And in one early study I did, we had 48% of cases initially for Actinos, we had 4-3-53. And about 25% were 11-3-52B. Later studies have shown those numbers are not keeping track, keeping pace. We can't say it's 75% of the cases yet. But there is hope. And we were hoping to come up with antigen treatments based on a mechanism of detecting those antigens which we have with GENIE.

[00:14:41] SCOTT: Before we leave the HLA-DR conversation and move into GENIE, which is really what I'm excited to learn from you about today, I've seen this question come up quite a bit in the community, both practitioners and patients. When someone has HLA-DR that is mold susceptible or multi-susceptible, is the antigen that the body has an inability or difficulty in recognizing the mold itself, the mycotoxin, or both?

[00:15:08] DR. SHOEMAKER: Well, it's a protein. That eliminates mycotoxins and most toxins right off the bat. If you look at the standard Penicillium or Aspergillus organism, there are over 300 protein antigens on the cell membrane. And there's even more antigens from mannans on the cell membrane. Chitins, not so much. Beta-glucans we think are going to be something. But it's not going to be a protein. The antigen detection we're looking for is not going to be a protein that we can describe illness to. HLA falls short along that way. But there's bound to be a son of HLA out there somewhere. Just a matter of finding time to do the research and do the patient volume of testing. We have about 14,000 specimens saved in our deep freezer. At sometime, our library can get it opened up and find out what we've got waiting for us. But it's not high on the research list as we sit here today.

[00:16:16] SCOTT: If I understood that correctly, it is the mold that is the susceptibility. Not the mycotoxin produced by the mold from an HLA-DR perspective.

[00:16:25] DR. SHOEMAKER: From the HLA-DR. That's correct.

[00:16:27] SCOTT: What are some of the newer pieces of inform information that we've uncovered through GENIE testing that maybe have an impact on CIRS treatment beyond the treatment approaches that we used previously? Has the result of GENIE led to any changes in the CIRS or biotoxin treatment approach? The 12-step biotoxin illness model that you created years ago. Or is that same model still working today for these newly understood CIRS triggers?

[00:16:56] DR. SHOEMAKER: The credit for the work in the laboratory work on GENIE goes to James Ryan. Jimmy, as he's called by everybody, has been using his skills as a molecular biologist for years. I'm still learning about genes. And my wife is still learning about genes as well. It's something for everybody to look at.

But what we are looking at first was Jimmy was seeing that in these chronic fatigue patients or chronic fatiguing illness, that means we're not trying to make distinction what the cause is, that he was finding marked suppression of mRNA that was leading to protein production by ribosomes. And that was unusual. But it means that if the proteins are not being made, then your low protein content of one kind or another, that'll have downstream effects.

I mean, there's a million ribosomes in every cell. And not every ribosome has got deficiency of protein production. But most of them do. And in organisms with chronic fatiguing illness, there is suppression of ribosomal activity, making proteins. But as people respond to treatment A, or B, or C, we see a return of the protein levels and ribosome function back to normal.

And then we come up, we find out in microbiology, there are bacteria over 6,000 different species that are known that are toxin antitoxin formers. And what that means is the genes for a given toxin can be activated when the organism is being stressed or attacked. And these toxins can make the organism kind of go into torpor or hibernation if you'd rather. They're not doing very much. But when it's time to wake up and Rip Van Winkle's 20 years are over, there will be antitoxins made by the same organism.

The adaptive success-driven approach is to lay low, Br'er Rabbit, and will throw you in the briar patch and Br'er Fox will be gone. And you can come out when Br'er Fox is gone. But specifically, that mechanism, only we're seeing with treatment. Now, Jimmy then noticed that a second phrase is that there are mitochondrial genes that were being suppressed. Now, remember, there's over a thousand genes that had the origin of being in mitochondria. There's only 37 left. I think my numbers are right. Less than 50. More than 25. But the rest of the mitochondrial genes are under control of nuclear transcription factors. That's where you'll find the mitochondrial genes.

And what that leads to is its so-called mitochondrial illnesses. You're not going to support by doing something in the mitochondria. You're going to do something to support their genes. And sure enough, what we see in mitochondria is that they have ribosomes themselves. They make their own proteins. So, mitoribosomes and then mitochondrial genes. And there's a whole series of those genes that Jimmy has lumped under one kind of grouping.

And they include ATP synthesis, and cyclooxygenase, and mitoribosomes large and small, and translocases. My goodness. Scott, are you familiar with translocases? Or have you been doing your homework done? Translocases, we'll take pyruvate from the cytoplasm. And somehow, wriggle its way and penetrate through the outer mitochondrial membrane into the inner mitochondrial membrane space. And then they'll be pumped against the gradient inside the matrix of the mitochondria. If you have translocases, you'll have pyruvate and you'll have ATP production. But what do you think would happen to ATP production if you don't have translocases?

[00:20:59] SCOTT: It sounds like it's going to be reduced.

[00:21:02] DR. SHOEMAKER: Reduced energy production is the critical issue. We also have voltage-dependent Na channels that are more driven by actinobacteria than other things. But translocases was a new term to me in 2012 and 2013 when Jimmy started doing this work. But he found there was reduced delivery of pyruvate. Well, what do you think happens to the pyruvate if it can't get into to the mitochondria? Will we be saying there's mitochondrial damage? Well, no. We're looking at translocases being damaged. Not the mitochondria.

Because when you fix the translocases, voilà, the mitochondria come back to being normal. If you go to your world summit on mitochondrial things you don't talk about translocases, I'm going to leave you. You guys are not talking – know don’t what you're talking about. But the real issue is that if we then look at mitoribosomes compared to ribosomes, the same function through the sarcin-ricin loop applies to both. And the sarcin-ricin loop can be damaged by small molecular weight toxins, ribotoxins, and ribosomal inhibitory proteins. Those are called RIPs, by the way. I think it's a good name. Rest in peace, ribosome inhibitory proteins. Because everybody who has these will have defective energy production. And everyone who has that in the later stages will have conversion of pyruvate to lactic acid. Three-carbon fragment. That's then secreted against the gradient into capillaries.

Well, what that creates is metabolic acidosis. And proliferative physiology was described by Otto Warburg years ago, in 1928. And again in 1955 with more work. But proliferative physiology is primarily due to translocase abnormalities, failure of penetration of pyruvate into mitochondria, and conversion of pyruvate inside the cell to lactic acid creating the problem that we now know. If we've got lactic acidosis as a forerunner, we'll find insulin resistance. We'll find deficiency of regulatory T-cells. We'll find an increased amount of grey matter and nuclear atrophy. And we'll be looking at proliferative physiology as a basic mechanism of chronic fatiguing illness. The long answer is that Jimmy's approach showed us where the mitochondrial problems lay and where the ribosomal problems lay. And we had recognized that we better stay away from RIPs.

Now, bacteria, especially Actinos, make ribosome inhibitory proteins. And they're some of the bad players. We didn't know that. I didn't know that. I should not use the word we. But specifically, finding out about sarcin-ricin loop led to this overall function of GENIE telling us about inflammation creating chronic fatiguing illnesses and metabolic acidosis.

[00:24:17] SCOTT: They say if you want to become smarter, to hang out with smarter people than yourself. And so, today I feel like I'm becoming a little bit smarter talking with you.

[00:24:27] DR. SHOEMAKER: Well, imagine talking to Jimmy Ryan, you know? You really –

[00:24:30] SCOTT: Let's talk about what some people might see as the elephant in the room. And then we're going to jump into GENIE. But we've used the term mold illness for many years to talk about biotoxin illness, to talk about CIRS. You've always talked about the soup of triggers found in a water-damaged building for as long as I can remember.

More recently, I've heard statistics suggesting that Actinobacteria are a trigger for CIRS in 42%, approximately. Endotoxins, 28%. Beta-glucans, maybe 23%. Mold and mycotoxins, only 7%. Wondering, did that come from GENIE findings? And for those people that maybe feel they've been chasing mold for years only to find out now that we're really talking more about bacteria, has the treatment focus been wrong? Or does proper environmental mitigation, remediation patients still address these other triggers? In other words, are patients starting over? Or is this emerging focus on bacteria rather than mold more of a refinement of the earlier understanding?

[00:25:41] DR. SHOEMAKER: Well, don't forget that inflammatory responses are still ones to be recognized as being due to exposure to water-damaged buildings with molds that we can show. ERMI and HERTSMI-2 are two of the mechanisms to identify old species. HERTSMI-2 is a little more specific and it gives you the answer of will – if I get better from my illness, will I get re-exposed to this place, will I get sick from re-exposure? Well, the answer is yes. And there are five organisms that leave the way along that way.

But the issue is that when we started looking at GENIE, the gold standard for me and the Holy Grail was specific causation. Because here we are looking at a moldy environment with this stew. And I've used that term over and over again, I'm not quite sure we can give 23% to beta-glucans. But the other elements we could and we're able to publish on the specific causation for molds, and specific causation for Actinos, and specific causation for endotoxins. And that number is 42, and 28, and seven. Plus or minus one or two in one study or another. But they're still holding their own after about five years of playing with them.

The key correlate, and I may be getting ahead of myself here, is that we can then look to see if we've got specific causation for Actinos and we're going to have metabolic acidosis, is there something that we can tell about NeuroQuant that will tell us about brain injury? And the answer is yes. Specific causation, we worry about a given kind of brain injury, a pattern of brain injury from a specific kind of specific causation.

Similarly, if we've got endotoxins, we'll find the worst brain injury. When we talk about brain injury, we're talking about cortical grey, being atrophy, or superior left ventricle being dilated if it's next to the cortical grey. You say, "Well, there's less pressure on the ventricle. It'll expand just like you blow up a balloon." Well, that's an analogy that holds some water. But not a lot.

But then, specifically, the grey matter nuclei we worry about. And there's six of them. Hippocampus and amygdala and caudate and putamen and pallidum and thalamus are the ones we worry most about. But by looking at specific causation and specific brain injury, we are now bringing what I consider to be the ideal time in the life and era of a CIRS provider, is that we can now fix the brain injury not as a matter of we got lucky one day, but a matter of we can expect to use the new protocols for brain injury to heal what we couldn't do with a 12-step protocol I used before.

[00:28:45] SCOTT: Now we're going to get into GENIE. GENIE testing, as I understand, shows each marker in shades of blue or red indicating either hypo, or under-expression, or hyper, or over-activity, over-expression. How dark the blue or red is indicates greater than one or two standard deviations from the norm. Lighter for greater than one. Darker for greater than two. Energy-producing genes could be blue or under-functioning. Inflammation genes could be red, or turned on, or overactivated.

Are all of the genes looked at in GENIE either up-regulated or down-regulated as a result of the patient's CIRS trigger? Or can there be other reasons for the up and down regulation that could be addressed independently of CIRS treatment? Like let's say a heavy metal or a chronic Epstein-Barr virus. In other words, might GENIE show abnormalities in someone that does not have CIRS? Are there specific criteria that suggest that someone does have CIRS?

And potentially then that, with treatment, they may no longer have that gene expression that is consistent with an ongoing Chronic Inflammatory Response Syndrome.

[00:30:00] DR. SHOEMAKER: What we can't do is use GENIE to provide a case definition. We have a case definition established in 2003 by my group. It was kind of changed by the USGAO in 2008 to be the current case definition. But there are some features about GENIE that let's us think that there probably is. Now, your color coding is almost right. Every gene is likely represented in a little oval. And there's a number in there. Those are the Z-scores. And, typically, 1.3 is the cut-off. If you're higher than 1.3, that's higher than expected. If you're lower than 1.3, it could be normal. But it's not going to be over-producing.

There's some exceptions to that. If we look at antigen presentation or T-cell synapse, any value less than 0.000 is going to meet the case definition for defective antigen presentation, which is critical in CIRS. And then for IRS2, which we're going to talk about as well, that will be looking at any value greater than 0.000.

If you're 0.01, your IRS2 is too high. And that will lead us to changing your diet away from a keto diet because there's a positive IRS in favor of then looking at what you can do with changing insulin uptake by the cell. But pretty much, if the Z-score is over 1.3, worry about it. If it's not, don't worry about it. If it's zero, you can't really call it one way or another.

Having said all that, if we combine genes in the metabolism venue, there are eight or 10 that are COX-2. There's like nine or 10 for ATP synthases. There's seven or eight for translocases. This is the only grouping of genes in which multiple genes are then used to generate a Z-score. Every other gene is a single entity. That was because this was so important. And Jimmy spent a lot of time on it.

Just a quick bit of history. When we started with doing gene transcriptomic testing, we wanted to sequence a human genome. It was done in 2003 and 2004. Price came down. We could do some of that. And there's 50,000 genes that we worry about in the human genome. 15,000 are protein coding and 25,000 are not. And then there are some other genes that were called junk DNA and all this sort of stuff. They turned out to have features we just didn't know about. And it was just too much to try to sequence the entire genome in affordable price. The price got down to $2,000. But the time and the expense, it's like we needed a better test.

What Jimmy did was to look and find what genes were upregulated the most. And he came up with 2,000 genes. We then started pairing those down based into what did we see more commonly in CIRS. And Jimmy came up with about 200 genes. We're giving you reports on 200 genes and not 50,000. GENIE does not tell you every disease is known to mankind. But if you have Lupus, for example, or renal failure, for example, or congestive heart failure and you're tired, lo and behold, GENIE has a contribution. You will find metabolism there.

Yes, GENIE will tell you about other illnesses. But it doesn't come with the case definition that was established before that we use for the proteomic lab testing. Now, we finally have another lab. EnviroBiomics is doing five protein testing. That's brand-new. Two days ago. September 9th was first day. And EBI in San Antonio and Gianni Rossini has been pioneering this.

But people were having trouble getting C4A done. That was a frustrating issue. TGFB1 had normal ranges that were screwy. VEGF had normal ranges that were screwy. And they're all nice in one little low-cost package. They're not accepting insurance just yet. But if you send your specimens down for less than $500 and actually less than $350, you'll get your five proteins done. You get an answer you can rely on. This has been a happy week for me.

[00:34:46] SCOTT: That to me is incredible. Because I will say, personally, I've recently tried – I live in Denver now. And I've recently tried to do C4A testing. National Jewish is here in Denver. But I didn't really want the exposure of going to the hospital. Managed to try and do it. Didn't get routed to National Jewish. We know that LabCorp’s TGFB1 methodology was completely changed. And the ranges are much higher. And so, that's maybe one of the more exciting things from our conversation. I didn't know about that. And that seems like a game changer.

[00:35:17] DR. SHOEMAKER: Well, one problem has been solved. There are a couple more left to go.

[00:35:21] SCOTT: Okay. Now let's talk more about each of the sections or categories on the GENIE. 20 of them or 19 plus a dispersion score. And let's talk about how those might inform either our understanding of the contributors or maybe the treatment of Chronic Inflammatory Response Syndrome.

Section one is that important section that you've talked about with the metabolic markers on GENIE that appear to give us some indications around energy production, potentially mitochondrial function.

Does under-functioning in section one correlate to the symptom of fatigue? I think you already answered that. When genes are downregulated or suggestive of an under-functioning or hypometabolic metabolism? That may not be exactly the right term that you'd want to use. But how do we address that? We know now that it's not treated by normal mitochondrial interventions that we might think about in functional medicine. You already talked about that. Is the focus on removing the CIRS triggers to allow the body then to move back to a normal state of metabolic functioning? Are there other treatment interventions that help address this when we see all blue in that section one? And what if someone has a hypometabolic expression but GENIE is not consistent with CIRS, do we see that hypometabolic gene expression as well?

[00:36:45] DR. SHOEMAKER: Well, you said you'd give more than one question in a mouthful. And I think you succeeded in doing that.

The nice thing about looking at metabolism is that the first five steps of the Shoemaker protocol will show resolution of the blue and the light blue and start returning to normal. There is what Jimmy called the CIRS curve that you will be suppressed in baseline with treatment beginning with removal from exposure from water-damage building or getting away from cyanobacteria kind of thing. Not eating more cytotoxic fish kind of thing. Not having more Lyme disease for a given reason or another.

But, specifically, there will be an overshoot of the genes that had been suppressed and they will be overly functioned. That overshoot has a function that we have used, is that if you go to stage one, and we've got four stages of genes that we worry about, one is untreated. Second is in the protocol for treatment. The third is with VIP. And the fourth is after all drugs are done and the illness is over. The fifth stage is relapse. I should be saying that we have five stages. It's less common.

The problem is that GENIE have expense to it. $720. It's an awful lot of money to spend. And we're not doing that like we would do a metabolic profile that cost $5. We'll do one of those a week and one of those a month and we're getting great information about metabolic acidosis. But we can't do GENIE the same way.

What we've done is look at findings at baseline, stage one, compared to findings in those patients who are stage two, compared to before VIP is getting kicked in on stage three. And then treatment is over at stage four. If we find persistent blue in metabolism and we think VIP is done, I got news for you, you're not done. What? But my patient feels fine. Well, there's something more to it. And, usually, it's in the brain. It's usually an indication of recurrent exposures that you're just not aware of.

The classic story is the plumber who makes house calls and crawls into the house…who's going to do some kind of work on your crawl space and condition it and all that. And their exposure – the symptoms, they're so used to them. It's like the mothers of Eskimo children when I used to work there years ago and the kids got green puss coming out of the ear and, "Well, that's not abnormal.  All the kids have got green puss coming out of the ear.” Well, they were used to having chronic ear infections and eustachian tube function. And some people will have a paucity of symptoms reported because they no longer think it's fatigue. That's just the way they are. Well, then we can say there's good news. We're going to make you Superman. And that's very popular when that happens.

[00:39:53] SCOTT: Absolutely. Absolutely.

Section two looks at insulin, and blood sugar, and the genes that are involved in that. What is the connection between CIRS and blood sugar regulation? What do you normally see in a CIRS patient in terms of fasting glucose, insulin, other factors around their blood sugar regulation? And are these more commonly upregulated or down-regulated? What does that mean in terms of blood sugar levels in the body? And then what aspect of the CIRS treatment addresses the gene expression in that section two insulin group?

[00:40:28] DR. SHOEMAKER: Where we got started on before GENIE was known was the role of polycyclic ether toxins and dinoflagellates are making more of those than some others. And what these polycyclic ethers would do is interact inside the cell with glucose bound to insulin and bound to an insulin receptor. They were internalized like a little bubble. And this was called an endosome. And there you would have an endosome ready to deliver glucose inside the cell as soon as the endosome was acidified. Hydrogen ion pumped into it. That was sort of the normal mechanism to prevent insulin resistance.

Well, with polycyclic ether toxins, the hydrogen ion pumping does not occur. What you have is sodium pumped. And what you have then is a reservoir of intracellular endosomes. And if insulin receptor are being taken in, they're not on the cell membrane, golly. What's going to be taken in the next glucose molecule that comes floating along if the insulin receptors are negative?

And we don't get a lot of publicity for that. But it was fascinating back when cholesterol was getting started with 1987, the National Health Education project. And people were being told to stop eating red meat and start eating chicken. And pork would be a second protein that they wanted to eat. Don't eat that nasty red meat stuff.

Well, it turns out that an organism called Eimeria, which is an apicomplexa, related to Babesia and malaria, is used as a poison given to little chickens and little pigs. If we give you a polycyclic ether, 100 milligrams per ton, and a lot of chicken tons go into those big long buildings you see on the Eastern shore. Smell, too. But, specifically, by avoiding red meat and eating chicken, we are eating polycyclic ether toxins. We're making more diabetes. And even worse, we're eating more pork. Around here where barbecue is popular, Eimeria was not popular. Now, they've got some other ways to go around Eimeria.

But it's just critical to look at the expanse of view that GENIE can give you. Because now what we look at are insulin transport proteins one and four. Glucose transport proteins one and four. That's under the control of the insulin receptor substrate 2. And if IRS2 is greater than 0.0, it will turn on a stimulus for the substrate proteins to bring more glucose into the cell. It's a way of bypassing the receptor in a way. And that will be delivered quickly into the cytosol where the glycolytic pathway, Embden-Meyerhof pathway is, and you'll have the 6-carbon ring of glucose broken down into two 3-carbon chains called pyruvate. Pyruvate will be transported inside the mitochondria. The Krebs cycle comes along. Out comes ATP. 38 or so if you get things going right. Usually not. But if you do, you get more than two, which you get from proliferate physiology, which would then make lactic acid and make people sick.

The insulin answer has to do with history. It also has to do with the effect of insulin receptor substrate 2, which will be suppressed in some cases. But, usually, it is turned on in the presence of hypometabolism. If you've got extra delivery of glucose into the cell and extra hydrolysis of glucose to pyruvate and it can't get into the mitochondria, we're going to have metabolic acidosis, which then creates insulin resistance.

When you say, "What does this have to do with insulin?" I'm looking at this one, we've got OGA that's upregulated. And that's one of the ones that creates glycation of insulin. It doesn't work quite right. You get insulin resistance. And then you've got OGT that takes the glycan group off. In our body's mechanisms, we're looking at are you insulin resistant? And is that due to OGA or deficiency of OGT? Or how does that work out? That then leads into the complication of metabolic acidosis that we've talked about briefly and we'll talk about some more.

But similarly, GAPDH is one of the key enzymes that will take glucose and split it into two 3-carbon fragments and that sets off pyruvate. If GAPDH is upregulated, you are then making more and more and more pyruvate just by being alive. But if GAPDH is suppressed, then you won't make pyruvate. And the mechanisms of how that's controlled – it's addressed in some of my paper from 2020 in trans of diabetes metabolism. I feel sorry for people who have to read that paper. It's so dense. But it's still a good paper. My grandmother liked it. But that's all right.

But anyway, curiously, IRS2 will also impact on AKT and mTOR. I'm sure you've done discussions with people looking at mTOR, the age-related functioning, all that. The problem is that if insulin resistance is suppressed, the keto diet will work beautifully. but mTOR won't be converted, won't be doing all that it wants. This helps you look at a number of different things all at one time. But the big deal in June of 2024, we finally took time to look into hypoxia-inducible factor.

In my original 2004 handout of the biotoxin pathway, you saw HIF being led to make VEGF. VEFG rising would turn on TGFB1. TGFB1 will suppress VEGF prematurely. But it'll correct hypoxia-inducible factor. What we wanted to know is what does our protocol do to HIF? Because HIF will also create pulmonary hypertension. Oh, my God. Here is the mechanism for these people in right heart failure or people with velocity of tricuspid regurgitation over 2.5 meters per second. And you can tell that with a simple Echo of the person with dyspnea or shortness of breath who goes to see the pulmonologist. It's not the pulmonology patient. Goes to see the cardiologist. It's not that. But he's got right heart failure, which is a leading cause of death. This used to be in CIRS. All of that information is coming on at one time. And if we can reduce your question, did we lump together a bunch of findings in one venue and they're not all related to insulin? Yeah, we sure did.

[00:47:31] SCOTT: Okay. We're going to talk now about section three, which is on apoptosis or our ability to dispose of damaged cells. Wondering if these genes are more commonly upregulated or downregulated in a CIRS patient? Does an upregulation mean an overactivation of apoptosis? And what does not disposing of damaged cells in an orderly fashion mean for a CIRS patient in terms of their health?

[00:47:57] DR. SHOEMAKER: You use the term apoptosis. And I do it as well. I think the people that focus on pronunciation would tell us we’re calling it wrong. They're going to say apoptosis. And I can't say that very well. I'm gonna say apoptosis. And just know that if I use the wrong word, we're talking about programmed cell death.

What we have is a group of ten genes. And if you have three of them together, they're CASP genes, they're part of organized one-step beginning with death cell receptors. One step followed by another, a programed cell death. And so, if you've got two capase genes, as it now turns out just by doing the addition and writing down what do we see, that's one of the factors that goes along with fungal source of apoptosis. That's a big deal.

Now, if we find one caspase. that's not two, that says you don't have fungal apoptosis. And that means we don't look further down the road at MAP kinases. Because if you got three MAP kinases up and two capases up, you've got mycotoxin effect. This is where this comes from. And this is talking to you right now in the third step, is specific causation. And this is such a – you got to remember. In medical legal factors, specific causation is where the money is. If you have specific – if you're exposed to a building, you've got specific causation, you got specific illness, here is your specific treatment. You should win your lawsuit. But you should also get 50 bucks extra money to treat the illness. And it bothers me that people are not going in litigation and then not treating the illness when they win their case. But that's different story. If you have all three caspases, that's still fungal apoptosis.

Now, interestingly, if you have BCL2, that gene upregulated, that is only upregulated by two different viruses, HIV and COVID. Oh, we got a test for COVID. We'll get to TGFB1 receptors, one, two, and three for people with COVID receptor toxicity. Oh, that's fun. But there are now mechanisms we can put on each one of these. If you've got BCL2 negative, you're at risk for COVID again because you don't have an antibody. But if you've got that gene, you've got antibody protection. Now, of course, you've got to have specific antigen presentation. We'll talk about that when we get to section of T-cell synapse. That's far for the genes.

CLU, clusterin. What a what a mystical gene that was. I've been looking at it for years. And there are all these cognitive issues going on with clusterin. How does it do what it's doing? Well, our paper that was accepted yesterday. And we don't even have the copy-edited format yet. So I can't send you a copy yet. Next week. Is looking at a triple positive. Well, the triple. What's that? CLU is one. That'll be positive. Then coagulation genes. You'll have three or more of those, that'll be the second positive. And then when we get to tubulins. One or two of those will be positive. That's the third positive. That tells us triple positive. That is the part and parcel of the pre-clinical stage for Parkinson's disease.

[00:51:38] SCOTT: And when you say triple positive, are we talking about upregulation, overexpression red on GENIE?

[00:51:43] DR. SHOEMAKER: Yes.

[00:51:45] SCOTT: Perfect.

[00:51:46] DR. SHOEMAKER: Because you had an important question of what if there's disordered apoptosis? If you have RIPK1 or RIPK3 as genes that are upregulated – we took away the RIPK3. So, it'll just be RIPK1. You're going to have defective apoptosis. Well, what's that mean? With regular apoptosis, the caspase genes are making sure that a bit of cell membrane coats the antigens inside the cell. Golgi bodies, and ribosomes, and mRNA, and DNA are all going to be coated and proteins will be coated. So, you don't have inflammatory mechanisms of protein detection.

But if you have defective apoptosis and RIPK1's elevated, you're going to have release of antigens from the host into the bloodstream. It is a form of endogenous apoptosis. And this is programed cell death gone on haywire. Now, there's about 12 or 14 different “ptoses” around. Ferroptosis is another one that comes to mind. That's a big player. And I'm sure you've talked other people about that.

But here we have all in one section, are we going to look at fungal source? Are we going to look at endogenous source? Are we going to look at COVID? Are we going to look at risk for CNS disease? Because we knew we published in December of 2023 on tubulins. We'll get to those in a few minutes. But, specifically, we now have got tubulin mixed up with Parkinson's disease. Oh, my Lord. And we could diagnose it. Does that mean we can treat it when it's preclinical, when it's a prodrome?

We've got a four-year-old who's got a triple positive. Do you want him treated for Parkinson's when he's four? Oh, we don't have answers to these things. But we're getting answers. Now that we can fix triple positives, and they do respond to the protocol, we're thinking, if we can follow these patients for 20 years, we should see a decrease in Parkinson's. Or we should see a reduction in Parkinson's symptoms. And I think that'd be a great idea. I'd love to have that. And I do.

Okay. Coag.

[00:54:06] SCOTT: There's a lot in this question as well. But this is an area, section four. We're talking here about coagulation abnormalities. This is an area that I felt like has been overlooked often in complex chronic illness. Wondering how often do you see an up-regulation or hypercoagulation versus a down-regulation maybe? We know commonly people with CIRS have nose bleeds and other things like that. Is there a tendency towards hypercoagulation, hyper-viscosity, clotting? And do you see these genes expressed more now since the COVID era began? We know COVID can be a trigger for CIRS as well. And when you do see some issues in this section, do you then look for other factors such as PAI-1, or Factor V Leiden, won Willebrands? Those types of things. And would you potentially then treat the coagulation with enzymes like nattokinase, or lumbrokinase, or even pharmaceutical anti-coagulants in some patients?

[00:55:07] DR. SHOEMAKER: An important part of the answer to the multiple questions is what are the coag factors we're talking about? We're looking for F13A1. And that's a sub-unit of factor 13. Coagulation 13 is the last compound to be activated in the blood coag cascade. One of the last clotting genes we've got is there represented. Also, one of the most commonly seen.

F5, coagulation factor five. Now, Factor V Leiden publicity. Only one in a 100,000 people with clots have got Factor V Leiden. Why does functional medicine focus so much money on Factor V Leiden? It's trivial. My gracious sakes. Only one in 100. Look it up on Wikipedia. Anyway, Factor V encodes a crucial factor in blood coag cascade. It circulates in plasma and it's converted by releasing the activation peptide by thrombin and coagulation. Factor V is after thrombin. It's earlier in this stage.

How about GP6? Glycoprotein VI is a platelet glycoprotein. Oh, my God. Platelets have the role to be playing here. And the immune situation with platelets. You are right. This is a huge area. The protein is a receptor for collagen. Oh, no. Collagen breached the lining of cells. Good gracious sakes. Platelets initiates activation cascade. Plays a key role in procoagulant activity. Subsequent fibrin and thrombin formation.

Here we are. Now we've got the whole cascade really laid out in just four genes. Factor IX or glycoprotein, GP9, here's von Willebrand's factor. This includes a small membrane, glycoprotein, found on the surface of platelets. It serves as a protein receptor for von Willebrand's. If you don't have GP9, you can have acquired von Willebrand's and have hemorrhage like crazy. That's not a clotting problem. That's a bleeding problem.

How about ITGA2B? This is a big deal. The integrin subunit. Encodes a member of the integrin family of proteins. The process to form Alpha 2, Beta 3 integrin cell receptors. This is where the first reduction of flow in the neural rim of the optic nerve head was detected with the Heidelberg retinal flow meter. Reduced flow from this integrin in cell adhesion blocking flow of red cells in tiny blood vessels.

If I'd been smart enough to figure that out, the integrins in 2001 and 2002, imagine now the people would have been saved all the clotting and vascular factum. It leads to rapid platelet aggregation that plug ruptured endothelial surfaces physically. There's another integrin, this ITGB3 includes the integrin beta chain. It's known to participate in cell adhesion surface signaling.

PF4, here's another one of your CXC. The sea of cytokines. You had RANTES. But the other one is PF4. You might want to look that one up to add that to your armamentarium of RANTES-like derivatives. The protein has a high affinity for heparin and participates in plated aggregation.

Here's a clot-dissolving mechanism in the setting of a chain that creates reduced blood flow and clot formation. And this is getting at the new era of the Tesla 3 and coils being the max we've got in Salsbury and Denver. But if you go up to Hopkins, they've got a Tesla 10. They can look in the brain. And what we used to call a TIA, they're looking at a small microclot followed by a micro hemorrhage and a binding of amyloid beta by these platelet growth factors by these 12 coagulation factors.

Here is the development of ischemia in a micro level based on the same kinds of things. You're looking at 10 separate times in GENIE on coag. Now the interesting feature is that when I found that the triple positive was possible, we surveyed the 70 some patients, the physicians who had done GENIE samples. And we found that we had 8, 9, and 10 members of this gene family all upregulated, all red. And Karen Johnson says – from Hawaii. Maybe you know her. She's very smart. She says, "I'm seeing this when three gene upregulated." I go, "Whoa. Boy, was she right."

Three or more genes. Now, we used to say three or more was needed to say you had a problem with coagulation. Now we say if you've got clusterin and you've got tubulin, you've got a danger problem for CNS hemorrhage. And is that the beginning of antigen binding or binding for, the least, Alzheimer's? Oh, boy. What a thing.

I'm after Parkinson's with one of these segments on coag. And after, Alzheimer's on the other. And you said it was important. Well, guess what, buddy? You were right. This is huge. Absolutely giant. Good job.

[01:00:40] SCOTT: Thank you. It's actually been one of the challenges I've had over the years because I have a PAI-1 4G/4G deletion and commonly have to be very careful about monitoring my hypercoagulation. When you see some of these genes up regulated in this section, do you then treat the hypercoagulation? Or do we still focus on treating the triggers of CIRS that might be causing those genes to overexpress?

[01:01:06] DR. SHOEMAKER: What we've done in the past is measure a D-dimer. If you've got evidence of a clot formation, then that is likely to be due to one of the elements of this cascade. If you don't have a D-dimer, we just observe.

We also have found that sed rates are good test for this triple factor. Sed rates are always normal in chronic fatiguing illnesses. It's fascinating. Why? They don't have interleukin-6, which is the main factor of elevated sed rates and C-reactive proteins. But, basically, if your sed rate's normal and your D-dimer is normal, we follow. Wishing we had Hopkins money. The 10 Tesla coil has its own room for cooling. $10 million to start. Maybe University of Colorado has one. I doubt it. But it won't be too long before the price comes down.

[01:01:57] SCOTT: Section five is where we get into cytokines. That can show an upregulation of cytokine production or production of inflammatory molecules. Do those give you some insight then into the inflammation potential for a given patient? Do they change treatment in any way? And does this section correlate with specific interleukins such as maybe IL-1, or IL-8, or others? Is there a correlation in this cytokine section with Transforming Growth Factor Beta 1? Do those with red or overexpressed TGFB genes tend to have higher levels of TGFB1 on blood tests? And are upregulated cytokine genes consistent with CIRS? Or might they lead you to a differential diagnosis?

[01:02:43] DR. SHOEMAKER: I was tempted to ask you to repeat the question. I had so much fun listening to it.

Anyway, let's take some of the latter parts of your questions first. There are three genes, TGFBR and TGFB1 receptor, is receptor one, receptor two, and receptor three. They are responsible fibrosis. No surprise with fibrosis being a problem. In cirrhosis, if alcohol is a problem maybe. Or renal fibrosis, or skin fibrosis, or pulmonary fibrosis. That's the big deal.

We all know that TGFB1 will bind to that receptor. But if TGF1 binds to a receptor, that lowers TGFB1. That's a body's mechanism, the coag feedback loop to actually reduce TGFB1. But then if you've got TGFB1 receptor and you don't have a MAP kinase, be thinking about a COVID vaccine. Because if we've got fibrosis, one of the most common problems associated with the COVID vaccine, cardiac fibrosis gets called myocarditis. I'm not sure that's correct.

But when our paper on COVID came out, we looked at the gene activation that COVID was a primer. And we would have people who were in a leaky building with Actinos and endos. Not sick. They got COVID. They suddenly got turned on. They turned on TGFB1. Turned on the TGFB1 receptors, one, two, and three. And then we can see now that 63% of post- COVID people have got endotoxin formation, endotoxin-specific causation. And 54% have got Actino causation.

All these things, your questions related to where does this fit in medicine is kind of my summary of what your questions are. It fits in many different ways. Now, if we look at CCL5, that's RANTES that you know about. I gave you another one to look at. There's about 20 of these different genes. And we'll talk – when we get to histamine, we'll talk about this. Because this is a fascinating issue. It's going to make some people unhappy because it blows apart what common diagnosis that's made in functional medicine.

But then we look at IL-1B. And if you've ever looked at measuring cytokines, cytokines are made by the cell. In the endothelial, usually. And that cell, the endothelial cell, can bind the cytokine it makes. You have an autocrine function. Or the cell adjacent to the one that made the TGFB1, the cell adjacent, that's called the paracrine function. When you measure TGFB1 in blood, will you measure autocrine or paracrine? No. All you can do is measure the endocrine source. And that's floating around in the blood after being made.

The question is are the assays for interleukin-4 a good anti-inflammatory gene? Interleukin-8, interleukin-10, interleukin 13. All these good anti-inflammatory genes, we want to know they're suppressed if we look if they got CIRS. But the assays stink. That's where the genomics come in. If we look at interleukin-1B, or TGFB1, or TNF, and that's elevated, we've got a problem with endogenous production of cytokines. It's not necessarily going to be due reaction to a foreign antigen.

Now, if you've got suppressor of cytokine synthesis or SOCS1, that's going to be turning on a mechanism to turn off other genes. It's Pan, anti-inflammatory. It'll turn off TNF. Turn off interleukin-1B. Turn off TGFB1. But then TGFB1, as we say we get to, is going to stimulate fibrosis. Create the damage. And TGFB1 levels will fall.

We see the same mechanism when we measure VIP. There's no point in measuring VIP at all. There's plenty of point in measuring VIP receptors. Because if VIP is bound to the receptor, we can measure it. It's not bound to the receptor, we can't measure it. It's a tough bite to chew. But that's the way it is. But the key issues is is we lump together TGFBR 1, 2, and 3 into one section. If you've got a problem with COVID vaccine, that's likely to be positive. But what it does, it gives your physicians something objective to follow.

[01:07:26] SCOTT: Section six then is the Lyme section, which says that it represents genes found in patients with acute and post-antibiotic Lyme disease. Wondering what if someone was undiagnosed for years with Lyme infections. They were never treated at all. Does that person have a post-antibiotic Lyme disease if they never took antibiotics or antimicrobials? Would an upregulation in these lime genes lead you to potentially then treating the patient for Lyme? Or is the focus more on that inflammation that's being produced from a potentially prior infection? How often does GENIE suggest Lyme is a component of a patient's CIRS presentation?

[01:08:10] DR. SHOEMAKER: I was laughing about the coincidence of you sending me these questions you wanted to go over a couple weeks ago. And a couple days later, I saw someone who fits that questionnaire completely. Had Lyme at age 20. She's now 40. She came in because she thought she was moldy. Well, she wasn't moldy. She had something else. And she had Lyme. Was not post-Lyme. Was never treated.

Now, data that we use to diagnose Lyme with transcriptomics come from a paper published in 2016 by Charles Chiu and Jerome Bouquet from the University of California in San Francisco and John Aucott at Hopkins. I'm sure you read his stuff. And he had an acute Lyme work, and he followed people for six months and showed that there are certain cytokines that were elevated and genes were elevated. But that he did not measure these entities beyond six months.

We can use Autcott’s genes for treated Lyme up to six months. We can't use treated Lyme if you sit seven, eight, or nine, or 10 months. If you come in and you say I had Lyme a year ago and I'm still sick. Is this post-Lyme syndrome? Or is this still regular just Lyme? We're stuck. The Lyme patients are stuck. I would wish that Dr. Aucott would do that and make it a little longer. But in the meantime, we're collecting data. And, hopefully, we can unstuck you next year or the year after. But we'll not change the controversy about Lyme as it is now.

What we have in the latest iteration is that when we made the panel for triple positives for Parkinson's, we had to kick out a lot of other genes and mix some of these in. You will see coag genes in this panel when you get a new GENIE. You'll see some of the defensins are going to be in that section as well. Because these are going on in Lyme as well. Defensins are still a good test for Bartonella. You got to be sure you got Lyme in there. But your Lyme will not give you defensins. Bartonella will. But that's got to be Bartonella in the bloodstream and on the lymph node. It's a little different story.

[01:10:18] SCOTT: That's a good segue into section seven, which is granzymes and defensins. Granzymes are proteases or enzymes that are used by natural killer cells and cytotoxic T-cells to destroy unhealthy cells. Defensins are anti-microbial peptides. When the genes in this section are upregulated, does that potentially suggest there could be an active infection? And does an upregulation of defensins genes inherently mean that there's a higher level of antimicrobial peptides and suggests the patient may need treatment for that infection? How do genes in this section guide patient care and treatment?

[01:10:58] DR. SHOEMAKER: I read a paper in Nature Reviews Immunology some years ago and looked at granzymes. And the authors were astounded to publish 26,000 different phenotypes of cells with granzymes. And I thought we wanted to know about granzymes because it's important in apoptosis. But we ended up just not – we kept the granzymes in the panel but apply no significance to it. It's just not specific enough. Jimmy just said, "Use the defensins."

Defensins, if they're elevated, will tell you about a bacteria or a virus. Now, don't be confused about Epstein-Barr virus. There are over a thousand different viruses that are intercalated in the human genome. And Epstein-Barr virus is one of those. If you get early antigen and late antigen, that could just be part of the virus intercalated in genome.

That's why chronic fatigue syndrome, physicians had trouble looking at viral reactivation. Because what's viral reactivation and what's just ongoing intercalation of viruses in DNA? That'll wait for another day and some other pros to figure that out. But if you find defensins – and there's only two of them. There's six we know of. Some of the other ones are less specific. They'll pick up fungi. I wish that we had that for fungi. But just because people are exposed to fungi all the time, it was non-specific.

But defensins, be looking for sinus infections, lung infections, urine infections, especially prostate infections. Look in vaginal tract infections. Look in gut infections. If you don't find anything, then you're stuck. You're stuck. You got to do a blood culture. And if you do all that, then just say to the patient I have looked for the source of defensins. And let's just continue on. We'll keep an open mind of what going to be coming on. But it's a warning that you've missed something in your differential diagnosis what defensins positive means.

[01:12:58] SCOTT: All right. Now we're going to move on to section eight, which I call Ikaros. I hope that's pronounced correctly. A family of transcription factors that are important for lymphocyte proliferation and senescence. What is the pattern that's most common in CIRS patients with regards to these Ikaros genes? Is there a connection to IL-10 expression? And is the way to modulate these genes with VIP? How many of these sections ultimately are regulated, or modulated, or addressed through the administration of VIP or other treatment steps in the CIRS protocol as compared to simply removal of exposure?

[01:13:38] DR. SHOEMAKER: This is a sensitive issue. I looked at the papers on lymphocytes, and Ikaros and the zinc finger proteins. There's more than three of them. And they have a lot to do with VIP receptors. And seeing people that got VIP and got worse, I thought, "Aha. Something with lymphocytes. And Ikaros could be telling us something about that."

It turned out, no. Nothing stood up. I was teaching a course with Andy Heyman. And for some reason, Andy has more people with environmental sensitivity than any other physician I've ever seen. But we started looking at why his patients had so much environmental stuff going on. And we found that if zinc fingerprints proteins, if the mean of the three genes is positive and VIPR1 is positive, that's normal. That's a match of positive-positive.

Or if it's negative-negative, the negative sum for VIP and negative sum for zinc finger proteins, that's also normal. But where it's abnormal of a positive-negative, which I'm looking at this case right here, we have a positive zinc finger protein sum, a negative VIPR1 sum, that person, just by writing down the piece of paper or writing down the results on a piece of paper and counting, that person's got environmental sensitivity. Either drug sensitivity, chemical sensitivity, or med sensitivity.

We've developed a low-dose VIP protocol for these people with sensitivities. They're eating five foods. Their chemicals bother them like crazy. I used to cringe seeing the patients with chemical sensitivity come in. Because so many things made them bad. And I couldn't fix it. With the low-dose VIP protocol, I don't cringe anymore. Usually, I just send them to other people. Because it's easy to fix now. And some of the most desperately ill people have environmental sensitivities in the low-dose VIP protocol.

In the textbook that Scott McMahon, and Andy Heyman, and I wrote is something to look at. Not to put in a plug for the book. But if you just get a copy of it, just take a look at it. And give a copy to your patient when you're going to do the low-dose VIP protocol. Because it is fairly complicated. But you'll be dealing with drug sensitivity. You can give them Welchol. You can give them cholestyramine if you want. You can give them VIP if you want. But if you were positive-negative, then you wouldn't necessarily have that luxury. We had some of it right with positive-positive. The second, negative-positive, goes with people with accentuated CNS injury. And insomnia was the first clue. Central nervous system dysfunction. But now we do that with psychiatric illness as well.

[01:16:22] SCOTT: Section nine, we get into the MAP kinases that you mentioned earlier. Those help to direct cellular responses to many different stimuli and can be overactivated or overexpressed in CIRS. What's the role of MAP kinases in CIRS? And what happens in the body when MAP kinases are overexpressed?

[01:16:40] DR. SHOEMAKER: MAP kinases are like AKT and mTOR in my mind. They do so many things. I don't pretend to be an expert in that. I count the number of MAP kinases that are there. Andy's got a nice paper coming out on MAP kinases. If he'd hurry up and publish it, – oh, shoot I was talking to Andy. Help us out.

If you've got three MAP kinases, that's the cut-off for fungal causation. If I've got two caspases and three MAP kinases, I've got an admissible in court as specific causation for fungi. If I've got one or two, then I've got Actino-specific causation if they've got TGFBR one, two, or three. One of those, two of those, or all three of those. But those two combinations are Actino-specific causation. And the third specific causation is done in toll receptors number 10. That's when we've got CD14, which is specifically for endotoxin. Toll-2 and toll-4, which are extracellular products. You had written about intracellular products. That's toll-3, toll-7, and toll-9. You're not going to be the same way. We don't test for those. But those are specific causation for endos.

But if that that's all we have, if that's all you get from GENIE, is a confirmation of what's wrong with you. You can win your lawsuit. Get your health back. Life's good. If you want to know if you're tired, fatigued, you can find out. Do you have ribosomal dysfunction? Do you have ribosomal gene dysfunction? Because that's fixable with the first 11 steps of the protocol. Every one of these things is tied to treatment. Every one of these is tied to the physiology of the illness involved.

[01:18:22] SCOTT: Section nine then, you talked about the fungal causation potential that could come out of that gene expression. You talked about the Actinobacteria potential. I know this is a little bit of a controversial question.

But are there any scenarios today where we might use antibiotics in the Actinobacteria realm to support the person dealing with CIRS? I know historically, antifungals are a no-no. Are we talking just about fungal triggers in the environment? Or are we suggesting that some people may now have true fungal colonization or infection?

[01:18:57] DR. SHOEMAKER: Well, I'm glad you asked that question because it's been one of my obsessions over this last year. What do we do about Actinos? How come they're so hard to get rid of? They move. For God's sake, they move. They can go from your living room to your bedroom and anywhere where there's moisture, in an armpit, you'll find Actinos.

Interestingly – and we've done a couple papers on this, what you will find is that, under the influence, primarily a Propionibacterium acnes or a Corynebacterium tuberculostearicum, those are the two big ones. CT and PA to make it easy to talk about it in a noisy room. But CT will like to stay in nose every once in a while. Eric Dorninger has been trying to eradicate those with Zithromax. Doesn't work too well usually because there's re-exposure and reacquisition.

But what they do is live deep to the skin in the 24, 25 square meter territory of a skin in the body. And the oil glands and the sweat glands is where you find the greatest amount of P. acnes and CT. And EBI does a skin biopsy or a skin test for Actinos. 7500 is normal. And you get people with three million P. acnes and say, "What are they doing?" Well, they're creating seborrheic-like changes to your helps. You might get some dandruff or some spots on your chest and back. That's one way that can go on.

But what these organisms do deep to the skin, deep in the sweat gland and the oil glands, they're right on top of the blood supply. The … ridge, if you will. That blood supply is only two-cell membranes away from the P. acnes, and P. acnes can be transported from the oil glands into blood. I used to think that blood was sterile, for God's sake. It is not. Oh, my God, is it not sterile.

But these extracellular vesicles have got bacteria in them; DNA, RNA, protein, toxins, and they're floating around. They create an endogenous of CIRS. Who would believe your armpit is making your brain disappear? It's like this is just phenomenal. And work done NIH, they've a whole section looking at this. It's been our reference. Sections are there. Just fascinating.

[01:21:32] SCOTT: It sounds like there is some potential for antimicrobial agents in the Actinobacteria realm. My understanding is that you are still at this point not supportive of using antifungals. Or we don't think that CIRS is a fungal colonization or fungal infection. Or has that changed in any way based on the GENIE findings?

[01:21:53] DR. SHOEMAKER: No. All fungals does is create mutants in MARCoNS, and other organisms. I have lectured and gotten in good fights with people about antifungals. You know my status on that.

[01:22:06] SCOTT: Section 10, you already essentially covered that the toll receptor section gives us some causation related to endotoxins. Maybe my question here is does that mean that the endotoxin has to originate from outside of the person from maybe a drain pipe or sewage backup? Or could it be endotoxins that are created internally, particularly if someone has GI dysbiosis? Might we have another scenario with endotoxin production where we have an internally-produced trigger of CIRS?

[01:22:40] DR. SHOEMAKER: We're working on a compound that binds endotoxin. It's involved primarily with red cells binding to endothelial cells. But it removes endotoxin from the bloodstream very, very quickly. The possibility of large bowel seeding for endotoxin has been attractive to me. We've not been able to prove that. The very fact that we don't have 100% of our patients with endotoxins says that not everybody gets it even though everybody's got a large bowel. Stay tuned on that one.

[01:23:07] SCOTT: Section 11 and 12, there's two sections related to the adaptive immune system. B-cells and T- cells. My understanding is part of the problem in CIRS is that we're more or less stuck in the innate arm of the immune system. That we don't have a proper adaptive response. What do these on the GENIE tell you if they're under or overexpressed? And how do we then support the functioning of the adaptive arm of the immune response?

[01:23:34] DR. SHOEMAKER: We don't use the B-cell parameter for any diagnosis. Jimmy was sure that some of the red B-cell genes, ones that are overexpressed, were part and parcel of causation of chronic pain. And we were studying that and studying that and looking at it. And here was a study in Norway when CD19 bearing cells were treated with Rituximab, their pain went away. And that was huge in my mind in the chronic fatigue world.

Unfortunately, a double-blind study did not confirm the anecdotal findings. We kind of tossed that away. But we still collect these four genes. CD19 is B-cell lymphoma. We use it for that. The CD79a and b, and then the CD81 are the ones we use for chronic pain. We're going to do something with it sooner or later. But right now, it's just for passing fancy and scratching your head on Sunday afternoon watching a football game and thinking about chronic pain instead.

T-cell synapse is all we use. NFAT. We just couldn't find anywhere else where CD48 is not specific. But CD3D together with molecular hypometabolism defines what I consider to be the biggest problem with CIRS. We're not talking about CIRS biomarkers section 13. If you got four of those genes, that's pretty much good enough for a case definition. You've got CIRS. But if you don't have four of the section 13 or 14, which is research use only, we still can say you need to be treated with molecular hypometabolism and the T-cell synapse.

Normally, an antigen will be bound by innate immune receptor. Taking that to the endosome inside of an antigen-presenting cell. It's hooked up to an HLA molecule. That's where that fix is. IL-10 gets on the cell surface and blocks this antigen all together. But, otherwise, the antigen with a receptor and HLA is then presented to a naive T-cell. And if you've got CD3D positive, that naive T-cell will present the processed antigen to B-cells and an antibody will be made.

95% of CIRS patients don't have positive CD3Ds. It's fascinating. But with treatment, the CD3D turns positive. It's one of the things we're assessing. Did you have CIRS? Well, maybe. Did we fix the CIRS? Yeah. How do we know? Molecular hypometabolism is fixed and CD3D is fixed. That's the short man's way to a diagnosis.

[01:26:15] SCOTT: All right. We've got a total of 19 sections plus a dispersion score. We're going to lump 13 and 14 together. These are the CIRS biomarkers typically found upregulated in that first section. Section 13, you already suggested that if there were four or more of those, that that could be then some additional confirmation of someone having CIRS. Are there any other details from section 13 or 14 that kind of lead you in other directions in terms of potential causation? Do they provide any root cause insights?

[01:26:49] DR. SHOEMAKER: The energy expenditure. No. There is some interest in LRRK. That's elevated. Louise Carder in the UK is fascinated with that over the past few weeks. And we'll probably be looking at it. But right now, no.

Now section 15 is looking at PTSD. I still remember making a fool of myself by saying that there were new objective parameters for PTSD. Boy, was I wrong? And Jimmy showed me that pretty early on. The FKBP5 is up and a lot in PTSD. There's other causes as well that's not specific. But if you see FKBP5, all transactions are stopped. Because now we're going to be looking at suicide.

We've had four suicides in the 25 years. That's not very many statistically. But, at the same time, that's a preventable cause of death. If you see FKBP5, stop what you're doing and just say, "Have you been in some stressful situations? Did you ever feel that you didn't deal with a stress?" Or however. You take a PTSD history. That needs – and then referral to a psychologist if someone's there, especially the anxious teenager. That's the highest risk of all.

[01:28:06] SCOTT: Section 16 then, we get into histamine. There's a lot of conversation in the functional medicine realm around mast cell activation syndrome. One of the genes in this section is CCL5, which my understanding is the same as RANTES, that can be upregulated in those with COVID. Bruce Patterson's using that as a marker. Based on GENIE observation, how often is histamine involved in CIRS?

[01:28:30] DR. SHOEMAKER: The second gene besides CCL5 is histidine decarboxylase or HDC. If you have either one of these genes positive, over 1.3, red in color, every nucleated cell in the body is making histamine. Every cell. It's not just mast cells. Mast cells make a ton of C4A. Nobody talks very much about it because you can't get the test. But mast cell activation syndrome, primarily with urticaria and hives, and some the other inflammatory things, that's C4A.

But if you've got elevated levels, it's common. In our population, about 40% of people will be in stage one with histidine decarboxylase and CCL5. It's also 40% in stage two. It's also 40% in stage three. It's also 40% in stage four. There is no impact of CIRS treatments at all on histamine. You can have it in control values and control patients. 40% have got histamine decarboxylase and CCL5. In controls and cases, not any of those is making just histamine in those two cells. I would be very cautious about diagnosing CD when crossing mast cell activation syndrome without a CD being negative.

[01:29:49] SCOTT: Section 17 is the cytoskeleton section. Giving us some insights on the dynamic network of interlinking protein filaments that support our cell structure. My understanding is those are tied to microtubules and to brain atrophy. Are upregulations in these genes ultimately addressed with the use of VIP?

[01:30:08] DR. SHOEMAKER: Yes. VIP fixes this lickety-split. Some people are better with the first protocol. I want to tell you about the fascinating issue about microtubules. Sure, it's involved in cells dividing. And mitosis and meiosis both have separation of chromosomes to the daughter cells, for example. But microtubules primarily in the brain run from the cell body through axons to the cell synapse. And if microtubules are dysfunctional, which what the positive means, you will have a defect in delivery of ions and nutrients through these microtubules. And you won't feed the synapse.

If the synapse is not being fed, the whole neuron dies back and dieback to generative CNS disease. And what we wrote about, because we found a person who had way too much in the way of ALS genes. And ALS is a specific genotype with tubulins. But they have some others. But we found that there are other genes of degenerative change in CNS. Not just muscle cell bodies in motor neurons. But this is also in Alzheimer's and also in combined white cell deficiency. Quiet matter in deficiency and in Parkinson's.

This is the third element of the triple positive. When you see it, get a NeuroQuant. I mean, don't walk to the MRI facility. Run. Because if we catch the NeuroQuant in time – even with the injury that endotoxins caused in the brain, the worst of all, we can fix that with a year of VIP. A lot of money. A lot of money. But last I saw, a brain was pretty expensive to buy.

[01:31:56] SCOTT: Absolutely. Section 18, as we're winding up here, Treg provides some insight on regulatory T-cells. If those are upregulated or downregulated, what does that tell you? Is there a correlation between Treg cells and autoimmunity or higher levels of TGFB1? And how do we bring more regulation or modulation to the immune system and support Treg cells?

[01:32:20] DR. SHOEMAKER: Let's take the last part first. Most importantly, what we found in the 2020 Trends in Diabetes Metabolism paper, 80% of our patients who had metabolic acidosis had Treg cell deficiency. 80%. And correction of the antigen specificity of metabolic acidosis fixed the Treg cell problem.

Now, if you don't have retinoic acid orphan receptor in tissue, TGF will be sent by white cells into the tissue to suppress inflammation and autoimmunity. If you don't have that TGFB1 receptor ROR present, then what your body will do is convert the Treg cell into a T effector cell. TGFB1 and ROR means T effector cells. And it is T effector cells that are responsible, we think, for autoimmunity.

A lot of people were talking about ROR, including me. But now we know more. It looks like T effector cells and where this is. But specifically, if I see Tregs, because I usually look at that first, I then go to say do I have metabolic acidosis? Usually, if I got proliferate physiology, then I've got that. If I fix metabolic acidosis and that's all I do, I'm going to help my patients get feeling better.

The interesting feature about all I've got to say about antifungals is that there a few people. Not with Itraconazole at all, but with a different antifungal, are getting some benefit in metabolic acidosis. I got to be a little careful these days about antifungals, is that there may be a way that it's fixing something with metabolic acidosis. Maybe about 10% or 15%. But not 80%. But it's hopeful over the future that folks who are benefiting from antifungals will have had Treg cell sufficient.

[01:34:17] SCOTT: Section 19 is the newest on GENIE. That's the Parkinson's disease section. You recently published a paper that will be out very soon on Parkinson's disease. You touched through our conversation on several of the correlations or connections to this section. Anything else that you'd like to highlight around your recent work on Parkinson's disease?

[01:34:36] DR. SHOEMAKER: One of the themes of today's discussion has been mistakes that I've made or time that I've haven't gotten the answer right away. That's just me. And everybody's got similar features. I'm looking at triple positives only from the Parkinson’s viewpoint right now. That may be a mistake. May be a mistake. I do know that people feel better when you fix triple positives.

And as we collect more data, it may be way more than Parkinson's. There may be something that triggers triple positive to convert pre-clinical Parkinson's to clinical Parkinson's. But right now, it's a new bit of data that people are looking at. And as long as smart people are thinking on Sunday afternoon and talking about diseases and not watching the football game, we'll have a chance for answer. I think that the answer is not yet with us on triple positives.

[01:35:31] SCOTT: Section 20 is the last section. It's the dispersion score. It's a statistical measure and not a molecular pathway category like section 1 through 19. What does that dispersion score tell us when it's below one? And is it essentially a quantification of how close to a healthy individual is that person?

[01:35:52] DR. SHOEMAKER: If the dispersion is 0.91 or lower, not 1.0, if it's 0.91 or lower, then you're good to go. If you have 0.92 up higher to 2.5 and things like that, you'll have more RNA being made in the body than our controls are making. And that's where we get some skewing of Treg cells and all the other genes that are a problem that GENIE focuses on. All I can say is that dispersion reverts to normal after the first month of treatment. Stage one, we've probably got 20% dispersion positives. Stage two, it's about 2% dispersion positives.

[01:36:38] SCOTT: What has looking at GENIE now for several years told us about the impact of MARCoNS in CIRS if anything? Is there anything in GENIE that points Us in that direction?

[01:36:49] DR. SHOEMAKER: MARCoNS is a pathogen when it makes polycyclic ethers. Remember, I talked to you about dinoflagellates. There's also some fungi that make polycyclic ether. And MARCoNS are ubiquitous in their ability to absorb plasma genes from other organisms. This is a mechanism of antifungal resistance and antibacterial infections we saw on people who took antifungals.

It's interesting to see that if we've got a MARCoNS making polycyclic ether, those are the ones we need to eradicate. We must eradicate those. But if you don't make polycyclic ethers, MARCoNS is just along for the ride. It's no big deal. One month of EDTA and that's all you need to do. And you can't just skip it. But you need just one month. You don't need six months.

As it is with six months, we're buying time to let the normal flora of the nose knock out MARCoNS. MARCoNS, it turns out, makes polycyclic ethers as one of the markers that with goes along with mitoribosomes. If mitoribosomes are normal, you can ignore MARCoNS other than the first month.

[01:38:00] SCOTT: For patients and practitioners listening to this, my understanding is that they can order the GENIE test through survivingmold.com. That you then are available to consult with practitioners to help with interpretation. They do not have to be a Shoemaker-certified practitioner, as I understand, to incorporate this into their practice. Anything else that you'd like to share on people accessing GENIE?

[01:38:22] DR. SHOEMAKER: Just a minor correction. You do need to order from progenedx.com. Surviving Mold is just going to send you there. And sometimes they're a little slower than what one I would like. Just go to progenedx.com. There are four presentations about GENIE on Surviving Mold. Lessons from GENIE 1, 2, and 3. One of them is 10 bucks. The other two are free. Then there's I think Jill Carnahan's posts on Surviving Mold that I did with her. And maybe you can help us put with this on Surviving Mold as well. Because this has been a learning experience for me. I thank you for your assistance in that regard.

I think for physicians who want to learn how to read GENIEs on their own, just call Debbie Waidner at 410-957-1550. She'll make an appointment for you to schedule time. We have 20 minutes. Usually, it takes about four sessions where people are comfortable being ready.

When Andy Heyman and I were doing that course for A4M, we're including GENIE as part of the format for the course. That's a thing in the past now. We'll probably be reappearing in in Georgetown University somewhere. But GENIE is not hard. Once you just learn it, once you learn the language, learn the little tricks and the gimmicks, then it'll be your best friend.

[01:39:42] SCOTT: My very last question, and you can be brief, because I know you have to get to another appointment, what are some of the things that you're focused on these days in support of your own health?

[01:39:50] DR. SHOEMAKER: I need to avoid water-damaged buildings. I'm really, really compulsive. When I go into Walmart to buy fruits and vegetables where they're spraying with water, it might not be a moldy place, but it might be. I live a pretty boring life. I don't go to movie theaters. I don't go to antique shops. And if I go somewhere on an airplane or go to a hotel – and I had my own problems with Parkinson's that had really nailed me for three years. And now that I'm finally over the worst and I'm able to travel again and lecture again, it's just just a lot of fun.

But I'm just compulsive about mold. I don't get exposed if at all possible. And I make sure that I have no problem with Actinos. I use a good old Selsun Blue medicated shampoo. And then Lava soap. Eric was using Defense Soap for a while. I thought he had good results. Those didn't stand up. Lava soap is corrosive and abrasive. It's not much fun to use. But if it opens up the sweat glands and oil glands in your armpits and around your hairlines, that's a small price to pay for no Actinos. And I have, in the last week, no Actinos in my skin biopsy.

[01:41:01] SCOTT: Amazing. For those people wondering why we didn't talk more about Actinos and endotoxins, there's a potential that Dr. Shoemaker and I will do a future conversation around that topic where we can get into more detail. Today, we wanted to really focus just on GENIE and the potential of that tool supporting bringing new insights to practitioners and support of their patients.

This has been a very informative discussion. I learned a tremendous amount. I want to thank you, Dr. Shoemaker, for bringing our attention to our external environment and to the many things outside of ourselves that can make us unwell. I appreciate your time today in generously sharing with us all of your knowledge or probably just a piece of your knowledge. I appreciate all the work that you've done and that you continue to do to make a difference in people's lives and to move the field forward. So, thank you so much.

[01:41:50] DR. SHOEMAKER: Well, thank you.

[OUTRO]

[01:41:53] SCOTT: To learn more about today's guests, visit SurvivingMold.com. That's SurvivingMold.com. SurvivingMold.com.

Thanks so much for listening to today's episode. If you're enjoying the podcast, please leave a positive rating or review, as doing so will help the show reach a broader audience. To support the show, visit betterhealthguy.com/donate. To get my newsletter, visit BetterHealthGuy.com/newsletters. To follow me on Facebook, Instagram, X, or TikTok, you can find me there as BetterHealthGuy. This and other episodes can be found on Apple Podcasts, Spotify, Amazon Music, YouTube, and Odyssey.

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Disclaimer

The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.