Chronic Inflammation 
& the Immune System

John: And really, at the core of it, inflammation arises from tissue damage. That damage can come from an injury, a cut, or a bruise. All of those things activate your immune system. The goal of your immune system is just to return your body or that tissue to a normal state, to homeostasis, so that the organism can reproduce.

Brent: Welcome to the Life Lab by Death Clock. I'm your host, Brent Franson. The mission of Death Clock is to help 100 million people live ten years longer. Today, we speak with Doctor John Wherry about inflammation. Doctor Wherry is a professor in the Department of Microbiology at the University of Pennsylvania's Perelman School of Medicine and the director of the Penn Institute for Immunology.

Brent: Doctor Wherry is one of the world's preeminent experts in immunology and inflammation. We spent most of the conversation talking about low-grade chronic inflammation, how we can think about that, and what the health effects are. But we also get into a topic that he's spoken publicly about, which is how much information about ourselves is too much or too little.

Brent: How should we think about the do-your-own-research approach to managing our health versus the follow-the-science approach? He's a wonderful guest. It's a wide-ranging conversation. I hope you enjoy.

Brent: Doctor John Wherry, welcome to the show.

John: Yeah, thanks for having me. It's great to be here.

Brent: Today I want to talk about inflammation and your work around that. But before we get into it, will you just give us a sense of your day job and your background?

John: Yeah, sure. So I'm a scientist and an immunologist. I study how the immune system interacts with all sorts of threats to our bodies. I started maybe 30 years ago trying to understand how the immune system recognizes and fights off infections. Our long-standing interest has been studying and trying to understand the immune system in settings where it's engaged in a chronic battle—whether that's a chronic infection, cancer (which is very similar to a chronic infection from the immune system's perspective in many ways), or autoimmunity, where we have chronic activation of the immune system in an inappropriate way.

John: So my day job is really guiding that science in a research lab, but I also run an institute and a large platform effort around immune health.

Brent: Okay, great. On that point: when we think of inflammation, we usually think of it around a cut or fighting a virus. We don't typically think about it in the context of cancer, maybe because most of us don't have cancer. How does inflammation interact with the body in the fight against cancer?

Brent: And how is that different from how it might give us a fever to fight a virus?

John: It's a great question, and it cuts to the core of a lot of what we're trying to study in the field. Cancer is something that shouldn't be there. One of the original definitions of cancer over 100 years ago was actually "a wound that never heals." It represents damage in your body.

John: There's something growing in a tissue that shouldn't be there, and that growth or aberrant form causes damage to the tissue. At the core of it, inflammation arises from tissue damage. That damage can come from an injury, a cut, or a bruise, but it can also come from abnormal growth or changes in how the tissue is maintained.

John: All of those things activate your immune system. Evolutionarily, the goal of your immune system is simply to return your body or that tissue to a normal state—homeostasis—so that the organism can survive and reproduce. What happens in the setting of cancer is that instead of acute inflammation returning the system to balance, you end up getting chronic evolution.

John: The immune system continues to try, but it can't win. In some cases, that actually helps the tumor grow; in other cases, it causes significant tissue damage and bystander inflammation.

Brent: In most cases when my immune system is activated, it feels very obvious to me—for instance, running a fever when sick. I can tell my body is fighting. But many people with cancer don't notice it initially; they might have a lump they don't notice until later.

Brent: Then they start treatment. Is the immune response to cancer fundamentally different from other cases where the body's reaction is much more obvious?

John: There are two linked points that are important to articulate. First, there isn't just one kind of inflammation; it comes in many flavors. Having a viral infection where you get a fever is very different from a fungal infection or other diseases where the type of inflammation and symptoms differ.

John: Second, short-term or acute inflammation can be very beneficial. A fever helps eliminate an infection because your body can tolerate the temperature increase better than the virus or bacteria. However, chronic inflammation—even if it's the same flavor—is interpreted very differently by your immune system and body compared to acute inflammation.

John: Acute inflammation can help eliminate infections or even small cancers early on. But chronic inflammation can sometimes do the exact opposite. Understanding that there are different flavors and temporal aspects of inflammation is key.

Brent: When talking about chronic low-grade inflammation, I tend to think of C-reactive protein tests—a simple blood test to check for low-grade inflammation. It's not something you necessarily feel, but it serves as an early warning sign.

Brent: In contrast, acute inflammation occurs at a higher, more intense level over a shorter period. How would you distinguish between those two? What should an everyday person who feels fine think about knowing their hs-CRP level?

Brent: This concept of low-grade inflammation can be hard to wrap our heads around.

John: It is, and it's actually hard to define. It's not just difficult from a non-expert standpoint; even experts struggle to pinpoint exactly what it is. To start, clinical laboratory tests like CRP are relatively blunt instruments.

John: These tests are like looking into space with cheap binoculars. You can see general outlines or moon phases, but you won't get a detailed picture of distant galaxies.

John: On the research side, we can gather vast amounts of data, but then we face the challenge of determining which specific markers actually matter. We are caught between clinical tools that are very blunt and research tools that offer overwhelming detail.

John: Clinically, it's hard to tell how significant chronic inflammation is. Research can give you 100,000 data points, but the key questions remain: Which ones matter? What do you do with them? Can lifestyle or therapeutic interventions reset things to optimal levels?

John: Good data shows that certain habits lower chronic inflammation—dietary changes, fasting, and other interventions. As you age, baseline inflammation rises as the immune system encounters accumulated exposures, environmental factors, or natural wear and tear.

John: Measuring and acting on chronic inflammation effectively are two key challenges our field needs to address over the next five years.

Brent: An analogy that comes to mind for chronic low-grade inflammation is a stove. When you're young and healthy, the stove is off—there is no active inflammatory response.

Brent: When you get sick, the stove turns on high (a fever), and when you recover, it turns off. Chronic low-grade inflammation is like leaving the stove on a low burner setting continuously.

Brent: As we age, that baseline low setting tends to rise when we aren't actively sick. Ideally, we want the stove as low as possible or completely off unless we are actively fighting something off.

Brent: If it's constantly running, negative effects accumulate over time. Does that analogy resonate?

Brent: I know chronic low-grade inflammation is bad even if I can't feel it, but I'd like to understand more clearly why it's harmful. Could you help clarify that?

John: That analogy is spot on. You have this slow burn. Ideally, the burner light is ready, but the stove stays off until needed. Rapidly activating inflammation when necessary is crucial for protection, but keeping it nearly off most of the time is ideal.

John: Why is low-grade chronic inflammation harmful? First, it fatigues the immune system. Second, it causes subtle tissue damage over time, impairing proper healing. Third, if the immune system is always activated, it cannot mount a strong, dynamic response when needed.

John: Consider two equally fit athletes: one is continuously running marathons, while the other rests until it's time to sprint 100 yards. The rested athlete will be much fresher and more effective out of the blocks. The immune system operates similarly.

John: We frequently study what drives variations in low-grade inflammation between individuals. It's a complex topic, but we can highlight a few key contributing factors.

John: One of the questions that we ask ourselves a lot about this kind of stuff is what drives that change in low grade inflammation, and why do some people experience that or have that and others don't? This is an incredibly complicated question, and maybe we can go through just a couple of things that we do know and then ask why they're different from one person to the other.

John: Most people carry 4 to 6 persistent viral infections acquired earlier in life. These viruses stay with us permanently, kept in check by constant immune system management so they don't cause active disease.

John: These persistent viruses maintain a baseline level of immune activity. Over time, factors like sedentary habits, sun exposure, diet, stress, sleep deprivation, and gut microbiome composition also trigger inflammatory responses.

John: These factors interact continuously. Poor sleep or high stress can allow dormant viruses to resurge slightly, requiring additional immune attention.

John: As we live longer, these cumulative demands on the immune system increase, driving chronic background inflammation.

Brent: Are you saying that viruses contracted when young stay with us permanently? I think of HIV/AIDS, where medication manages it long-term, but it remains present in the body. Is that true for most viruses, just in less severe forms?

Brent: Once contracted, do they remain indefinitely, even if unmeasurable?

John: No, that isn't true for all viruses. For instance, influenza replicates in the upper respiratory tract for 7 to 14 days before the body clears it completely. That is an acute, fully resolved infection.

John: Conversely, herpes simplex virus type 1 (HSV-1), which causes cold sores, is present in about 90% of Americans and persists permanently.

John: Similarly, Epstein-Barr virus (EBV), which causes mononucleosis, infects roughly 92% of adults and remains indefinitely. If immunosuppressed, it can reactivate.

John: Cytomegalovirus (CMV) is another example. Most individuals harbor 4 to 8 of these latent viruses, along with resident bacteria and fungi in the gut, skin, and oral cavity that require constant immune regulation.

John: To survive, our immune system maintains a balance with these organisms—sometimes eliminating them outright, and other times maintaining a stable equilibrium.

John: Other times, this is an ongoing management battle, like a kind of a I don't know what you want to call it, but like an equilibrium between our immune system and the virus or the immune system and the microbe of interest.

Brent: Often, the body's inflammatory reaction to a virus causes more severe long-term issues than the initial infection—as seen in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or EBV complications. Should we actively try to avoid these viral exposures entirely?

Brent: Is avoiding these viruses practically impossible outside of using vaccines and targeted post-exposure treatments?

Brent: Since we can't live in isolated bubbles, should we focus on vaccines and general health rather than trying to avoid every viral exposure?

John: It's a fascinating question. Completely avoiding viral exposure is impossible. We can reduce risk through sensible hygiene, public health measures, vaccines, and maintaining overall immune fitness.

John: While conditions like Long COVID are debilitating, encountering SARS-CoV-2 without an immune response would be fatal. A functional immune system is essential despite the risks of post-viral complications.

John: Developing effective vaccines for certain pathogens like HIV or EBV remains challenging, but the potential long-term health benefits to society are substantial.

John: And so, you know, is it better to be alive with long Covid and hope that we figure out how to how to treat it? Or is it better to be dead from acute acute SARS-CoV-2 infection? I'll take the former. But I think that that part of the point is we should be trying to decide which of these things do we want to address from a medical and a public health standpoint?

John: And frankly, from a societal cost standpoint, what makes the most sense here? Because we want people having effective, productive lives, contributing to society. The vaccines for some of these things are, frankly, relatively easy not to diminish some of the work, which was remarkable, but making a vaccine for SARS-CoV-2 like we did it. And we could have another discussion about vaccine hesitancy and things.

John: We did it making a vaccine for HIV really, really hard. We've been trying for for decades, and it's really hard making a vaccine for Epstein-Barr virus really, really difficult. Should we keep trying? Yes. And actually the benefit to society could be very large, although we'll have to define it over the course of a lifespan, which is different from our previous vaccines, where you look, you define their utility over the course of one flu season.

John: And so we have to have a different perspective on what the value is for doing some of these things.

Brent: So the role of vaccines isn't necessarily preventing infection entirely, but reducing acute severity, which in turn reduces post-acute lingering issues?

John: Exactly. Vaccines rarely provide complete sterilizing immunity to block all viral entry. Instead, they significantly limit viral replication and spread within the body, preventing severe systemic disease.

John: But it's not what vaccines do. What they do is they reduce the amount of virus getting in and getting through. And what I mean by that, if we just kind of walk through like, like literally what happens when you get infected with something like influenza virus or SARS-CoV-2? First thing that happens is it gets in your nose, your mouth, your eyes, and from there it infects a couple cells.

John: It might only be tens or hundreds of viral particles that get in there, and some of them infect a few cells locally. It replicates. They're making more virus over the course of the first 12 to 24 hours. That virus then gets out and spreads locally, and some of it may get down into your lungs if it gets down into your lungs day 2 or 3 and starts replicating in your lungs.

John: Now you have sort of throat hit there along the way, and you start getting respiratory symptoms. That replicates unchecked. Now that virus gets out of your lungs into the bloodstream and starts going other places in your body. Each of these steps is the place you want your immune system and your vaccine induced immunity stopping things. Very unlikely. You're going to stop those first dozen viral particles getting in your nose from landing somewhere?

John: Great if you can. Really hard to know if you've ever done it. What you want to do is you want to stop that next wave from getting down to your lungs, and certainly want to stop the wave getting from your lungs to the rest of your body. That's where vaccines work.

Brent: If most adults carry 4 to 7 persistent viruses, should we aim to minimize that number? Should parents actively try to minimize viral exposures for their children?

Brent: All right. You know, I'm here in San Francisco. People wear masks when they're walking around alone, outside or whatever. I spent my time in Boulder, Colorado and San Francisco. There's a place where people are really worried about getting viruses and they're wearing masks, in my opinion, that they're doing a little bit too much of it. But is there some benefit to that, to being really cautious about the kids going to daycare when there's something going around?

Brent: Because I really want to get my kids 18, only having four of these and not having seven, or is that just totally impractical? And there are other benefits of exposure to these environments that are not purely pristine, is it? Is it just, hey, you don't need to worry about fighting that battle. Get the vaccines that are recommended. Live your life.

Brent: Is hyper-vigilance unnecessary compared to getting recommended vaccines and living normally?

John: I lean toward living normally. Hyper-vigilance based on incomplete data can be counterproductive.

John: For example, acquiring certain infections like EBV as an adult rather than as a child may actually carry a higher risk of complications or autoimmune triggers.

John: If you acquire Epstein-Barr virus as an adult, compared to as a kid.

Brent: Similar to how chickenpox is much worse when contracted as an adult.

John: Exactly. That's why context matters when interpreting medical data. However, one clear recommendation for adults over 50 is getting the zoster (shingles) vaccine.

John: Now, should we study these things? Should we try to limit some of the exposures that that we don't need to have? Absolutely. One thing I can't recommend highly enough based on the data is if you're over 50, get the zoster vaccine right. So you don't get that.

Brent: The shingles vaccine.

John: Strong evidence shows the shingles vaccine reduces the risk of post-herpetic neuralgia as well as dementia and Alzheimer's disease.

Brent: What is the practical utility of testing C-reactive protein (hs-CRP)? It indicates whether low-grade inflammation is present, but we don't treat hs-CRP directly with specific drugs the way we use statins for LDL cholesterol. Do you recommend routine hs-CRP testing?

Brent: Like we might take a statin to bring down our LDL cholesterol. So I don't know, do you do you regularly test your HSC? Is it something that you recommend for people or is it okay? It's good to know it's not going to hurt you knowing, but actually, you know, sleep, diet and exercise and make sure you know what's happening with your heart health and make sure you know what's happening with your blood sugar.

Brent: But I don't know, something like C-reactive protein is not that useful or or no, it is useful.

John: When combined with other clinical markers, elevated CRP is useful information that can prompt lifestyle improvements. However, a normal CRP level doesn't rule out low-grade inflammation elsewhere in the body.

John: It doesn't tell you you don't have chronic low grade inflammation in some sort, but so it's not bad.

Brent: So a high CRP level strongly indicates inflammation, but a low result isn't definitive proof of its absence?

John: Correct. In many settings, CRP levels can be non-informative even when specific inflammatory cytokines are significantly elevated, depending on the type of immune response.

John: CRP is a helpful directional guide, but it acts more as a positive indicator than a rule-out test.

Brent: And then the other markers you would referred to earlier in the conversation, hey, in a research setting, we can do this. And then in a clinical setting. And what that means to me, what that says to me is research means in a way that's not accessible to anybody, but just a few of us who are doing research, okay, we can do these things and clinical meaning in a way that's accessible to everybody.

Brent: Regarding advanced inflammatory markers used in research: Are any of these ready for clinical use, or should consumers focus on standard health metrics for now?

Brent: But now they're not really available to you today. You don't need to worry about them.

John: In medicine, tests shouldn't be performed unless they inform a clear clinical action. Unnecessary testing can lead to anxiety, incorrect treatments, and inflated healthcare costs without improving outcomes.

John: And if you can't make a clinical decision based on it, then we shouldn't measure it, because more information clinically isn't always a good thing. If you don't know that, it's telling you that there's an action you can take that's corrective or that's that's medically that you can do something medical about. You can actually make wrong decisions with with too much information because you don't know what it means.

John: So for it to be measured clinically and then to for you to be able to take action on it clinically, the assay that you use, the way you measure it has to be incredibly well validated and super rigorous. And the the sort of positive and negative control have to work every single time and be within range. And that's incredibly expensive to develop.

John: Should we develop an incredibly expensive test for every one of these inflammatory markers? No, that would be a waste of resources, frankly. And health care costs would balloon even further than they are. So I think we need to sort of thread the needle on what we're looking for here. I think what we're looking for is something where we can actually inform lifestyle choices, where we might have a different bar for what the assays are telling us and how they're used and interpreted.

John: We'd love to take this complex stuff that we do in the lab, which, like we might have some meaning for and convert it into something that we can use to make a clinical decision. And we're working towards that, and many people are. But we'd also like to think, you know, tons of us wearing these sort of lifestyle trackers and sleep trackers and Fitbits and what have you.

John: Are there things that one could do in that arena that might be useful to help people make the right to make lifestyle decisions, or when there's a lifestyle change to monitor what's happened and where should that be? I do think we need some regulation in that space so that we're not actually so we're so the science is rigorous, but I'm not sure all of these need to be regulated.

John: Like when you get an insulin test at your physician. And then that would trigger a clinical decision to give you a drug or put you on a clinical trial. So I don't know if that makes sense, but there's a space in between measuring something clinically and measuring something in the research side that I think warrants some, some thought about what we want to do there as a society.

Brent: Well, and I agree, I mean, I think it's, it's on, on in the discussions that we've had here, I can think of one exception, but all of the researchers and the MDS who we talked to are in this camp of, hey, we don't want to just measure everything. Full body scans. There's false positive risk. You can interpret the findings in the wrong way.

Brent: A lot of this stuff doesn't matter clinically. We were talking about these lipoprotein fractionation tests, which will give you the size of your basically your cholesterol particles. And it's you know, the conclusion there is okay, it's interesting to know, but it doesn't change anything clinically. We're going to look at your LDL and determine whether or not you need a statin and sleep diet, exercise are going to matter.

Brent: If you've got all the cholesterol it doesn't really matter. And then almost exclusively on the bio hacker nonempty non researcher side, if I were to walk out on the streets of San Francisco right now and ask people, they'd say, you want to know everything, I want the select all blood tests. And we definitely want the full body scans.

Brent: And so it creates this tension. I think that's exacerbated maybe by what we're seeing at the CDC and some of the political divisiveness as well. The expert class, they're you know, they don't know what they're talking about or they're in the pockets of big pharma. And so I got to do my own research and I got to do it myself.

Brent: And I think there's not a lot of truth to that. I tend to be on the side of, I don't know, people spend their whole lives researching this. And and it's a pretty smart perspective. I think I'm going to go with the docs and the researchers on this. And so you can agree or disagree with that if you want, but you're saying this is in that category, hey, we have some markers that we can measure, but we don't really we don't really think that they ought to be available just for anybody to, to or that you ought to use them in understanding your own health because that might be harmful.

Brent: We don't see a way that it's clinically useful today. More is not necessarily more information is not necessarily better. In fact, it can be harmful.

John: Unnecessary testing or screening without clear medical indications can lead to cascading interventions, false positives, and avoidable harm.

Brent: But I think, I think you've got to be careful with that argument because people don't if it if it's going to save me, I don't really care about the broader health care system. And I think there are there are versions of that argument that are like, I ended up I had an incidental finding on a on a heart scan.

Brent: And so I have an anomalous right coronary artery. I've got my right coronary artery originates on the left side. And this isn't a false positive. It's a it's a true positive. It's like, okay, I didn't know that I had this thing. And I end up getting a heart cath that at Cleveland Clinic that's got a 1 in 100 chance of stroke or death.

Brent: I mean, and it turns out it's fine. I don't you know, it doesn't present in a way that creates a lot of risk. And so as soon as you're getting a lot more information about yourself, you're putting yourself in the track and you might be putting yourself down a diagnostic path, a I need to figure out what this is.

Brent: Path. And those paths carry risk. And sometimes they actually carry more risk than the underlying thing that you're trying to get the diagnostics about. And so I didn't mean to chastise you for the way that you're presenting that point. But I think.

John: No, no, no, no. So I completely agree with you. And I think if I could if I could interject, I completely agree. I think we have to figure out how to sort of find that middle ground here because the, the other side of what you're saying or the other part of what you're saying, not the other side, is something that I advocate for incredibly strongly all the time, is we have to be our own biggest health care advocates for ourselves.

John: We are the ones that care more about our health than anybody else, even a good meeting physician. We have to continue to push to get those evaluations that we need. And there's a there's a balance between measuring everything on everybody and measuring a lot of things on the right people. And I think we have to find that balance.

John: And I think it should be paired with more individual advocacy on the patient side. And, you know, there's there's deference to the health system in some communities that that I think means that people don't ask for an advocate for themselves enough. And so I'm with you on this idea that we should actually take advantage of those things are going to give us the incidental findings that allow interventions in the right way.

Brent: Well, I was actually I mean, I was making the case that that was a case where I was being wheeled in for the calf and they said, oh, 1 in 100 chance of stroke or death. And I thought, wait a minute, I'm trying to figure out whether or not I should do an open heart surgery with this cath.

Brent: And open heart surgery is a 100 chance of stroke or death. What am I doing here? And you can. And it's the same thing can happen with a full body scan. Oh, there's a lump. We don't know what it is. There's a lump on your lung. We don't know what it is. Okay, well, you can go into when you buy biopsies, that lump and you can have a stroke, or you can have a heart attack during that procedure, and then it can be negative.

Brent: It can be nonpolitical. And so I do think on the consumer side, on the bio hacker side, we're a little bit casual about, hey, more information. I think we're agreeing with that. More information is better. It's way more complicated than that. More information can actually be harmful. In some cases. It can save a life. And that's the trickiness.

Brent: The point I was making is I think that people are too selfish. I don't even mean this in a negative way to care about the health care system. If you said, hey, don't get a full body scan because you might overload the health care system, it's like, well, wait, could it save my life? And if the answer is yes, then, well, I don't really care about the health care system.

Brent: It seems like it's going to get overloaded anyways. But the answer is no, no, no, you get a false positive and then you could actually end up being harmed unnecessarily.

John: I agree, and then I think the other the other part of this is, you know, on the sort of measure everything and then solve the problem myself part of things. Right. So now I have this information, I'm going to go to GNC or no offense, GNC, I'm going to go to some supplement store and buy whatever and, you know, manage it with my own turmeric.

John: The four greatest public health developments in human history are clean water, antibiotics, vaccines, and the randomized placebo-controlled clinical trial. Without control groups, it is impossible to determine whether a given intervention had a true causal effect.

John: And so the anecdotes of, well, I took X, Y, or Z, and now I'm better or I'm, I'm different than I was, whatever that may be. There's no way to know whether that thing you did was causal. And correlation is not causation, these kind of things. So the idea that we should just put all this information out into the community and let people do whatever they want with it, is not necessarily totally against that, although I think it comes with huge risks.

John: But what we lose, which is really important, is we lose the knowledge advancing from from knowing whether any of the things that have been done have actually had causal effects going forward. So we should try to at least capture what's happening when we're trying to disseminate information and think about how to use measurements of immune health more broadly.

Brent: Okay. And then on back on on inflammation. So is there is there anything that is not sleep, diet, exercise for the chronic low grade inflammation that we'd be thinking about? Is there a supplement you would mentioned? Turmeric. I think just as an example, I don't think you were promoting it or not. You weren't. You were just using it in passing earlier in the conversation.

Brent: Are there non-obvious tools or medications for reducing chronic low-grade inflammation beyond sleep, diet, and exercise—such as GLP-1 receptor agonists?

John: There are no simple magic bullets, but GLP-1 receptor agonists show remarkable promise in reducing systemic chronic inflammation, and future iterations may offer even better tolerability.

John: Beyond basic sleep and exercise recommendations, periodic fasting or fast-mimicking approaches show strong scientific evidence. Entering ketosis signals tissue stem cells across the body to regenerate, helping lower baseline inflammation.

John: And that seems to link to sort of lowering chronic inflammation. So I've been impressed by the places where you think just a little bit more deeply about what sleep, diet and exercise means, and then using that science to say, so it's really about this kind of sleep in this way and with this consistency or it's this kind of exercise, I don't need to, you know, be passed out on the floor of the gym after each workout.

John: Additionally, regular resistance and strength training as we age appears particularly important—perhaps even more critical than pure cardiovascular training—for preserving tissue health and reducing systemic inflammation.

Brent: Of the kind of sleep and exercise matter. Yeah, the annoying thing about strength training is you. I feel like I keep getting injured. Strength training. It's I'm in my mid 40s and I'm like, man, it's hard to really strength train regularly. And then, you know, you're you're doing you're doing work in t cell exhaustion. So basically back to your hey you've got you've got two runners and one is one is constantly running a marathon and one is ready to run the race.

Brent: But resting okay, the one who's resting is going to be faster. I assume that refers to some of the work on T cell exhaustion or that that analogy hold somewhere. But what are you most excited about? If you could wave a magic wand and you could do the AI search in 50 years, where you could look at what happened with the work that's ongoing for you or for somebody else, or more broadly, for the field, you know, what would you be most excited to look at the results of?

Brent: Looking ahead over the coming decades, what developments in immunology research excite you most?

John: First, studying T-cell exhaustion will help us understand how the immune system sustains responses over decades without causing tissue collapse. Second, I am optimistic that routine blood profiles will eventually predict disease trajectories and personalized treatment responses.

John: This ongoing fight is really remarkable. And not many tissues can do that and maintain that fight or that that regenerative process that long. So I think we can learn something about fundamental biology by studying this sort of chronic T cell exhaustion offense. The second is that I'm optimistic that we will be able to take a sample of your blood at some point and be able to predict the trajectory of inflammation, the trajectory of future disease.

John: And actually, I think in the short term or intermediate term, your response to different kinds of drugs, what we know from inflammatory diseases over and over and over again is that if you take 100 people with the same clinically defined chronic inflammatory disease, those hundred people respond differently to the same therapeutics. So why is that? If those hundred people all have the same disease, why are they responding differently?

John: And I think from a sample of your blood, we're going to be able to predict which drug you would respond to better, depending on what your immune system history is and how your immune system has been educated over time.

Brent: Personalized medicine—I hope you're right! Doctor John Wherry, thank you so much for your time and for all the work you do.

John: Thank you, Brent. This was a lot of fun.

Brent: The Life Lab by Death Clock is recorded in Boulder, Colorado, and San Francisco, California. Produced by Patrick Guardino, with music by Patrick Lee, and hosted by yours truly, Brent Franson, founder and CEO of Death Clock.