Podcasts about ruslan medzhitov

If there's one person you'd want to talk to about immunology, the immune system and Covid, holes in our knowledge base about the complex immune system, and where the field is headed, it would be Professor Iwasaki. And add to that the topic of Women in Science. Here's our wide-ranging conversation.A snippet of the video, Full length Ground Truths videos are posted here and you can subscribe. Ground Truths is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Transcript with many external link and links to the audio, recorded 30 April 2024 Eric Topol (00:06):Hello, it's Eric Topol and I'm really thrilled to have my friend Akiko Iwasaki from Yale, and before I start talking with Akiko, I just want to mention there aren't too many silver linings of the pandemic, but one for me was getting to know Professor Iwasaki. She is my go-to immunologist. I've learned so much from her over the last four years and she's amazing. She just, as you may know, she was just recently named one of the most influential people in the world by TIME100. [and also recognized this week in TIME 100 Health]. And besides that, she's been elected to the National Academy of Medicine, National Academy of Sciences. She's the president of the American Association of Immunologists and she's a Howard Hughes principal investigator. So Akiko, it's wonderful to have you to join into an extended discussion of things that we have of mutual interest.Akiko Iwasaki (01:04):Thank you so much, Eric, for having me. I equally appreciate all of what you do, and I follow your blog and tweets and everything. So thank you Eric.Eric Topol (01:14):Well, you are a phenom. I mean just, that's all I can say because I think it was so appropriate that TIME recognize your contributions, not just over the pandemic, but of course throughout your career, a brilliant career in immunology. I thought we'd start out with our topic of great interest on Long Covid. You've done seminal work here and this is an evolving topic obviously. I wonder what your latest thoughts are on the pathogenesis and where things are headed.Long CovidAkiko Iwasaki (01:55):Yeah, so as I have been saying throughout the pandemic, I think that Long Covid is not one disease. It's a collection of multiple diseases and that are sort of ending up in similar sets of symptoms. Obviously, there are over 200 symptoms and not everyone has the same set of symptoms, but what we are going for is trying to understand the disease drivers, so persistent viral infection is one of them. There are overwhelming evidence for that theory now, all the way from autopsy and biopsy studies to looking at peripheral blood RNA signatures as well as circulating spike protein and nucleocapsid proteins that are detected in people with Long Covid. Now whether that persistent virus or remnants of virus is driving the disease itself is unclear still. And that's why trials like the one that we are engaging with Harlan Krumholz on Paxlovid should tell us what percentage of the people are suffering from that type of driver and whether antivirals like Paxlovid might be able to mitigate those. If I may, I'd like to talk about three other hypotheses.Eric Topol (03:15):Yeah, I'd love for you to do that.Akiko Iwasaki (03:18):Okay, great. So the second hypothesis that we've been working on is autoimmune disease. And so, this is clearly happening in a subset of people, again, it's a heterogeneous disease, but we can actually not only look at reactogenicity of antibodies from people with Long Covid where we can transfer IgG from patients with Long Covid into an animal, a healthy animal, and really measure outcomes of a pathogenesis. So that's a functional evidence that antibodies in some people with Long Covid is really actually causing some of the damages that are occurring in vivo. And the third hypothesis is the reactivation of herpes viruses. So many of us adults have multiple latent herpes virus family members that are just dormant and are not really causing any pathologies. But in people with Long Covid, we're seeing elevated reactivation of viruses like Epstein-Barr virus (EBV) or Varicella-zoster virus (VZV) and that may again be just a signature of Long Covid, but it may also be driving some of the symptoms that people are suffering from.(04:32):So that's again, we see the signature over and over, not just our group, but multiple other groups, Michael Peluso's group, Jim Heath, and many others. So that's also an emerging evidence from multiple groups showing that. And finally, we think that inflammation that occurs during the acute phase can sort of chronically change some tissue tone. For instance, in the brain with Michelle Monje's team, we developed a sort of localized mild Covid model of infection and showed that changes in microglia can be seen seven weeks post infection even though the virus is completely gone. So that means that inflammation that's established as a result of this initial infection can have prolonged sequence and sequela within the person and that may also be driving disease. And Eric, the reason we need to understand these diseases separately is because not only for diagnostic purposes, but for therapeutic purposes because to target a persistent virus is very different approach from targeting autoantibodies, for example.Eric Topol (05:49):Well, that's great. There's a lot to unpack there as you laid out four distinct paths that could result in the clinical syndrome and sequelae. I think you know I had the chance to have a really fun conversation with Michelle about their joint work that you've done, and she reminded me how she made a cold call to you to start as a collaboration, which I thought was fantastic. Look what that yielded. But yeah, this is fascinating because as I think you're getting at is that it may not be the same pathogenesis in any given individual so that all these, and even others might be operative. I guess maybe I first delve into the antibody story as you're well aware, we see after people get Covid a higher rate of autoimmune diseases crop up, which is really interesting because it seems to rev up self-directed immune response. And this I think many people haven't really noted yet, although obviously you're well aware of this, it's across all the different autoimmune diseases, connective tissue disease, not just one in particular. And it's, as you say, the idea that you could take the blood from a person suffering from Long Covid and give it to an experimental animal model and be able to recapitulate some of the abnormalities, it's really pretty striking. So the question I guess is if you were to do plasmapheresis and try to basically expunge these autoantibodies, wouldn't you expect people to have some symptomatic benefit pretty rapidly or is it just that the process is already far from the initiating step?Akiko Iwasaki (07:54):That's a great question. Plasmapheresis may be able to transiently improve the person if they're suffering from these autoantibody mediated diseases. People have reported, for example, IVIG treatment has dramatically improved their symptoms, but not in everybody. So it's really critical to understand who's suffering from this particular driver and appropriately treat those people. And there are many other very effective therapies in autoimmune disease field that can be repurposed for treating these patients as well.Eric Topol (08:34):The only clinical trial that has clicked so far, interestingly, came out of Hong Kong with different types of ways to manipulate the gut microbiome, which again, you know better than me is a major modulator of our immune system response. What are your thoughts about taking advantage of that way to somehow modulate this untoward immune response in people with this condition?Akiko Iwasaki (09:07):Yeah, so that is an exciting sort of development, and I don't mean to discount the importance of microbiome at all. It's just the drivers that are mentioning are something that can be directly linked to disease, but certainly dysbiosis and translocation of metabolites and microbiome itself could trigger Long Covid as well. So it's something that we're definitely keeping our eyes on. And as you say, Eric, the immune system is in intimate contact with the gut microbiome and also the gut is intimate contact with the brain. So there's a lot of connections that we really need to be paying attention to. So yeah, absolutely. This is a very exciting development.Eric Topol (09:57):And it is intriguing of course, the reactivation of viruses. I mean, we've learned in recent years how important EBV is in multiple sclerosis (MS). The question I have for you on that pathway, is this just an epiphenomena or do you actually think that could be a driving force in some people?Akiko Iwasaki (10:19):Yeah, so that's really hard to untangle in people. I mean, David Putrino and my team we're planning a clinical trial using Truvada. Truvada obviously is an HIV drug, but it has reported antiviral activity to Epstein-Barr virus (EBV) and others. So potentially we can try to interrogate that in people, but we're also developing mouse models that can sort of recapitulate EBV like viral reactivation and to see whether there's any sort of causal link between the reactivation and disease process.Eric Topol (10:57):Right now, recently there's been a bunch of anecdotes of people who get the glucagon-like peptide one (GLP-1) drugs which have a potent anti-inflammatory, both systemic and in the brain. I'd love to test these drugs, but of course these companies that make them or have other interests outside of Long Covid, do you think there's potential for a drug like that?Akiko Iwasaki (11:23):Yeah, so those drugs seem to have a lot of miraculous effects on every disease. So obviously it has to be used carefully because many people with Long Covid have issues with liver functions and other existing conditions that may or may not be conducive to taking those types of GLP-1 agonists. But in subset of people, maybe this can be tried, especially due to the anti-inflammatory properties, it may benefit again, a subset of people. I don't expect a single drug to cure everyone. That would be pretty amazing, but unlikely.Eric Topol (12:09):Absolutely. And it's unfortunate we are not further along in this whole story of clinical trials, testing treatments and applauding your efforts with my friend Harlan there to get into the testing which we had hoped RECOVER was going to do with their more than billion dollars or allocation, which didn't get us too far in that. Now before we leave Long Covid, which we could speak about for hours, I mean it's so darn important because so many people are really out there disabled or suffering on a daily basis or periodically they get better and then get worse again. There's been this whole idea that, oh, it's going away and that reinfections don't pose a threat. Maybe you could straighten that story out because I think there seems to be some miscues about the risk of Long Covid even as we go along with the continued circulating virus.Akiko Iwasaki (13:11):Right, so when you look at the epidemiological evidence of Long Covid, clearly in the beginning when we had no vaccines, no antivirals, no real good measure against Covid, the incident of developing Long Covid per infection was higher than a current date where we do have vaccines and Omicron may have changed its property significantly. So if you compare, let's say the Delta period versus Omicron period, there seems to be a reduced risk per infection of Long Covid. However, Omicron is super infectious. It's infected millions of people, and if you look at the total number of people suffering from Long Covid, we're not seeing a huge decline there at all because of the transmissibility of Omicron. So I think it's too early for us to say, okay, the rates are declining, we don't need to worry about it. Not at all, I think we still have to be vigilant.(14:14):We need to be up to date on vaccines and boosters because those seem to reduce the risk for Long Covid and whether Paxlovid can reduce the rate of Long Covid at the acute phase for the high risk individual, it seems to be yes, but for people who are not at high risk may or may not be very effective. So again, we just need to be very cautious. It's difficult obviously, to be completely avoiding virus at this time point, but I think masking and anything you can do, vaccination boosters is going to be helpful. And a reinfection does carry risk for developing Long Covid. So that prior infection is not going to prevent Long Covid altogether, even though the risk may be slightly reduced in the first infection. So when you think about these risks, again we need to be cognizant that reinfection and some people have multiple infections and then eventually get Long Covid, so we're just not safe from Long Covid yet.Nasal Vaccines and Mucosal ImmunityEric Topol (15:24):Right. No, I think that's the problem is that people have not acknowledged that there's an ongoing risk and that we should continue to keep our guard up. I want to applaud you and your colleagues. You recently put out [Yale School of Public Health] this multi-panel about Covid, which we'll post with this podcast that gave a lot of the facts straight and simple diagrams, and I think this is what you need is this is kind of like all your threads on Twitter. . They're always such great educational ways to get across important information. So now let's go onto a second topic of great mutual interest where you've also been a leader and that's in the mucosal nasal vaccine story. I had the privilege of writing with you a nice article in Science Immunology back in 2022 about Operation Nasal Vaccine, and unfortunately we don't have a nasal vaccine. We need a nasal vaccine against Covid. Where do we stand with this now?Akiko Iwasaki (16:31):Yeah, so you're right. I mean nasal vaccines, I don't really know what the barrier is because I think the preclinical models all support the effectiveness against transmission and infection and obviously disease. And there is a White House initiative to support rapid development of next generation vaccine, which includes mucosal vaccine, so perhaps that's sort of pushing some of these vaccine candidates forward. You're probably more familiar than me about those kinds of events that are happening. But yeah, it's unfortunate that we don't have an approved mucosal booster vaccine yet, and our research has shown that as simple as a spray of recombinant spike protein without any adjuvants are able to restimulate immune response and then establish mucosal immunity in the nasal cavity, which goes a long way in preventing infection as well as transmission. So yeah, I mean I'm equally frustrated that things like that don't exist yet.The Neomycin and Neosporin SurpriseEric Topol (17:52):Well, I mean the work that you and many other groups around the world have published on this is so compelling and this is the main thing that we don't have now, which is a way to prevent infection. And I think most of us would be very happy to have a spray that every three or four months and gave us much higher levels of protection than we're ever going to get from shots. And your whole concept of prime and spike, I mean this is something that we could have had years ago if there was a priority, and unfortunately there never has been. Now, the other day you came with a surprise in a paper on Neomycin as an alternate or Neosporin ointment. Can you tell us about that? Because that one wasn't expected. This was to use an antibiotic in a way to reduce Covid and other respiratory virus.Akiko Iwasaki (18:50):Right. So yeah, that's a little known fact. I mean, of course widespread use of antibiotics has caused some significant issues with resistance and so on. However, when you look at the literature of different types of antibiotics, we have reported in 2018 that certain types of antibiotics known as aminoglycoside, which includes Neosporin or neomycin, has this sort of unintended antiviral property by triggering Toll-like receptor 3 in specialized cell types known as conventional dendritic cell type 1. And we published that for a genital herpes model that we were working on at the time. But because it's acting on the host, the Toll-like receptor 3 on the host cell to induce interferon and interferon stimulated genes to prevent the replication of the virus, we knew that it could be pan-viral. It doesn't really matter what the virus is. So we basically leverage that discovery that was made by a postdoc Smita Gopinath when she was in the lab to see if we can use that in the nasal cavity.(20:07):And that's what Tianyang Mao, a former graduate student did, in fact. And yeah, little spray of neomycin in the nose of the mice reduce this infection as well as disease and can even be used to treat shortly after the infection disease progress and using hamster models we also showed that hamsters that are pretreated with neomycin when they were caged with infected hamsters, the transmission rate was much reduced. And we also did with Dr. Charles Dela Cruz, a small clinical trial, randomized though into placebo and Neosporin arms of healthy volunteers. We asked them to put in a pea size amount of Neosporin on a cotton swab into the nose, and they were doing that twice a day for seven days. We measured the RNA from the nose of these people and indeed see that more than half the participants in the Neosporin group had elevated interferon stimulated genes, whereas the control group, which were given Vaseline had no response. So this sort of shows the promise of using something as generic and cheap as Neosporin to trigger antiviral state in the nose. Now it does require a much larger trial making sure that the safety profiles there and effectiveness against viral infection, but it's just a beginning of a story that could develop into something useful.New Frontiers in Immunology and Tx CellsEric Topol (21:51):Yeah, I thought it was fascinating, and it does bring up, which I think has also been underdeveloped, is our approaches for interferon a frontline defense where augmenting that, just getting that exploiting the nasal mucosa, the entry site, whether it be through that means or of course through even more potent a nasal vaccine, it's like a missing, it's a hole in our whole defense of against this virus that's led to millions of people not just dying, but of course also sick and also with Long Covid around the world. So I hope that we'll see some progress, but I thought that was a really fascinating hint of something to come that could be very helpful in the meantime while we're waiting for specific nasal vaccines. Now added to all these things recently, like last week you published a paper in Cell with your husband who's in the same department, I think at Yale. Is that right? Can you tell us about that and this paper about the whole new perspectives in immunology?Akiko Iwasaki (23:05):Yeah, so my husband Ruslan Medzhitov is a very famous immunologist who's in the same department, and we've written four or five review and opinion pieces together over the years. This new one is in Cell and it's really exploring new perspectives in immunology. We were asked by the editors to celebrate the 50th anniversary of the Cell journal with a perspective on the immune system. And the immune response is just a beautiful system that is triggered in response to specific pathogens and can really provide long-term or even sometimes lifelong immunity and resistance against pathogens and it really saves our lives. Much has been learned throughout the last 20, 30 years about the innate and adaptive immune system and how they're linked. In this new perspective, we are trying to raise some issues that the current paradigm cannot explain properly, some of the mysteries that are still remaining in the immune system.(24:22):And we try to come up with new concepts about even the role of the immune system in general. For instance, is the immune system only good for fighting pathogens or can it be repurposed for conducting normal physiology in the host? And we came up with a new subset of T-cells known as, or we call it Tx cells, which basically is an interoceptive type of T-cells that monitor homeostasis in different tissues and are helping with the normal process of biology as opposed to fighting viruses or bacteria or fungi. But these cells, when they are not appropriately regulated, they are also the source of autoimmune diseases because they are by design reactive against auto antigens. And so, this is a whole new framework to think about, a different arm of the immune function, which is really looking inside of our body and not really fighting against pathogens, but we believe these cells exist, and we know that the counterpart of Tx cells, which is the T regulatory cells, are indeed well known for its physiological functions. So we're hoping that this new perspective will trigger a new set of approaches in the field to try to understand this interceptive property of T-cells.Eric Topol (25:59):Yeah, well, I thought it was fascinating, of course, and I wanted to get into that more because I think what we're learning is this immune system not only obviously is for cancer whole. We're only starting to get warmed up with immunotherapy where checkpoint inhibitors were just the beginning and now obviously with vaccines and all these different ways that we can take the CAR-T cells, engineered T-cells, take the immune system to fight cancer and potentially to even use it as a way to prevent cancer. If you have these, whether it's Tx or Tregs or whatever T-cells can do this. But even bigger than that is the idea that it's tied in with the aging process. So as you know, again, much more than I do, our senescent immune cells are not good for us. And the whole idea is that we could build immune resilience if we could somehow figure out these mysteries that you're getting at, whereby we get vulnerable just as we were with Covid. And as we get older, we get vulnerable to not just infections, but everything going wrong, whether it's the walls of our arteries or whether it's the cancer or the immunity that's going on in our brain for Alzheimer's and neurodegenerative diseases. How can we fix the immune system so that we age more healthilyThe Immune System and Healthy Aging Akiko Iwasaki (27:37):Oh yeah. A lot of billionaires are also interested in that question and are pouring money into this question. It's interesting, but when you think about the sort of evolutionary perspective, we humans are only living so long. In the very recent decades, our life expectancy used to be much shorter and all we had to survive was to reproduce and generate the next progeny. But nowadays, because of this amazing wealth and health interventions and food and everything else, we're just living so much longer than even our grandparents. The immune system didn't evolve to deal with such one to begin with. So we were doing fine living up to 30 years of age or whatever. But now that we're living up to a hundred years, the immune system isn't really designed to keep up with this kind of stressors. But I think you're getting at a very important kind of more engineering questions of how do we manipulate the immune system or rejuvenate it so that we can remain healthy into the later decades? And it is well known that the immune system itself ages and that our ability to produce new lymphocytes, for example, decline over time and thymus that is important for T-cell development shrinks over time. And so anatomically it's impossible to help stop that process. However, is there a way of, for example, transferring some factors or engineering the immune cells to remain healthy and even like hematopoiesis itself can be manipulated to perhaps rejuvenate the whole immune system in their recent papers showing that. So this is a new frontier.Eric Topol (29:50):Do you think that some point in the future, we'll ex vivo inject Yamanaka factors into these cell lines and instead of this idea that you know get young plasma to old folks, and I mean since we don't know what's in there and it doesn't specifically have an effect on immune cells, who knows how it's working, but do you foresee that that might be a potential avenue going forward or even an in vivo delivery of this?Akiko Iwasaki (30:22):Yeah, it's not impossible, right? There are really rapidly evolving technologies and gene therapies that are becoming online. So it's not impossible to think about engineering in situ as you're suggesting, but we also have to be certain that we are living longer, but also healthy. So we do have to not only just deal with the aging immune system, but preventing neurodegenerative diseases and so on. And the immune system may have a role to play there as well. So there's a lot of, I mean, I can't think of a non-genetically mediated disease that doesn't involve the immune system.Eric Topol (31:03):Sure. No, I mean, it's just, when I think about this, people keep talking about the digital era of digital biology, but I actually think of it more as digital immunobiology, which is driving this because it's center stage and in more and more over time. And the idea that I'm concerned about is that we could rejuvenate the relevant immune cells or the whole immune response, but then it's such a delicate balance that we could actually wind up with untoward, whether it's autoimmune or overly stimulated immune system. It's not such a simple matter, as I'm sure you would agree. Now, this gets me to a broader thing which you've done, which is a profound contribution in life science and medicine, which is being an advocate for women in science. And I wonder if you could speak to that because you have been such a phenomenal force propelling the importance of women in science and not just doing that passively, but also standing up for women, which is being an activist is how you get things to change. So can you tell us about your thoughts there?An Activist for Women in ScienceAkiko Iwasaki (32:22):Yeah, so I grew up in Japan, and part of the reason I left Japan at the age of 16 was that I felt very stifled because of the societal norm and expectation of what a woman should be. And I felt like I didn't have the opportunity to develop my skills as a scientist remaining in Japan. And maybe things have changed over the years, but at the time when I was growing up, that's how I felt. And so, I was very cognizant of biases in society. And so, in the US and in Canada where I also trained, there's a lot less barrier to success, and we are able to do pretty much anything we want, which is wonderful, and that's why I think I'm here. But at the same time, the inequity still exists, even in pay gaps and things like that that are easy to fix but are still kind of insidious and it's there.(33:32):And Yale School of Medicine has done a great job partly because of the efforts of women who spoke up and who actually started to collect evidence for pay gap. And now there's very little pay gap because there's active sort of involvement of the dean and everyone else to ensure equity in the medical school. But it's just a small segment of the society. We really need to expand this to other schools and making sure that women are getting paid equally as men in the same ranks. And also, I see still some sexual harassment or more just toxic environment for people in general in academia. Some PIs get away with a lot of behavior that's not conducive to a healthy environment, so I have written about that as well and how we can have antidotes for such toxic environments. And it really does require the whole village to act on it. It's not just one person speaking up. And there should be measures placed to make sure that those people who does have this tendency of abusive behavior that they can get training and just being aware of these situations and corrective behavior. So I think there's still a lot of work left in academia, but things have obviously improved dramatically over the last few decades, and we are in a very, very good place, but we just have to keep working to achieve true equity.Why Don't We Have Immunome Check-Ups?Eric Topol (35:25):Well applauding your efforts for that, and I'm still in touch with that. We got a ways to go, and I hope that we'll see steady and even more accelerated and improvement to get to parity, which is what it should be. And I really think you've been a model for doing this. It isn't like you aren't busy with everything else, so to fit that in is wonderful. In closing up, one of the things that I wonder about is our ability to assess back to the immune system for a moment isn't what it should be. That is we do a CBC and we have how many lymphocytes, how many this, why don't we have an immunome, why doesn't everybody serially have an immune system checkup? Because that would tell us if we're starting to go haywire and then maybe hunt for reactivated viruses or what's going on. Do you foresee that we could ever get to a practical immunome as we go forward? Because it seems like it's a big missing link right now.Akiko Iwasaki (36:33):Yeah, I think that's a great idea. I mean, I'll be the first one to sign up for the immunome.Eric Topol (36:40):But I'm depending on you to make it happen.Akiko Iwasaki (36:44):Well, interestingly, Eric, there are lots of amazing technologies that are developed even during the pandemic, which is monitoring everything from antibody reactivity to reactivated viruses to the cytokines to every cell marker you can imagine. So the technologies out there, it's just I think a matter of having the right set of panels that are relatively affordable because some of these things are thousands of dollars per sample to analyze, and then of course clinical validation, something that's CLIA approved, and then we can start to, I guess the insurance company needs to also cover this, right? So we need to demonstrate the benefit to health in the long run to be able to afford this kind of immunome analysis. But I think that very wealthy people can already get this done.Eric Topol (37:43):Yeah, well, we want to make it so it's a health equity story, not of course, only for the crazy ones that are out there that are taking 112 supplements a day and whatnot. But it's intriguing because I think we might be able to get ahead of things if we had such an easy means. And as you said during the pandemic, for example, my friends here in La Jolla at La Jolla Immunology did all kinds of T-cell studies that were really insightful and of course done with you and others around the country and elsewhere to give us insights that you didn't get just from neutralizing antibodies. But it isn't something that you can get done easily. Now, I think this immunome hopefully will get us to another level in the future. One of the most striking things I've seen in our space clinically before wrapping up is to take the CD19 CAR T therapies to deplete the B cells of people with lupus, systemic sclerosis and other conditions, and completely stop their autoimmune condition. And when the B cells come back, they're not fighting themselves. They're not self-directed anymore. Would you have predicted this? This seems really striking and it may be a clue to the kind of mastering approaches to autoimmune diseases in the future.Akiko Iwasaki (39:19):Yeah, absolutely. So for multiple sclerosis, for example, where B cells weren't thought to be a key player by doing anti-CD20 depletion, there's this remarkable clinical effects. So I think we can only find the answer experimentally in people when they do these clinical trials and show this remarkable effects. That's when we say, aha, we don't really understand immunology. You know what I mean? That's when we have to be humble about what we think we understand. We really don't know until we try it. So that's a really good lesson learned. And these may be also applicable to people with autoimmune phenotype in Long Covid, right? We may be able to benefit from similar kinds of depletion therapy. So I think we have a lot to learn still.Eric Topol (40:14):Yeah, that's why, again, going back to the paper you just had in Cell about the mysteries and about some new ideas and challenging the dogma is so important. I still consider the immune system most complex one in the body by far, and I'm depending on you Akiko to unravel it, not to put any weight on your shoulders. Anyway, this has been so much fun. You are such a gem and always learning from you, and I can't thank you enough for all the work. And the fact is that you've got decades ahead of you to keep building on this. You've already done enough for many people, many scientists in your career, and I know you'll keep going. So we're all going to be following you with great interest in learning from you on a frequent basis. And I hope we'll build on some of the things we've talked about like a Long Covid treatment, treatments that are effective nasal vaccines, maybe even some dab of Neosporin, and keep on the momentum we've had with the understanding of the immune system, and finally, someday achieving the true parity of gender and science. And so, thank you for all that you do.Akiko Iwasaki (41:35):Thank you so much, Eric.************************CreditsHeadshot photo credits by Robert Lisak, Yale School of MedicineMy producer for Ground Truths is Jessica Nguyen, Scripps Research and our technical support for audio/video is by SInjun Balabanoff at Scripps Research.I hope you found the spot informative. Please share itThe Ground Truths newsletters and podcasts are all free, open-access, without ads.Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in.Comments are welcome from all subscribers. Get full access to Ground Truths at erictopol.substack.com/subscribe

Videos :   ELDERLY SUICIDE – This is Agenda 21 – MUST SEE! 2022 Fauci, meet 2004 Fauci. FACT CHECK: it did not go well for 2022 Fauci.  (1:23) Sam Bailey & Jessic Rose Part 1 (22:33) Gary Null Speaking Out at the NYS Assembly Hearing  (25:00)   Higher omega-3 levels linked to better sleep University of British Columbia, September 14 2022.  Having higher blood concentrations of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) was found to be associated with a reduction in excessive sleep in an analysis reported in 2022 in the American Journal of Clinical Nutrition. Sleep duration of over 9 hours per night has been correlated with an increased risk of cardiovascular disease and premature mortality from all causes. The analysis included 21,653 participants in 12 studies for whom information was available concerning sleep duration and/or difficulty falling asleep and blood levels of the omega-3 fatty acids EPA, DHA, ALA and, when available, DPA, and the omega-6 fatty acids AA and LA. When men and women whose fatty acid levels were among the lowest 20% of participants were compared to those whose levels were among the top 20%, individuals whose DHA intake was highest had a 22% lower risk of excessive sleep. Being among those who had the highest intake of EPA plus DHA and DPA was associated with a 24% lower risk. The authors noted that DHA's role in regulating melatonin production helps regulate sleep.  Twice-daily nasal irrigation reduces COVID-related illness, death Medical College of Georgia at Augusta University, September 13, 2022 Starting twice daily flushing of the mucus-lined nasal cavity with a mild saline solution soon after testing positive for COVID-19 can significantly reduce hospitalization and death, investigators report. They say the technique that can be used at home by mixing a half teaspoon each of salt and baking soda in a cup of boiled or distilled water then putting it into a sinus rinse bottle is a safe, effective and inexpensive way to reduce the risk of severe illness and death from coronavirus infection that could have a vital public health impact.  “By giving extra hydration to your sinuses, it makes them function better. “We found an 8.5-fold reduction in hospitalizations and no fatalities compared to our controls,” says senior author Dr. Richard Schwartz, chair of the MCG Department of Emergency Medicine. “Both of those are pretty significant endpoints.” The study appears to be the largest, prospective clinical trial of its kind and the older, high-risk population they studied—many of whom had preexisting conditions like obesity and hypertension—may benefit most from the easy, inexpensive practice, the investigators say. They found that less than 1.3% of the 79 study subjects age 55 and older who enrolled within 24-hours of testing positive for COVID-19 between Sept. 24 and Dec. 21, 2020, experienced hospitalization. No one died.  Researchers know that the more virus that was present in your body, the worse the impact. “One of our thoughts was: If we can rinse out some of the virus within 24 hours of them testing positive, then maybe we can lower the severity of that whole trajectory,” she says, including reducing the likelihood the virus could get into the lungs, where it was doing permanent, often lethal damage to many. Baxter says the nasal irrigation with saline helps decrease the usual robust attachment. Saline appears to inhibit the virus' ability to essentially make two cuts in itself, called furin cleavage, so it can better fit into an ACE2 receptor once it spots one. Participants self-administered nasal irrigation using either povidone-iodine, that brown antiseptic that gets painted on your body before surgery, or sodium bicarbonate, or baking soda, which is often used as a cleanser, mixed with water that had the same salt concentration normally found in the body. Those who completed nasal irrigation twice daily reported quicker resolution of symptoms regardless of which of two common antiseptics they were adding to the saline water. Eating more spicy foods decreases your risk of early death by 14% Chinese Academy of Medical Sciences, September 7, 2022 According to an international team of researchers led by the Chinese Academy of Medical Sciences, eating spicy foods may be the key to longevity. They found that eating such foods on a regular basis can help prevent people from dying prematurely by 14 percent. While a variety of spicy foods are excellent, one in particular caught their attention. It was noted that consumption of fresh chili pepper, compared to other spicy foods, was most effective in providing people with a lower risk of dying from cancer, ischemic heart disease and diabetes. It's explained that fresh chili pepper's combination of powerful ingredients are responsible for such health-boosting benefits.(1) “Compared with non-fresh spicy foods such as dried chilli pepper, chilli sauce or chilli oil,” says Lu Qi, associate professor at Harvard School of Public Health, “fresh chilli pepper is richer in bioactive ingredients, including capsaicin, vitamin C, and other nutrients such as vitamin A, K, and B6 and potassium.”(1) To conduct the study, the experts from the Chinese Academy of Medical Sciences assessed nearly 490,000 participants. After a follow-up that averaged approximately seven years, 20,224 deaths were noted. Analysis of these people led to the finding that compared to those who ingested spicy foods less than once weekly, people who ate such foods one or two days per week had a 10 percent reduced risk of death. More impressive however, was the discovery that those who enjoyed spicy foods nearly every other day were at a 14 percent lowered risk of death compared to those who ate them less than once a week. In this large prospective study, we observed an inverse association between consumption of spicy foods and total mortality, after adjusting for potential confounders. Compared with those who ate spicy foods less than once a week, those who consumed spicy foods almost every day had a 14% lower risk of death. Inverse associations were also observed for deaths due to cancer, ischemic heart diseases, and respiratory diseases. The associations were consistent in men and women. Meditation holds the potential to help treat children suffering from traumas, difficult diagnoses or other stressors Wayne State University, September 13, 2022 Children actively meditating experience lower activity in parts of the brain involved in rumination, mind-wandering and depression, our team found in the first brain-imaging study of young people under 18 years old. Over-activity in this collection of brain regions, known as the default mode network, is thought to be involved in the generation of negative self-directed thoughts – such as “I am such a failure” – that are prominent in mental disorders like depression. In our study, we compared a simple form of distraction – counting backward from 10 – with two relatively simple forms of meditation: focused attention to the breath and mindful acceptance. Children in an MRI scanner had to use these techniques while watching distress-inducing video clips, such as a child receiving an injection. We found that meditation techniques were more effective than distraction at quelling activity in that brain network. This reinforces research from our lab and others showing that meditation techniques and martial arts-based meditation programs are effective for reducing pain and stress in children with cancer or other chronic illnesses – and in their siblings – as well as in schoolchildren during the COVID-19 pandemic. Researchers know a lot about what is happening in the brain and body in adults while they meditate, but comparable data for children has been lacking. Understanding what is happening in children's brains when they meditate is important because the developing brain is wired differently from the adult brain.  Pace as important as 10,000 steps for health, finds new research University of Sydney and University of South Denmark, September 13, 2022 Two studies, published in JAMA Internal Medicine and JAMA Neurology, monitored 78,500 adults with wearable trackers—making these the largest studies to objectively track step count in relation to health outcomes. The researchers from the University of Sydney, Australia and University of Southern Denmark found lowered risk of dementia, heart disease, cancer and death are associated with achieving 10,000 steps a day. However, a faster stepping pace like a power walk showed benefits above and beyond the number of steps achieved. “The take-home message here is that for protective health benefits people could not only ideally aim for 10,000 steps a day but also aim to walk faster,” said co-lead author Dr. Matthew Ahmadi, Research Fellow at the University of Sydney's Charles Perkins Centre and Faculty of Medicine and Health. Key points: Every 2,000 steps lowered risk of premature death incrementally by 8 to 11 percent, up to approximately 10,000 steps a day. Similar associations were seen for cardiovascular disease and cancer incidence. A higher number of steps per day was associated with a lower risk of all-cause dementia 9,800 steps was the optimal dose linked to lower risk of dementia by 50 percent, however risk was reduced by 25 percent at as low as 3,800 steps a day Feed a virus, starve a bacterial infection? Yale University, September 8, 2022 A new study puts some old folk wisdom to “feed a cold and starve a fever” to the test. In mouse models of disease, Yale researchers looked at the effects of providing nutrients during infection and found opposing effects depending on whether the infections were bacterial or viral.  Mice with bacterial infections that were fed died, while those with viral infections who were fed lived. “We were surprised at how profound the effects of feeding were, both positive and negative,” says senior author Ruslan Medzhitov, David W. Wallace Professor of Immunobiology and a Howard Hughes Medical Institute investigator at Yale School of Medicine. In the first series of experiments, the investigators infected mice with the bacterium Listeria monocytogenes, which commonly causes food poisoning. The mice stopped eating, and they eventually recovered. But when the mice were force fed, they died. The researchers then broke the food down by component and found fatal reactions when the mice were given glucose, but not when they were fed proteins or fats. When the researchers did similar studies in mice with viral infections, they found the opposite effect. Mice infected with the flu virus A/WSN/33 survived when they were force fed glucose, but died when they were denied food or given 2-DG.

In this episode, I converse with Zuri Sullivan, an HHMI Hanna H. Gray Postdoctoral Fellow in Prof. Catherine Dulac's lab at Harvard University. Zuri earned an AB in Molecular and Cellular Biology from Harvard and then pursued her interests in global health and host-microbe interactions as a Fulbright Scholar at the KwaZulu-Natal Research Institute for Tuberculosis and HIV in Durban, South Africa. Wanting to delve deeper into the biology of host defense, Zuri earned a PhD in Immunobiology as an NSF Graduate Research Fellow at Yale University under the auspice of Prof. Ruslan Medzhitov. Zuri is fascinated by interactions between the immune and nervous systems, passionate about sharing science with the public, and dedicated to increasing the representation of women and people of color in STEM. We indulge in a fantastic conversation on her stellar journey in science; brilliant research at the intersection of immunology and neuroscience; battling the ubiquitous imposter syndrome; wonderful mentors who've guided and inspired her; rooting out inequities in science and society; her passionate outreach and communication to inspire future generations to pursue science; her eclectic reading list; and many more things!!

------------------Support the channel------------ Patreon: https://www.patreon.com/thedissenter SubscribeStar: https://www.subscribestar.com/the-dissenter PayPal: paypal.me/thedissenter PayPal Subscription 1 Dollar: https://tinyurl.com/yb3acuuy PayPal Subscription 3 Dollars: https://tinyurl.com/ybn6bg9l PayPal Subscription 5 Dollars: https://tinyurl.com/ycmr9gpz PayPal Subscription 10 Dollars: https://tinyurl.com/y9r3fc9m PayPal Subscription 20 Dollars: https://tinyurl.com/y95uvkao ------------------Follow me on--------------------- Facebook: https://www.facebook.com/thedissenteryt/ Twitter: https://twitter.com/TheDissenterYT Dr. Stephen Stearns is Edward P Bass Professor of Ecology and Evolutionary Biology, and Director of Undergraduate Studies at Yale University. Dr. Stearns specializes in life history evolution, which links the fields of ecology and evolutionary biology, and in evolutionary medicine. His books include “Evolutionary Medicine” (Sinauer, 2015) with Ruslan Medzhitov, “Evolution, an introduction” (Oxford, 2000, 2nd Ed 2005) with Rolf Hoekstra, “Watching, from the Edge of Extinction” (Yale, 1999) with his wife Beverly Peterson Stearns, “The Evolution of Life Histories” (Oxford, 1992), and two edited volumes, “Evolution in health and disease” (Oxford, 1998, 2nd Ed 2008) and “The Evolution of Sex and its Consequences.” In this episode, we talk about life history theory, and evolutionary medicine. We discuss life history theory extensively, including how it links ecology to evolutionary biology, and r/K-selection. We talk about individual variation in life history strategies, phenotypic plasticity, and culture. We then get into evolutionary medicine, where we talk about evolutionary mismatch and diseases of the modern world, and evolutionary public health. We end with a question from a patron. -- A HUGE THANK YOU TO MY PATRONS/SUPPORTERS: KARIN LIETZCKE, ANN BLANCHETTE, PER HELGE LARSEN, LAU GUERREIRO, JERRY MULLER, HANS FREDRIK SUNDE, BERNARDO SEIXAS, HERBERT GINTIS, RUTGER VOS, RICARDO VLADIMIRO, BO WINEGARD, CRAIG HEALY, OLAF ALEX, PHILIP KURIAN, JONATHAN VISSER, ANJAN KATTA, JAKOB KLINKBY, ADAM KESSEL, MATTHEW WHITINGBIRD, ARNAUD WOLFF, TIM HOLLOSY, HENRIK AHLENIUS, JOHN CONNORS, PAULINA BARREN, FILIP FORS CONNOLLY, DAN DEMETRIOU, ROBERT WINDHAGER, RUI INACIO, ARTHUR KOH, ZOOP, MARCO NEVES, MAX BEILBY, COLIN HOLBROOK, SUSAN PINKER, THOMAS TRUMBLE, PABLO SANTURBANO, SIMON COLUMBUS, PHIL KAVANAGH, JORGE ESPINHA, CORY CLARK, MARK BLYTH, ROBERTO INGUANZO, MIKKEL STORMYR, ERIC NEURMANN, SAMUEL ANDREEFF, FRANCIS FORDE, TIAGO NUNES, BERNARD HUGUENEY, ALEXANDER DANNBAUER, OMARI HICKSON, PHYLICIA STEVENS, FERGAL CUSSEN, YEVHEN BODRENKO, HAL HERZOG, NUNO MACHADO, DON ROSS, JOÃO ALVES DA SILVA, JONATHAN LEIBRANT, JOÃO LINHARES, OZLEM BULUT, NATHAN NGUYEN, STANTON T, SAMUEL CORREA, ERIK HAINES, MARK SMITH, J.W., JOÃO EIRA, TOM HUMMEL, SARDUS FRANCE, DAVID SLOAN WILSON, YACILA DEZA-ARAUJO, IDAN SOLON, ROMAIN ROCH, DMITRY GRIGORYEV, DIEGO LONDOÑO CORREA, TOM ROTH, AND YANICK PUNTER! A SPECIAL THANKS TO MY PRODUCERS, YZAR WEHBE, JIM FRANK, ŁUKASZ STAFINIAK, IAN GILLIGAN, SERGIU CODREANU, LUIS CAYETANO, MATTHEW LAVENDER, TOM VANEGDOM, CURTIS DIXON, BENEDIKT MUELLER, VEGA GIDEY, AND NIRUBAN BALACHANDRAN! AND TO MY EXECUTIVE PRODUCERS, MICHAL RUSIECKI, ROSEY, AND JAMES PRATT!

Dr. Sarah Huen is originally from Chicago, IL. She received her initial medical training at Northwestern University. She completed her Internal Medicine residency training at New York University Medical Center. Intrigued by the pathophysiology of acute kidney injury and frustrated by the lack of any viable therapeutic options, she pursued a research nephrology fellowship and a Ph.D. degree in Investigative Medicine at Yale University in the laboratory of Dr. Lloyd Cantley studying the role of macrophages in ischemic kidney injury. She was a post doctoral fellow in the laboratory of Dr. Ruslan Medzhitov at Yale where she studied the mechanisms of tissue tolerance and changes in metabolism in systemic inflammation. Dr. Huen joined the faculty at UT Southwestern in 2017 as an Assistant Professor. Her research interests include investigating renal metabolism in sepsis and other states of inflammation. Outside of medicine and science, she enjoys cooking, photography and hiking. You can find Sarah at https://twitter.com/DrSarahHuen. This episode is hosted by Dr. Shawn Baker MD. Find him at https://shawn-baker.com

Dr. Ruslan Medzhitov provides an overview of the field of inflammation and outlines its role in pathology and homeostasis. Medzhitov explains how Inflammation is generated when pathogens, allergens, or other perturbations are recognized by sensor cells that then release inflammatory mediators (cytokines and chemokines) to activate effector cells. Inflammation is then followed by a resolution phase that brings the system back to homeostasis.

Why do we experience fatigue and loss of appetite, as well as other symptoms when we get ill? Sometimes what we associate with a pathogenic response and illness is the effect of inflammation. In his second talk, Medzhitov outlines the symptoms that we often feel when we get sick, like the lack of appetite (anorexia), and unveils the molecular mechanisms that explain why we have evolved this way. In addition, he compares and contrasts how anorexia affects the outcome of bacterial and viral infections.

When he was a graduate student, Dr. Ruslan Medzhitov read a theory written by Dr. Charles Janeway that foresaw the existence of a set of receptors that would directly detect pathogens and signal to T- and B-cells to generate an immune response (adaptive immunity). Medzhitov was determined to find such receptors! In this discovery talk, Dr. Ruslan Medzhitov provides a historical perspective that frames his involvement in the discovery of Toll-Like Receptors. By following the clue that NF-kB was involved in the immune response, he searched for receptors, like Toll, that had the capacity to activate NF-kB.

Ruslan Medzhitov (Yale School of Medicine) explains in this talk that the intricate connection between homeostasis and inflammation is rooted in underlying principles of control circuits.  He then describes these principles and their implications for human diseases. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 31606]

Ruslan Medzhitov (Yale School of Medicine) explains in this talk that the intricate connection between homeostasis and inflammation is rooted in underlying principles of control circuits.  He then describes these principles and their implications for human diseases. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 31606]

Should you feed a cold and starve a fever? We’ll see what the science says, with Ruslan Medzhitov, Cell (00:00). Also, just in time for Oktoberfest: a look at the history of beer yeast, with Kevin Verstrepen, Cell (6:15). Finally, a STAR is born as Cell Press unveils a new approach to the methods section. Find out what’s changing, and how it’s designed to help you, with Ann Goldstein (13:10).

In this month's Cell Podcast, we learn about getting neural stem cells out of the lab and into the clinic, with Sally Temple (0:00), an important role for rare copy number variations in autism, with Matthew State and Michael Wigler (8:30), the dangers of midnight feasts for fruit fly fertility, with Amita Sehgal (18:04), and fitness costs and crosstalk in the evolution of host defense pathways, with Ruslan Medzhitov (24:32).