Episode 68: Learning From The H1N1 Pandemic Of 1918 To Combat COVID w. Dr. Krishnan Chakravarthy

Oct 12, 2020

This Episode

Interview w/ Dr. Krishnan Chakravarthy

You Will Learn

– Dr. Chakravarthy talks about a “Eureka” moment from his career

– The comparisons that Dr. Chakravarthy sees between the 2 pandemics

– We discuss how we can take a strain from over 100 years ago, and use it to understand new strains like COVID

Resources & Links

This week, I’m joined again by Dr. Krishnan Chakravarthy. Dr. Chakravarthy has has extensive experience working with the CDC, making him a great guest to discuss the similarities of COVID to the H1N1 pandemic of 1918, and what it might mean for the future of interventional pain practice.

Justin (00:56):
Welcome to episode 68 of anesthesia and pain management success. I’m very pleased to have a guest back from episode 59, Dr. Krishnan Chakravarthy Dr. Sacrum Farsi in addition to being anesthesia and pain, boarded, interventional pain specialist and serial entrepreneur. And nanotechnologists Xtrordinair also has extensive experience in studying influenza and a lot of work at the CDC that uniquely positions him to talk about kind of the things we’re seeing right now with COVID and the ties that it has to the H one N one pandemic of 1918 and what it might mean for the future of interventional pain and the future of our society. We got a lot of great stuff we’re going to dig into. So, Dr. Chakravarty thank you for joining me today. Yeah, thanks Justin. It’s always a, I really enjoy coming back. I mean, I had a chance to share all of my personal experiences last time on the entrepreneurship side, but really this this was my life’s work for that three years in the lab.
Justin (01:55):
So happy to talk to you about all this stuff that I did with CDC, et cetera. Yeah. So obviously for any of our listeners, you can go back to episode 59 and hear more about the personal side for Dr. Chakravarty. Maybe you could just give us a brief overview of sort of your current professional and clinical undertakings. And then we’ll talk about that time at the CDC. So it’s interesting. I I’m so I trained so I did the whole MDPHD program and a lot of my PhD work actually trained as a viral immunologist and it’s, I’m going to, what I’m going to tell you is how that bridges into anesthesia. It’s really a fascinating story of science and serendipity. Right now, actually I have a really cool practice. I see blood patients at the university as well as at the VA San Diego healthcare is, and about 50 to 40% of my time is dedicated to a pretty robust, active clinical trial.
Justin (02:48):
We do a lot of different startups. And so, you know, it’s, you know, at the heart of what I’m going to convey today is how powerful translational research is. And one of consistent themes that we are starting to witness is history repeats itself. It’s fascinating human beings that, you know, we think that we are inventing something new for the first time, but the reality is like most times is not the first pandemic in human history. And certainly I think one of the other major lessons that we’re starting to learn is as our population continues to grow, and we are interacting with the environment in a very different way with deforestation, with the amount of exposure to different types of wild animals, as well as things that we are looking at the concept of novel viruses, novel types of Zuno license, which is the definition of viruses that come from a different vector to humans is going to be a bigger and bigger issue. And I, I think what’s fascinating is that whether you’re at a individual person looking at the effect of the pandemic on your life, all the way to, from a Countrywide level to the world level the lessons are pretty consistent it’s and the things that they learned in 1918 to a large extent sets the precedent for all of the public health measures that we shouldn’t be adopting. And I think it’s really it’s, it’s a fascinating conversation. So looking forward to it.
Dr. Krishnan Chakravarthy (04:25):
Yeah. So maybe to start off, tell me about how you got interested in like immunology and biology and how, how was it the MDPHD and time at the CDC. I remember you saying in our last interview, you sort of, I think you carved your own path and maybe people didn’t love it because you’re not sort of fitting the mold of the normal trajectory. So tell me about how that unfolded.
Justin (04:46):
Yeah, so it’s interesting. I came into grad school with really an interest in tumor immunology. I really wanted to study cancer and I was interested in looking at how the immune system to helps in fighting cancer. So at that time we had four, four of us that were applying for different labs. And of course the MD PhD director, Dr. Paul Knight, who you know, probably one of the single most important influences in my life. Career-Wise he always says he got the booby prize of getting me as the graduate student, because the person that I wanted to work with Dr. Dick banker at that time took my close colleague and friend Jen. So I was like, Aw, man, I can’t get into that lab. And he’s like, ah, alright, chocolate art that you can come into my lab. So is the story is really interesting.
Justin (05:36):
So what happened was in the eighties he’s an anesthesiologist and he was doing pizza anesthesia. And at that time he made a really interesting observation. So he was looking at kids that had RSV respiratory syncytial virus, which causes a lot of upper airway problems in kids. And what was observing was that if you put these kids on anesthetic, for whatever reason, they wouldn’t develop secondary infections. So that was odd. Why would anesthesia have anything to do with infections to bacteria after viruses? So he kind of published this first paper probably in the late eighties, early nineties. And he had got totally shunned by the anesthesia community because people are like, well, what is this guy saying? If somebody has active airway disease, the first thing we think about is to cancel cases, are we proposing that maybe anesthetics could be protective against viruses?
Justin (06:35):
So I got in the lab and he’s like, look, I know you’re not studying cancer, but here’s, you know, why don’t you look at this immunology model with anesthesia and look at it in the flu model? And I was like, Oh, okay. This is kind of interesting. I mean, this might be a totally different question that we don’t really relate to. And I was thinking more translational has an anesthesiologist that I had at that point when I was in medical school, that was one of the things I saw that he had really bridged that gap between his clinical and research. I was like, Oh, this might be a great field to consider. So we started doing some of the work and the fascinating part was like, I started with developing a animal model and we really replicated a lot of the flu infection model, pretty consistently to what you see in a human human model today.
Justin (07:23):
And so the first you know, people in all always talk about this, when you’re in science, there are moments where you’re like two o’clock in the lab and you’re like, man, this is the moment Eureka. So it took me a literally a year to establish this model. I set it up. And finally I came on this very interesting observation. So I was inoculating these animals with flu, and then I would give them a secondary infection insult looking at the effect of the anesthetic in reducing incidences of like bacteria, improving bacterial clearance. So around two o’clock one morning we’re testing and testing and you, I mean, I poor animals. You go through so many by the time you actually want to be that you want, and you think like nobody’s paying attention to you as a graduate student. You’re finally in the lab, I’m counting some colonies.
Justin (08:10):
And fascinating. So the animals that had the anesthetic were completely not sick, so they wouldn’t actually have any of the symptoms that were displayed by animals that were getting the flu. And essentially they were able to combat the secondary infection way better. So it, all of a sudden was like, wow, good moment. Like his observation clinically was translating to something I was seeing in a, in a very controlled setting. So I took that idea and you started to really exp or history. So yeah, what happened was what people don’t really realize when you go back to the 1918 strain when they actually dug the patients up, what they found was it wasn’t ever influenza. That was a primary cause of mortality. It was actually bacteria that would grow out of these lungs of these patients are, and especially in the military barracks where in the 1918 sprain really spread, it was really secondary bacterial infections that were the primary cause of mortality.
Justin (09:17):
So what was happening was at that time, the advent of antibiotics and distribution of that was a major limiting factor in combating Spanish flu. So the, the idea that, you know, we could combat pneumonia, wasn’t actually really well established in the public health guidelines and measures weren’t necessarily set. So in, in this model from a scientific perspective, what we started to realize is that if you temper the response to any viral infection and the initial point that actually caused a significant protective effect to the host to any kind of secondary insult. And so I took that concept and then I went to CDC. And at that time man, it’s amazing experience because you get to work with all of the some of the most lethal pathogenic strains in the world, including Hanta Bola the 1918 strain. So it was like literally living in that, you know, the contagion movie with Dustin Hoffman and it’s exactly like that. So you’re in the hole,
Dr. Krishnan Chakravarthy (10:26):
You get to the CDC, I want to hear more about that, but I want to go back to this sort of, this type of testing. And then I was really interested. You said you went back, what, when you sort of made this observation about these animals that were responding really well to the secondary infections, your, your instinct was to say like, let’s look at historical incidences that have been similar. I I’m curious, kind of is that first of all, is that like a normal second step or, or what made you want to do that and how did you land on the Spanish flu pandemic?
Justin (10:56):
Yeah, so, you know, I think so you know, our heart of translational research is the idea that as a clinician, you can take an observation and apply it to the broader story. And the truth is that a lot of people understood that bacterial pneumonia was the most common cause of mortality, even from the 1918 strain to fast forward to every other pandemic that happened in history. Interestingly, this is not the first instance that we’ve had pandemics. You look at the Hong Kong flu, you look at bird flu and you hear a lot of this concept of like what they define a cytokine storm, which is if we can up regulation of inflammatory things activity, but essentially, you know, I’m a big proponent of, and I think we’ve had past conversations about this. You got to apply research to the, ultimately to individuals in the clinical setting.
Justin (11:49):
That’s what really separates translational scientists. I, you know, at that time when I was a clinician, when you’re studying a problem, I had to feel like I could understand the relevance of it to the larger population. And when you look at historically where flu has been as a, both a seasonal and a larger infective strain, I mean, it’s one of the most common issues that we deal with. I mean, seventh leading cause of death at one point is influenza and bacterial pneumonia. So the history served and reinforcing this concept that what I was doing in my model and the observations that I was making was at least consistent and reproducible. Hmm.
Dr. Krishnan Chakravarthy (12:29):
Is it, I guess what I’m asking also is like, it would others in your situation, can I made that same connection and say, let’s go to the history books and see where else we can find something that looks like this, or was that sort of something that you had, did you,
Justin (12:41):
Yeah. I mean, I guess it could say both ways. I kind of feel like do people spend the time really looking back into history for evidence maybe, maybe not, but that’s just been, I kind of was looking at it in that approach, but I guess it’s a good point because I looked at the 1918 strain and then part of what prompted my ability to want to test it at the CDC was knowing that it had an effect that was on a local seasonal strain. What if it could really have an impact on kind of a strain that could cause so much devastation to humanity? So yeah, in some way it’s serendipity that I kind of look back through all of that data, but it was certainly it made a lot of sense at that time.
Dr. Krishnan Chakravarthy (13:24):
So then you’re down in Atlanta and I’m, I’m curious, you know, is there like a big vault that like swings open there’s this light and like dry ice kind of like mist that comes out where they keep all the really crazy stuff or what’s that like?
Justin (13:37):
Yeah. So that’s a very least of it. So there’s actually, so what happens to the CDC? There’s about a 23 to 27 buildings, incredible that you don’t even actually see on any of the actual maps you get there. The campus is like adjacent to Emery. I was working for the influenza division. So everything from the ferret models, all the way to the Les BSL to containment, I mean, literally the suits, retinal scans folks on top of the building, you cannot avoid it. I mean, essentially it is like high level protection of all of these strains. But fascinating, I mean, amazing experience, the level of rigor, access to tools. I mean, they have state-of-the-art tools for studying genetic expression. So at that time Dr. Sam Barra, who was now kind of the head chief of the infectious disease for influence at CDC, he was like, look, I’m, I love this concept.
Justin (14:41):
So I have this theory that we may be able to genetically create a therapeutic target that’s universal to different food strengths. So he’s like based on your work, maybe we could adapt that theory into some form of consistent genetic strain that maybe could be efficacious for secondary infections as well as the primary infection. So we ended up testing a lot of the human cell lines with with the 1918 strain and amazing. So we were doing a lot of what were called gene therapy and a nanomaterial delivery of those gene therapy targets for actually looking at seasonal and pandemic flu strains. So yeah, it was, it was something else.
Dr. Krishnan Chakravarthy (15:26):
So just cause I’m curious for something like the 1918 strain. Yeah. How does that, how does that end up in a vial in a freezer 102 years later, that that we can still access and test and run experiments and things on.
Justin (15:43):
Yeah. You know, you would think that these things would disappear, but the reality is a lot of the gene sequences were already preserved. So they actually coded a lot of the high path strains, you know, and this is where it’s, it’s an interesting conversation. So should research in such like a potential scary strains exists, but a lot of the potential therapies that come from it are because they’ve been able to preserve some aspects of those very lint strains that you study today. So all of the smallpox, anthrax, I mean, all of these things that we think about our high lethal bio warfare agents we studied them all the time. I mean, as long as you have strict regulations, which they do a phenomenal job yeah. But you know, you look at some of these movies they’re, they’re not completely accurate.
Dr. Krishnan Chakravarthy (16:37):
Yeah. That’s so interesting. First of all, how, how was your time there? What what was it like using those types of tools, having everything, all the cool stuff at your fingertips and being able to just dive right in.
Justin (16:48):
Yeah. I mean, I, I, you can compare, I mean, one of the few places in the world that is as equipped as, or thinking as I mean, some of the most intelligent people studying infectious disease, where were, are at the CDC and it’s a culmination of that. And I think just the, what it’s really impressive is the amount of bar that goes into folks that are focusing on health officials that really think about not just today, but what to plan for in five, 10 years. And, you know, one of the things we looking at the current CRA kind of pandemic, there is a tremendous amount of knowledge that drives how fast innovation happens in terms of vaccine development, in terms of new drug development. So people think it’s, Oh, it’s just serendipity that we think about all of these different ways to target COVID. But the truth is a lot of that preface work was by scientists, rigorously and other models that has led to, I think, arguably some of the fastest drug and vaccine candidates that we’ve ever seen. And so I think what you appreciate is how much cross disciplinary work happens at the government level that happens in partnership with universities. So you know, it was, it was a life once in a life experience from that perspective.
Dr. Krishnan Chakravarthy (18:15):
Yeah. So as you look back at the 1918 experience and think about the similarities, you know, between that strain and that public health experience and that historical event and sort of the cycle that it, as it unfolded, how does that map onto our current experience? And what does it tell us about what might happen like next month or next year?
Justin (18:36):
Yeah. Great question. So look, I mean, I think one part of it is let’s talk about, I split it into what we think about therapy development and then the social measures and public health measures. So what people learned in 1918 was that social distancing was highly effective and curbing spread. So what happened essentially in the 1918 model was that you had military barracks where a lot of people were in close proximity and you hear a lot of infectious disease experts even talk about the classic analogy between Philadelphia and st. Louis. So back then, what happened was they had the, during Philadelphia, they had a lot of the parades in preparation immediately after the world war looking at bringing people together and st. Louis at that time was very strict on those guidelines. So when you talk about, you know, you look at this, you hear all of the epidemiologists, talk about this rise in the peak to how fast that happens and comparison of the two different States and why public health measures like social distancing contact tracing, which is essentially testing somebody and isolating them for the effective incubation period, how important they were in laying the groundwork for why public health measures work in reducing morbidity mortality.
Justin (20:05):
Now, what I think the other part of that lesson is people keep saying that COVID is 200,000 deaths, 7.5 million people. How bad is it really? How bad is it? I mean, seasonal flu affects 50,000 people every year in depths. So are we that much worse off the problem that people don’t account for is the numbers that you see is a reflection of active intervention through social distancing, through masking, through all of these things. So if you let this run rampant, naturally the mortality rate will climb. So that’s the challenge for most people because they, they look at the hard and they don’t really reflect on what is the, what is a public health mitigation strategy that leads to that effective statistic. And the other part that really is critical in that is it’s not just the peak, it’s the, how fast you rise to the peak, because it’s really a matter of utility usage of resources, right?
Justin (21:09):
So at that time in 1918, part of the reason why the second wave was so disastrous is because by that point, you’re overwhelming the health system. So I think a lot of times people forget that. I mean, I think we are fortunate that in 2020 we’ve come where technology has advanced much further, but the essential lessons are the same. I mean, things spread, contact, tracing, social distancing, all of these things were lessons we learned from that aspect. The second piece of this is that I think very interesting, which is a part two where I think the future of therapy in this with COVID, it’s going to be, is that what we noticed in our research was that if you wait out, when is the most severe city for the disease is seven to 10 days. That’s typically when influenza essentially destroys a majority of the lung through a robust immune response, and you have a essential environment for bacteria to outgrow.
Justin (22:10):
Now, you could say, well, the most lethal strains of flu don’t actually cause as much devastation because if you commit the host to significant injury right away, you don’t have as much spread. So this is why they talk for I’ll just talk about H not and how effect infective a viral strain is. But essentially the point in that is earlier intervention in terms of diagnosing and infection through immunomodulation may actually have an impact to the morbidity. Somebody who’s facing at seven, 14, 21 days after. So the hypothesis being that if you can actually curb the initial response, maybe you may be able to mitigate some of the downstream effects. And that’s a really interesting paradigm because we talk about one aspect of testing being contact tracing, and social isolation, but maybe is testing, going to have a role potentially for future therapy development, where you can have earlier stage interventions and patients potentially mitigating longterm morbidity.

Speaker 4 (23:20):
Hmm. So what would it look like if we were able to sort of take that concept and systematize it and roll it out scalably right now, you know, create that earlier intervention that you’re describing, how, how in a perfect world, how might you see that sort of,
Justin (23:37):
Yeah. You know, I think that challenges, I’m getting some getting clear there, but I think the challenge like, look you, if you, in a perfect world, contact tracing means you would test everybody. If you were positive, it would be isolated. If you tested positive and had some form of viral sequella, you would end up putting, be put in the appropriate isolation techniques for both aerosol as well as inhalational contact. But that, that can happen prior practically, because there’s obviously so many restraints to the economic pressures. That’s reality. I mean, we look at how you compare a university pain center all the way to a private practice center and the pressures of what COVID did, two, one versus the other. But the truth in the matter is that I think we goes back to my feeling that people say, if I’m not, if I’m can’t do it, the a hundred percent is any bit of benefit garnered by at least attempting some of the social, social distancing strategies.
Justin (24:45):
Sure. I think the concept of wearing a mask is a classic example of that. I think there’s clear scientific benefits to wearing a mask you’re effectively preventing the spreads of that droplet to the surrounding environment. So to me, I think if, if we could have it ideally, and the reality is that as we learn more and more about COVID, maybe certain drugs are going to be more germane. But if you, you know, at the end of the day, what’s ultimately the treatment for flu it’s supportive care, meaning you don’t go in every time for treatment. When you have influenza infection, you pretty much hydrate fluids stay at home and you hope your wife is nice enough to make you some chicken soup or whatever you decide to do. But essentially the point is that the testing needs to lead to some form of active intervention. And I think we’re not really quite certain how, you know, we’re still starting to learn the, the kind of effect of COVID short and longterm on folks and based on age and demographic, that being said, we have to err on the side of being more precautious. And I, I think that testing is a critical component of that.

Speaker 4 (26:01):
Do you expect waves of this to happen as public response continues to be maybe not quite coordinated or, or what do you think the next six to nine months is going to hold?
Justin (26:13):
Yeah, I think it’s challenging because, you know, some people said you look at the 1918, 19 19 it’s two years, so it wasn’t really, it wasn’t actually the first wave that was bad for 1918 strain was a second subsequent wave, an influenza infection. So the challenge with viruses is that they have a, in almost an inherent mutation rate. So you can create some form of response the faster they mutate, the more foreign they become. And again, you are kind of essentially creating a response, an antibody response to that new infection. So I think if people think that COVID is going to be a short term issue, I don’t see that happening. I think we are looking at probably an impact that is going to extend all the way through next year. And I, I’m still thinking that, you know, a lot of that impact, we’re still trying to sort out we’ve already seen a large part of our life changed.
Justin (27:12):
I mean, in things, the amount of access to certain types of things that the social setting has drastically changed vaccines, probably. I mean, I think best case scenario, everybody says something different, but the vaccines, not just, you have to test their efficacy and safety. But you’re really looking at distribution and that’s a huge undertaking. Who’s going to be the first to get it. Can everybody get it? How effective is it? Do we have a good incidence of understanding the benefits of it? So I think nobody’s going to doubt the benefits of vaccines, but it’s really a combination of not just effectiveness, but distribution and use.

Speaker 4 (27:52):
How, how soon from now do you think you’ll be getting a vaccine? At what point would you be comfortable like getting in line with CVS for that?
Justin (28:01):
I think, you know, I, my, my thought is that as healthcare workers, we have a responsibility to protect our patients as well as other colleagues that are in the healthcare place. I think if, if all of the infectious disease and public health experts recommended that there is a good vaccine that should be taken, I think it should be the responsibility to get vaccinated. I think that we have seen the benefits of it across multiple platforms and I think good science and data should drive decision making. So from that perspective, I, I think that that’s, you know, we follow the guidelines and rules set by folks that are experts in the field.

Speaker 4 (28:46):
If you think about, and we’ll wrap up with this, if you think about the way that, you know, this has impacted the practice of medicine and even just the way that society is existing right now, and physicians are now wondering when, not when we get back to home, but when, when are we going to be able to have a sort of practice on our specialty that is like no longer dominated by a fear or an awareness, I call it like a constant vigilance of trying to manage this situation. What, how does your experience and your research shaped the way that you’re thinking about that question and what it’s going to mean for practice of, for example, pain management or whether it’s anesthesia, any the, or how has that kinda evolved, do you think?
Justin (29:28):
No, I think look I think every thing that sometimes we think is a bad thing can actually be a a lesson for change and in good, good can come out of it. It’s hard to imagine something from a pandemic that could be good, but, you know, I think we’ve learned a lot about from a society level, from an individual practice level to how we respond to these types of situations. And one of the things that I think has really spurned is the impact of technology and interaction between physicians and patients, nowhere in history. Have we seen such a almost the next celebration of things like telemedicine, things like a component of interacting with somebody long distances without even being able to have the physical interaction, you know, medicine in its heart used to be this idea of the empathy and being the touch or the feeling of the doctor, patient touching as a part of the therapeutic and the healing part of it is that dynamic going to change the way we think about care.
Justin (30:37):
I mean, I think certainly a lot of pain doctors across the country have been implementing telemedicine very successfully. You know, I, I think the other part of that is we have seen how much emphasis in digital education. And I think you’ve been a big champion of this, like, you know, an amazing job with the amount of content that you put out. I think it’s here to stay. I think there is the idea of doing conferences in a different manner and the idea of even talking about COVID our first webinar at ESPN, we had about 1800 people log in. Yeah. And so it’s, it’s kind of amazing the breadth and reach you can essentially have if the digital platform is done in the right manner. So I, I think that the entire care platform for pain got pain physicians across the country is changing. We’re just going to have to adopt to that in that way. That’s a lot of opportunity, you know, for innovation and creativity. That’s not something you ever wish upon society. Thank you very much for your time. Thanks. Thanks Justin. I appreciate it.

Speaker 1 (31:59):
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