Regaining Trust through Education - Dr. Michael Whitt, University of Tennessee Health Science Center

DR. RISHI DESAI: I'm Dr. Rishi Desai, and today on Raise the Line, I'm happy to be joined by Dr. Michael Whitt, the Associate Dean and Chair of Medical Education at the University of Tennessee Health Science Center in Memphis. Dr. Whitt and other researchers have helped in the development of COVID-19 vaccines. I'll be asking him about what that was like as well as other impacts of COVID on his work and on medical education. So thank you so much for being with us today. 

DR. MICHAEL WHITT: Yes, it's a pleasure. Thank you very much. 

DR. RISHI DESAI: I'd like to start out just by learning more about you. What got you first interested in science, and specifically microbiology?

DR. WHITT: It's kind of the classic story. I had a tremendous science teacher in high school who just really got me interested in the methodology of science even as a high school student. I then went to the University of Kansas and had an opportunity to work in a virology lab, and it kind of clicked and from there I applied to graduate school and stayed in virology. I then went to Yale Medical School where I did my postdoctoral training also as a virologist but really learning more about cell biology. Microbes and certainly, viruses, provide just a really easy-to-understand system. So that appealed to me because I don't like complex things. I like to break things down. I'm a reductionist for sure. 

DR. RISHI DESAI: That's awesome. Most people I think would hear your story would say you don't sound like someone that likes simple things. You've obviously gravitated towards what most people think is quite complex. What is it about your experience? Because most students in high school shy away—and I'm putting it mildly, like some run away—from things like viruses and biology and all that, and you had a great teacher. What do you think attracted you to that when most people are usually kind of fleeing in the opposite direction at that age?

DR. WHITT: I think it was just the opportunities that I was provided and I don't know that in high school, I thought, "Oh jeez, I think I want to be a microbiologist." But I found things interesting and I read a lot and it just, again, it just kind of clicked. It was better than physics. It was certainly better than business. So I ran away from accounting and those types of things. It was just a good fit for me, and maybe that's just the way my brain works. I'm not sure.

DR. RISHI DESAI: You've taught it for, I want to say 30 years or so at the university. What have you seen change over that time? What are the macroscopic things that now we think about maybe routinely that 30 years ago was not on anyone's radar? Are there issues like that that you've come across?

DR. WHITT: Well yes, the entire way of teaching really has changed. I've been at the University of Tennessee Health Science Center for almost 30 years. It'll be 30 years in July. The way that we used to teach was really department-based. We would teach microbiology and biochemistry and physiology, but one of the big changes has been to embrace a kind of adult learning theory. Our students are adults, postgraduates, and our brains work a little bit differently, and so that's been one of the really big changes is going from the subject-based teaching to organ-based, all-encompassing type of teaching. 

We've also moved from a very passive lecture style to what we call active learning, where we provide pre-studies. Then in the class, it's really more about finding out what the students learned and what they didn't learn, and to help them navigate their way, because what has happened over the past 30 years? An explosion of information. The rate of publications and scientific knowledge has just grown tremendously. So, I'm in awe of our medical students and our physician assistant students who are able to digest and somehow put into packets all the information that we didn't know 30 years ago. It's just remarkable. Certainly, for microbiology and virology, my content each year changes pretty dramatically because of development of new antivirals. There were really very few antivirals. There was antivirals for herpes and for HIV, but we have them for many viruses now. So, just keeping up with the technology has really been one of the biggest changes over the last 30 years.

DR. RISHI DESAI: It's not lost on me that over the last 12 months everyone's vocabulary has changed. People talk about things like herd immunity, or, like you said, antivirals. These are words that a lot of people know, and they didn't know these words, or may not have felt familiar with these words, before a year ago. So in that sense, virologists and public health specialists I think have become, in some ways, much more respected and understood, like what you do matters for the general person now, in a way that maybe felt distant before. Have you gotten the sense that now that people know what you do, is there more and more interest in it? Do you see more and more students wanting to pursue that or caring about that as a profession more? 

DR. WHITT: Yes. I'll break this up into two parts. When I would tell our neighbors—they would ask, "What do you do?" and I would start telling them I research viruses. That's about when their eyes started to glaze over. But now people are very interested, they ask good questions and I know they're really thinking about it. 

As far as students now becoming interested in infectious disease, as an infectious disease physician, you know that's not the highest paying career as a physician, but I think there's going to be a lot more interest in it now. I haven't necessarily seen it yet in our students, but they're honestly just trying to survive COVID, and graduate, and get a residency position. So it'll be interesting to see over the next five years, the new crop of physicians coming out of medical school. Are they interested in infectious disease? Epidemiology? Immunology? All the things that are really kind of at the forefront now.

DR. RISHI DESAI: You've also been working on vaccines, specifically. For so many people, I think now—I mean, who knew, up until now, what the manufacturer's name was for a certain vaccine that you got, but let alone naming the disease that you're fighting off. People would just say, "Oh, I'm getting my vaccine," but could barely articulate anything beyond that. Now, people are saying, "Oh, I'm getting my second Moderna.” Or, “I'm getting my first Pfizer.” “I'm getting the J&J." It's part of our normal conversation now. 

Can you give us a peek into, what does it take to make a vaccine? What did you do to help with that effort? I'd love to get a deep dive on what was your involvement in it? What are the things that most people don't know about vaccine development?

DR. WHITT: One of the things that is truly earth-shattering, kind of groundbreaking, is the development of this new vaccine platform that Moderna and Pfizer, and BioNTech developed, which are these messenger RNA-based vaccines. Vaccine development before COVID really involved kind of two strategies: One, if it was a virus, or it could be a bacteria—either involved selecting for an attenuated or weakened strain of that particular pathogen. For instance, the oral polio vaccine, one of the great success stories in vaccinology was by passaging the virus multiple times through non-typical host cells. Eventually, the virus acquired mutations and it became non-pathogenic, and that was kind of the route. 

Then the next level of development was utilization of subunit vaccine. So, let's just take the parts that our immune system recognizes, and let's just put that into our vaccine formulation. So we generate a nice immune response against those parts. The other things? Let's leave them out because they may also contribute to disease if you have everything together. 

This new messenger RNA technology has provided us with the ability to very quickly pivot to new threats that we have. For development of these, it's not that they just decided to do this the day after COVID was recognized as a threat. It was something that had been in development. But in the case of working with attenuated pathogens, there is a long series of tests that go from— initially, small animal models: typically rodents, mice, or rats, then moving up into another, higher-level species, eventually maybe going into primates, until eventually, it gets into what we call, “phase I” safety trials for humans. That road, that path, is extremely long—20 years or more. Can you imagine us living with COVID for 20 years before we have a vaccine? 

We've learned a lot about what it is that causes disease, what components we can add into a vaccine formulation to more rapidly get a vaccine to market. I'm just amazed at the developments that have been made—really over the past probably five years or so—in vaccine technology.

DR. RISHI DESAI: Do you mind saying a bit more about your role in the vaccine development? I'd love to hear about that. 

DR. WHITT: Yes, my lab was really interested in understanding how viruses assemble, particularly for enveloped viruses—these are viruses that have a membrane that they typically acquire from the host cell. What we learned was that we could remove the glycoprotein of this virus, which is actually a veterinary pathogen that infects primarily horses, cattle, and pigs, and it could assemble the spike protein of a lot of different viruses. So this system that we have is a virus that expresses what we call a reporter protein. This is a green fluorescent protein, so it makes cells glow green if they're infected, or they express a protein for the enzyme that makes fireflies light up at night, and this is called firefly luciferase. So we can now assemble the spike protein of SARS-CoV-2 into this virus that doesn't cause disease in humans, and we can easily assay the infectivity of that virus. 

What the vaccine companies were doing was to use this system, which we call pseudotyping, to actually test whether their vaccines were efficacious. So that's really been our contribution. We've been working with one of the companies, Moderna, who has got one of the vaccines, generating pseudotypes of all different combinations of the variants to ask, "Do people who are currently vaccinated with the most recent vaccine, are they protected against the variants?" We can do this in a regular lab setting. Whereas if you're working with the authentic virus, you have to do it under in a special laboratory called Biosafety Level 3. 

So one, it just made it very easy and safe to actually test the efficacy of the vaccine, and we're also able to now test whether people who are vaccinated are protected against the variants. I think it's a really neat system and the companies have found it useful, I think. 

DR. RISHI DESAI: Yes. I mean, generally speaking, when things are safer and easier, that also translates to faster. Clearly this is something that we all need information on, so that's incredible work. As we've reported on, or has been reported, on vaccine hesitancy, a lot of it is based on the speed at which this has been developed. Many people equate speed with sloppiness. Having seen it from the inside, what do you say to people who say, "Well, gosh, the way they got this done makes me really concerned about safety." Is there any merit to that? If so, what is the merit to that, and if not, why do you think that that persists? 

DR. WHITT: Always, something new is going to cause concern in individuals who really don't understand how things work. It's fear of the unknown. That's been one of the big problems is all the misinformation that's been on the internet and spouted by various people. So what do you say to someone when they say, "Oh well, this was developed too fast. I'm not going to take it because it may cause this, that, or the other thing?" What I try to do is say, "Well, let me explain what the components are. What these vaccines do is provide an instruction that our cells are normally making. It's just instruction to make the spike protein of this virus. This is something that our body is normally doing. We have all the machinery needed in order to produce this one protein, and our immune system then says, 'Oh, this is not something that I'd normally have made,' and so we generate an immune response against it. So it's not like the old vaccines where you did have to worry about reversion of these weakened strains to the pathogen again.”

Sometimes that works, sometimes it doesn't work, and then people will ask, "Well, I hear people are getting really sick after they get the vaccine," and I also try to explain that feeling bad is actually a good thing when you get a vaccine. That means your body's responding. So it's not that it's dangerous. It's not that it was rushed through and that's why people are having some of these reactions. The technology has been tested in animals. It's been tested in people, and it's proven to be safe. So again, maybe this is just the teacher in me. I try to teach. 

DR. RISHI DESAI: I've heard the opposite, too. I've heard people say, "Well, I've heard that when you get a fever, muscle aches, it's because your body is responding. And when I got the vaccine, I had no response. That's why I'm worried it had no effect.” Then I'm like, "Oh my gosh, well, not in everybody,” and that's where you talk about percentages. So some of this information can cut both ways, because when you have a little bit of information, but then you don't take into account the fact that not everyone reacts homogeneously to everything, and that these things can vary person-to-person, then people start misinterpreting the counterfactual in that sense.

DR. WHITT: Yes, you're absolutely right. People say, "Oh, I didn't feel bad. I don't think it worked.” Or, “Maybe they gave me water." I don't think that's true. [laughs]

DR. RISHI DESAI: To me, it gets to this other issue. I was thinking about this recently, of how people think about institutions. You've been a part of a couple of institutions, and you, growing up, were attracted to the institution of science and all that kind of goes with it. In your role as an educator, I'm curious how you respond, either viscerally or in the classroom, when people say, "Well, you just can't trust the science. The experts, they're always wrong," or kind of make these blanket comments. What is your gut reaction when people say things like that, which I've heard more and more commonly in the last probably, three years, than I did like 20 years ago? 

DR. WHITT: There is a lot of distrust for the medical profession, and certainly, for, I think, science in general. I don't know if it's growing up with movies of the mad scientist. So how do you dissuade people? Well, I think the easiest way is, you start providing examples of things that science has brought us and where people would be without science. The history of some of the really bad things that have happened by, I guess you would call it the scientific community, but it's more the renegades. Things certainly with the Tuskegee experiments and all the issues that are going on with race and racism. It's hard not for the general public to really distrust scientists and some physicians. 

It's our job now to build that trust again. That's absolutely what we have to do. How do you do that? It's by showing that we are normal people. That we really are working for the benefit of people. It's not that we're looking to make a fast buck off of someone. It's not that we want to take advantage of people. We're really in the business of helping people live better lives, and that's resonated with people I think in certain discussions. Building trust is going to take a long time, and that I think is one of our challenges. We have an opportunity now to show that yes, indeed, you can trust us and we can help, and you have to believe us at times. 

It's a very tough nut to crack, and I think it's difficult to speak in language that everyone can understand. I know I find myself very often when I start to see the eyes glaze over, I go, "Okay, now, I've got to-- let me whip in an analogy of some type," and that often helps. So being cognizant of who your audience is, is also really important. 

DR. RISHI DESAI: Yes, absolutely. I think more and more, it's insufficient to just teach with facts. You have to be able to teach and also hold someone's attention, like you said. One of the things that I've realized is that people tie together data points. For example, they'll see things improving. Prior to two weeks ago, things were generally getting better in the US, and I think people thought that that was related to the vaccine. That's a reasonable idea. I don't think it's factually correct. I think it's mostly based on behaviors. It's mostly that our behaviors were good, and therefore we reap the benefits of that. We're socially distancing, wearing masks, these are good behaviors. Then on the other side, you've got the virus and it's got its behaviors, and it's behaving sometimes in a way that's static, so that's great. Sometimes it misbehaves and things get worse, and that's when we have mutations and variants, things like that. 

So a lot of this is like our behavior, its behavior. I think that one of the things that has been challenging for science, in general, is to articulate a strategy that feels cohesive but also nimble enough to explain these things. I think at the beginning of this, say, eight months ago, we talked about the vaccine in most people's minds like, "Let's just wait till the vaccine gets here." 

DR. WHITT: Yes. 

DR. RISHI DESAI: Now, the vaccine is here, and it feels like the goalposts have shifted. Even though they may not have actually shifted, but it feels like the goalposts have shifted to like, well now we've got variants. Because we've got variants, we've got to keep our masks on, we've got to keep doing this due diligence to keep our wits about us so we don't get slammed. Again, we've gotten slammed three times. I'm just curious to get your thoughts on how to hold a population's attention.  I think Dr. Fauci does an incredible job of it, but from your standpoint, how do you hold a population's attention when it can feel like the goalposts are shifting, and things are kind of like, "Well, you said this, but now you're saying that," that kind of thing?

DR. WHITT: Yes, that is extremely difficult. There's just social weariness. People are tired of being in isolation and wearing masks and not being able to do all the things that they wanted to. It's very difficult to convince a population that we could really have controlled this virus very early on, by doing what we were doing a few months ago, which is really paying attention to social distancing and wearing masks and washing our hands. We learned how to do this, but it's something that we're going to have to learn again with the variants. People don't really understand the virus is replicating, and you give it an opportunity to replicate with a little bit of selective pressure which is maybe a mild-to-moderate immune response after your first vaccination. You think you're protected and you go out. 

So, unfortunately, what can we do? We're going to have to learn our lesson again, and that's something I really struggle with, as I see our neighbors having parties, and I'm going, “Please, don't do that. Let's really wait till we get this under control.” So I don't know, that's a really tough one. I don't know how to deal with that. 

DR. RISHI DESAI: Tied to your point about neighbors is that, on a local level, you've got your neighbors that live next door to you. Also, as a country, you have neighbors: Canada, Mexico. We have a global group of neighbors and not every country—most countries—don't have robust immunization plans at the moment. 

I think that's another thing that hasn't become part of the mainstream conversation yet, but will, because there will be a date when America seems to have hit herd immunity, whatever that threshold ends up being based on our nod and all that. But the same cannot be said for Bangladesh, and you still have travelers going from Bangladesh to San Francisco, or Memphis, or wherever, and there is an opportunity for variants to emerge in Bangladesh because they're not fully immunized, and those variants, we don't have the same level of protection. So you can quickly imagine a scenario where people say, "Well, let's just shut our borders down to those countries." Or "Let's just try to blame that country," right? There's a lot of blaming going on. 

Every time it spins out of the science and into the political fields is where I feel we all go astray and we lose ourselves. But this will happen. Clearly, this will happen if you look at the data and say, "Well, gosh, not every country is responding," just like you said, your neighbor's not responding the way you are. If we do this on a global level, the same thing will play out.

So I'm just curious if you have any thoughts on that or how to message around that, because clearly today we're focused very much on, “How do I get a vaccine?” Not too many people are asking the question, "How do we make sure Bangladesh—" I'm picking on Bangladesh as a country only because I'm thinking of a low-income country, but there are many countries in that tier where it will be a challenge to get that whole community immunized. What are your thoughts on that?

DR. WHITT: Yes, vaccinations in under-resourced countries is going to be a challenge. Whose role is that, I guess, is the question. Is it those governments of those countries? Well, they don't have the resources. Is it an institution like the World Health Organization? Is it some of the private institutions, for instance, Gates Foundation? Is that their job to provide the vaccine to those countries? 

You nailed it. You hit the nail on the head in that this virus is going to be with us for a very long time. It's very likely going to be like influenza where we see recurring infections. So eventually, there will be a level of herd immunity just because of how infectious the virus is. People will develop immunity, but there will always be this ability to escape. The whole socioeconomic and political kind of content around this is extremely difficult. What we're seeing in Brazil is just devastating. They are really in crisis mode. So, I know you mentioned Bangladesh. We don't hear a lot of news about what's happening in Africa or parts of the Middle East. We probably will never know. But right now there's just not enough of a coordinated effort to say, "Let's vaccinate the world." Not, "Let's vaccinate my city, or my county, or my country." If I had the answer to that, I would be in a different job, I think.

DR. RISHI DESAI: Well as a virologist, you remember smallpox eradication? 

DR. WHITT: Yes. Absolutely. 

DR. RISHI DESAI: Smallpox was eradicated in many high-income countries, and they spent a lot of resources—and you could decide what you call that, but let's call it national security or health security. They spent a lot of resources to protect themselves against ongoing, imported cases from India, and because that was so wasteful, they basically said, "We can't keep doing this." So maybe it's useful for us to go and invest American dollars to get India free from smallpox.

DR. WHITT: Yes.

DR. RISHI DESAI: Not only is it kind of the right thing to do to alleviate human suffering, but it's actually protective for human lives in the US. I'm wondering whether something similar might start playing out as we start thinking, hearing these stories, and getting more cases, like, what was happening with Brazil and the variants coming out of Brazil, it's disastrous. If that keeps happening, then all of our efforts of the last 12 months—they won't be a waste, definitely not—but they will be set back, because now we're dealing with a different virus. So I think a lot of folks are just so fatigued, because this has, in a way, been shaped as a sprint—albeit at a 12-month sprint—which at some point stops being a sprint. But I think as you said, I think as people start coming to the realization that it's not a sprint, there's no end date, actually. This is just our new reality. This is going to open up a lot of frustration, anger, a lot of feelings, and hopefully, at the end of that, we get to a point where we're like, "Okay, now let's figure out the solution." 

DR. WHITT: Yes, I kind of liken this to the measles eradication effort. There was a very big push, again, primarily through the WHO and other institutions to eradicate measles. Measles is a great candidate because it's one of the few RNA viruses that doesn't really mutate to generate variants that can escape immunity. So immunity is long-lasting, but we still haven't eliminated measles. It still causes hundreds of thousands, if not close to a million, deaths of children every year. It's a different kind of virus, very infectious, spread by the respiratory route. Sounds really similar, doesn't it? It causes the immunosuppression characteristic of measles, but I think your point of, this is no longer a sprint, but this is a new way of life. 

One of the benefits that has happened is, we have seen such a reduction in flu cases this year. And what is that due to? It's not because people are getting vaccinated against SARS-CoV-2, it's that we're practicing social distancing. We're practicing wearing masks. So, can we do it? Yes, we could do it. It's going to take a little bit of effort, and it's going to be for the long haul. 

DR. RISHI DESAI: So one thing I'd like to then close on is, as new early-stage health professionals are entering the field, and have entered over the last year through this very unusual year of COVID, what is your advice in terms of how they can best kind of meet the moment, especially given that your own career has kind of been amazingly well-suited for the moment? What would you say to them? 

DR. WHITT: This is providing a tremendous opportunity, despite the devastation, and all the heartache and deaths. For our budding physicians, this is really a time for us to learn important lessons about epidemiology. What do we need? We need better surveillance. We need better early warning systems. There will be another pandemic, just because we are always encroaching on kind of new habitats. There are viruses that circulate in a variety of animals and bats are kind of our big reservoir of choice. 

So for the budding physicians, it's always to educate the public and I think that that is probably the thing that if I tell any of our students, I say, "Go out to your friends, your neighbors, who are not in science and just talk to them." One, it's getting back to building the trust, and if we had a better-educated public to where there's not fear, to where we're all working towards a common goal, I think that would be fantastic. That's a lofty goal, but it is something that—Yes, physicians, we're there to treat people who are sick, but at the same time, we can educate them, and hopefully they will be able to pass that on. 

DR. RISHI DESAI: Well that's a fantastic note to end on, and something that's very actionable for all of us, to go out, and talk to people, and have those kind of face-to-face or person-to-person interactions. So, thank you so much Dr. Michael Whitt for being with us today. 

DR. WHITT: Absolutely. It was a pleasure. Enjoyed it. 

DR. RISHI DESAI: Well, I'm Rishi Desai. Thank you for checking on today's show. Remember to do your part to flatten the curve and raise the line. We're all in this together.