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Please Note: In this week’s episode we mention the work of Dr. Katalin Karikó. Dr. Karikó laid the groundwork for the mRNA vaccines, turning the tide of the pandemic. Please see more about Dr. Karikó and her fascinating work here:
Full Transcript Below:
Jessamyn 0:10
Welcome to You’re Up Next, a podcast by Bright Club Ireland that explores what comedy can do for research and society. I’m Jessamyn Fairfield, and I’m physicist, comedian, and science communicator. In this second season of You’re Up Next, we’re exploring some important topics through the lenses of science and humour. Today, we’re talking about Covid-19, and I’ll be speaking with Stephanie McCalla who is a bioengineering professor and a good friend.
Jessamyn 0:41
We are living through a time when the process of science, and public understanding of that process, are more important than ever. Most of 2020 was spent watching the public health crisis of COVID-19 unfold. The global spread of a deadly virus that sits at the intersection of high transmissibility, frightening long-term effects, and complex immunology. And how well each of us understands this science, or trusts in the scientific process, is very much connected to our behavior: how likely we are to wear masks, or sanitize our hands, or avoid enclosed indoor spaces. And these are all in turn connected to our likelihood of getting sick or not, which then affects the likelihoods of everyone we come into contact with getting sick.
Jessamyn 0:10
Welcome to You’re Up Next, a podcast by Bright Club Ireland that explores what comedy can do for research and society. I’m Jessamyn Fairfield, and I’m physicist, comedian, and science communicator. In this second season of You’re Up Next, we’re exploring some important topics through the lenses of science and humour. Today, we’re talking about Covid-19, and I’ll be speaking with Stephanie McCalla who is a bioengineering professor and a good friend.
Jessamyn 0:41
We are living through a time when the process of science, and public understanding of that process, are more important than ever. Most of 2020 was spent watching the public health crisis of COVID-19 unfold. The global spread of a deadly virus that sits at the intersection of high transmissibility, frightening long-term effects, and complex immunology. And how well each of us understands this science, or trusts in the scientific process, is very much connected to our behavior: how likely we are to wear masks, or sanitize our hands, or avoid enclosed indoor spaces. And these are all in turn connected to our likelihood of getting sick or not, which then affects the likelihoods of everyone we come into contact with getting sick.
Jessamyn 1:22
Understanding the science of COVID is a literal life or death matter for so many of us, and our choices could have terrifying impacts on people we might never meet through the web of interconnection that defines modern society. If you love that interconnection, this has probably been a tough year for you, as we’ve had to isolate ourselves so much from each other. But if you buy into Jean-Paul Sartre’s idea that hell is other people, well, it’s also been a tough year, because we are more dependent on each other than ever before, with the societal weight of our actions amplified by this crisis, and hence the judgment amplified too.
Jessamyn 1:58
This societal interconnection, in a way, actually mirrors the interconnected feedback loops that come together to make our immune systems. Immunology is a notoriously arcane subject, and I’m no biologist, but to me it has a lot of resemblance to a natural ecosystem, like a forest or an ocean. There are a lot of interlocking life cycles, everything depends on the overall ecosystem survival, and Small changes can have a big impact. In the same way that removing something small like krill in the Southern Ocean has a knock on effect on everything else up to whales, changes in the behavior of the smallest pieces of the immune system can lead to big health issues that are very obvious to you and me.
Jessamyn 2:43
The immune system can be roughly divided into an innate piece that can act fast, and an adaptive piece that’s a bit slower, but can learn from past history. When something like a new virus enters the body, innate immunity comes from interferons that tell nearby cells to slow the spread of the virus, and cytokines that tell the circulatory system to get white blood cells onto the scene. Those white blood cells can arrive via the bloodstream, break down the virus and return bits of it via our lymph nodes to the thymus and bone marrow, where the adaptive immune system is waiting. Here’s where we get immune cells that specifically target the new virus, called T cells and B cells for where they are made, the thymus and bone marrow. See, immunology isn’t so hard: B stands for bone marrow. The B cells are trying to develop specific antibodies to the bits of dead virus, and most of them get discarded, but when there’s a match, the successful B cell will then start to replicate. And in the thymus, T cells are being made that can distinguish which cells are supposed to be in the body and which aren’t, looking for the self ends and the virus begins. So these adaptive B and T cells are the slower but smarter part of the body’s immune response, and they are what vaccines against new viruses are usually looking to shortcut to.
Jessamyn 3:59
One of the things that’s so dangerous about the current coronavirus is how it skips part of the innate immune response. It doesn’t trigger interferons, the guys who tell your neighboring cells to slow the virus down, but it still triggers cytokines. So if you’ve heard about the ‘cytokine storm’, that’s basically the virus spreading a lot and then getting a huge immune response, which is kind of a mess all around. The interlocking mechanisms are thrown off by missing that initial interferon suppression of viral spread, and then even when the adaptive immune system kicks back in, it’s hard to pick up the pieces. That’s actually also why this virus is so hard on older people. They have more cytokines circulating already, and also their T cell production has slowed. And their T cells have a lot of memory on how to fight viruses used up already from all the other things that they’re immune to. So the cytokine storm is a lot worse, and adaptive immunity takes longer to rev up which means they get sicker. Ironically, because their adaptive immune system is actually smarter than that of a younger person.
Jessamyn 4:59
Immunologists have to consider all of these interacting systems when they attempt to design a vaccine. It’s not as simple as blocking or allowing the virus to act because there’s so much going on. It’s actually kind of a microcosm for how we have treated the virus at a macro scale. You can’t just tell people to make one behavioral change to stop the spread of the virus. You need lots of things, like wearing a mask, washing your hands, staying apart. And you need to think about what behaviors could break those rules and why. I spoke to one of my oldest friends about this, Stephanie McCalla, who is a professor of bioengineering and an RNA diagnostics expert at Montana State University.
Stephanie 5:42
My background is biomedical engineering. And most of my research involves molecular diagnosis. Diagnostics, so finding sort of faster, cheaper, better ways to diagnose disease.
Jessamyn 5:55
Now, I definitely want to hear about faster ways to diagnose disease, but I also want to ask if you’re wearing a Slanket.
Stephanie 6:02
I am wearing a Slanket, thank you for noticing! It is very comfortable, and stylish. The Slanket is basically the Louis Vuitton of personal warmth options, so…
Jessamyn 6:14
That’s true. Everyone says it. Can you tell us a little bit more about your research now, because I know you’re doing, like you said, molecular diagnostics and detection, right? But I’m a simple physicist. So tell me more about it.
Stephanie 6:30
Yeah so, a lot of what I’m doing in my lab right now involves RNA detection. So we are largely focused on short RNA. RNA is basically the software of your body. So your DNA hangs out, and it stores information over a long period of time, but the RNA is what gives marching orders to make different genes, different proteins. And so the presence – they don’t really stick around for a long time – so their presence or absence tell you if you’re going to be sick, if you have foreign RNA, like viral RNA. I feel like that’s topical for something, I don’t know. That could tell you whether or not you have an infectious disease. So that’s a lot of what we do, and that could range from figuring out better ways to take that RNA, which could be in really low amounts and pull it out of your bodily fluids, and make sure it’s stable so you can figure out if it’s there or not, to figuring out faster ways to just detect it – to take the RNA that you pulled out of your sample and see how much of it is there,
Jessamyn 7:37
Correct me if I’m wrong, but it seems like RNA detection became incredibly important about a year ago, and your lab was one of the labs that already had all this stuff set up to do it. So you must have felt very important and relevant as a scientist.
Stephanie 7:55
I don’t know about that, but it was interesting to see all of these techniques that were just staples in my lab, or things that I had published on, just all of a sudden in everyone’s mouth. Like, everyone was talking about it and that was – yeah, that was definitely interesting. I ended up temporarily donating one of the instruments in my lab to the local hospital so that they could do testing, because at that time, what we really needed was people who had big labs and approved labs. You actually have to get your lab approved to do these diagnostic tests. We needed them to be able to really ramp up, to scale up, and do a lot more testing. So that was, I mean, the immediate need. So that was my first reaction was just to donate that machine for a while, while they needed to scale up. And since then, it’s been kicking around ideas as to how to use some of the research techniques that we have to help more long term. But that’s not something we need in the short term. In the short term, we just need things to happen now, not research on what to happen in the future.
Jessamyn 8:01
Yeah, totally. Well, and I feel like one of the things that has really come out of the pandemic is the importance of like, equality and access to these laboratory methods. Even now, with like the vaccine distribution, right, and like, who has freezers and who doesn’t? Who had PCR machines, who didn’t? I know, you’ve done research on the low cost methods for RNA detection and that kind of thing. Do you want to talk about that some?
Stephanie 9:04
So that is definitely a huge motivation for what we do in our lab, because it very quickly becomes an issue in places where there aren’t a lot of resources. And that’s definitely an issue in Montana, where I live in the US. There are a lot of rural communities that don’t have access to a lab, or the more expensive equipment or really the, you know, the trained personnel who are qualified, or really allowed to run these tests. And so some of my previous work was on stabilizing RNA and taking a large sample. Like let’s say you have a, I mean in a clinical sense it’s pretty large, but a couple mls of saliva or nasal aspirate and trying to get the RNA out, make sure it doesn’t degrade, because RNA is meant to not stick around. You don’t want it to stick around. It’s meant to carry short term information and then go away, when that information is no longer relevant. So that’s one area that I’m pretty excited about. And we have some other – a lot of the techniques that we actually are developing ground up in my lab are more applying to short RNA, so it wouldn’t really apply to viral RNA, but some of the other things I’ve done in the past could definitely be used, and are being used to detect the RNA as well. So just putting that whole system together, that is definitely something that we are in the future interested in doing, for sure.
Jessamyn 10:57
And is that- the fact that, like you’re saying, RNA is kind of designed not to stick around for a long time, like DNA. Is that related to why mRNA vaccines are so hard to store and distribute and haven’t been used before?
Stephanie 11:10
It absolutely is. So RNA is pretty flimsy. And so the reason that these vaccines, a lot of them are being stored at -80°C, and that’s very, very cold. That’s- your freezer is not going to get down to that I actually have one ‘negative 80’ in my lab, and they’re very expensive, and you basically need special gloves to even go into them. They’re so cold, you can’t touch them. So that is to keep that RNA stable, absolutely. And there are a lot of other things that keep it stable. It’s enclosed in a little lipid bilayer, which is similar to, you know, what your cells or a lot of other microorganisms are enclosed in as well. So, yes, there were a lot of scientific considerations that had to be ironed out before we could get the vaccine, like the Moderna vaccine or, you know, the mRNA vaccines that are out there now, really, to the public. I think people are working on this type of research for like 30 years.
Jessamyn 12:14
Yeah, I mean, in a way we’re really lucky that people had already been researching mRNA vaccines, even though they hadn’t been successful yet. It’s probably laid a lot of that groundwork.
Stephanie 12:26
Definitely, and so many people contributed to that effort and a lot of federal research dollars. And yeah, if we had just started working on it now because all of a sudden it seemed relevant, we’d be in a whole lot of trouble. So definitely grateful that that was an area of research, for sure.
Jessamyn 12:44
Yeah. Well, I think that leads in nicely to something I know we’ve talked about a lot before about like, how academia promotes some types of research over others. And some types of people over others – Shaun, edit this out [laughs]. You know, like in the pandemic, I think it’s been really interesting watching kind of who gets lauded as an expert and, who are the people that are just like donating their time and their lab equipment to help, versus the people that are maybe trying to use it to further their own career. So could you talk about that some, but you don’t have to name names [laughs]?
Stephanie 13:24
Yeah, I mean… I think it’s, yeah… So, academia is not necessarily a meritocracy. And I don’t really think that that’s a controversial statement, though there are people who who would disagree with it. And certainly a lot of the people who are getting rich and famous off of, for example, the mRNA vaccines worked really hard and contributed to the effort, but I think there was some mention – I think you maybe were talking about this earlier – of the person who was really contributing to allowing this vaccine to be injected into the human body without making the immune system completely freak out. I mean, your immune system is designed to freak out if some weird unknown RNA is there. And the person who figured out how to make sure your immune system didn’t freak out because of weird unknown RNA, and just go in complete overdrive, is getting very little benefit from this. So again, I think you guys already talked about this, but I do think yes, a lot of who become successful or the people who can play the game, can talk a big talk, and go out there and give the 10,000 foot view to investors, and really invest the time. And that type of, sort of brash, overconfidence is less likely to be accepted if it comes from a minoritized person in science. This is just my two cents on that. Yeah.
Stephanie 15:17
I can say, sort of from experience, sort of straddling the world between chemical and biological and biomedical engineering, that there’s a bit of a bias against the more pure biology side. And let me be clear, biology is really hard. Like these experiments, you have to be just a wizard at experimental design to really figure out what’s going on in a biological system. But there is this attitude that the more biological you are, the less, you know, rigorous and mathematical. And there’s- it just to me always feels a little bit coated in sexism. Personally, that has been my experience. And so there is this attitude that I’ve seen from a lot of, for example, chemical engineers, that they invented bio engineering, that biomedical engineering is their effort, and they can go in and do anything, but only a chemical engineer can be a chemical engineer. I’ve actually heard those exact words from many chemical engineers, and I think that’s a bit harmful, personally. But I mean, more in reference to COVID, I think it’s important for people to realize – and this is just my opinion, obviously – that when somebody is being held up as an expert are trying to explain a certain field of science, it’s not always going to be the person who knows the most, it’s going to be the person who has the platform, or who wants the platform.
Jessamyn 16:54
Do you think that any of those kind of, like biases in academia or in like biomedical research are going to get any better as a result of what we’ve seen happen with COVID over the last year? Like we’ve seen a big, you know, kind of core area of research finally pay off, and and we’ve seen that there are equality issues around this kind of research as well. So do you think that there are going to be some positive outcomes from this, aside from obviously, vaccinating everybody?
Stephanie 17:23
Yes. Honestly, on the social level, I think there could be some positive things that come out of it. I’m not sure I see it happening in science, and maybe I’m just being a pessimist. I’m really excited about mRNA vaccines, they’ve sort of never been approved before fully. And they are- so some of the methods to create RNA in a lab are things that are so standard, I’ve definitely done them before. They’re so easy, it’s so easy to scale up. So I think hopefully, that’s going to be a big part of what comes out of this, is more accessible vaccines that eventually will help scale up the number of vaccines that can be put out there. Socially in science, it’d be cool if this made scientists sort of more trusted, better figures, but I just don’t see a big change in sight, for looking for the most viable expertise over the loudest voices in the room. I don’t know if you agree, Jessamyn?
Jessamyn 18:26
Well, obviously this could be a topic for a like five hour podcast [laughs], because I think a lot of things- a lot of things need to be fixed, even though every little thing is an opportunity to make a small change. But yeah, so I guess in terms of COVID too, do you feel like COVID and you know, having such a big public health thing happen in your research area, has it changed the way that you talk about your work at all, like the tone you use, or how you frame it?
Stephanie 18:53
A little bit. Honestly, it probably should change the way I talk about my work. I have a tendency, I think a lot of scientists have the same problem, that we want to give all the nitty gritty details because the answer is never simple. The answer is always “well, it depends”, and “let me explain to you, for half an hour, every tiny detail of what could happen and what could go wrong, and what could go right”. And you know, most people just don’t have the time for that. So I think what I’ve learned from talking to a lot of people about diagnostics – and how do you diagnose COVID? And how do you do it better, faster? What are the different uses of different tests? – is to find a way to pull out the most important message. So I guess that is one thing that has changed for me is instead of trying to tell everybody every little nitty gritty detail, is to actually try to do some science communication that I am admittedly not very good at, I don’t have a lot of experience with, but to try to really find a way to tell people why what I do is important and why they should care.
Jessamyn 19:59
What Steph said is a great reminder that science communication isn’t just about the facts, especially given that research shows telling people facts does not change their minds. It’s the bigger picture, how those facts matter, and what stories we tell about them. The science by itself is not enough. We need the social sciences to tell us about vaccine uptake, behavioral change, how different communities and different parts of the world are affected differently, and we need arts like storytelling and comedy to help us get the most important messages across. Going to the same pedantic talking heads as experts is unfortunately very likely to alienate the public, as we’ve seen, and more interdisciplinary forms of expertise are needed. This is where comedy can play a role.
Jessamyn 20:45
At the very start of the pandemic, Kyle Marian Viterbo ran a comedy event in New York City called Asians Strike Back: A Coronavirus Comedy & Science Show, which brought together some of New York’s best Asian comedians with Asian and Asian American virologists and epidemiologists to dig into COVID, xenophobia, and the Asian diaspora. The comedians called out the racism in early coverage of the pandemic, challenging biases at the intersection of science and society. Sadly, this has only become more important in the year since, when physical and verbal assaults against Asians have continued to rise. We can’t just focus on the science. We also need to think about how science is discussed, and about who has power in these conversations. In a year or two, when vaccination is widespread, we can hopefully look back at this pandemic and learn a few things about how to bring science, experts, and the public together. Science communication could be hugely changed by this experience, and I think it will be for the better.
Jessamyn 21:49
This episode was made possible by support from the Community Knowledge Initiative, the CÚRAM Medical Device Research Center, the research office at NUI Galway, and Science Foundation Ireland. We’re grateful to our guests, our host, which is me Jessamyn Fairfield, our producers Maurice and Shaun, and to you our listeners and our Bright Club Ireland community. A transcript of this episode is available at brightclub.ie, where you can also find more information about what we do at Bright Club Ireland.