“Which one did you get, Pfizer or Moderna?” This was the big question at the start of the COVID-19 vaccine rollout but how do these vaccines work? Why do they have to be kept at ultra cold temperatures? What is mRNA?
These questions are answers in this episode featuring WWU Biology professor and RNA researcher, Dr. Suzanne Lee.
Lastly, if you haven’t already, Spark Science would like to encourage you to get any COVID-19 Vaccine available, mRNA or not.
Spark Science Podcast
mRNA Vaccines w Dr. Suzanne Lee
[Podcast start-up music: chimes and drums.]
Regina Barber DeGraaff: Welcome to Spark Science. I’m your host, Regina Barber DeGraaff, and I teach physics and astronomy at Western Washington University. In this episode, we get to talk about the mRNA vaccine with my friend and colleague, Dr. Suzanne Lee.
In our previous episode, we spoke with an infectious disease specialist on the status of the COVID 19 pandemic, and how vaccines can definitely help. This time, we’re speaking with Dr. Lee, an assistant professor here at WWU, regarding her research on RNA pathways. Let’s take a closer look at just how these new vaccines work.
[Music swells and fades for interview session.]
I am here with an awesome biologist, somebody I’ve known for a long time, Dr. Suzanne Lee.
Dr. Lee: Aww, thanks. It’s super-awesome to be on your show. I’m a big fan, so…. [Laughing.]
DeGraaff: I wanted to bring you on because, actually, one of the students who works on the show–we have student volunteers that edit the show and give me ideas and help me storyboard. One of them is a biology major, and he wants to talk about the RNA vaccines. He asked about that. Your research is with RNA, so we’re going to go back in time and talk about your path to your research.
Dr. Lee: I wouldn’t say I was really “science-leaning” until I was in college. Growing up, I was pretty sheltered and pretty much a homebody. I really didn’t go anywhere. And so, it just doesn’t really….
I was definitely an avid reader, but I read, you know, just storybooks and things like that. You know this, Regina. I wanted to go into the performing arts. That was my secret passion. But it was definitely secret because my parents are–if they listen to this, they’ll– [laughing.]
DeGraaff: And they are going to listen to it!
Dr. Lee: I’m not going to be ashamed, no! [Laughing.] No, I ended up not going into the performing arts, but I love the performing arts so much. I mean, I just love the communication and the storytelling that’s a part of the performing arts, and that connection with the people you’re telling a story with and to. But it was not a very practical career path. And so, I started taking premed classes to basically satisfy the parents, who really wanted me to be a doctor.
And that of course was intro biology and intro chem. And I actually did really poorly in my intro chem class. My very first semester, I got a D- on one of the major exams, and I was like, “Ugh.”
DeGraaff: But on the exam, not on the final, right? I know you pulled out of that, right?
Dr. Lee: Yeah, and the only reason how I managed to pull out of that was because that particular instructor had this wonderful policy of dropping the lowest grade! [Laughing.]
But yeah, I was not so into science initially. And biology…. We were talking a little bit about this before we started. The biology just seemed to me like a lot of memorization. I’ve never been particularly good at memorizing a bunch of things, like terms, if it’s not something that’s deeply interesting to me. That’s never been my thing.
And so, I just wasn’t really into it. But then, I took a chemistry class from this awesome professor/mentor, Dr. David Hanes, at my college. He was a chemistry professor. He taught intro chem and he also taught organic chemistry, and organic chemistry is like the chemistry of biological reactions, is kind of how I think of it.
He helped me realize that I really love… that I really got into the problem-solving of science. It’s really through organic chemistry but uncovering how things work. I realized I was really interested in that aspect of science. The memorization may be just like learning a language, but really, that was to be able to understand how things work.
And then, I needed to earn some money in college, so I stumbled on a research opportunity in the summer in New York City. And I was like, “Performing arts? New York City? Broadway’s there! Oh my god!”
DeGraaff: But you said summer? It was a summer internship?
Dr. Lee: It was a summer research program, yeah.
DeGraaff: But you went to undergrad in San Diego, right?
Dr. Lee: No, no, I was an undergraduate just outside of Boston, in a small college.
DeGraaff: Okay, okay. But you did go to…. San Diego was grad school?
Dr. Lee: San Diego…. I eventually got to San Diego in my postdoc so many years ago.
DeGraaff: Postdoc, yeah. So, you’re outside of Boston, you want to do a summer thing in New York.
Dr. Lee: Yeah, I want to do a summer thing in New York. There was this hook, I think, in the advertisements of “fun excursions” you could go on, including Broadway shows. I was like, “I am there!” [Laughing.]
But it placed me in a cancer biology lab, which opened my eyes to this different view of biology. It wasn’t mind-numbing memorization, but like detective work. There was a nice melding of chemistry and biology in the field of molecular biology, which is…. Ultimately, that was what pulled me into studying biology and biochemistry, basically.
So, that was kind of how I got in, I would say. From there, I ended up majoring in biological chemistry as an undergraduate. When I graduated–when I got close to graduating, I wasn’t really sure what I wanted to do and I was still trying to like, okay, maybe I can do science but still do the med school thing. If I try to think about MD/PhD programs, but if I do medical school, that might be really expensive. So I’ve got to work for a while. That was my argument for why I needed to just work for a while.
So, I worked for a while in a lab in Boston as a research assistant. That was an awesome time of life, just generally, because I was working as a scientist in a lab, learning a lot, and also getting to play a lot and do some local theater.
Then, I got to a point where I felt like I had kind of hit a ceiling in what I was being allowed to do in the lab. I remember I worked really hard to figure out how to do some kind of microscopy experiment and I was taking too long. My advisor, who was a wonderful person, Dr. Stephen Volk [sp?] in Boston–he was like, “Suzanne, I know you spent some time on this, but actually I’m just going to have someone else do that experiment.”
Dr. DeGraaff: What?!
Dr. Lee: I got really mad!
Dr. DeGraaff: Yeah. [Laughs.]
Dr. Lee: I got really mad. I remember, whatever I was, probably 21 or something. I remember I went up to Dr. Volk and I was like, see? If I were a grad student or a post doc, that would be so not cool. But I understand. I’m just a research assistant.
I look back at that and I laugh. I mean, he took it so well. He was like, “you need to go to grad school.” [Laughing.] That sort of led me to grad school. I realized I was just really interested in the fundamentals of how things work. Lots of respect to doctors all over. For me, I realized that I was just really into the problem solving and the discovery, the detective work.
I went to Berkeley for my graduate degree and then traveled around a bit after that. I did my post doc. First year of my post doc was in Boulder, Colorado. Then I ended up in San Diego because the lab moved to San Diego.
As a post doc, I took a class that was about approaching teaching like you approach science and trying to figure out what’s going on with students, and then making sure that you’re really supporting students, and all of your students. That got me really excited to think about teaching, and integrating my love of science with teaching and mentoring.
That is really, I think, what put me into looking for positions like the one I have at Western where I get to basically do it all. I love getting to work with students. I love it so much. I love getting to have a little lab and I get to have that lab be someplace where me and my students are trying to figure out what’s going on, how things work.
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Dr. DeGraaff: This is Spark Science and we’re talking at Dr. Suzanne Lee about the mRNA vaccines and the science behind them.
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Dr. DeGraaff: Let’s tell a story about how these mRNA vaccines work. I know that when this happened, I remember you talking to me and how excited you were. Help our listeners understand what this mRNA vaccine is all about.
Dr. Lee: Yeah. It is just so amazing to me that what might lead us out of this mess is RNA. It’s so much fun. People are probably pretty familiar now with these images of the coronavirus. It’s like a blob with these spiky little things, like a dog toy kind of thing.
Dr. DeGraaff: [Laughs.] Again, for our listeners, Dr. Lee is making a ball with her hands like two claws. [Laughs.]
Dr. Lee: Totally. [Laughs.] Exactly. Coronavirus–the reason why we call it corona is because it’s got this spiky crown, and corona means spiky crown in Latin.
So, those spikes, those pointy things, they are proteins. The mRNA vaccine encodes–not the coronavirus–it’s not introducing in virus. It’s just introducing the instructions for your cells to make some of the spike protein. Then, what happens–because the spike protein on the coronavirus, it’s exposed out. The spiky ball–the spikes on the–basically, in the cells, when it’s expressed, that spike protein gets put on the surface–displayed on the surface of the cells that the vaccine gets into.
Basically, this vaccine is really cool. It’s got these mRNA molecules packaged inside, essentially, a globule of fat that then can be taken up by your cells when it’s injected in. Then those cells that take it up can start to make a bunch of spike protein and display the spike protein on the surface of your cells, which then is recognized by your immune system as, “wait a minute, what’s that thing?”
The immune system will start to make antibodies and it’ll make, eventually, hopefully, some memory immune cells that can recognize something that looks like the spike protein. So that, if your body ever actually encounters real SARS-CoV-2, your immune system will instantly recognize, “oh, what are these spikes? We’ve seen that before. Let’s get rid of this thing.”
Dr. DeGraaff: So, it’s really cool because older vaccines, the vaccines that we’ve had before, are the actual virus–not alive, but injected into people. This way, they’re like synthetic. It’s not the actual virus. But it’s doing the same thing. Your body is training for when the day comes, I’ll know what this thing is and I’ll know how to defeat it.
Dr. Lee: Yeah. Exactly. Some of the more classical approaches to making these vaccines have been what are called attenuated viruses. Or there’d be similar viruses, but from another organism. But then kind of weakened so that it can’t actually make you sick, but it stirs up your immune system so that if your body ever encounters some other virus that looks a lot like what you got in that vaccine, it’ll be able to attack it.
But in this case, what’s really clever about it is that it’s just the instructions to make a particular part of the virus that your immune system would see first, and then it can attack it.
I think the reason why I’m so excited about that is because all those other methods of, sort of, an attenuated virus, or weakened virus, or some other virus from some other organism but has some similarity to the virus that you’re trying to vaccinate against–those other methods take a really long time to make a lot of. Whereas, the mRNA vaccine is not as hard and it’s also easier to change the sequence pretty quickly. So that, if you need your immune system to recognize something slightly different, we can do that really easily.
A good example is the flu vaccine. Annually, scientists have to kind of predict, well, what’s this year’s flu going to be? Alright, let’s look for some flu viruses and inactivate them and maybe this is approximately what’s going to be right, that’s going to help vaccinate people this year.
But, the flu vaccine is something like 50 percent. I’m not an immunologist, I’m not a clinician, so don’t quote me on this! [Laughs.]
Dr. DeGraaff: It’s a general statement.
Dr. Lee: [Laughs.] This isn’t being recorded! But yeah, it’s efficacy is pretty good, but some years it’s not quite on. Some years it’s better than others. But it takes a while to do that.
In this case, it’s the sequence that gets taken up by the cells and can get your cells to basically make this molecule that then your cells display and your immune system can recognize.
Dr. DeGraaff: When we have these variants of COVID-19 and you have the vaccine and your body is like, okay, I recognize this, this spikiness. How different is the spikiness for the variants? How can it deal with that?
Dr. Lee: It’s interesting. So, the immune system will generate a bunch of antibodies, which will fight anything that has resemblance to the spike protein that you’ve introduced. It’ll be able to recognize stuff that’s exactly the same thing and stuff that looks similar, but isn’t exactly the same thing. So, there’s some flexibility in our immune systems.
Dr. DeGraaff: That’s good! [Laughs.]
Dr. Lee: It is really good. Certainly, the proof of how well something works is going to be in the data. My understanding is, so far, the variant that’s called the UK variant–that one, our current vaccines work great against. I think there’s two other variants that people are starting to get worried about. That would be the South African one and the Brazilian one. Those particular variants.
Even so, even with those, even though the studies seem to be that our vaccines are not as active against those, it’s still pretty good for protecting against serious disease. So, it’ll help to keep people out of the hospital, which is important.
As we were saying, I think also the ability to tweak that sequence relatively easily is very promising to being able to update it if we need to.
Dr. DeGraaff: So, then we’ve kind of gotten to that place then. Then what’s the future for RNA research? How can we use it in the future? Are more and more vaccines going to have this now? Because they didn’t really before. What else is this going to produce? What kind of solutions are we now going to get from RNA research?
Dr. Lee: Yeah. It’s so exciting from that point of view. I mean, as horrible and disruptive as this pandemic has been, it is really just awesome that we have gotten our first RNA vaccines. Even before this point, some of the companies that had been working on vaccines had been developing RNA-based vaccines for other things. Like, Moderna was working on a vaccine for the Zika virus. You might remember Zika.
Dr. DeGraaff: It’s still around, right?
Dr. Lee: It’s still around, exactly. Dengue. A lot of countries really suffer because of dengue. Then there’s also phase 1 trials now being worked on for a universal flu shot that is mRNA-based.
I’m hopeful that this is sort of paving the way towards having more flexibility in the kinds of vaccines that can be used. It’s nice to have lots of options for things that either are changeable or have been really hard historically to vaccinate against. Now we have something that is a more flexible platform and faster turnaround, potentially.
Just based on these particular mRNA vaccines that we’ve got going, the efficacy is so high! I mean, it’s just like–remember in the fall, when the first Pfizer announcement came out and it was like 95 percent efficacy under their clinical trials in phase 3. I was just like, that is so amazing!
Dr. DeGraaff: Because you were saying that regular vaccines don’t have that kind of percentage.
Dr. Lee: Typically not. I mean, some do. Again, we can go back to the flu vaccine. It’s not nearly as high, is my understanding.
I think, too, it’s like there are certain things that could be improved about the current RNA vaccines. Hopefully there’ll be more investment and research in trying to understand how to improve it, how to start to limit some of the responses that folks have. With these shots, some people are having mild symptoms that don’t last for a long time. It’s kind of transient, but as folks investigate, what is it about the packaging of these things? How can we improve it so that it’s less of a reaction? How can we make it more temperature stable?
Dr. DeGraaff: I was going to ask you about that. All of these vaccines that we’re talking about–RNA–they have to be at super cold temperatures. Then they go bad super fast, right?
Dr. Lee: Yeah. It’s so interesting. I’ve been very curious about that. First of all, they go bad really fast. So, once you open a vial, you got to get that into people’s arms. That’s been the thing. Got to get it into people’s arms!
So, then, the temperature requirements. For Pfizer, minus 80. For the Moderna, minus 20.
Dr. DeGraaff: 20 what? What units?
Dr. Lee: Celsius. [Laughs.]
Dr. DeGraaff: There we go. These are the points I take off of students’ tests. You can’t–no units? No. No, Suzanne!
Dr. Lee: Oh, I just got a D! [Laughs.]
So, minus 20 would be like your household freezer. So, minus 80 is even more–Celsius. [Laughs.]
So, the temperature stability, I think it’s interesting. Of course, a lot of this is, I think, proprietary, so it’s hard to dig into why. But I think the temperature is likely related to the relative instability of RNA. That it’s packaged in a fat droplet, so if you heat up fat, you can think of your butter when you heat it up. It sort of melts. So, some of that kinetic, thermal energy of temperature can be disrupting that.
Dr. DeGraaff: That is the best–I have not heard anyone talk about that. Like, why do we need it to be cold? Just like when you make cookies and you cut the butter into the flour and then it melts when it’s in the oven, but you still want it to be like held together and kind of chunked before you put it in there.
Dr. Lee: Yeah. And then the sort of not lasting very long–I just recently learned this–that these vaccines actually don’t have any preservatives in them. That’s why they expire quickly and you have to get them into arms, which for some folks may be really comforting because it’s lacking some of those preservatives that people–the CDC has said those preservatives in other vaccines is not harmful, but some people have concerns about preservatives generally. So, these don’t actually have preservatives, which I thought was really interesting.
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Dr. DeGraaff: You’re listening to Spark Science and we’re talking to Dr. Lee about the development and application of mRNA vaccines and also how they relate to her ongoing research here at WWU.
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Dr. DeGraaff: So, what does this all mean for your own research then? What questions do you want to answer and what problems do you want to solve with your research with RNA?
Dr. Lee: Oh. [Laughs.] Yeah, that’s a good question. I mean, so we have been studying this RNA pathway that, like I say, the genome has these regions that don’t encode proteins. So, the mRNA vaccines here they encode the spike protein, that RNA molecule. We’re really interested in the parts of the genome that allow for RNA to be made, but that those bits of RNA sequence actually don’t code for anything. They can’t be decoded into a protein–or they don’t seem to be decoded into a protein.
We’ve been studying this pathway that takes some of those transcripts and converts them into these really short RNAs. Kind of, evolutionarily, these are pathways that were thought to evolve to actually fight off viruses. It’s basically a pathway that chops up RNA in a cell into small pieces and then uses those small pieces to trigger the degradation of RNAs that share the same sequence.
But the cells, over evolutionary time, have coopted them to help serve some kind of important function in the cell, be it gene regulation, or organization of the genome in particular ways. We’ve been trying to study the function that this pathway has in the model organism that we study.
It’s hard to study pathways that are important for human health in humans because it’s expensive and also complicated.
So, what we do is we use a model–
Dr. DeGraaff: Like ethically complicated.
Dr. Lee: It’s ethically complicated. It’s also logistically complicated and highly expensive. So, we’re really interested in trying to understand this pathway, even though it is conserved in humans. But we study in what we call a model organism, which is a single-celled creature called Tetrahymena thermophila. It’s basically a single-celled creature, normally lives in freshwater environments.
We’ve been trying to understand what this RNA interference pathway does for cells. We’re starting to uncover some clues that I’m really excited about. But we’re trying to get this one paper out soon. Soon, hopefully. Fingers crossed!
Dr. DeGraaff: You actually have students working on that research, right? So, students will be on this paper, right?
Dr. Lee: Oh, yeah. There’s a very long list of students who worked in my lab over a few years. This particular manuscript that we’re working on, we’re just trying to put the final touches on this year.
It stretches that back, I would say, at least 3 or 4 years of work has gone into this study. I think we finally actually have a handle on what this pathway is doing in our cells. What I’m really excited about is it seems like what this pathway is doing in our cells is something that we’ve been getting whispers for happening in a lot of different organisms, including humans. It has some really important implications in terms of the conservation of this pathway and in terms of the molecular mechanisms of this pathway.
Dr. DeGraaff: I really like–I mean, you can tell you’re really excited about your research, which is great. But also, for me, a non-biologist, many of our listeners are not biologists, it’s surprising for us to hear that there are so many things about the human body we don’t understand or about cells. So, it’s really interesting that you’re saying, we have to understand what this specific pathway is doing because we didn’t know beforehand.
Dr. Lee: Right. The origins of the COVID vaccine go back 20 years to a time when people were just trying to understand something and were driven by their curiosity. But didn’t know where it was going to lead. It’s these fundamental discoveries of how do things work, how can we do things, that put us in such a good position last year this time, basically, to have something like a vaccine. You can never know what your fundamental discoveries are going to lead to.
Dr. DeGraaff: Because we don’t totally understand–we’re still discovering biology, we’re still discovering physics, we’re still discovering astrophysics every day–science is a dynamic thing! All of the fields have new stuff happening, which brings me to pop culture.
[Laughing.]
Because there are so many movies out there with, you know, cloning dinosaurs.
[Laughing.]
And the movie Evolution with David Duchovny and just like–mutants, X-Files–I mean, X-Men, and stuff like that. Whenever you’re seeing that in the media utilized stereotypes or misconceptions in society, do you have anything that you’ve seen the past where you’re just like, “there’s no way we could do that!”
Dr. Lee: I mean, I think the thing that strikes me, and even with the examples you mentioned–and I think I’ve confessed to you that I’m a Shonda Rhimes fan. I’ve watched Grey’s Anatomy. [Laughs.] There are these depiction of scientists who are involved in some research. It’s like this one person–and then they’ve discovered something amazing all of a sudden. Everyone recognizes that’s like really important and everyone cares and they win all these great awards. And like, that–science doesn’t work that way. It’s rare that people really recognize the importance of something right when it happens. [Laughs.]
Dr. DeGraaff: [Laughs.] I love that that’s what you took away. They’re like, it doesn’t happen this fast. My husband is a lawyer and I remember I had a friend in graduate school. When I was getting my PhD, my husband had just gotten his first job as a lawyer, and my friend wanted to go to court with him. She was like, can I just please watch you in court? Is it just like Boston Legal? [Laughs.] Jake is like, it is not like Boston Legal.
Dr. Lee: Exactly! In the case of a scientific discovery, it’s not just one person who makes this amazing discovery and then everybody’s like “wow!” It’s like years. Going back to the vaccine, like 20 years of discovery, 20 years of work, of lots of different people involved.
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Dr. DeGraaff: Thank you so much to Dr. Suzanne Lee for being a guest on our show. It’s a great privilege to have a friend so well versed on the complexities of RNA. If you haven’t already, Spark Science would like to encourage you to get any COVID-19 vaccine available, mRNA or not. We can do this. We’re almost out.
Spark Science is produced in collaboration with KMRE and Western Washington University. Today’s episode was recorded in Bellingham, Washington, in my house on my computer, during the great pandemic that’s still going on in April 2021.
Our producers are Suzanne Blais and myself Regina Barber DeGraaff. Our audio engineers for today’s episode are Ariel Shiley and Zerach Coakley.
If you missed any of our show, go to our website at sparksciencenow.com. And, if there’s a science idea you’re curious about, send us a message on Twitter or Facebook at SparkScienceNow.
Thank you for listening to Spark Science.
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