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Penn Medicine’s Women On the Frontlines of History - an Interview with Dr. Susan Weiss.

Susan Weiss, PhD, a professor of Microbiology and co-director of the Penn Center for Research on Coronaviruses and Other Emerging Pathogens, talks about her 40 years of experience researching coronaviruses, how her field reacted to the 2002 SARS and 2012 MERS outbreaks, and the importance of studying diseases that transfer from animals to humans.


Hosts: Elisabeth Berry Drago

Senior Producer: Mariel Carr

Producer: Rigoberto Hernandez

Researcher: Jessica Wade

Additional production: Dan Drago



Transcript

Lisa Berry Drago: Hello and welcome to Distillations. I’m one of your cohosts—Lisa Berry Drago. In response to the coronavirus pandemic we’ve launched a brand-new series focused entirely on COVID-19. Over the next several weeks we’ll be bringing you interviews with people working at the heart of the crisis, including biomedical researchers, physicians, and public health experts. On this episode our producer Rigoberto Hernandez talked with Susan Weiss, a professor of microbiology at the University of Pennsylvania here in Philadelphia. She’s also the director of the Penn Center for the Research on Coronavirus and Other Emerging Pathogens. She has been studying these types of viruses for the past 40 years. One note: Throughout the episode you’re going to hear us refer to the novel coronavirus as SARS-2. That’s because this virus is in fact very similar to the SARS virus.


Rigo: So can we just get some terminology out of the way? So first, SARS-CoVid-2, which is the name of the virus, and COVID-19 is the name of the disease.


Susan Weiss: No, the name of the virus is SARS-CoV-2, not COVID, just C-O-V, coronavirus.


Rigo: Got it. Actually, I haven't been able to find a straightforward answer. Why is the “2” after that?


Susan Weiss: Oh, that's really a very simple reason: because it's so similar to the original SARS-CoV. That one wasn't called CoV-1 because we didn't know there was going to be another one. But it's basically very, very close genetically to the original SARS. And that's why it's called SARS-CoV-2.


There was some dispute about the name of the virus. So there's an international committee that's charged with naming viruses, and they named it SARS-CoV-2 because of its genetic relationship to SARS. There are people that work on these viruses, and I think the World Health Organization wanted to call it COVID-19, and there was a bit of a dispute.


It's mostly called COVID-19, even though that's not the correct name of the virus.


Rigo: I see. So actually I was reading that the WHO doesn't even refer to it by the specific name, SARS-CoV-2. And I was reading that it was because people are going to be associating it with the SARS outbreak.


Susan Weiss: No. And isn't that ironic? When this virus is so much more, has done so much more damage that it's ridiculous. You know what I mean? Like they were afraid to be associated with this horrible epidemic, but really this epidemic is much more extensive.


Rigo: So coronaviruses get their name because of their crown-like shapes, and you've been studying these viruses, plural, for decades. And so this is a two-part question: one, how did you, I did not realize that there was actually like hundreds of them living in bats. Could you tell us about the coronavirus family of viruses and which ones we might be concerned with? Humans might be concerned with?


Susan Weiss: Okay. So it's a really large family, and it's divided up into actually four genera: alpha, beta, gamma, delta. Human viruses are only found in alpha and beta, but there are many animal viruses that should be of concern to us as well because they kill animals. And so for a long time since, I mean, I think I reviewed the chicken virus; I found references from the 1930s.


And certainly in the ’60s and ’70s, people were studying some of the bovine virus, pig virus, cat, dog. And they were important for a vaccine; they were making vaccines against these viruses. And then the other important virus—it's not human—is the mouse hepatitis virus [MHV]. That was the virus that I studied for a long time. And the reason that it was important or still is important, I think, is that it causes, it's used as a model for hepatitis, encephalitis, and chronic demyelinating diseases [e.g., multiple sclerosis]. And even one of the strains causes a severe acute respiratory syndrome. So these viruses can infect their natural host, the mouse, and cause very interesting diseases with different tropisms.


And so you can actually study a SARS coronavirus in its natural host in which you can manipulate both the host and the virus. So MHV was really the virus that a lot of the very fundamental stuff was done on, like showing the first receptor, showing that there's this furin cleavage site. All was done in MHV first, plus a lot of really interesting pathogenesis studies.


So all of that happened before—so during the time that people were studying both MHV and all these animal viruses, the only human viruses we knew about were 229E and OC43 that caused the common cold. Everyone knows about them now, but so they're common viruses and people didn't study them a whole lot in the early days.


And then of course, in 2002 SARS emerged from bats in China. And at that point NL63 and HKU1, two other—people looked for more human viruses and they found those two. Those are the only two I know of that have really been described. They're kind of intermediate pathogenicity. They cause bronchiolitis, and croup, and also pneumonia. And so people, there's not a, there's some studies of those viruses but not a whole lot. And then, you know, then we had MERS in 2012 and SARS-CoV-2 in 2019–2020. So I think, so there, so those are all the human viruses we know about: the two cold viruses, the two intermediate viruses, and the three really virulent viruses.


But then there's this, you know, there are many, many, many viruses, and just about any species of animal can be infected by some coronavirus. So, yeah, even wild animals, deer, ruminants.


Rigo: So there are like seven of them, right?


Susan Weiss: Of human ones, seven that we know of, but we don't know how many other ones have maybe crossed from animals into humans. But maybe, and this is what I think, that maybe we don't know that because they didn't cause any really obvious diseases or bad diseases, so they're just unnoticed because it's hard to imagine why they would've crossed from bats into humans every 10 years. It just, you know?


Rigo: So I want to kind of break down the timeline of coronaviruses as we understand them. Some of the earliest recorded coronaviruses were from the 1930s.


Susan Weiss: The IBV: infectious bronchitis virus. Yeah. All the coronaviruses are very similar in their structure, in their genetic structure, in their gene organization.


So we can actually—they're important, aside from being animal pathogens, they're important because people did a lot of early work on IBV as well: the infectious bronchitis virus, the mouse virus, and the bovine virus.


rigo: Okay. The next chapter in this timeline is the 1960s.


Susan Weiss: I think so. And at that point, I mean, I just, again, looking in the literature, I was, you know, in the 1960s I was still in high school. I, you know, people described OC43 and 229E as common cold viruses, and that's really all that I know about them. There's a famous picture that's been going around now, the woman that's, you know, that one about the woman that saw, I think she was in Scotland, she visualized 229E on an electron microscope. But you could see the spikes, that was maybe in the ’60s, and she didn't ever get much credit for it. And now I see her pictures being circulated in a lot of places.


Rigo: So just to be clear, when you say the cold viruses, that's the viruses that we experience every year?


Susan Weiss: Well, it's not the, I mean, there are many viruses that we experience, but among them are these two coronaviruses, yeah.


Rigo: Got it. So that was around the 1960s.


Susan Weiss: Yeah. I mean, they, I'm sure they were around before that, but I, that's the earliest literature that I really found, just like looking through PubMed for papers.


Rigo: There was actually like a conference that started around this time.


Susan Weiss: The first conference, the first international coronavirus meeting, was in 1980 in Wurzburg, Germany, and that's the first. I had just moved to Philadelphia and gotten my lab here. So just by chance, the guy who organized it, Volker ter Meulen, was passing through Philly, and someone said, “Oh, you should invite Susan to your meeting. She's working on, she's just starting.” I hadn't published anything yet. I was brand new, and he invited me to this wonderful meeting in Germany that—there were 60 people there, and that was the whole field pretty much.


Rigo: Is that, like, contextualize that for us. Was that like, like was that an emergent field at the time?


Susan Weiss: It was small. I guess I would say it was an emergent field. There were some people that had worked on it for a while that I met. That meeting was wonderful because it was so—first of all it was held in a Schloss, or a castle. This beautiful old building, and everybody got to give a short talk, and it was small enough.


We had wine tasting. We had just, it was a very, really nice meeting where everyone had a lot of time to talk to each other. So for me, as a brand-new assistant professor at Penn, it was such an opportunity to meet people and make connections, because a fair number of that field was in the Netherlands and in Germany at the time.


Rigo: Yeah. And at the time, I'm assuming that—was the thinking that these viruses that you got, an emergent field, you guys are studying it, that it would become such a threat the way that we see it today?


Susan Weiss: Absolutely not. I mean, I think we studied them because there was interesting molecular biology; they have a very interesting replication cycle. The way they make their RNAs and proteins is unusual and complicated. So it was that which was just beginning to emerge. We were just beginning to understand that.


And then there was the interesting biology of some of the viruses. So I think it was an era when you could really start doing molecular biology on viruses. I mean, you could for a while, but it was relatively new. And this field was ripe for the picking, kind of.


Rigo: I see. And so nothing really happens until 2002.


Susan Weiss: Right. And it was a shock.


PBS Newshour: For nearly a month, the rapid spread of a deadly flu-like disease has triggered anxiety and some drastic precautions in Asia and elsewhere. The illness is called severe acute respiratory syndrome, or SARS for short. The symptoms are similar to flu: high fever, coughing, muscular aches, and shortness of breath. In the past month, more than 1,600 people are known to have contracted it, and 61 people have died. The new disease has scientists baffled on how to treat it.


Susan Weiss: Well, what happened was this virus emerged in the south of China, Guangzhou Province. And pretty soon it was identified as a coronavirus. Initially, I think by its morphology and then by—we already knew some of the sequences, and it was a shock to the field. It was an absolute “whoa.” Everybody was calling each other up, and wow, it's a coronavirus, a coronavirus.


We were like shocked because there was no precedent for that kind of thing. Although in retrospect, I mean, some coronaviruses cause pretty—like FIPV [feline infectious peritonitis] is a fatal infection of cats. And you know, there were other coronaviruses that—and MHV certainly kills mice. So, you know, it was a shock because all we knew about was the cold viruses.


And in fact, because the mouse virus causes demyelinating disease, people had for a long time tried to see if it was associated with any human diseases like MS [multiple sclerosis]. And people looked for enteric, human coronaviruses for a long time based on the precedents with the animals. But nobody found anything.


So it was an absolute shock that happened. And it was like a horrible, horrible thing. I mean, in retrospect, it's dwarfed by what's going on now. There were 8,000 people were the total number infected, and it stayed pretty much restricted to Asia, except for Toronto where there was quite an outbreak. So, yeah, that was shocking.


Rigo: Yeah. So was the shocking part the fact that it was a zoonotic disease, that the coronavirus went from animals to humans? Was that the shocking part?


Susan Weiss: No. The shocking part was that it was killing people. And, I mean, we didn't know immediately that it came from animals. That was, that took, I don't remember how long that took to figure out. Maybe not that long, but yeah, that was another shocking part. But in retrospect, we now know that, for example, the human OC43 is very closely related to bovine coronavirus and in fact may have evolved from that.


So 229E may also be, have an ancestor. I mean, we know that now. But at the time, I don't think we knew any of that stuff at the time. In fact, when I first started in this field, we all believed that coronaviruses were extremely species-specific because mouse hepatitis virus that most of us worked on wouldn't infect hamster cells. Or rat cells. So it was very, very specific. But that turns out to be really incorrect.


Rigo: So in that time it's capturing the world's attention because of the high mortality rate in China. What happens in your lab? What do you, what do you work on?


Susan Weiss: Well, we right away got the virus from CDC. And we started to work with it, but we were a little bit limited because my institution didn't have an animal BSL-3 [Biosafety Level-3] facility, so we couldn't really work on an animal model. We worked on it for a while, and then one day CDC called up and said, it's become a select agent.


Which means that, a select agent is, there's certain—I'm not even sure exactly how to define it—but there are agents that are maybe possible bioterrorism agents or they're not necessarily the most dangerous viruses but viruses the government is somehow worried about security-wise. So they made it, which meant that you had to go through all kinds of hoops to, your institution would have to be certified to work with SARS-CoV-2, I mean, SARS, the original SARS. And you would have to keep track of like every tube, every bit of it. And even the RNA, not even the virus, the RNA itself, with the select agents. So it became incredibly difficult to work with them. So we were told either do the select agent process, which is a long bureaucratic process, or get rid of the virus. So we opted to get rid of the virus.


In retrospect, maybe that was a mistake because now—oh, and then MERS and SARS-2 are not select agents. So there's no logic to that, really.


Rigo: When you say “in retrospect it was a mistake,” was it because you could have studied it more?


Susan Weiss: Yeah, yeah, yeah.


Rigo: You basically couldn't study it after they said, they labeled it as such.


Susan Weiss: Well, you could, we could have, but if we had pushed our university to go through the whole process, which maybe we should have done, you know, because now we're looking, we're working on SARS-CoV-2. And it'd be great to compare it to SARS-1, but we're sort of stuck cause we don't have SARS-1 in our...


I mean, I, yeah, we don't have it anymore. We could get it, but we'd have to go through the SARS, the select agent. I don't know why they did that. Everybody was very irritated that they did that because it caused a lot of extra bureaucratic stuff for places or people like us. There was one other person, one of my colleagues at Penn, we just decided to autoclave it.


Rigo: I see. When this is going on, it had the potential to become really bad in the likes that we're seeing today. And I'm wondering if at that time you guys were suddenly, this is the new threat. Suddenly this is a thing you have to study because it could have devastating consequences.


Susan Weiss: There certainly was a lot of fuss and excitement and, you know, immediacy that we have to do something about this virus. And, you know, we did write grants, so we got funding and that kind of stuff. But then, like I said, and actually NIH gave us extra funding. Anyone that worked on coronavirus has got some extra funding, but it was over so quickly. Really, it was over by July. It started like around January, so that everything calmed down then, and some people continued to work on it. We were working on it during that period, and I can't even remember when the select agents started because it was strange because it didn't happen right away.


I was invited to lots of meetings that year because there weren't that many coronaviral, there were very few. So I even got invited to China in 2003, which was quite amazing, right after the epidemic. And I met a lot of people. So it was pretty exciting in the sense of a lot of activity and things like that, but it never seemed as, obviously wasn't as threatening here because it was so far away.


It didn't ever seem, I don't remember people worrying about it coming here. Actually, in retrospect, which was maybe it was kind of dumb, nobody, I don't remember that.


Rigo: So in fact, that virus, it didn't become what COVID-19 is. I mean, that disease didn't become what COVID-19 is. And what was the reason for that? I actually …


Susan Weiss: Ok, the reason, I mean, I think what we think now is because of the way it spreads, because the new virus, SARS-CoV-2, everyone knows now, asymptomatic people can be spreading virus. So, and in fact, we know now from hospital, clinical samples, we get that by the time people are in the hospital, they're basically getting, having less virus in their nose anyway where we sample them. So, you know, the person can be walking on the streets spreading virus. With SARS, when people—people did not spread, or shed virus until they were symptomatic. That's a huge difference, and it has nothing to do with—you can't look at the viral genome and know that. That's just, nobody understands that. I think that's a really important thing to understand.


Rigo: Also the fact that it was more deadly.


Susan Weiss: It was more deadly. Yeah. SARS had a higher death rate than SARS-CoV-2, which is sort of ironic in a way, because you have a choice of a virus that kills a high percentage versus a virus that kills more people, I mean, way more people. Right. That was 8,000 people was the total number of people infected with SARS and about 10% died.


Rigo: Yeah. It's like maybe the volume wasn't as big, but the death was higher, versus here the volume is bigger, but because the volume is bigger, the death rate is also higher.


Susan Weiss: The death total is higher, right? The rate is lower, but MERS has a higher death rate, even 35%, I think.


Rigo: So let's go to now MERS, which is 2012. So it's about 10 years.


CBS News: The Centers for Disease Control reports the deadly MERS virus has reached the United States. Last month an American man traveled from Saudi Arabia to Indiana via London and Chicago. He was admitted to a hospital suffering from shortness of breath, coughing, and fever and diagnosed with Middle East respiratory syndrome, MERS for short. Previously MERS had been found in a dozen countries, all in the Middle East and Europe.


Rigo: So first of all, like that time period is interesting, like the 1960s to 2002, then 2002, 2012. Like you alluded to earlier, like there are these 10-year intervals going on. What's going on?


Susan Weiss: During that period, I'm just trying to think, I mean, we continued to work on the mouse hepatitis virus mostly, a little bit on SARS, until we couldn't anymore. And then MERS arose, and everybody else went crazy again. Like, whoa, not as much as the first time, but wow, it happened again. So it was really quite amazing.


But this time was different in a way, because it turns out that MERS had a reservoir in camels, and it's found in a lot of camels, like in Africa and the Middle East. And it continues to infect people, but it doesn't seem quite as, to spread as quickly among people, but it spreads from camels, so I guess camel handlers get it a lot. And there's a lot of mysteries. For example, I mean, someone just told me this recently, that it doesn't seem to spread to humans in Africa, or like, I met someone from Israel, and he said Israeli camels have it, but they don't, people don't get sick, which is really curious, really strange.


Rigo: What were your takeaways from that particular outbreak?


Susan Weiss: Well, that it could happen again. So we should be a little bit more wary or prepared, which we didn't do. I mean, some people in our field did work on vaccines and antivirals, and to their credit, but the big, you know, the pharma didn't, there was no, I mean, they did initially, but then I think things—it became clear that MERS is kind of a chronic, like chronically infecting lower numbers of people.


I think there—I looked it up—I think there were 2,500 people infected with it, something like that, up to today. There are still new infections this year. But we didn't work on it initially, but what happened with me, we got into it. So during this time we worked on MHV a lot, the mouse virus, and we found something really interesting: that the MHV encoded a protein called NS2. This enzyme had the ability to completely shut down an antiviral pathway. So for this, for the mouse virus—if we could mutate this protein, it completely made the virus avirulent, uninfected, unable to cause pathogenesis in a mouse and really unable to replicate very much in cells that had an innate immune response. So this was a really amazing finding because it's one small protein, you make one amino acid change, one mutation, and the virus becomes essentially dead for infecting mice. And we, so we found a collaborator named Bob Silverman, and we started working very closely with him because he worked on that pathway a lot, that RNA cell pathway.


He was like the king of that pathway. And so with him we did a lot of interesting stuff, and somehow we found that some of the other coronaviruses, we found that MERS also in fact encoded the same protein, but in a different part of the genome. It was very interesting that there's similar proteins, but not that similar because when we did homology searches, the way you look for a similar protein, nothing came up.


It was only when my postdoc was clever enough to, he looked for structural homology; there’s a database that has structural protein structures. And this MERS protein came out. And so we started studying this MERS NS4b protein that had some, has a similar function to the MHV protein.


So that's how we got into MERS. And so then from there we started working more generally on MERS pathogenesis. And then I'm so sorry we don't have that animal facility. I've been agitating for it for years. So we did quite a lot on the innate immune response to MERS. And so when the SARS, when this new virus came, we were only one of two labs that had, was approved to work in the BSL-3 facility, in the biocontainment facility. So we were primed to work for this virus. Plus, ours is a similar kind of virus, so we were really, this was, there was no way we weren’t going to work on this virus.


Rigo: So SARS-2 is known as a zoonotic disease, which basically means that it's a disease that spreads between, among animals to humans or from animals to humans.


So SARS-1, it started with a bat, civet, then human. MERS, bat, camel, human. And then SARS-2 is, we don't know what. Why is it so important to understand that intermediary animal?


Susan Weiss: Well, I guess to keep away from it, to prevent it from happening again. That's one reason. And I guess it's just also as just as a virologist, you want to kind of know that. Where did it come from, and is it, and is it hard—is it like camels where there's lots of it, so you know it’s going to happen again?


Or is it really a rare, with the civet. I think we believe, most of us believe it's a pretty rare event. Like it didn't, you know, it didn't, it doesn't hang out in the civet as an endemic infection. I mean, in China, I think after SARS they tried to destroy civets. I don't think they completely did it, but they were outlawed for food and stuff like that.


Rigo: Oh, I see. So is part of it, is part of the intermediary animal’s function, is that where it kind of mutates? I don't know if I'm using the right, even the word “mutate” is like a really weird word to use, but is that where the virus develops so that it can transfer to humans?


Susan Weiss: Yeah, I mean, the word I would use is “adapts,” and it adapts by—so what happens with all these viruses is as they replicate their RNA, they make lots of mistakes, lots of errors, lots of mutations, and they're meaningless usually. But when there's some selective pressure that selects for a mutant, like for example, if you know, say, a whole swarm of viruses, there are lots of—they call them quasi-species. They're going to have lots of different sequences that they go from, say, a bat to a civet. Then the one that replicates the best in the civet will survive. Right? So it selects for new species.


And it turns out the civet virus and the human virus are quite close. And that was true also for the camel and the human virus. Whereas the bat virus is somewhat different because it has to do with what receptors it can use. Like the bat virus may not be able to use a human receptor. So it may have to adapt and then adapt to the human.


So I mean, but then people found there are viruses in bats that can infect human cells. So that's kind of frightening.


Rigo: So where are we in understanding what is the intermediate animal for SARS-2?


Susan Weiss: We don't know. I mean, there's a lot of rumors that—you probably read about the pangolin?


Rigo: Which is the scaly anteater.


Susan Weiss: Yeah, yeah. But I don't think there's any data really supporting that. I mean, the data that are used to support that are that the—there's a virus with a similar spike protein in the pangolin. I think it's like—I forget the numbers—it’s pretty closely related.


And it has a receptor binding domain. That's the part of the spike that recognizes the receptor. So it's really important that that is very similar to the one in SARS-CoV-2. Whereas, but the rest of the protein is kind of different. And then there's also a bat RaTG13, you've probably heard about that one.


That's the one that's a bat virus that's very close to the SARS-CoV-2 spike. But the receptor binding domain has some different amino acids. So neither one of those viruses really looks like an immediate precursor.


It’s really, the whole thing is fascinating, I think, the interspecies transfers.


Rigo: Yeah. So I had no idea that bats have hundreds of coronaviruses in them.


Susan Weiss: Maybe thousands.


Rigo: Thousands! I was reading that most labs at the University of Pennsylvania are not operating, but yours is. What's your lab working on right now?


Susan Weiss: Right now? Well, first of all, we started by getting the virus. I mean, this sounds like—there's a lot of prep stuff, getting the virus, getting the cells, which takes like permissions and things like that. And then, so it all takes time. Then growing up a stock of the virus and titering the virus.


So just getting set up to work with the virus. Then we started helping the clinical people figuring out how to inactivate the virus, how to measure virus in clinical samples, very basic stuff like that. And then more recently, we finally started to do our own research, which is, we have a good cell type now.


So this virus is usually grown in Vero cells, which are monkey cells. And then you don't really want to do experiments in monkey cells. They may be good vessels for growing the virus. The virus grows very well. It's easy to work with, so that's good. And so we're now starting to compare the virus to what we know about MERS and MHV as far as the innate immune response that induces the interferon responses.


So that's where we're starting out, is just to look at virus-host interactions. We're also working with some colleagues at Penn to infect some primary cells. So like one person gave us nasal epithelial cells. Someone's also giving us like cells from the lung, primary cells. So we want to see how the virus interacts with real cells, not just cell lines.


So that's where we are.


Rigo: I see. What is the, I want to talk about briefly the polarization of this virus. I was reading that there was funding that was taken away for someone who is studying bats in China.


Susan Weiss: That just happened. That was terrible in my opinion.


CBS News: The Trump administration has abruptly pulled funding for U.S. research into bats and coronaviruses. The nonprofit EcoHealth Alliance worked in China to trap bats and collect bodily fluid samples. The aim was to try and identify new coronaviruses. Their funding was yanked over the group’s ties to the Wuhan Institute of Virology.


Susan Weiss: I mean, this guy was, he was just, I heard him talking about being cut off like that, and that's so unusual. I've never heard of that happening unless there's scientific misconduct. And there was no evidence or whisper of anything like that. But he was accused of, from what I understood, he was accused of giving money to Dr. Shi’s lab in Wuhan, and he said he hadn't. He hadn’t collaborated with her in the past. And I think that's such a shame because I think his work is really important. He's trying to find viruses in bats that could infect humans. And that's really important. You know, it's part of this, I don't know if it has to do with this conspiracy theory about someone making the virus or it escaping from Dr. Shi’s lab, and it's, I mean, the idea that someone made this virus is ridiculous.


It's just not possible.


Rigo: Right. Can you tell us—I feel ridiculous to even ask you to do this—but can you tell us why it's not possible that it came from a lab?


Susan Weiss: If you look at the genome, like I said, it looks like SARS, but it's different. And it's different all across the genome. It's not like it has a chunk of SARS in it, and so there's, it doesn't resemble any other virus. So it would be inconceivable that somebody would know how to construct a virus de novo without modeling it on another virus.


It's just like, and then on top of that, that it comes out so incredibly virulent. It just, it’s just preposterous. Nobody could, nobody could be smart enough or diabolical enough to figure that out. It just doesn't, it makes absolutely no sense from a scientific or virology perspective. It's totally paranoid—conspiracy theory.


Rigo: What are some things, so you've been at this for like 40 years.


Susan Weiss: I can't believe how old I am. Yeah.


Rigo: When you look back, what are some things that you, that kind of are affirming, and what are some things that we'd, you feel worried about?


Susan Weiss: Well, I think like everybody else, I think the government did a terrible job. We didn't, weren't prepared, we didn't have enough testing. We sort of, and now people are talking about opening up when I think that's crazy. It's certainly around, you're in Philly, right? I think that's crazy. I mean, I go outside every day for a really long walk early in the morning and then I'm sheltered in place.


I just think it's a mistake to go back to open up things. I think we'd get more infections. I don't understand that thought really. I'm kind of worried. I don't know what's going to happen. I've worried about my children and what their life's going to be like and that kind of thing. Yeah.


Rigo: What about you as a researcher? Like what has this pandemic brought you to think about or reframe?


Susan Weiss: Well, for me it's been incredibly crazy. Like all of a sudden I've been giving talks in the National Academy of Science, for a panel for the New York Times. I mean, talking to you, talking to numerous, I talked to a TV station in Portugal today. I mean, I've just, all of a sudden, for me, the knowledge I’ve acquired over all these years has become valuable to someone, which is sort of, it's very gratifying.


And it's also kind of like shocking because, you know, I knew the same thing a year ago, but nobody cared. So from my life it’s been crazy. And of course I was thinking about retiring, like not immediately, but in a couple, say, three years from now when my last student finishes. But now I don't want to retire.


I just feel like there's too much to do. I mean, important and interesting and, you know, I don't want to, this is really, I mean, it's horrible, horrible, horrible what's going on, but it also presents all kinds of interesting, for me, scientific collaborations, people wanting to work with, work together and that kind of thing.


So it's quite invigorating.


Rigo: So for you—just want to clarify—so for you and your lab, the things that you're working on are to, the end goal is to have, is it a vaccine, to help a vaccine, or is it to, for testing, or is it for immunology?


Susan Weiss: Okay. So it's not really either-or. It's kind of like my work is really basic. So we want to understand these basic mechanisms of how the virus interacts with the host. So I guess if anything, you could say actually sort of for both, but it would be more like identifying targets for antivirals. But this is like way down the road, and, you know, my stuff is way-down-the-road kind of stuff.


But when I look back on what I've done over the last few, the last 40 years, stuff is applicable. We did some of the first description of the polyprotein encoded in the replicase gene. And so now we know that these very long proteins that we, that we identified in the early ’80s, you know, we code all these important proteins and antiviral targets.


So it's really early kind of work. And we know that this enzyme that I told you about in the mouse virus, if we could inactivate that enzyme or target that pathway, we know that the virus can't replicate. So just things like that we’re really trying to understand. And we also learned a lot about, in the mouse system, about the importance of the furin site and how that affects tropism and pathogenesis.


So those are the really basic kinds of questions. I do feel kind of in a way bad that I'm not making a vaccine or making an antiviral directly, but those are not the kinds of things that I actually feel really comfortable or really competent doing. I feel like other people can do that better than I can do it, but I can do this really well because that's what I know how to do.


That's what I've done over these years. So I'd like to get into the animal model this time because I do know a lot about animal models, at least in the mouse virus. So I think I could be useful understanding, you know, like how you, how different viral genes affect pathogenesis.


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