TWiV 1293: The enemy of your parasite is your friend

from microbe tv this is twiv this week in virology episode 1293 recorded on january 30th 2026 i'm vincent racaniello and you're listening to the podcast all about viruses Just like that, January is over. Joining me today from Ann Arbor, Michigan, Kathy Spindler. Hi, everybody. Here, it's 16 degrees Fahrenheit, and I don't have a feels-like temperature, and I don't have a Celsius temperature. But, yeah, it's sunny, and it's just amazing to have a nice sunny day. So it seems warm and balmy, even though it's only 16. Here in Chelsea, it's minus 8 Celsius. Feels like minus 13. It is sunny, but it doesn't matter because the angle is too low to do any warming. And it's supposed to go to minus 14 tonight. This is the coldest I have ever experienced here in the Northeast. Also joining us from Austin, Texas, Rich Condit. Hi, everybody. we have 52 degrees Fahrenheit and cloudy that's chilly um we've had several uh days of freezing temperatures at night which means that jack frost has come through and rebooted my garden which is good i'm happy with that um we have two more uh i guess tonight uh yeah tonight and tomorrow night. Two more sub-freezing nights in the long-range forecast, and then I think winter's over. But it has been cold. It's not the coldest I've seen it here, but it's been cold. It is going to be cold forever. It's through a week from today. It's all negative 9, 10, 12, 17 Saturdays. Negative 17 is the low. Oh my gosh. Next Saturday, next Sunday, there's no end in sight. And you know, I'm tired of the cold. It hurts. It's cold here at the incubator. The heat can't keep up with it. You know what they say about the cold and clothing. There's no such thing as bad weather. There's only bad clothing. Well, you know, you have to see, so you need to leave your eyes open. I used that as an excuse to justify living in cold weather for a long time, that I could always put on more clothes, but I can't take off more than a certain amount of clothes in the hot weather. But I'm not sure that really holds water. I mean, I get you, Kathy. I mean, you're right. There's a lot of snow around here. Last weekend we got over a foot. And it's been cold, so nothing has melted. And here in New York, there's no place to put the snow. I'm going to show you a picture of New York in the snow. I'm going to airdrop it to this. What computer am I on? No. Oh, I don't have that. I read something in the paper about in New York them trucking snow to places where they're going to melt it down. Yeah, they do that sometime. They do that sometime. They're doing that now, evidently. Okay, so let me see here. I got this picture. Supposedly, I could share it. So let me see. Share screen. Where is that? There it is right there. Share screen. Here it is. Oh, yeah. Oh, my goodness. That's pretty ugly. It's very ugly, and there's no place to walk. They just shovel little pathways. And then to make it even worse, this sidewalk across from Penn Station, the week before it snowed, they decided to rip up the whole sidewalk and do something. And now they can't. So the sidewalk's closed. You can't cross. You've got to go out of your way. and they can't repair it because you can't do mortar. You can't do cement stuff when it's so cold. Oh, boy. That picture reminds me of when I lived in Buffalo. Niles and I used to walk home from work together, and the snow piles on the side of the road over the season would get huge. And we'd wind up walking home on top of the snow piles so that you're looking down on the tops of the cars going by. Yeah. yep anyway that's the way it is nothing you can do about it right you can't do anything about the weather except complain it's good it's okay yeah mark twain said you know everybody complains about the weather nobody does anything about it personally i'd rather be hot than cold yeah because it's more fun to be hot you could be with nature you could be you know i'd like to be I'd like to be in San Diego or maybe Honolulu. I'm thinking of going to Australia for our winter, but I hear it's like 50 degrees Celsius down there now. Horribly hot. It depends where you go. Australia's big. It's a big place. Well, Melbourne, which is where they're having the Australian Open, it's really hot. Everybody's sweating like crazy. Anyway, a few things to tell you. The Rosenfeld Lab has moved to Philadelphia. They're looking for a tech and a postdoc. They work on enteroviruses, cross-reactive immunity, pathogenesis. They are trying to understand what cross-reactive antibodies mean. They're trying to make animal models for these enteroviruses, and all this will help make the next generation of anti-enterovirus biologics. Although, if you've heard lately, supposedly polio vaccination is now going to be optional. So you can work on anything again, I guess. Anyway, I hope that's not true. But that's what the idiot said. If you want to find out about this job, Rosenfeld, A, at MLHS.org. And a meeting announcement. Peter Soudmont from Berkeley, David Ennard from the University of Arizona, and Lucie Etienne from France are organizing host adaptations to viral infections International Meeting May 10th through 13th, 2026 at the CNRS Station Biologique de Roscoff, Brittany, France. That's all the way in the north, folks. That's usually where the Jacques Monod conferences are. An abstract submission. Well, I'm sorry, everybody. You're screwed for abstracts because that's tomorrow. I only got this this week. Oh, that's right. It's going to be posted. But you can still go to the meeting if you'd like to go to Brittany in May, which would be a little chilly, to be frank, but not bad, end of May. Anyway, we'll put the link to that in the show notes. Kathy, tell us about ASV. Well, as we know, it's going to be in Minneapolis, July 27th to 30th at the University of Minnesota. The abstract deadline is Tuesday, February 2nd. So unless you're listening to this and get right on it, you're pretty much almost guaranteed to miss the abstract deadline. And this one is one that you cannot miss. I was just thinking about a lot of European meetings. Sometimes they have an abstract deadline, and then a week later they say, oh, we're extending it. But that's not the case for ASV. The travel award deadline is a week later, February 9th. And so you have a little more time for that, but presumably you have submitted your abstract because that's what you need to have to get a travel award. And you have to be a current member, and it's easy to join. So act now. And the easiest way to find all of these things, just go to ASV.org, and on that homepage you'll see a thing about the meeting, and click on Learn More, and there you are. So that's ASV. Several people have died recently. one of them is uh bill fogey who was uh one of the people involved with the smallpox eradication you know anything about that rich uh yeah well i know a lot about smallpox but him you know about him um you know i may have actually met him this is a little embarrassing but i I chaired the virology section of the International Congress of Virology. I think that was it some time ago. So I had to arrange speakers. And some of them were smallpox eradication luminaries. And I swear to God, actually it's pronounced Feige, that he was part of that. But I am not sure. six feet seven that's right fagy right you're right you're right six feet seven inches tall and both of these uh obituaries that were posted uh are uh really amazing what an amazing guy i mean yeah he played a central role in the uh smallpox uh eradication campaign starting you know i guess uh according to the obituaries i didn't know any of his stuff it's all in the obituaries but he was essentially a missionary in Africa when the eradication campaign came around and he got interested. I think he already had an MD but he was on a on a mission trip and he got interested and got involved and importantly he was the guy who developed the technique of ring vaccination because there wasn't enough vaccine to go around where he could just mass vaccinate everybody. And so he developed the concept of identifying where there was a local outbreak and you would vaccinate as vaccine supplies allowed. You would vaccinate the direct contacts and then the secondary contacts and then the tertiary contacts in a ring and contain that particular outbreak. that way rather than just trying to sweep through the whole country and vaccinate everybody and it was enormously effective uh and can still be effective uh for other things but you know that's just one of his accomplishments he was uh active in sort of um uh public health measures throughout his career. He was, did he head the CDC for a while? He did. And then he was involved with the Carter Center as the executive director there. And then he got involved with the Gates Foundation. So he really spanned a lot of different places with his infectious disease epidemiology knowledge. The story about the ring vaccination, there were two stories from the obituary that I read. One that just described how he put it together, that it was like from his firefighting experience as a kid. Yes, right. Yeah. And that, you know, you put out the fire, you know, and then you do the surrounding areas and then you do the surrounding areas. And then one time he was somewhere in Africa and they were not making any headway with some politician who wanted to just do a mass vaccination, which was going to waste resources. And some young guy from that country stood up and said, no, it's like when you have a fire burning, you don't put water on all the houses that aren't burning. You put the water on the houses that are. And the politician got it, and it saved the day, basically. Yeah, great. Cool. So good on you, Bill Fogey. Thank you very much for everything you did. And I just have so much respect and admiration for people with this kind of dedication. I don't know where it comes from. They just can't not do stuff. It's amazing. This is the kind of public health person. person we used to have here in the u.s and which we don't have anymore we have people who are not qualified yeah that's gonna go away i love this picture i have an obituary from university of uh wisconsin and there's a picture of obama putting the the presidential measure presidential measure medal of freedom around his neck and it's just so cool he's i mean this The president has just got his arms around him. I love it. He's got a nice smile on his face in that picture, too. I'm sure. It's amazing to have the president. Obama's not a short guy. No. No, it's true. It's true. And Feige's a half head taller than him. Six, seven, man. That's really huge. Okay. Somebody visited the incubator. who corresponded with me, I don't remember which, who grew up in Hawaii and went to high school with Obama. And I said, do you remember anything? And he said, only he was really tall. Yeah. I didn't realize that. Also, another death, Peter Duisburg. Peter Duisburg. I have two links. I have Kathy's New York Times link, which I can see. Someone else did that, not me. That was me. I'm sorry. That's Rich. You had that. Yeah. When I share. How do you say fogey again? What's it? Fagey. Fagey. Fagey. And I don't know. Anyway. Yeah. When I share New York Times links now, I'm a subscriber. So I don't know if that makes a difference, but I can click on this link, share full article. Right. And, you know, put it in as a gift link. So I think everybody ought to be able to see that. Yep. Anyway, he was a professor at University of California, Berkeley. He was well-known because in the early 60s or 60s, 70s, he discovered the SARC gene in Rouse's sarcoma virus that was the first oncogene. And, you know, he was a well-known viral oncologist. But then with the onset of AIDS, he said HIV doesn't cause AIDS. And that's what he said the rest of his life. And so for me, it just taints his whole career to be so wacky because he's wrong. And the last line of this article, I love it. It says, some editorial, the editorial described him as a leading scientific torchbearer for the so-called AIDS dissidents, but noted, as wrong as Duisberg surely is about HIV, there's at least a chance that he is right about cancer. So he actually said, he discovered this Sark oncogene, and then he decided that oncogenes don't cause cancer. And actually, nowadays, there is some truth in that. It's not the only thing, right? Because, well, I can't go into it now. Cancer is a metabolic disease. It's got genetic components, but there are so many arguments why it's not just about the oncogene. It's really interesting. So he was partially right. So it's good to have contrarians, but you have to be contrary when it makes sense. And HIV clearly causes AIDS. I mean, he said it was lifestyle and all this other garbage that people still say to this day. Yeah, he said it was AZT even. Even AZT. Oh, my gosh. I mean, AZT did cure some people. It was very toxic. So very sad, you know, that you have to do this. I just don't get it. He's clearly wrong. Anyway, he has passed away at the age of 89. Okay, one more thing I wanted to point out. This is an article in Science. The U.S. government by Monica Hersher and Jeffrey Mervis. The U.S. government has lost more than 10,000 STEM PhDs since Trump took office. Science did an analysis and looked at how many were fired, retired, or quit across 14 agencies. And, you know, this is—it's 14 percent of the total number. of PhDs in STEM, who were employed at the end of 2024 when Biden was at the end of his presidency. And they have nice graphs here that express this. But of course, the problem is that these are well-trained people and the core of science is you don't want to lose it because it takes a long time to restore it. Yeah, you don't lose just the people. You lose all the expertise that's associated with them. I mean, people say, oh, this will be over. We'll get CDC back. You can't turn on the light switch and get CDC back. It doesn't happen overnight. Well, this expertise takes years to build up. These are people who quit, retired, or terminated because of reduction in force, fired, transferred out of an agency, or left for other reasons. So, very bad. Really bad. I hate to see it. what's happening to science with everything else in the U.S. I hate to see all of it, but science is our thing, and we really hate to see that because science makes your life better, whether you believe it or not. You'll see. Whether you want it or not, just have a look at your iPhone, okay? Yeah. Technology, science and technology, that's right. Okay, we have science for you today. As we do every week, we tell you what's going on, and as usual, two cool papers. One of them is in Lancet. Is it Lancet Infectious Diseases? Lancet Public Health. You know, when I was young, there was just one name for journals. I can't remember them anymore. I saw a new one the other day I never even saw before. It's like a cell journal. It reminds me of going to the grocery store, you know, and uh it's you know i actually saw an analysis at one point that said that the uh talked about there being an epidemic of depression in the u.s and um uh blaming it on the fact that there were too many choices and i think about that when i go to the grocery store and you know you want like a tube of toothpaste, right? And there's 80 choices. And each brand has a dozen, right? And it's just because it's, you know, it's salesman, it's marketing, okay? And even you go to Amazon, you want something, and there are too many different versions. At least stores have a little less inventory, you know? Well, you know, this is a good reason to go to Trader Joe's. They make the decisions for you. Yeah, that's true. Like the other day, I was trying to buy some clear medical tape. There were like 15 different ones. What the heck? And so I just picked one. I ran them, and it sucked. I threw it out. Didn't stick. It was no adhesive at all. That's good. Anyway, this is Lancet Public Health, And the title is Herd Effect of Human Papillomavirus Vaccination on Incidents of High-Grade Cervical Lesions, a Population-Based Cohort Study in Sweden by Ava Meglik, Alexander Ploner, Mark Clements. Isn't that Mark Twain, Mark Clements? Samuel Clements. Samuel Clements. Close enough. Miriam Efstrom and Jayao Le. You know, we're doing a bunch of HPV in the last year. And one of them was this meta-analysis we did, which showed that it's actually beneficial to get HPV vaccine when you are older, even after you're infected, before you have surgery. Now, this one is very interesting. So the question is, you know, we know that HPV, human papillomavirus, certain genotypes cause cervical cancers and oral cancers and anogenital cancers. we know that vaccination is very effective at reducing these cancers. But what we don't know is if it helps people who are not vaccinated, right? There is some evidence that it might, but there's less evidence on a population basis. And that's what they're doing with this study in Sweden, where they have... Sorry, go ahead. No, I was just going to say, so to give you the summary, they could change the title to say something like, there is a positive herd effect of human hapillomavirus vaccination on incidence of high-grade cervical lesions. That's the bottom line. They find an effect through this analysis. In Sweden, they have had good HPV vaccination programs. They have had school-based initiatives. targeting young adolescents. That really works well. They've had catch-up and subsidized programs for older individuals, and they say the effects of those are variable. But what they did in this study is to ask whether there is protection of people who have not been vaccinated. So they evaluated the incidence of HSIL positive in unvaccinated women born from 1985 to 2000 in Sweden. Rich, you want to explain what an HSIL is? Sure. We did this a couple of episodes ago. There are actually two sort of measures of dysplasia of the cervical epithelium associated with the pathology. One is called cervical intraepithelial neoplasia, and the other is called squamous intraepithelial lesion. But they're both basically the same thing, slightly different grades. So this involves the epidermis, that is the skin layer, the exterior layer on the cervix, which in normal circumstances at the bottom has a bunch of basal cells which proliferate and give rise to cells above that that migrate up to ultimately to keratinocytes, which are basically dead cells that provide an actual physical barrier at the apex of the epithelium. And there's a whole differentiation routine that goes through that. And when you have a cervical dysplasia, that is when the cervical epithelium is not looking right, which is nine times out of 10 or more because of a papillomavirus infection, then you can see cells that look abnormal. These always originate at the basal level at the bottom, which is where the virus initially infects. And then depending on how serious or the seriousness of the pathology is judged based on how much of the epithelium is involved. So in a low-grade squamous intraepithelial lesion, you'll just see a few abnormal cells around the basal layer. and a high-grade cervical inter-epithelial lesion, you may see almost the entire, certainly more than 50% of the epithelium, starting at the bottom and going towards the top, is abnormal. And that's significant because if you have more than 50% involvement, that's you know, essentially a significant precancerous lesion. Now, it depends on what virus is causing it, what strain of HPV is causing it, what the risk is of progressing from there to a cervical cancer. But if you've got an HSIL, it gets your attention because you know there's something potentially not good going on. And it's an easy pathological way to look at the condition of the cervix. But you can also take the same samples and do PCR and look for the genome of the virus and you can even type it and determine whether or not it a high risk virus or not At any rate that what they looking at here is those high squamous intraepithelial lesions Sorry that a little long but I hope we get the idea It's good. You can never repeat things too many times. All right, so let me tell you a little bit about the methods. It's based on the Swedish total population register, the TPR, which they can do in Sweden because they're all in the register. They all have health care. It looked at people from January 1st, 2006 to December 21st, 2022. And it included a population of girls and women born between 1985 and 2000 who were living in Sweden at the time of the study. In May 2007, Sweden started a subsidized HPV vaccination program for girls 13 to 17 years of age, which was then followed by a free catch-up program in 2012 for women 13 to 18 years of age. And then at the same time, in 2012, a school-based vaccination program was introduced for girls 10 to 12 years of age. Women who were 23 to 64, interesting, 64, were also invited to participate in the screening program from 2015 onwards with screening scheduled every three to five years, depending on age. And from 2022 onwards, the guidelines extended screening to women aged 23 to 70 years, every five to seven years. A really good, really good program. I really appreciate that. So what was the oldest date, the first date? In the studies, 2006? 2006. Because I'm just looking up here. The FDA, of course that's in the U.S., but I imagine it's similar in Sweden, approval of the first vaccine, Gardasil, was in 2006. So they've been doing this since the, or they're looking at people from the very earliest dates of vaccination. And of course, one of the reasons they have these different groups is that the availability or methods for distributing the vaccine have evolved over time. culminating in this study, at least, in this vaccination of school-age children, which, you know, can pick up a lot of people at the right age. So the eligible people, the girls and women were followed up from their 10th birthday, were until January 1st, 2006, from that, sorry, until December 31st, 2022, to or when they got a vaccine or if they were diagnosed with HSIL+, when they left the registry, died, emigrated from Sweden, or had their 35th birthday, whatever came first. Right. And those groups then were defined by birth year of the individuals. And so the opportunistic vaccination group, in other words, were the ones who could get it. They just could at the very beginning. Those are the ones born 1985 to 1988, and that was their reference group. And then it progressed to those with subsidized vaccination, 89 to 92, and then catch-up vaccination, and then a school-based vaccination, which was from 1999 to 2000 in this set of cohorts. And that last one, the school-based one, turns out to be pretty interesting and important. And maybe you said this, but it's close to a million people. Right? Almost 900,000. Right. So they want to know who's vaccinated or not, right? Because they want to see if unvaccinated people were protected from HSIL lesions. So they got vaccine information on these people from a couple of different sources. They have a vaccination registry, which documents all the HPV vaccines and a few others as well. and then the occurrence and diagnosis of HSIL plus could be identified in the Swedish National Cervical Screening Registry. So this country has its act together. They really do. I don't understand what's the problem with the U.S. Oh, wait a minute. You can't tell me what to do. You can't take all that information from me. Okay? It might save you and your countryman's lives. Oh, I don't care about anybody else. I only care about me. Okay? You can't have my information. No. Okay. Can I ask you a question? Sure. Do you think people who want a choice in vaccination, do you think they stop at red lights? Oh, yeah, probably, because it's pretty obvious that if you don't do that, you might get T-boned. It's less obvious that if you don't get vaccinated, you might get T-boned. And also, they probably wear seatbelts, too, right? Yeah, probably. Some of them begrudgingly, you know. So Kathy already told you the birth cohorts. These are the different groups, the 85 to 88, 89 to 92, 93 to 98, and 99 to 2000. That's the key to this study. They're looking at these different groups. And they have a lot of demographic information, especially who was vaccinated and who got diagnosed with HSIL and so forth. And so let's see. The results are really short. It's like one, two, three paragraphs, mostly numbers. So during the study period, right, 9 million. Oh, gosh. All these people in this study, 857,000, contributed 9,476,610 person years of at-risk time. 42,274 cases of HSIL plus were identified, which is an incidence of 4.46 cases per thousand person years. And they have a figure that shows the cumulative incidence of HSIL plus across these birth cohorts, the 85, 88, 89, 92, 93, 98 cohorts had similar patterns of steadily increasing incidence with age. Incidence was highest in the subsidized vaccination cohort 89 to 92, followed by 85, 88, and 93, 98. Remember, the subsidized is not great. It doesn't cover everyone. The percentage of people covered is pretty low. I think that we're going to hear about that in a moment. The 99-2000 cohort had a lower incidence before the age of 23 than the other cohorts. So that's a good one. Now, the infection risk ratio, or is it incidence rate ratio? Yeah, incidence rate ratio is calculated for these. Anyone want to explain what incidence rate ratio is? Yeah, I stuck this thing in here. She stuck it in. Yeah, I stuck it in because I didn't know. That was the one, you know, abbreviation that they assumed everybody knew. Yeah, they didn't define it. Yeah, so I had to look it up. It compares how quickly a disease or event occurs in two different groups, for example, exposed and unexposed, calculated by dividing the incidence rate in the exposed group and the incidence rate in the unexposed group. So basically, it's just the degree of protection relative to a control group. So the IRR has varied across the cohort. So in the 89 to 92, the age adjusted was 1.18, which is a higher incidence rate in this than the reference group. The 93 to 98 was 1.03. And the risk for 99-2000 was 0.53. It's much lower than the other groups. And that was that school-based vaccination cohort. Yeah. I don't know. I think everybody should get vaccinations in schools. Right. So many programs. The point is that as time went on, they moved the vaccination to just random, you know, what was their word for it? Opportunistic. And then subsidized. And then they got to everybody school-aged getting it. So interestingly, that actually makes the point for mandated vaccinations, right? Because that, in terms of getting a herd effect, that worked the best. You know, I don't know that it was mandated. It was just available at school. I don't know the details. I'm not sure of the details. Good point. Good point. But it was certainly at least available. But it gets around parents. I don't have time to take my kids to the doctor. Right. And you do it at school. And you probably get parental permission. I remember getting Sabin oral polio vaccine in school. Absolutely. Right? In the gym, they had these big tables covered with little white cups. And they gave you one and you ate the sugar cube. Yeah. Sugar cube with a little pink stuff on it. We did it in a school, but we did it on Sundays. It was Sabin oral Sundays. That's how I've always been able to remember that the Sabin vaccine is the oral one, because it was Sabin oral sundaes. Wow. Gosh, I remember that paper cup with the little folds in the side. And I look in, and there's this pink, was it one sugar cube? I think it was just one. Yeah. And you got to eat a little cube of sugar. They actually wanted you to eat it. And the pink stuff, of course, was phenol red, the color indicator used, the pH indicator used in the cell culture medium. Vincent, that was your future looking at you in the face when you were a kid there. That's right. How did I know that, right? Back on this, whether it was mandated or just available in the schools, since they found individuals who were not vaccinated, I suspect that it was not mandated. Right. Good point. Yeah. I think that's okay. But I think it still is better than opportunistic because it's in school and many people are just going to do it. I think it would be a nice way to do it in the U.S. for all these vaccines. But anyway, so then they do fully adjusted, age-varying IRR. They get similar numbers, basically, to the ones I've just told you. the 1999-2000 is 0.53. So in other words, this is good evidence that at least in 1999-2000, that the vaccination program helped people who weren't vaccinated, reduced the incidence of lesions in people who did not get vaccine. And it was not evident in the other cohorts at all. So there's more evidence that you should use this vaccine, which doesn't have any problems, no severe side effects. Yet it helps people who are not vaccinated, and it helps you if you're already infected, and it helps you if you're going to have a lesion removed as well, as we saw before. One of the safest vaccines around. I'll bet you that, you know, it's just a protein. There's, you know, it's no big deal. Anticapsids, yeah, with just one protein. There was some... So they say this provides real-world evidence of a reduction of HSIL among unvaccinated individuals in this cohort. And they say it aligns with evidence from a recent Swedish study that used population-based virus screening data, HPV screening data. Remember, this study, they used lesions. They reported that in 2023, HPV 16 prevalence went from 2.6% in the 1984 birth cohort to 0.54% in the 2000 birth cohort. That's for 16. 18 went from 0.84% to 0.09%. These are the high-risk HPVs that cause cervical carcinoma, the two main ones. So basically by vaccinating people, you are reducing, maybe eliminating the load of virus and therefore it's not likely to spread because that's how this virus is spread from person to person, right? Sexual activity. And so if you're vaccinated, people claim that this is a sterilizing vaccine and that there's data. I have to look for that data one day and we should talk about it because I would like to see how they decided that. But at worst, it just reduces the amount of shedding. It's probably enough to reduce the transmission to other people. And actually, they talk about transmission. They say our study evaluated lesion-based measures, but herd effects are commonly assessed using transmission models, right? Herd immunity, reducing transmission. And so they say here, a pooled analysis of 16 transmission models projected herd effects at coverage as low as 20%. Yeah, that blew my mind. With reductions in HPV-16 prevalence of 53% at 40% coverage and 93% at 80% coverage and even greater reductions for 18, 6, and 11. So they saw a herd effect here, of course, but they say it was lower than what was seen in these modeling studies. And they say that the modeling studies go out for 70 years to make their predictions, right? And we only look for a couple of years, so we can't probably get the full effect. But they did find it. So I think that's really good. They say this data source allows for reliable. So they said we had a lot of data here. We had a lot of people. And that allows for reliable generalizations of these findings to other countries with similar HPV vaccination and screening programs. It would be interesting. I mean, you can't do this in the U.S. because we don't have these registers. But it would be interesting to know in other countries what's happening. uh uh it probably worth mentioning that the population of sweden is less than the population of new york city uh sweden is that right 10.6 million people oh my it's small yeah so that makes it a little easier to keep track of people probably and they aren't all necessarily crazy either so is the bottom line that all countries should be small uh good luck with that So the U.S. could be 50 different countries, basically. Sometimes it seems like it is. Anyway, they say, given the effects of this school-based cohort, policymakers should have prioritized maintaining high vaccination coverage, particularly among younger populations. Makes sense, right? Those are the ones who are going to spread virus to others. But they say, and this is really important, caution is needed when applying the findings to settings that have differing vaccination policies or health care access. I mean, they have really good health care access in Sweden, right? Anyway, I like this because we have a little HPV arc going in the past year. Yeah, it's good. It's good. I originally had this as our paper, and I just realized it's a snippet. Yeah, in particular and compared to the other one. I got halfway through the other one and I thought, whoa, this is a snippet. In the other one, they've done everything. Oh, my gosh. That's amazing. I mean, from lab to the field, as you will see. This is a Science Advances article. Arboviruses manipulate rice's volatile emissions, protecting insect vectors from natural enemies in the field. First two authors are Xing Liu and Shan Wang. And then the last two are Ian Baldwin and Xiaoming Zhang. They're from the Chinese Academy of Sciences, Peking University, Shanghai Institute of Plant Physiology and Ecology, the Max Planck Institute for Chemical Ecology. Can I ask, why is it that it's Peking University, but it's Beijing is the city? Why is that? Do you know? It's historical because until they switched to calling things like Beijing, they called it Peking. And so they haven't changed that. So the university decided to keep it Peking, which was, okay. Always surprising. I like Beijing. It's cool. All right. So this is about plant viruses, which we don't talk about a lot. But I thought this is very cool, as you will see. Yeah. So let me do a very brief summary. This is an open access paper. When I first started reading the abstract, I started drawing a diagram. And then I thought, they must have a diagram. And certainly they do. It's figure six. And I recommend that you take a look at figure six. On the left side is the healthy situation. The right side is the virus infected situation. They have three different arcs starting at the ground level and then an upper arc that's white and then a higher arc that's a different color green. And they explain it all in the figure legend, but it's really a nice framework. And my brief summary is that this is a complicated situation because they are revealing the complex interrelationships among pathogens, in this case viruses, host plants, in this case rice, vector insects. insects, and those vector insects are these plant hoppers and a couple other kinds, and then natural enemies, and those are enemies of the vector insects, and those are the parasitoid wasps. So we're going to try and bring you through this and see why it's so exciting and so interesting without getting confused. Someone said to me, they really like how we are simplifying the papers on TWIV lately. In the beginning, we used to go a lot deeper into the experiments and data. We simplified them. And I think it's good. I think it makes it more accessible to people. I'd like to try and can I, would you mind if I tried a little more detail in the summary here? And just keep building it. And I'm looking at figure six here, which I didn't see until the very end. Oh. Because this has got so many components that are interacting that it is confusing. So, plant hoppers basically feed on plants, and the plants don't like that. It hurts them. Okay. And we're talking about rice here, which is a big deal in China. So, the plants have evolved away indirectly to get rid of the plant hoppers, which is that when the plant hopper attacks the plants, the plants respond by making a volatile compound called methyl salicylate. Okay? and that basically is to some critters out there smells good and that includes a parasitoid wasp that then comes and lays its eggs in the eggs of the plant hopper and therefore gets rid of the plant hopper so to reiterate the plant hopper insults the plant the plant sends off a chemical signal, the signal attracts another insect that then wipes out the plant hopper. Okay? All good. Now, the plant hopper is also a vector for a virus that can also hurt the plant. And it's a necessary vector. So the virus resides in the plant. I don't know if this is, I don't know if it replicates in the plant hopper. I don't think so. I think it's just a mechanical vector, but I could be wrong about that. At any rate, the virus is in the plant hopper. So the plant hopper lands on the plant and introduces the virus, right? Now the plant would ordinarily respond by sending off this signal and attracting parasitoid wasps to kill off the plant hopper. But the virus doesn't want that, right? The virus wants the plant hopper to succeed. So the virus makes a protein that suppresses the synthesis of the volatile compound and then makes it so that the parasitoid wasp doesn't show up and the plant hopper is successful and the virus is more successful. And this, so this has implications down the road for knowing this, how can we use all this information to protect our crops against both the plant hopper and the virus. Right. Unbelievable. So what do we got here? We got plants, plant hoppers, parasitoid wasps, and viruses in this complex interaction. And compound related to aspirin, basically. Yeah. Methylsalicylic acid. So a lot of these plant viruses that really damage crops, right? So this is a big problem. Yeah, it's a big deal. Over 75% of plant viruses rely on these insect vectors. Rich told you about plant hoppers, but they're also white flies and aphids. And so that's hard to control them. And by the way, we have talked about parasitoid wasps in the past. What is that? The guy from Georgia. What's his name? Yeah, Strand. Mike Strand. Mike Strand. He was on, I think. Yeah, we had him on TWIV. What was that virus called? Oh, it's a polydinovirus. Polydinovirus, yes. And I forget exactly what it is. It introduces even another complication that we won't go into now. Well, I mean, when Rich said the wasp, the parasitoids, lay eggs in the eggs of the plant hopper, it also introduces this polydinovirus to immunosuppress the immune response in the eggs, so it allows the wasp to develop. Which is only a sort of a virus. Yeah, that's right. It's encoded in the wasp genome, too. That's an amazing thing. Right. And in packages, immunosuppressive genes, blah, blah, blah. Kathy, you were going to say something. Only that there's multiple cases where these things come into play. So there's multiple viruses of rice. Primarily, they're looking at rice-dripe virus here, but they also do comparisons with a couple of other viruses. And then, as Vincent said, not only is it the leafhoppers, but the aphids and some other things that come into play there. As Rich said, these vectors damage the plant, but the viruses on top are introduced, and that causes even more damage. So what do you do? So you can use chemical insecticides, but obviously that's not great because it has off-target effects. And so paper like this tries to figure out what else do we have. And so methyl salicylic acid is a big part of this. It restricts, actually salicylic acid, which is part of the plant defense, restricts viral replication. It actually does so by inducing RNA silencing pathways. And methyl salicylic acid is volatile and attracts these parasitoid wasps to the plants to get rid of the leafhoppers, etc. The wasps have receptors for methyl salicylic acid so they can respond. They say, hmm, something smells good, and they fly over to it. And in fact, people have used applications of methyl salicylic acid for biological control in various crops. They say vineyards, hop yards, red maple plantations, strawberry, soybean, and wheat fields. I thought the strawberries I had today tasted weird. I'm just kidding. I'm just kidding. So it's one compound. It was methyl salicylic acid. So it has a nice simplistic approach, right? Okay so that what we going to look at here What is methyl salicylic acid doing And it an incredibly complex thing And you have to keep it straight in your head because you know a positive here and a negative there you just got to figure out the outcome And I have to sit and stop reading and try and run it through my head several times. Okay, so first question is, does methyl, let's call it MISA, okay? MISA supplementation suppress vector populations and reduce virus transmission. They actually have an eight-acre rice field where they're going to do this experiment. Oh, that would scare me to death to have an eight-acre rice sphere. They put these spheres that release Misa at a certain rate per day across this eight-acre rice farm. This is in the Jiangsu province during the 10-week growing season. and they made blocks where they had their experimental and control designs. You can see there's a diagram of it there. But no differences were observed in the proportion or the numbers of natural enemy and herbivorous insects between the two fields before the Misa release. So they were attracting these leafhoppers, plant hoppers, et cetera. But over 10 weeks of release of the MISA, they saw differences with both the percentage and the number of insects varying between the MISA-treated and control fields. The natural enemies, like parasitic wasps, increased, and herbivorous insects, like plant hoppers, went down. It's very clear from the graphs there. You can see that happening. So virus vectoring plant hoppers and leaf hoppers in particular had substantial reductions. And then this is correlating with the release of Misa, right? So this is reducing their population. So those are the bad guys, right? Those are the ones that damage the plant and carry the virus. Now, the parasitoid wasp, it's Anagros niliparvatae, okay, is a natural enemy of plant hoppers. As we told you, it parasitizes their eggs. And so they did an experiment to see how they respond to Misa, these wasps. They have a Y tube, okay? It's interesting. It's a Y tube, and in the two heads of the Y, they put either Misa or a control, which is hexane. And then they introduce the wasp, and they see where it goes. They just watch and see where it goes. And they can see that the wasps prefer Misa over the hexane. I don't know what Misa smells like, but I don't like hexane either, and I wouldn't prefer that. And then they have an H-tube assay, which they can—it's a similar thing, but it's set up as an H. They can put the two different compounds in. And they show that Misa repels one of the plant hoppers. It's called SBPH. So this abbreviation is going to come by later. It stands for small BPH. I don't know what BPH stands for. Brown, I think. Brown plant hopper? I found it somewhere, yeah. Yeah, I did also. I forgot where it is. I think it had brown plant hopper, yeah. So anyway, the MISA repels them. And this plant hopper transmits multiple viruses, multiple arboviruses. So basically, this suggests that MISA could enhance natural enemies and get rid of insect vectors, right? So maybe it'd be good for the crop. So they go back in the lab and do some more experiments. So they're going to start with rice stripe virus, which is transmitted by SBPH. Very destructive. Small brown. Plant hopper. Plant hopper. Just call them the hoppers. It's one of the most destructive rice pathogens in East Asia. Huge losses. And this virus is presumed to suppress defenses of the host. So they decided to look at Misa. So they have rice plants that are mock inoculated or RSV infected. Okay. Then we have a word, which we did have before, but this is viruliferous. Right. It means carrying virus, right? Yeah, it's a perfectly cromulent word when you know it. Cromulent. We did not use it. Containing or carrying viruses. Non-viruliferous and viruliferous plant hoppers. And then they put those on the plants. So the SBPH infested rice plants, and then they have virus plus SBH treated rice plants, which they get. And then they measure volatile compounds. That's tricky. And throughout this paper, because it's open access, I have to tell you that if you look at it, they have diagrams. They have like so you see the rice plants infected, uninfected, and the infected ones are like a yellowish green. I mean, it's all very visual as well as words. Nice pictures of these insects, too. So they measure the volatiles with very fancy chemical techniques, and they find three that were emitted in higher amounts from the SPBH-infested plants compared to mock-inoculated plants. Okay. So the SPBHs can induce volatile compounds. Okay. when they looked at these profiles, they found that lower MISA emissions were found when the virus infected the plant. Okay. With the virus, lower MISA than without virus. And the other two volatiles didn't change. So this, they focused on MISA from now on. And they say, it suggests that the virus is suppressing MISA. This is the focus for the rest of the paper. Now we're going to find out exactly how it suppresses Misa, which is amazing. They just kept going and going and going, you know? I mean, more and more granular. It's amazing. Yes, absolutely. So they ask, do other plant viruses do this? So they have Southern Rice Black Streaked Dwarf Virus. Oh my gosh. SRBSDV. Wow, what a name, but I like it. Southern Rice. And Rice Ragged stunt virus transmitted by a white-backed plant hopper, which is WBPH, and also another plant hopper, BPH. And these are bad viruses also, cause a lot of loss. And these also attenuate M. MISA production by the same assay, which is good, which means you could use MISA to hit more than one virus, right? Okay. I don't think we described, this is a little peripheral, but I don't think we described rice-stripe virus, right? No. Because it's interesting in itself and takes me back to that, what was it, European Congress of Virology. And we interviewed the guy, a plant virus guy. I forget his name, unfortunately. Stephan something. Blanc? Stephan Blanc? Yeah, Stephan Blanc. Who worked on this problem. So this virus consists of four or five single-stranded RNA segments, mostly negative scents but some ambi-sents, that are each encased in a nucleocapsid. But they are not collectively encased in some capsid beyond that. You have four separate, essentially four separate particles. uh and so the question becomes and this is what stefan blanc dealt with and i can't reproduce it uh how do you get a productive infection if you need all four of these in one cell but they aren't all packaged in the same particle does it require a really high multiplicity infection is there something else going on he had a great way of explaining it and he resolved the whole thing. You'd have to look back at that episode. It was really good. But it's a very, very interesting virus. And it's only one of several that are like that in plants. Okay, so next, we know that in their field experiment, virus infection knocks down MISA emission. And if you add Mesa to the fields, it brings in the parasitoids. So they want to see what's the impact of viruses on parasitoid recruitment. So now they have a glass house, and they have a diagram of a little glass house with plants in them. And the reason is that that the parasitoids don't want them to go from experimental condition to experimental condition. So they have 15 virus-infected and 15 mock-inoculated rice plants in separate clear glass houses, so they have a barrier between them. And then they have 45 female leafhoppers, which can't cross the barrier. They're allowed to lay eggs for three days on these plants. And then after that, 75 female parasitoid wasps, which could cross the barrier, were introduced to assess parasitism. And so parasitism is lower on virus-infected plants compared to mock-infected plants. So 38% versus 67%. So the virus is reducing the parasitism, right, which is beneficial for the plant, but the virus doesn't want that to happen. Well, viruses don't want anything, but you know what I mean. And if you think back to Rich's summary, the parasitoid wasps are attracted to the plants because of that odor. Right. And so now we know that for some reason, these wasps are not attracted to the infected plants. So is the virus doing something to the odor? That's right. And also the parasitism rates, in other words, the laying of parasitoid eggs in the BPH, in the leafhopper eggs, is suppressed on virus-infected plants. They also look at these other two viruses that I mentioned before with the long names, works on them too. Okay. So in other words, these arboviruses suppress the plant defenses in the form of MISA, I suppose. They also did some behavioral choice assays using volatiles from insect-infested and virus-infected rice plants. So it's a nice two different words. So when you add insects to plants, you infest them. And when you add viruses, you infect them. And so they find, so they're basically asking, what do you have a preference for? So the leafhopper has a preference for, sorry, A. niliparvitae. Is that the, that's the wasp. That's the wasp. The parasitoid wasp has a preference for leafhopper infested plants. But when given a choice between the volatiles from leafhopper-infested rice plants and virus-treated rice plants, why do you think the parasitoid prefers the leafhopper infected? Because the virus must be suppressing the volatiles, right? So RSV is somehow, the virus is somehow attenuating defenses of the plant by modulating these organic compounds. And if they spray Misa on the control and the leaf hopper infested plants, the parasitoids don't have any more preference. They like them both because Misa is attracting them. So the Misa application restored parasitoid preference. So they conclude from all this that Misa is the crucial volatile that attracts the parasitoids to the plant. and which the virus is reducing, these volatiles. Let's see. Other behavioral assays show that non-viruliferous leafhoppers prefer RSV-infected plants over mock inoculated plants. Okay, that's very interesting, which they say means that the plants somehow attract SPPH, and it's consistent with the finding that the arbovirus has suppressed MISA. So something else is going on there, right, to attract the virus-infected leafhoppers. We're not going to get into that, but that's a really interesting other finding. So how does this suppression work, right? The virus is suppressing this volatile MISA. So this is a perfect use of RNA transcriptomics, in my view, right? And in fact, you're going to see, they're going to figure something out using just transcriptomics. So they look at the transcriptional responses to try and figure out what's happening with MISA. And it turns out that there's one gene called Sabbath 3, which I like, but they call it OSBMS, BSMT1. I kind of like Sabbath, Black Sabbath. But it has the pattern of increased transcript accumulation on leaf hopper infestation and decreased transcript on virus infection. So this is a gene that, well, anyway, they see this gene that goes up and down under the right situations. Turns out that encodes an enzyme that methylates salicylic acid that makes Mesa. And it also does it in other Arabidopsis and E. coli. So that's how they say, oh, this must be the thing here. And in fact, they can now monitor OSB-SMT1 RNA, and they can see it goes up with leafhopper infestation. It goes down with virus infection. So very cool. So now we have one candidate gene that is methylating salicylic acid. So they make transgenic plants with this gene, and they put a little reporter on the protein so they could see it and they could track it without having to do mass spec and all that stuff. So this is an overexpression experiment. They're overexpressing this enzyme now that methylate salicylic acid. And when you do that, you get more MISA emission, and you're more attractive to leafhoppers in these choice assays that they do. So this tells you that this enzyme, OSB-SMT1, is the key enzyme catalyzing MISA biosynthesis. So just think of this. They have figured out one enzyme that does this. and in years before before nucleic acids could be manipulated you'd have to do this with biochemistry it would take you 20 years probably right now you do transcriptomics you get a candidate you test it with an over oh my gosh this is amazing right there's only one two three four five six seven eight nine ten authors on this paper it's pretty good we aren't we aren't We're done yet. We aren't done yet. So then what do they do next? They knock out this gene, this methylation encoding gene. So now you're not going to get any MISA emission, right, in the plant. And, well, of course, the results are exactly as you would expect. The leafhoppers are not attracted to it anymore, and neither are the parasitoids. They're not attracted to it because there isn't any MISA. So that shows you that this gene is the whole thing that controls MISA levels. And it goes up and down depending on whether there's a leaf hopper biting the plant or a virus infecting it. And they look at other plant hoppers and their viruses, and they show that this works for all of them. This one gene and this one compound, MISA, is key. Really cool. But they do find some differences with other viruses. So not all rice viruses are going to be susceptible to this compound, but many of them are. Okay, so this is the gene that methylate salicylic acid, right? And it goes up or down. Why does it go up or down? That's the next question. Well, both Kathy and Rich would probably say it must be a transcription factor. And yeah, that's what it turns out to be. They have these reporter lines that make the, they have the gene in it with a reporter that they can measure. and it's got the promoter, and they find that the virus negatively regulates transcription. You have reduced polymerase occupancy at the promoter in virus-infected plants. And they end up sequencing this, and they find MYC-like promoters, and they find a protein, which they call OSMIC2, that binds to the promoter. Again, of this gene that methylates, whose gene product methylates salicylic acid, and this is controlling the levels of the transcript. All right, so then you get more granular. How is the control affected? Okay, what's happening? We know it's this transcription factor, but what's happening to it? Well, to make a long story short, it turns out that one viral protein retains this transcription factor in the cytoplasm where it can't function to turn on the promoter of this gene. There's like a half a page describing these experiments, but I don't have to tell you because that is what's happening. The transcription factor is relocalized from the nucleus where it needs to be to work to the cytoplasm by this viral protein. The viral protein binds to it. They show that it binds directly. And that's amazing. That in itself would be a paper. Yeah. They show this binding by yeast-2 hybrid assay. Yeah. I haven't seen that in years. Years. Yeah. So, you know, to me, it's like, okay, give them one author to do the yeast-2 hybrid screen. Exactly. You know? Oy, yi, yi. But then they do a field experiment now. That's a couple more authors. Now that they have all this information, they want to know how can they use MISA in the field. So they have, again, rice plants in the field. they infest them with virus-infected or mock-inoculated leafhopper for three days to allow eggs to be laid. And then they transplant them into two rice fields. And then four days later, they collect the plants, they count the eggs, and they assess parasitism. So the parasitism rate for the leafhopper eggs on mock inoculated plants was 62%, and it was reduced to 41% on virus-infected plants. So in the field, the virus reduces the parasitism, the attraction of these parasitoid wasps, which would destroy the plant hoppers. So then they ask, will MISA affect this? So they add Misa to the equation, as they did before, in the field, and this restores parasitoid attraction. So the parasitoids come back when they smell the Misa, and then they can lay their eggs in the leafhoppers and kill them. And they find this with multiple viruses. It reduces the virus infection, reduces parasitism rates, and MISA supplementation restores it. So basically, in the field, MISA is like a good option for recruiting parasitoids, a natural anti-leafhopper, right, which will then reduce the virus infection because the virus is being transmitted by the leafhopper. leaf hopper. So they call this a potential field applicable biocontrol strategy. And in my view, Misa is a natural compound made by plants, so people shouldn't object to that, right? Right. I wonder, I'm still thinking through this, but I wonder if rather than using, you know releasing misa into the fields yeah you wouldn't be better off making a transgenic plant that could well that's a problem people don't want to eat transgenic plants but i'm i'm thinking the trans there there may be a downside to having a plant that doesn't make Misa at all. There may be other... Sure, sure. The other thing I want to do here, pardon me just a second, but I get into the techniques. When they say they're going to slow release Misa in the field, I wonder how the hell are they going to do that? They have the description in the methods. First of all, the average release rate of Misa per rice plant, they measured that, following insect herbivory was measured at 1.15 nanograms per hour. With an average of 60 rice plants, approximately 40 to 80 cultivated per square meter, the total emission of Mesa in these bug-infected plants, infested plants, was 69 nanograms per hour. Over a 10-week period, this corresponds to accumulation of 1.45 mg of Misa. To mimic this emission rate, a Misa slow-release solution was prepared by adding 5.87 grams of pure Misa to 40 ml of liquid paraffin. then 20 grams of porous resin particles were placed in four by six centimeter fabric bags and two mils of the paraffin solution was infused into each bag yielding a total MISA content of 0.23 grams per bag so they've got these bags that are four by centimeter bags that now have Mesa soaked porous resin particles in them. And they got control bags. All bags were inserted into vented plastic spheres that are four centimeters to create the final slow-release devices. And they put 20 of these. Oh, they prepared 20 of them before each day. So they got, in the end, they've got these four-centimeter diameter devices. that have particles, Misa-soaked particles in them that's in paraffin, but it slowly releases the Misa. God. It's amazing. Amazing. So let me summarize. So basically, a leafhopper bites a plant. The plant's not happy with that. It makes Misa. Actually, how the leafhopper induces Misa is an interesting question. I'm surprised they didn't look at that here. But if the leafhopper delivers a virus, the virus will then suppress the formation of MISA by taking this necessary transcription factor for the gene out of the nucleus into the cytoplasm. And that makes the parasitoid wasps not come anymore because they would be reducing the leafhopper population because they would normally be attracted by the MISA. But if there's a virus in there, the parasitoid wasps aren't coming. And what they show here is, aside from the mechanism of how MISA works, they show you can reverse the virus-induced inhibition of MISA production by adding MISA, and it restores the natural order of things in the rice field. And so they say maybe this could be a broadly useful thing. We have to do more studies, of course, but maybe it helps multiple other crops. That would be great. Yeah, in the discussion they go through some other literature that come to the conclusion basically that Misa is kind of the central character in a lot of these similar interactions. So it's a good target for a lot. And I have to say. Go ahead. I have to admit I'd never heard of Misa. Oh, no. No. Because, you know, yeah. I've heard of salicylic acid but not methyl salicylic acid. And they say that there are a lot of these volatiles that are implicated in this kind of thing. Yes But they were able to get the effects that they got simply by tinkering with Misa So it probably the main player in all this So you know years ago we did a paper on how aphids they deliver a virus to a plant and the virus upregulates volatiles which attract other aphids to the plant, something like that. They talk about this here. Oh, it's so cool. What viruses do to plants is amazing. My other thought about this is that Dixon would have loved this paper. Yes, I thought that would have. And he's shown up for the discussion here. Yeah. Right behind my ear. Yeah, he would have liked this a lot. Yeah. I spent a little time just now trying to figure out exactly how the wasps do something to the eggs, and I couldn't find that. They lay their eggs in the eggs of the leafhopper. Are you sure? Yes. Because it just says they parasitize. I looked it up. Oh, okay. I looked it up. Because I was curious about that. Because the polydinoviruses that we looked at before, those parasitic wasps actually lay their eggs in the larva. And that's what gives you down the road these caterpillars with these other larva emerging from them that are really spooky. Right. But in this case, they're infecting the host. At an earlier stage, they're actually infecting the eggs. So the eggs never even make it to larvae. But they hatch, and they must be huge eggs, relatively. And the parasitoid wasp produces its own larva right out of the eggs and it destroys the eggs. Got it. Okay. That's right. In this paper, they measure parasitoid eggs in the eggs of the leaf hop. Okay. I don't know how they measured them, if they did PCR or something else. That's what they did. Yeah. I'm sure they look at them under a microscope and count them. But who knows? Maybe they did. Wow. Let's do a couple of email. Kathy, can you take the first one? Sure. Charles writes, hello, Twivers. 32 Fahrenheit zero Celsius was 17 Fahrenheit minus 8 Celsius. Clear, cold, and not much fun when I got up this morning. Dr. Reconyelo's pick on TWIV 1279 was scoop. FDA vaccine chief's memo cited 10 pediatric COVID-19 vaccine deaths, but the agency's own analysis found zero to seven. Dr. Vinay Prasad circulated a memo before FDA scientists finished their work. His conclusions overshot what the agency's own analysis ultimately found by Jeremy Faust, MD. Dr. Jeremy Faust is the editor-in-chief for MedPage Today. I signed up for their email many years ago. It is a nice collection of health-related articles. I had read the article about Dr. Vinay Prasad's going beyond the data, again, with his memo about 10 children dying from the COVID-19 mRNA vaccines. I just checked their homepage, and it includes that article and one entitled, RFK Jr. Tops This Year's Shkreli Awards. I will read that one tonight. As much of an ass as Shkreli is, I'm not surprised he is not part of the Trump administration, And he gives a link to MedPage Today. And that was from Charles. So one of the things that occurs to me reading this is that this phenomenon in the new administration, in particular in these health sectors, that the way that this kind of thing should be done is that the staff at the CDC or the FDA or whatever agency it is, does their scientific work, creates a report that's appropriately reviewed in-house or whatever, and then that report is communicated to the director, and the director makes an analysis, okay, or presents or makes it public, okay? This is bass-ackwards, right? Yep. A director gets some idea or an inkling or a rumor that fits his narrative and blabs it all over the place prematurely before the science is done. Yeah. Yep. I'm just subscribing to... MedPage today. MedPage today. Select your profession. What am I? I'm not a physician. I'm not a health administrator. I'm not a medical student. I'm not a nurse. They don't have anything for me here. Do I have other? No. They have consumer patient. I'm not a consumer patient. I'm not a physician assistant. Oops. Sorry. I'm not going to subscribe just because of that because you don't have what I am. An educator. You know, it was scientist. Educator. Anyway. Anyway, so Martin Shkreli, American investor and businessman. He's a MAGA guy. What does he have to do with anything? Money, I guess. I guess he gives awards and he gave RFK an award, which tells you right away that he's an idiot. Wow. Yeah, Martin Shkreli, an American investor and businessman. Wow. Too much money these people have. Yeah. Oh, by the way, Charmaine, who's the next email, sends us an article by Jessica Koerik. No, Nurik, sorry. What has been lost one year into the Trump 2.0 administration, which is kind of an expansion of my, of the. Yeah. news thing I had above saying all the PhDs have been fired. Jessica Nurik has an Instagram account, and she makes really good summaries of why things are screwed up. I like her very much. Check it out. This is quite a list. Yes. Oh, this is a great list. It's fabulous. Because she goes from food assistance, nutrition access, food safety and regulation, rollback, scientific research, public health infrastructure, communication suppression and scientific censorship, vaccines and immunization policy. Oh, my gosh, it just goes on and on. So we could say it's a thorough list, but maybe it's not a good list. It's not good to have these things on the list. Not at all. Rich, can you take the next one? Kelsey writes, hello, TWIVs. My name is Kelsey and I'm a bioanalytical scientist out of Kalamazoo, Michigan. I currently work in the veterinary therapeutics industry where I use LC-MS-MS tandem mass spectrometry, attempt to pronounce at your own risk, to extract and quantify relevant drugs and metabolites out of biological matrices. I find myself with a sincere interest but often profound lack of expertise to understand much of the world of virology. I have a bachelor's degree in biochemistry and molecular biology and a master's degree in pharmacology from Michigan State University. Sorry, Dr. Spindler. Even with all of this background, it is astonishing how little I understand your associated fields of expertise. I wanted to give a quick thank you to all the TWIV hosts for your ability to guide me and my friends through our first pandemic and for providing so much entertainment to me since I started listening six years ago or so. Final question for you all. Feel free to not answer or read this out loud, but if it seems too ignorant. But can we describe viruses as information with possibly dire consequences and their vehicles? Seems possibly accurate, at least for the simplest model of RNA viruses, best, Kelsey. Well, I read this before the show and immediately leapt to mind a quote from Sir Peter Medawar that's famous amongst virologists, which says, quote, a virus is a piece of bad news wrapped up in protein. So, Kelsey, you're right on the money. Though the aficionados might say it's not always bad news. Yeah, so Kelsey put possibly in there. I think that's good. Yeah, that's good. Possibly dire consequences, yeah, for their viruses. Phil writes, Dear Twiv Team, the letter read by Rich in episode 1291 from historian Rob Schaefer contains an immensely powerful statement that TWIV should consider elevating through science and solidarity, succinctly summarizes TWIV's and MicrobTV's ethos and the ethical stance that many of us live our lives by, and that our current government is actively subverting. Approach and purpose in one beautifully concise statement. And I'll read that again in a bit. Phil is a former high school science teacher, undergrad in biology, focus on immunology, ardent listener for the valuable, actionable, and professional information provided for the current state of infectious disease risk in the world. Lover of the scientific summaries and updated information. Supporter of the authoritative reviews you provide on the political implications of current actions our government and fellow citizens are taking. Started listening at the start of COVID and have listened to the entire catalog. Have relied on you for sharing critical information to my family and friends in health care and business to help them make informed decisions. Thank you. Thank you. Thank you for what you do. Thank you, Phil. It's very nice. So the email that Rich read was from German historian Rob Schaefer, who was responding to RFK criticizing Germany. And he wrote, you seem to be laboring under the delusion that Germany is a colony for your conspiracy theories. Let me be blunt. Your brand of freedom, the freedom to die of preventable 19th century diseases is an export we have no interest in buying. We established the world's first universal social health care system under Bismarck in 1883. You still do not have anything comparable. We are the nation of Koch and Virchow and have spent 140 years using state power to defeat disease through science and solidarity. You, meanwhile, preside over a system where insulin is rationed like gold dust and medical bankruptcy is a national pastime. The fact that you think you have the moral standing to lecture the country that invented modern medicine on medical decisions is not just arrogant, it is grotesque. Keep your chaos on your side of the Atlantic. It's so good. Yeah, that is good. Kathy, can you take the last one, please? Sure. Michael writes, when I berated a local DJ on our college radio for repeating the lab leak theory about COVID and suggested he listen to TWIV, he responded as follows. Curious about your answer. As far as COVID is concerned and that podcast you mentioned, their biggest contributors are the WHO, CDC, and other major pharma corporations. Not at all saying they're lying about the origin. However, they lied about a whole bunch of other stuff about this virus that kept me from seeing. Curious to your response, although I have a feeling what you will say. Michael is from Maine. Rich's response is? Show me the money. So this is the response of everyone, particularly the anti-vaxxers, when they have nothing good to say. They say you're getting paid. They make it up out of thin air. And we're not getting paid by WH or CDC or any major pharma. Or anybody. The only people that pay us is our listeners to make these programs, right? Right. So, Mr. DJ or Ms. DJ, you're making this up because you've got nothing else to say. Probably never listen to the podcast, doesn't know a thing. Right. There you go, Michael Levi. DSC. Yeah. Let's do some picks. Kathy, what do you have for us? Well, I'm not sure if we've ever picked this before, but I was fortunate enough recently to go to the Galapagos Islands, and it was a fantastic trip. I highly recommend it, and if anybody wants information, I really liked the trip I went on. And in preparation for that and concomitant with that, I listened to The Beak of the Finch by Jonathan Wiener. It won a Pulitzer Prize. It was published in 1995. And it's about Peter and Rosemary Grant and their evolution studies on Daphne Major, which is one of the very small Galapagos Islands. And then it brings in ecology studies from a number of other fields. It's an amazingly written scientific book. And the narrator, if you do audiobooks, the narrator is fantastic. He's figured out how to pronounce all the words correctly as far as I could tell. And so I highly recommend The Beak of the Finch. I had known about it for years. And then when it came up on one of the book lists before my trip, I looked and I already had downloaded it. And then the next one that I'm going to do is The Song of the Dodo by David Quammen, which I've also already downloaded. And it's a lot about island biogeography, I guess, and we'll have a whole section about the Galapagos. But The Beak of the Finch is just an amazingly good book, and I highly recommend it. This picture you put in here, is this Jonathan Weiner in front of the Wallapolio? Yeah, it is. So Jonathan's a professor at Columbia, and he teaches a journalism course, so to journalism students on science writing. And I usually teach in his course. I give a lecture every year. And he came to TWIV years ago. That's why he was in my office. I don't remember what episode it was, but that's his picture in front of the wall. So he used to be at Princeton. He and his wife did the research based in Princeton. And the narrator pronounces his name Wiener. So that's why I pronounced it that way. That's probably correct. I asked him once, and he said, ask my mother. Okay, Kathy, you got me. I'm going to have to read this. Oh, yes. He has actually written some other books as well that are great. Oh, I've just conflated the author with the characters. Right. So Peter and Rosemary Grant. They were at Princeton. Were at Princeton. Yes. And Jonathan Wiener is the writer at Columbia. Got it. Okay. So he was on Twevo number 19. Okay. I probably have listened to that because this looks familiar. Yeah. I'll go back and do that again. So I see him every year. And he's a very interesting guy. Okay, Rich, what do you have for us? Okay, this is not a science pick, but I thought it was appropriate for the time. It's a book I read recently. It turns out that I have a penchant for reading biographies of U.S. presidents. And this is Ron Chernow, the guy who wrote the Hamilton biography that inspired the Lin-Manuel Miranda musical Hamilton. Ron Chernow is his biography of George Washington. And what can I say? It goes through his whole life, which is basically two major things, right? Being the commander-in-chief of the Continental Army during a revolution and then being the first president of the United States. And it is quite enlightening about sort of the issues ongoing during the revolution and during the founding of the United States. And I think it's all relevant to all of the turmoil that we're experiencing in the moment. Among other things, as many people are familiar, when the country was being founded, it wasn't sort of like unanimously everybody thinks, oh, this is a great idea and this is how we're going to do it. No, there was a lot of controversy. And in fact, in particular, when Washington was president, there were very polarized debates with, in particular, Hamilton on one side and Jefferson on the other side about what the priorities should be for how to run the country that Washington had to navigate and did so quite well. One of the interesting things that came up in a news broadcast that I saw the other night, it was a, it doesn't matter, is Article 2 of the Constitution that describes the executive office is like a couple of sentences long, right? And it's just like wide open. And one of the reasons for that, according to Cherno and others that I have heard describe it, is that the Constitution was basically written with Washington in mind as president. And there are those who say that if that hadn't worked out and he hadn't been president, we might not even have the United States of America as we know it now, that he is truly the father of the country. And he had this vision of, you know, how things should be done that involved looking at all sides of a question and making a morally appropriate decision, okay, that he was very good at doing. Well, he refused to take a third term, right? That's right. They wanted him to be president. That was one of the most important things, right? And the thing is, though, I read it. There was an interesting article in The Atlantic, I think. I just read. They were trying to figure out what to call the president back then, right? And all these things, including like his honorable excellency or his excellency, the president. And actually, Washington wanted one of those excellency titles. But Jefferson said, no, no, it's just Mr. President. And that's what it ended up being. So he was a little bit enamored with this issue. So at any rate, I recommend this. It's good. Cool. All right. Well, I'm on a book streak now. I've been reading on the train lately. And this one is fiction. I started reading one of Brianne's recommendations today. And I'm just, when the train got to New York, I said, where am I? I don't feel like I'm in the real world. So it really transported me. I like Henning Mankell. He's a Swedish detective fiction writer, right? Police procedural type stuff. And I've read a lot of his crime novels. and I was just browsing my Kindle and I saw this one suggested, The Man from Beijing, which I hadn't read and it's published in 2008. It's actually first published in Swedish like most of his books. But anyway, it starts with police finding 19 people murdered in this tiny hamlet in northern Sweden. and the main protagonist is Birgitta Roslin who is a judge from Helsingborg she realizes she has a connection with some of the victims and starts to investigate it and eventually the story heads over to Beijing it goes back a few hundred years and then it comes back to the present and has an interesting ending so I liked it a lot I don't know. I think the Swedes write the best crime novels. I think he's very good. And also, there was a pair, a husband and wife team, who wrote 10 crime novels in the 60s. And they're perfect. If you've ever, I picked them on Twiv before. They're perfect. They're the perfect crime novels. You can't get, and they're old and nothing modern about them. but they're still perfect. All right, that'll do it for TWIV 1293. You can find the show notes at microbe.tv slash TWIV. You can send us questions and comments and picks of the week to TWIV at microbe.tv. And if you like these programs, we would love to have your support. If you're a WHO, CDC, or big pharma, we don't want your support. We can't take it. Okay, sorry, because that would be a conflict of interest. Yeah, don't want that. But we don't have such conflicts because we depend on your support. And, you know, you can help us to produce these programs. Someone said the other day on livestream that our programs are now TV quality, broadcast TV quality. Well, thank you very much for that. It's because of your support that we can do this. So you can help us out. Go to microbe.tv slash contribute. We do have some hats left, some hand-knitted wool caps that are a listener made for us and which we are selling. And they're at micro.tv slash contribute. We have about 15 left out of the original 30. So if you would like one, go check it out. They're beautiful. They are absolutely beautiful. Kathy Spindler is Professor Emerita at the University of Michigan in Ann Arbor. Thank you, Kathy. You're welcome. This was a lot of fun. And because, you know, I did the compendium of Picks of the Week from last year, I noticed that all three of our picks today are books. They are books. Yeah. It's not always the case. Nope. Yeah, I usually don't pick books, but I'm back on a book roll again for some reason. Yeah. Rich Condit is an American. Sorry. Rich Condit is an emeritus professor. Everyone said American. You are American. That's true. More importantly, emeritus professor, University of Florida Gainesville, currently in Austin, Texas. Thank you, Rich. Sure enough. Always a good time. I'm looking at these hats. I didn't realize they existed. They're pretty cool. Yeah, there's some toddlers and young kids in adult hats there. So who did this? A listener who wishes to remain anonymous. Okay. So a crocheting maniac or a knitting maniac. Knitting. It's knitting. Knitting. Knitting. The listener took 10 hours per hat. Holy cow. Wow. So that's like 300 hours. Yeah. It's amazing. And they're really beautiful. Oh, I should say they have a DNA on them. They have a double helix. They're beautiful, all different colors. Really nice. You want to see one? I'll go get it. Wait a minute. Hang on. Okay, so I just looked it up again. And the link is www.microbe.tv slash contribute. Yeah. Yeah. And, yeah. There's some headbands. And they got pictures of the house. You see the house? You see the hats? Yeah, yeah. A lot of double helices. Yeah. Man, you could buy one of these right out of Vincent's hand here. Yeah. Now I have a camera that does autofocus. So here's a stack of them here, right? So we have this one. Yeah. Very cool. This one is a toddler. It's pink. Isn't that pretty? This one is adult. I have any toddler would want. I like this green and some brown and multicolor there. Nice double helix. This is a cool one. Yeah. I like the band at the bottom. Bands are nice. This is a big pink one for mommy. It's another brown. Oh, this is one of my favorites. I like this. Ooh, yeah, that's nice. Brown with the gold. Anyway. Very nice. The adults are $40. The kids are $30, and the toddlers are $20. Man, that's a real bargain. Actually, it's too little for the work involved. Yeah. If you went to a store, you'd probably pay more. But I want people to have them, and your purchase supports our work, right? Excellent. Anyway, thank you to our listener who did that very much. We're really grateful. I'm Vincent Racaniello. You can find me at microbe.tv. I'd like to thank the American Society for Virology and the American Society for Microbiology for their support of TWIV, Ronald Jenkes for the music, and Jolene Ramsey. the timestamps. You've been listening to This Week in Virology. Thanks for joining us. We'll be back next week with another Quim is Virology.