transcript

Speaker 1:
[00:00] This Week in Virology, the podcast about viruses, the kind that make you sick. From Microbe TV, this is TWiV, This Week in Virology, episode 1315, recorded on April 17th, 2026. I'm Vincent Racaniello, and you're listening to the podcast All About Viruses. Joining me today from Austin, Texas, Rich Condit.

Speaker 2:
[00:33] Hi there, Vincent. We've got 84 degrees Fahrenheit, and right now, cloudy. There's occasional patches of sun. I think that this is pretty much a seasonable weather. Maybe a little on the warm side. We're about to get, McFadden is about to send us a little cold blast here. It's going to be high of 66 on Monday, which is fine with me.

Speaker 1:
[01:01] Yeah, it's interesting. It's been more unseasonably warm here. Today, it's 24 and cloudy. It's a bit of rain, but next week, it's going to go back down into the threes and fives overnight. But that's like spring here in the Northeast. It doesn't settle down until almost summer. Also joining us from Montreal, Canada, Angela Mingarelli.

Speaker 3:
[01:23] Hello, everyone. Hello, Rich. Your cold weather is our very nice weather today. Today, it is 18, which I think is like 65 Fahrenheit. People are outside in t-shirts. They think it's great. It's literally the warmest it's been all year. But also Vincent, we are going down again to zero, I think on Monday or minus three or something overnight. But anyway, I'm going to go outside for a walk after the podcast and definitely take advantage of the warm weather.

Speaker 1:
[01:54] As soon as it gets warm, the students don't come to class anymore, right? So my Virology class still has a couple of weeks left. And suddenly, the other day, Wednesday, there were 30 people in class and I have 110 students in the class. I cannot compete with good weather. The problem is, of course, that I record my lectures and so they can listen afterwards. Also joining us from Western Massachusetts, Alan Dove.

Speaker 4:
[02:18] Good to be here. And here in Western Mass, it's been pretty wild weather. It was in the 80s for a couple of days. That's like 30 C today at 72 Fahrenheit, 22 C and not currently raining. Last night, we had a really loud thunderstorm much of the night. And it's yeah, it's just kind of well awakened.

Speaker 1:
[02:42] I was awakened by birds this morning. Can anyone tell me why they start singing when on chorus?

Speaker 4:
[02:48] Why?

Speaker 1:
[02:48] Why do they have to do that?

Speaker 4:
[02:50] That's their...

Speaker 3:
[02:50] I mean, it's beautiful though, no? It's better than my children's singing. No, it's fine. I just want...

Speaker 1:
[02:54] I was lying awake and thinking, what are they doing? Are they saying, hey, it's another day. Let's go get some worms.

Speaker 4:
[02:59] Yeah, they're celebrating. Yeah.

Speaker 3:
[03:01] They're excited for spring, I think. My birds are also very loud in the morning now.

Speaker 1:
[03:05] Well, yeah. I mean, the thing is in the winter, you never hear the birds. So that's pretty cool. I think it's great that some animals on earth are very excited for a new day.

Speaker 4:
[03:14] I don't know if excited is exactly right, but they certainly are loud.

Speaker 1:
[03:17] They're not excited. Are they actually talking to each other?

Speaker 2:
[03:19] Sure.

Speaker 4:
[03:20] They're communicating. They're definitely, a lot of what they're communicating is, you know, hey, baby, check me out. You know, or they're saying, this is my branch. This is my branch.

Speaker 2:
[03:32] Keep the hell away from my branch.

Speaker 4:
[03:34] Yeah.

Speaker 1:
[03:35] I saw this video of a, what is it, a cockatiel, those white ones with the big crests. And it was just talking so well. It was amazing. And it's just stunning to see this bird saying, hello, how are you doing today? Or, don't get near me with that. In a reasonably complicated, and then it would curse also, because probably the owners curse. I think it's very funny when animals talk.

Speaker 2:
[03:58] I had a friend who had a parrot that had a smoker's cough.

Speaker 4:
[04:05] Oh my God.

Speaker 2:
[04:08] Because the owner had a smoker's cough. Oh.

Speaker 3:
[04:11] That's sad and hilarious.

Speaker 1:
[04:16] If you enjoy these programs, these science discussions, we would love your support. You can go to microbe.tv/contribute. We have a number of ways you can support us. We're a 501c3 non-profit, so in the US, your contributions are federal US tax deductible. Speaking of the US, this week, someone emailed me and said, with all the problems in the US, ASM and ASV should be out of the country. I said, well, last year was in Montreal, actually, so it's not bad. I don't know, ASM doesn't leave the country, and it's too big a meeting. It's hard to find venues.

Speaker 4:
[04:54] Well, I mean, they are also the American Society for Virology, so technically, they probably ought to stay.

Speaker 1:
[05:00] Well, they could stay in North. Well, they could do in the Americas.

Speaker 4:
[05:03] The Americas, yes, they could do it in...

Speaker 1:
[05:05] That gives you a lot of leeway.

Speaker 4:
[05:07] Yeah.

Speaker 1:
[05:08] Anyway, microwave.tv/contribute. Don't forget the Rosenfeld Lab in Philadelphia is looking for a postdoc and a technician. They study enteroviruses, the cross-reactive immune response and its significance to pathogenesis, making animal models to study them, and also developing new vaccine platforms. Today we're going to learn about a new vaccine platform called the Mosquito.

Speaker 4:
[05:33] Yes.

Speaker 1:
[05:35] It's not really new. Anyway, you should email Amy at rosenfelda.mlhs.org. Speaking of ASV, the American Society for Virology, they have their annual meeting this summer, July 27th through 30th, at the University of Minnesota, which is in Minneapolis. Go to asv.org and click learn more below the ASV 2026 logo and you can find information about accommodations, the scientific program, biographies of the three local leaders who are Yuying Lan, Lu Manski and Wei Zhang. And the link for the ASV Care Grant Application for ASV members, that's for dependent care, is available. And also the link for KiddyCorp, Child Care Services signups. And the deadline is May 22nd for those.

Speaker 4:
[06:31] And Minneapolis is really almost in Canada anyway.

Speaker 1:
[06:36] I did. It's a nice city. I've been there to this meeting.

Speaker 4:
[06:39] Isn't it north of Toronto?

Speaker 3:
[06:42] North of Toronto? Impossible, no?

Speaker 4:
[06:45] I don't think that's... Because it's around the side of the lake. Actually, maybe.

Speaker 3:
[06:51] It is very cold there, colder than Toronto, for sure.

Speaker 4:
[06:54] It may have a higher latitude than Toronto.

Speaker 3:
[06:57] That would be a little bit crazy.

Speaker 4:
[06:59] Anyway.

Speaker 1:
[07:00] Anyway, so go to the website and you'll see ASV 2026. You hit a drop down and you'll see Child Independent Care. And Early Bird Registration is open now until June 1st, 2026.

Speaker 4:
[07:14] Was I right?

Speaker 3:
[07:15] You're right, it is, which is kind of crazy to me.

Speaker 4:
[07:18] It's north of Toronto, which means it's probably north of most of the population of Canada.

Speaker 3:
[07:23] It's also north of Montreal, actually.

Speaker 4:
[07:26] Right. Yeah.

Speaker 3:
[07:28] Well, Minneapolis. Yeah, sorry.

Speaker 1:
[07:30] The curvature of the earth does these things, right?

Speaker 4:
[07:32] Well, also the curvature of the US border as it goes past the Great Lakes. It curves way up. Yeah.

Speaker 1:
[07:42] What was I going to say?

Speaker 4:
[07:44] Sorry, we got through the ASV announcement.

Speaker 1:
[07:46] Oh, I was in... I don't know what Minneapolis winters are. I've only been there in the summers. I was in Toronto in November.

Speaker 4:
[07:52] I can hazard a guess.

Speaker 1:
[07:54] December, it was really cold. Toronto was very cold in the winter.

Speaker 3:
[07:58] Our new postdoc is from Minnesota, and he said that it's comparable to Montreal. Like he got here, it was minus 15, and he was wearing like a light jacket. I was like, oh, you're used to this. I was like, okay. He's like, yeah, yeah, it's extremely cold there.

Speaker 1:
[08:11] So my former student, Angie Rasmussen, she was in Saskatchewan, Saskatoon. I don't know what, what's the city?

Speaker 3:
[08:18] Saskatoon is the city, Saskatchewan is the province.

Speaker 1:
[08:21] Okay, Saskatoon. And she says it can be minus 40. Your eyes will freeze between blinking.

Speaker 3:
[08:26] Yeah, it's very cold.

Speaker 1:
[08:27] Isn't that horrible?

Speaker 3:
[08:28] That's pretty bad. It's also so cold because it's just, the prairies are very flat. So it's just windy and freezing. There's nothing to block the wind. It's really, really cold there.

Speaker 2:
[08:37] Sounds delightful.

Speaker 3:
[08:38] I would not want to live there. Tell them it's terrible.

Speaker 1:
[08:42] Another passing today or this week, Bernard Roizman, a well-known herpes virologist. He passed away on the 13th of April. He was 96. Oh wow. Wow. He's originally from Romania, which I did not know. Came to the US for training and eventually ended up at the University of Chicago where he spent most of his career. He published a huge amount on herpes viruses and very big lab. A lot of people came from his lab. Saul Silverstein, my colleague and former chair, trained with him, was a postdoc with him.

Speaker 4:
[09:21] Had great stories.

Speaker 1:
[09:23] Always story. The thing I remember about Royce, he was a great virologist. You could barely hear him when he talked. His voice was so low. I don't know if you remember that, Rich.

Speaker 2:
[09:34] No, I don't remember that bit.

Speaker 1:
[09:37] Yes. I mean, you had to get really close to him to understand. And even when I was young and I had good hearing, I had trouble hearing him.

Speaker 2:
[09:45] I think he probably has in his time and surrounding the most, the biggest role in shaping what we have as herpes virology today. You know, a lot of the work that came out of his lab and a lot of the people that came out of his lab were really critical for advancing that field. He is really instrumental in doing the whole thing. His, you link to his autobiography, which is quite lengthy, I didn't read, but I at least skimmed through it and read some of the first parts. Growing, he was born in 1929 in Romania, and in the run-up to World War II, they were dodging both Russians and Germans. And he had quite, shall we say, an adventure. You can read about his family's history as essentially refugees from this or that place trying to get out of the way of various evildoers. So it's quite something, quite a background.

Speaker 1:
[11:02] I'm going to link to his autobiography in the annual reviews of Virology. It's called The Maturation of a Scientist in Autobiography. And he writes, I was shaped by World War II, years of near starvation as a war refugee, post-war chaos, life in several countries, and relative affluence in later life. The truth is, as I was growing up, I wanted to be a writer. So it came to an end when I took courses in microbiology. It was love at first sight. So this is an interesting autobiography. It's really good. He was in many countries, as he said. I got to meet him multiple times.

Speaker 2:
[11:43] Did you ever interview him for the book?

Speaker 1:
[11:47] I never did. Interesting. I never did. We never had him on TWiV. Never had him interviewed for the book. I don't know why. It's just, you know, they're just people that just... You never get around to it.

Speaker 4:
[12:03] And then they're gone.

Speaker 2:
[12:04] And then they're gone.

Speaker 1:
[12:05] Yeah, and there are some people who I regret having not talked to. And so Bernard would have been nice to have here many years ago. Not when he's 96, but when he's maybe 80 or 75, right? Like the guy from Philadelphia we interviewed.

Speaker 2:
[12:23] Not Fred Murphy. Murphy, he's not from Philly. Who do we interview from Philly?

Speaker 1:
[12:29] The vaccine guy, right? Alan should know. He's the youngest here.

Speaker 4:
[12:34] Maurice Hilleman?

Speaker 1:
[12:35] No. Stanley Plotkin.

Speaker 4:
[12:39] Stanley Plotkin, yes. So we never had Hilleman on the show either.

Speaker 1:
[12:44] I meant he's the youngest among the old folks in Virology.

Speaker 3:
[12:47] Don't worry. Don't worry.

Speaker 1:
[12:49] Because you're not really an old virologist, you know.

Speaker 3:
[12:53] I mean, I also had no idea who you were talking about, so I didn't even, I wasn't thinking.

Speaker 1:
[12:57] That's okay.

Speaker 3:
[12:58] You were talking to me.

Speaker 2:
[12:59] I wonder if Bernard ever retired. You can't tell from his Wikipedia entry. It doesn't mention retirement, but he was one of these guys who we figured would never retire.

Speaker 1:
[13:14] Yeah. You know, it's interesting when he, so he invited me to give the Hilleman Lecture at the University of Chicago many years ago, which was a nice honor, right? And at the time, my mother was dying of cancer, right? And she was in the last stages. And I said, I don't know if I can come. I don't know when she's going to die any day now. And I'm not going to be here. And he got me on the phone. He said, Vincent, you can't run your life this way. It just doesn't work that way. We'll just wait forever and not do anything. And I said, yeah, you're right. So I went. So you've got to take your own life in your hands. I thought that was good advice. Just do it. Otherwise, you could wait forever. All right, RIP Bernard Roizman. Now we have some very, we always do interesting papers here on TWiV and because we can only do two a week. And in the field of virology, immunology, public health, there's a lot of papers every week.

Speaker 4:
[14:21] So and doing boring papers sucks.

Speaker 1:
[14:23] We don't do boring papers. So we have two and they're, they're both in science journals today. So in the first one, our snippet is in science. It's called Wildlife Trade Drives Animal to Human Pathogen Transmission Over 40 Years.

Speaker 4:
[14:45] The first author is Jerome Gippett and the senior author is Cleo Bertelsmeyer. The team is from University of Freiburg in Switzerland, University of Lausanne in Switzerland, Yale University School of Public Health in New Haven, University of Idaho, Moscow, and University of Maryland College Park. Go Terps.

Speaker 1:
[15:02] Moscow, Idaho.

Speaker 2:
[15:05] That's where Lois Miller was for a long time.

Speaker 1:
[15:08] Yeah. You know, everyone who listens to TWiV should know that understanding what shapes the spread of zoonotic diseases, right? These are pathogens that go from animals to humans. And it's not just viruses, it's viruses, bacteria, and parasite. This is important to understand because it helps. It happens often and we really cannot put our head in the sand and ignore it. We need to understand it, and that's what science is all about.

Speaker 4:
[15:40] Well, we can put our head in the sand and ignore it, but it will still keep happening.

Speaker 1:
[15:44] Well, there are some people who want us to do that. That's why I mentioned that. There are some people who feel we should not be investigating zoonotic potential because it's too dangerous, which is absurd. It's just absurd. It's far more dangerous to just wait for a pandemic to come around. So this paper looks at the wildlife trade because this is one form of the interaction between animals and humans that creates opportunities for spillover from animals to humans, right? And this takes place during harvesting, breeding of the animals, transport, stockpiling, warehousing, retail consumption, and companionship. Those are pets. That means companionship, right? The steak in your freezer is not your companion. For example, they say here.

Speaker 4:
[16:30] Hopefully it was not previously your companion.

Speaker 1:
[16:32] Yes.

Speaker 3:
[16:32] It could have been.

Speaker 4:
[16:33] Yes.

Speaker 1:
[16:33] Although, the more I see cows, the more I like them. They're so nice.

Speaker 3:
[16:39] Remember I told you this once, Vincent, cows are the best.

Speaker 1:
[16:42] You did say that. I always remember that. They can look really nice and peaceful, right? I feel bad for them because they have a tough life except for one day. No, they have a good life except for one day.

Speaker 3:
[16:55] Dairy cows, remember I told you dairy cows have worse lives than meat cattle. Cattle that are grown for meat technically have better lives in general. They're normally out in fields eating grass, things like that as opposed to dairy cattle. A lot of the time are tied in stalls or just like roaming one stall, they can't go outside. Their lives kind of suck.

Speaker 1:
[17:16] That's the opposite of Jurgen Richter. He told, I met him in Kansas. He's a veterinarian.

Speaker 4:
[17:20] He's allowed outside?

Speaker 1:
[17:22] He said the dairy cattle can wander around and eat grass and stuff, but the steer, they're restricted so they gain weight faster. Anyway, it doesn't really matter.

Speaker 3:
[17:35] It depends. Exactly. It depends if they're free-ranging dairy, which is more expensive, like organic. They can be free-range, but the ones that are just like regular milk, there's nothing special about the milk. Normally, they're in tie stall, which means they're in a farm that are tied up, they're in a barn that are tied up, because it's more expensive to have them outside, because then they get dirty, it increases their risk of mastitis. There's like lots of other problems with them being happy outside.

Speaker 4:
[18:01] The beef cattle, it depends if you've got free-range, grass-fed beef, they're doing their normal beef thing, out grazing like you'd imagine. But most of the beef that we have here in the US is from confined animal feeding operations, CAFOs, which are these massive acreages of little pens of cattle that are just gorging themselves on corn, which is not their natural food.

Speaker 1:
[18:25] So, Jurgen told me a lot of interesting tidbits. So, first of all, the cows are kept pregnant all the time, right? It's just...

Speaker 3:
[18:36] Except for two months.

Speaker 1:
[18:38] They dry out for two months.

Speaker 3:
[18:39] Well, they're ten month pregnancy.

Speaker 1:
[18:41] And then they give birth.

Speaker 3:
[18:42] And then right away...

Speaker 1:
[18:43] When they're no longer good at making milk, the meat goes to McDonald's because nobody wants to eat steaks made from... Is that true, Angela?

Speaker 3:
[18:51] So, you cut out for a second. I don't know if it was my internet, but I think you said dairy cattle, when they get like a cheap type of meat. Exactly. Those go to fast food. Those go to fast food normally.

Speaker 1:
[19:02] They said there's some operations in the US that have like 10,000 or more dairy cows. They milk 23 hours a day. They have these circular things that the cows walk into, they get milked, and then they walk out continuously. But they have to be milked twice a day.

Speaker 3:
[19:19] But it's not the same cow, exactly. So, each cow is twice a day. But that it's yes, that the machines are working constantly. That is true.

Speaker 1:
[19:26] That's amazing. You get an hour off.

Speaker 4:
[19:28] Well, I think they close for an hour to clean the thing.

Speaker 1:
[19:32] It's amazing. Anyway, I don't know why I got onto that.

Speaker 3:
[19:35] I love how animal wildlife to talking about cows and milk.

Speaker 1:
[19:38] For example, a person buying three Finlayson's squirrels in a Laotian.

Speaker 4:
[19:44] Things that you cut out.

Speaker 1:
[19:46] Yeah. Well, you're cutting out, actually.

Speaker 3:
[19:49] Whose Internet is it? I also see only Vincent cutting out.

Speaker 1:
[19:52] Well, I have gig Internet here, so I think they're cutting out.

Speaker 3:
[19:57] I also have gig Internet now.

Speaker 1:
[20:01] We just got it actually at the incubator because we used to have 200 megabit and it crapped out for a week, and so I said, the heck with it. So anyway, if you buy three Finlayson squirrels in Laos in a wildlife market, you have an 83 percent chance of getting at least one infected with leptospirosis.

Speaker 4:
[20:22] So you should really buy four or five to make sure that you get the leptospirosis.

Speaker 1:
[20:27] It's the same wildlife trade, of course, leads to human outbreaks like COVID-19, which they say, including the COVID-19 pandemic. So I'm very happy because this article acknowledges that, like the data say, COVID-19 originated from wildlife.

Speaker 2:
[20:45] They reference two papers with that statement, both of which we did on TWiV.

Speaker 4:
[20:49] Yeah.

Speaker 1:
[20:50] So hunting and consumption of wild meat, HIV, Ebola outbreaks, other human infections linked to wildlife, anthrax, hides sourced from wildlife, used for drums among musicians.

Speaker 4:
[21:05] Yes.

Speaker 1:
[21:06] Can you imagine?

Speaker 4:
[21:07] I remember that story. I think some of those drums actually ended up in New Hampshire.

Speaker 1:
[21:17] Yeah.

Speaker 4:
[21:17] Because I remember seeing like a local New England story about this, that this drumming group had ended up with multiple people with inhalation and anthrax from drums.

Speaker 1:
[21:31] And then the exotic pet trade, like getting emparks from prairie dogs is a 2003 outbreak in North America. Salmonella traced to bearded dragons. So, you know, when you buy those exotic pets, just be careful. You should know the history.

Speaker 4:
[21:49] Swab them. Swab them. Yeah, so this paper is really, it's taking something that we already pretty much know is going on and trying to figure out the scope of it and exactly where it's coming from and the way they approach that is really cool.

Speaker 1:
[22:09] Yeah, this is not what people study. People study like what pathogens are in such bats or whatever, but nobody really studies the dynamics of the trade and so forth and so...

Speaker 4:
[22:21] Right, can we have a grand unified theory of spillover? Is something more likely to spillover if it's in the animal trade than if it's not?

Speaker 1:
[22:28] And their idea is that traded wildlife should be more likely to share pathogens with humans because they have frequent contact as opposed to non-traded, right? And that can happen through zoonotic spillover, which we know is animal to human or reverse zoonosis, humans to animals, right? They gave deer SARS-CoV-2, for example, in mink, on mink farms. And so the more frequently the trading, the more pathogens they should share. And that's what they're looking at. They look at links between the global wildlife trade and pathogen sharing. And they focus on mammals here, but there are other, I mean, fish and birds can also be involved in this. Snakes. And they have three wildlife trade data sets that they use to get their information. And these are totally new to me. I had never...

Speaker 4:
[23:24] I had heard of one of these.

Speaker 1:
[23:26] One is the Convention on International Trade in Endangered Species of Wild Fauna and Flora. That's CITES, the Law Enforcement Management Information System, and the data set of seized wildlife and their intended use.

Speaker 4:
[23:41] Which sounds great.

Speaker 1:
[23:44] So the CITES one documents legal international wildlife trade in wild, live animals and animal products. So it's global and it spans 1975 to the present. But it doesn't have all species. It has 13% of all mammalian species.

Speaker 3:
[24:02] Most of them are just endangered species or soon to be endangered. Like if you have any sort of animal or even at a zoo or anything like that, they all have to be registered with CITES. And if it's going to be traveling between different countries, if you're going to be exporting it or importing it, it all has to be also through CITES as well.

Speaker 4:
[24:21] And there are species on the CITES list that may be locally abundant, but they are globally regulated as part of this. Alligators are a prominent example. They're all over the place in Florida. And Florida actually has an alligator hunting season. But if you do that, if you hunt alligators in Florida, apparently one of the things you have to do is tag your gator with a tag identifying it under CITES. And so it can be tracked and all that. I just read a book about alligator farming.

Speaker 1:
[24:53] That's so niche. The Lemus database has records of live animals and products imported into the US between 2000 and 2022. It includes all mammal, even though it's limited to the US., it has all mammal species. And so they use CITES and Lemus to look at the taxonomic extent.

Speaker 4:
[25:14] And they cite a statistic here that the wildlife trade affects a quarter of terrestrial vertebrates. And there's another later in the story that it's a similar percentage of mammals that are, the wildlife trade is hugely dominated by mammals. And so like a large section of taxonomy is being traded commercially, apparently.

Speaker 3:
[25:39] But it's interesting because they don't specifically define what wildlife trade means, like they do say that they don't include illegal wildlife trade, but then they just say wildlife trade, which could mean so many things in so many contexts. And what's like domesticate?

Speaker 4:
[25:52] Yeah. So my take on that is that they mean stuff that shows up in these databases, basically.

Speaker 3:
[25:59] Yeah.

Speaker 4:
[25:59] So the site's database is tracking wildlife trade, and you can take that as your block of data. And then law enforcement and seized wildlife are to get at, you know, how much are those regulations actually followed? And they do peek a little bit at illegal wildlife trade, but they don't. That's not the main focus here.

Speaker 1:
[26:20] And the third database is DSW, which is actually a shoe store. It's the most comprehensive compilation of seizures of illegally traded wildlife. So they use these three to make a picture of the species that are involved in illegal and illegal global wildlife. And they also have a database called the Clover database, which is a resource of mammal pathogen associations that we know about. And they have over 190,000 associations between mammals and viral, bacterial, fungal, helminth, and protozoan parasites, pathogens. So then they combine these data. Yes, Rich.

Speaker 2:
[27:00] I got it. It's at this point that I want to out my questions. In the form of... Here's what I think I understand. First of all, those first three databases, what was it? Sites, Lemmas, and DSW.

Speaker 1:
[27:19] Yeah.

Speaker 2:
[27:19] They just tell you where the animals are and a little bit about how they got there, maybe where they're going, that kind of stuff. So it's sort of who's where and why. They don't tell you anything about the pathogens.

Speaker 1:
[27:35] That's right.

Speaker 2:
[27:36] Clover, without really necessary... They may have some information on where the particular animal was, but mostly it's about which animals... What is the... What pathogens are in these various animals? It's almost like... I don't know how they collect it, but it may be metagenomic sort of data or at least include that. So I got that right, right? So now you got to put those things together and try and sort that out. But my biggest issue here is that what you're scoring is pathogens in non-human animals, all right? And I think what you're looking for in terms of understanding zoonoses is human pathogens associated with the animals, right?

Speaker 4:
[28:34] Yeah, you're looking at... So you're looking at shared pathogens.

Speaker 2:
[28:39] Okay, shared...

Speaker 4:
[28:39] There are animal pathogens that have shown up in humans and human pathogens that have shown up in animals.

Speaker 1:
[28:45] Yeah.

Speaker 2:
[28:45] Right. But you're not... The thing is, that's more subtle than what the title implies where it says drives animal to human pathogen transmission. You're not looking at pathogens in humans, okay? You're not looking directly at animal to human pathogen transmission. You're looking at the animals and looking at shared pathogens. To me, that's a subtle or maybe not so subtle difference. And I'm not quite sure how to think about that. But I wanted to make it clear that that's what's going on.

Speaker 4:
[29:20] I think you can... Yeah, it's an inference that they're making.

Speaker 2:
[29:24] Right.

Speaker 4:
[29:25] That if you see a pathogen in this clover database that is associated, known to be associated with an animal and that has appeared in humans, and you could conclude that it went either way. But I think the way they're doing the statistics on this is to try to disentangle the directionality by focusing on things that are unusual in humans.

Speaker 2:
[29:55] Yeah.

Speaker 4:
[29:57] So you're not. Okay. So you find, I don't know, SARS-CoV-2 in the clover database. It's certainly going to be in there because it's in a lot of animal species. But you're not going to say that that was animal to human because we know it wasn't. Whereas you find, I don't know, well, salmonella, the examples they gave at the beginning, leptospirosis, salmonella, these are not commonly transmitted human to human. You can say realistically that that came from the animals.

Speaker 3:
[30:30] But I don't know if they make that distinction specifically. I know that's what you're saying, Alan, but I don't know if they make that distinction. I think they're just looking at within all of the microorganisms in the Clover Database, which ones can infect humans, or which ones have infected humans in the past, and then saying these mammals that are traded have these pathogens. So the likelihood of them infecting humans is lower or higher, considering the diversity that those mammals have of human-infecting pathogens.

Speaker 2:
[31:00] It would have helped me reading a paper if they had made some of that logic clearer. They just said, we got this stuff out of the Clover Database, and these are shared pathogens, and I'm left to wonder exactly what we're discussing here. Fine. Good.

Speaker 4:
[31:18] Although the other aspect of this is, regardless of which direction the transmission is taking place, what it shows is, what you can show and what they are looking at here, is whether traded wildlife share more pathogens with humans, which tells you a risk of spillover.

Speaker 1:
[31:39] That's right.

Speaker 4:
[31:39] Because if the traded wildlife has the same risk of spillover as wild wildlife, if that's the term, then we don't have to worry about the animal trade being uniquely causing unique vulnerability.

Speaker 2:
[31:51] Yeah. To me, the shared pathogen says that transmission between these species occurs at a certain probability.

Speaker 4:
[32:01] Yes.

Speaker 2:
[32:01] And now we can compare probabilities as you point out.

Speaker 4:
[32:05] Yeah.

Speaker 1:
[32:05] So there are three things of testing, whether traded mammal species are more likely to share pathogens with humans, compared with non-traded, as you just heard, whether illegal trade and live animal markets increase transmission risk, and whether the number of years that a mammalian species has spent in this wildlife trade predicts the number of pathogens it shares with humans. And among the things they accounted for are wild mammals consumed as food, because they're more likely to be traded and transmit pathogens to humans, and also the influence of sinanthropy, right, tending to live in or near human modified environments.

Speaker 4:
[32:49] And they also include this sort of controlling factor for research intensity. Because some things have been studied a lot more intensively than other things, and those are going to be overemphasized in things like the Clover database. So they control for that. They have, in their statistical modeling, they're trying to account for that.

Speaker 1:
[33:16] Okay, so now for the data. Among 2,079 traded mammal species, 41%, 41% shared at least one pathogen with humans, and that's compared with 6.4% of non-traded animals.

Speaker 2:
[33:33] Yeah, so that's a big number.

Speaker 4:
[33:35] Yeah.

Speaker 1:
[33:35] Yes. Yep. So then using statistics, they show that traded mammals are one and a half times as likely to share pathogens with humans. Synanthropic species are 1.2 fold as likely to share pathogens with humans, whereas species used as wild meat show a weaker marginal association. It's very interesting. They have a model that links trade, synanthropy, wild meat use research effort, and zoonotic status, and the model confirms a strong positive effect of trade on zoonotic host status and a smaller direct effect of synanthropy. So overall, mammals in the wildlife trade are substantially more likely to share at least one pathogen with humans, and this is partially mediated by greater research attention and reinforced by synanthropy and use as wild meat. I'm thinking of deers with chronic wasting disease. Yeah. Deer. So they say that the trade is complicated. The simple presence of an animal is a predictor, but the whole thing is really complicated. In fact, for example, they're both legal and illegal channels, and the illegal trade is more likely to pose higher risk because people aren't following the rules, right? Hygiene protocols and veterinary inspections. We don't need to do that. We're slipping by. So they expand the previous model to account for whether mammal species are found in live animal markets or illegal trade. And this improves the model fit. Species traded alive were 1.34-fold as likely to share pathogens with humans. So live animal markets represent a riskier interface. Makes sense. Yeah, makes sense, right?

Speaker 3:
[35:34] They're breathing, transmitting, especially if there's aerosolization of pathogens.

Speaker 1:
[35:39] Yeah. So...

Speaker 4:
[35:41] Yeah, even if you cook them well done, the ones that you're eating are probably not nearly as high risk.

Speaker 3:
[35:47] Exactly.

Speaker 1:
[35:48] Even if you cook them well. They also say that despite this, you can't just focus on one aspect of trade, right? You can't just say we're going to shut down the wildlife markets because there are other ways that these things happen. So you have to think about all of them.

Speaker 4:
[36:02] And the other thing is, as they point out, I think in the discussion is if you ban something that is in demand, you're going to get illegal trade and then that's just going to make the problem worse.

Speaker 1:
[36:16] All right, then they look at this time in trade, right? The idea is species that have been traded longer should host a greater number of zoonotic pathogens. So to test it, they have an analysis of the global trade in animals over the past 40 years. That's the CITES database. And they looked at 236,000 trade records for 583 mammal species that have been traded at least once between 1980 and 2019. They found that the time in trade increased the number of pathogens shared with humans. They estimate on average over this period they looked at, a wild mammal species shared one additional pathogen with humans for every 10 years of presence in the trade.

Speaker 3:
[37:05] Which also makes sense, like there's more numbers of animals if it's in 20, 30 years, there's going to be thousands as opposed to hundreds or whatever the number is. There's just more risk because there's more n.

Speaker 4:
[37:15] More opportunities.

Speaker 3:
[37:16] Yeah, exactly.

Speaker 1:
[37:17] So the idea is if you have a pathogen in a traded species and it doesn't currently infect humans, they're more likely to do so in the future compared with those hosted by non-traded species because the new species are expected to enter the wildlife trade, right? So additional pathogens and potential future zoonotic outbreaks. One last thing, their model also showed that among the traded mammals, the ones found in live animal markets share on average one and a half fold more pathogens with humans than those traded solely as products. The species in the illegal trade shared 1.4 more pathogens with humans than those traded through legal channels. That's consistent with this idea that the illegal trade and the live animal markets facilitate cross species transmission. Although they say that the effects are less strong than the effects of time spent in trade. That's really stronger. Well, so that's it. This is a correlational study, of course, right? It doesn't prove anything. But animal to human transmission is a driver of pathogen exchange, given this asymmetry of human-animal interactions. They say humans regularly consume wildlife, but the opposite is extremely rare.

Speaker 2:
[38:44] Yes. As Angela was saying in the pre-show, it's like these results are expected. But it's really good to have data that you can point to. And good numbers study well done.

Speaker 3:
[39:03] I'd also like to add, though, that two of the largest mammalian orders, which are Rodentia and Chiroptera, so rodents and bats, are also very much so underrepresented, at least in something like this, because they're not used for horns and skin and meat and things like that, so they won't be sampled as much and they won't be traded as much. But that doesn't mean that they don't have as many zoonotic viruses, even just by number of species. 25 percent of all mammals are rodents and 22 percent of all mammals are bats. Between that, there's almost 50 percent of all mammals. I think that's over 3,000 species of mammals, which we know have very, very, very high diversity of viruses and unknown if they could have zoonotic potential or not. Every time someone samples a bat, there's a new virus that could be potentially zoonotic. So I think it's also important to say that there's still reservoirs that have tons of viruses that are not necessarily being traded, and that, like we said in the beginning, us encroaching on their habitat is still increasing risks very, very high for us. We can get back to that after we talk about the paper about bats and the vaccines that we're going to talk about. But I think that it's just this sampling bias that distorts the zoonotic potential risk of other mammalian orders.

Speaker 1:
[40:22] No, it's true. I mean, for example, cutting down the Amazon forest, people in there have a lot of contact with exotic viruses, and they're not being traded, the animals, right? But they can still acquire them.

Speaker 4:
[40:34] Yeah. And that is more true for bats than for rodents. There are a lot of rodents that are traded in the pet trade especially. But bats, not generally kept as pets, not really a lot of meat on them. So yeah, very good point.

Speaker 3:
[40:49] Yeah.

Speaker 1:
[40:51] So the big conclusion is we have an urgent need to improve biosurveillance of traded animals and animal products for pathogens. And I totally agree with this. But try getting that. Try doing it. I think it's going to be difficult because as they also mentioned, a lot of the wildlife trade, even the legal trade, is culturally based in different countries, and they may not appreciate your incursions because they may think you want to terminate it. And then countries won't let you do it, right? So there's a lot of, well, in many countries there are wildlife markets, but in China, they wouldn't let anyone get near the Huanan Seafood Market, right?

Speaker 3:
[41:34] Vincent, what was the name of that guy we met at ASV that was doing environmental sampling with robots?

Speaker 1:
[41:40] Do you remember that? That was Eric.

Speaker 3:
[41:43] Oh, yeah. What's his last name?

Speaker 1:
[41:44] From Cambodia.

Speaker 3:
[41:45] Exactly. Well, they were doing environmental sampling in pig farms and in wet markets and things like that, and that was really cool. So if somebody could implement something like that, where they literally had little robots driving around sampling in, let's say, a pig farm. They also had people that were working in the wet markets with filters on them. They had these, I'm trying to remember, but filters on their sleeves to detect viruses. They had a little filter that then they would do PCR on and stuff like that, but I think it was Tolgino, if it was like metagenomics. But that was really interesting. So they were detecting tons of viruses just circulating in the markets.

Speaker 1:
[42:21] Eric Carlson.

Speaker 4:
[42:22] Carlson.

Speaker 3:
[42:23] That's it.

Speaker 1:
[42:23] He is at the Virology Unit at the Institute Pasteur du Cambodia. Yeah. I want to go visit because he said he would show me all his sampling methods.

Speaker 4:
[42:33] That sounds cool.

Speaker 3:
[42:34] They had drones too. They had like drone sampling.

Speaker 1:
[42:37] It was very cool.

Speaker 3:
[42:38] It was very cool.

Speaker 1:
[42:39] Because there are a lot of markets there, right? Also, he said, well, actually, I had him on a TWiV. He was in Australia and I was here. He said, just the rice farming introduces a lot of pathogens to the people who are doing it, right? Because there are lots in the waters and so forth. Okay. That is our first. Then our second paper is in Science Advances. Let's have a journal called Science Retreats. Ecological Vaccination. Dickson would object to that. A strategy to prevent zoonotic spillover from bats.

Speaker 4:
[43:24] And the three co-first authors are Hongyue Li, Fei Yuan and Yan Fang Yao. Two senior authors are Chao Shan and Ai Hua Zheng. The group is from the Chinese Academy of Sciences in Beijing, the Wuhan Institute of Virology, Kunming Medical University, Henan Normal University in Xinjiang, Jilin Hei Yuan Bioengineering in Jilin, and Beijing Mihai Biotechnology in Beijing.

Speaker 1:
[43:52] Okay, so bats, as Angela says, 22% of all mammalian species are reservoirs or many zoonotic viruses, coronaviruses, rhabdoviruses, paramyxoviruses. They often don't have clinical symptoms and they've been linked to outbreaks, right? Ebola, SARS, MERS, COVID-19. And their idea, yes sir.

Speaker 4:
[44:16] I do have a bone to pick. I would be reviewer three on this introductory paragraph. So the way they phrase it, bat-borne viruses have caused major outbreaks, including Ebola, SARS, MERS, and COVID-19, okay? We don't know for sure, we haven't proven that a bat-borne virus caused that, okay? We don't actually know the wild world.

Speaker 1:
[44:40] But we never will.

Speaker 4:
[44:41] We never will.

Speaker 3:
[44:42] I like to say ancestral virus, very, like, for example, whenever I, because I have a bat project in my lab, half my thesis is on bats. Whenever I present it, I say there are lots of, specifically RNA viruses, most of them are RNA viruses that are lethal to humans, but that present very few, like, bats are seemingly unharmed by them, but that it's, I totally forget what I was going to say. What were you, I blanked. Alan, what were you saying?

Speaker 4:
[45:10] So I was going to say, I would rewrite this as bat-borne viruses have been linked to major outbreaks.

Speaker 1:
[45:16] That's a good way to show totally.

Speaker 3:
[45:18] I'm sorry, I say ancestors of these viruses, most recent common ancestors of SARS-CoV-2, like RAGTG13, LOWS.

Speaker 4:
[45:25] I'm totally on board with their point.

Speaker 3:
[45:26] Exactly, ancestral viruses.

Speaker 1:
[45:28] It's totally right because the virus that you have today, which you think is associated, is not the same one that you, you know, it's fine.

Speaker 3:
[45:35] Exactly. And especially because most of them are RNA viruses and they're constantly recombinating, so it's never going to be the same virus.

Speaker 1:
[45:40] Yes, of course. In fact, if you looked for the ancestor of SARS-CoV-2, you wouldn't recognize it because it's changed so much. So anyway, their idea is to immunize bats, wild bats, to decrease zoonotic transmission. Now, this is a crazy idea, but the paper is nicely executed, so I thought it would make for some nice discussion. But with a bat, you're not going to give it intramuscular.

Speaker 3:
[46:05] Definitely not.

Speaker 4:
[46:06] Have a blind-reader vaccination clinic with a sign out front.

Speaker 3:
[46:09] Just so people think about. So bats, there's over 1,400 species of bats, and they live in colonies of up to millions of bats. So you can have, where's that place in the United States? They come out from underneath that bridge.

Speaker 4:
[46:21] Austin.

Speaker 2:
[46:21] That's Austin.

Speaker 3:
[46:22] Yeah, in Austin. There's millions of bats coming out from out of that bridge. Imagine trying to vaccinate every single one of them. But there have been strategies in the past. I think they mentioned it in their introduction for the vampire bats, the hematophagous bats, where they give oral baits. So oral vaccines, where they leave food that has blood on it. Basically just pieces of meat that have the vaccine in them. They can eat that. But this paper is interesting, because it's doing, as Vincent will get into, it's using a vector, which can be quite dangerous in the wild. We can talk about that. Yes.

Speaker 2:
[46:56] I think it's also relevant as background, that the notion of vaccinating wildlife against a disease in and of itself is not only not crazy, it has, there are successes with this. And we've done this on several twifts in the past. The classic example is throwing a vectored rabies vaccine in a poxvirus vector that's in bait out of airplanes into the wild to get foxes and raccoons and some of the more common mammals. And that has been extraordinarily successful in reducing the burden of rabies in the wild, and therefore as a source of rabies in the human population in both Europe and the US. So, so, vaccinating wildlife is not crazy, but...

Speaker 3:
[47:44] Depends how.

Speaker 2:
[47:45] Depends how. And what animals you're talking about. I mean, as you described, the bat population, Angela, it's a bigger problem.

Speaker 3:
[47:55] And it is a flying mammal.

Speaker 4:
[47:57] And because of the diversity of the order, I mean, you gave the example of the vampire bats, that's great if you are dealing with that particular species or one of the species that feeds on blood, but that's not going to work for the frugivorous bats or the insectivorous bats. They're not going to come to meet. And you certainly, as you said, you can't walk into the hibernaculum cave full of millions of bats and go around with a needle. That's not guano work.

Speaker 2:
[48:26] Not guano work, is that what you said?

Speaker 4:
[48:29] You're still trying to slur that in there.

Speaker 3:
[48:32] To your point, Alan, there's two huge, which is another, we can get into that after Vincent, but the type of bat that they choose to do their experiments on doesn't necessarily make sense fully, which bat they chose. And also, to Alan's point, there's fruit bats, there's vampire bats, and there's bats that only eat insects. And they're extremely phylogenetically diverse. Like some of them are 20 grams, some of them are 2 kilos, the flying foxes. Their metabolisms are different. They're very different, and doesn't necessarily mean that this would work through all of them. But let's look at the vapor. Yes.

Speaker 1:
[49:09] So this has been tested before in laboratories. Nobody has tested vaccines in the wild. They have tested them in captive bats, which we're going to see here. But interestingly, I didn't know they did this. In Latin America, to control rabies, they do bat culling, which seems like a really bad idea.

Speaker 3:
[49:30] Yeah.

Speaker 1:
[49:31] And wouldn't work either, right? Because there's just so many of them.

Speaker 3:
[49:35] Oh, and it's terrible, because they use rodenticide, and they end up killing lots of other species that are around those bats, because they use warfarin and things like that, which are terrible, like anticoagulant drugs. They just give them anticoagulant drugs, and basically the bats bleed out. It's horrific how they kill them. And lots of other mammals end up dying because of it.

Speaker 4:
[49:53] And that's a horrible idea, because you're going to, I mean, even on its face, you're going to disrupt that whole ecological balance with the bats and the insects. And they're a critical part of that ecosystem, which is going to make the risk of spillover even higher. Yeah.

Speaker 2:
[50:08] This comes under the heading of what could possibly go wrong, right?

Speaker 4:
[50:12] Yeah.

Speaker 1:
[50:14] So there are two viruses they're going to look at here. Rabies virus, right? Which you can find in bats, and often dogs get it from contact with wildlife. So it's a public health problem. And as we've said already, they've tried vaccinating wildlife, and it does a good job in like foxes and raccoons, but it doesn't do anything in bats. And then Nipah virus is the other one. It's a paramyxovirus, which is mostly found in frugivorous bats, like terrapis bats, the ones that are big, that Angela mentioned, with a couple of feet wingspans.

Speaker 4:
[50:54] And if you want a quick summary, or if you want an entertaining summary of the Nipah virus spillover potential, watch the beginning of the movie Contagion.

Speaker 3:
[51:04] Or you can just think that they're a very fast summary, is that the flying foxes, they're also called flying foxes, they hang from the trees, they eat lots of fruit, their saliva is full of virus, it falls to the ground, other intermediate hosts, either people are underneath them getting infected, or other mammals, terrestrial mammals, are eating the fruit, and basically that's it. It's just, they're just eating, throwing their food.

Speaker 1:
[51:26] They also contaminate date palm sap, which is being taken out of the palm trees in these containers. The bats like to drink it, they contaminate it, and people drink it, and they get infected. It is highly lethal in people. So there actually is a Nipah vaccine, which is available. It's been tested. It is actually the Hendra glycoprotein, which is a related paramyxovirus, which is also spread from bats to horses in many places. And it's available for horses, but it also works for Nipah, and it's been tested in people. So if there's an outbreak, they could go in and immunize people. So what they're doing here is they're using vesicular stomatitis virus to make vaccines to carry antigens for rabies virus and Nipah virus. This virus can infect insects and mammals, right? And that's what you need for this. They will have two delivery approaches. First, they will have mosquitoes carrying this virus, and they will use saline traps to attract bats, and they will drink in the trap, and the trap is loaded with the vaccine. And then, sorry, the mosquitoes bite bats, and the mosquitoes bite bats, and the bats eat mosquitoes. And so the saline trap exploits the bats' mineral-seeking behavior.

Speaker 4:
[53:06] Right, so the two strategies are this mosquito strategy and the saline trap strategy.

Speaker 2:
[53:10] But the mosquito strategy has two arms to it. Mosquitoes bite bats, and bats bite mosquitoes.

Speaker 4:
[53:21] Yes.

Speaker 1:
[53:23] And so they're gonna look at these vaccines for rabies and DIPA, both rodent and bat models. And we're gonna see what happens. So they put the glycoprotein of rabies virus into the VSV genome, between the M and the G genes. There's also a deletion in the M protein of VSV, which makes it attenuated. It's no longer pathogenic. And they grow this virus in cells. They can show that the rabies glycoprotein is made by Western blot. And then they infect lab-reared Aedes aegypti via blood feeding with this recombinant VSV rabies virus. And just the glycoprotein.

Speaker 4:
[54:02] My understanding is that this, in addition to attenuating the VSV, this change may also limit its ability to spread. Is that accurate?

Speaker 1:
[54:13] Spread, you mean transmission from?

Speaker 4:
[54:15] Transmission to a new host. Because they talk a bit about the potential of this VSV to go, for example, once it gets to the bat, to another bat. And they seem to think that is unlikely.

Speaker 1:
[54:31] Yeah, I think we're going to look at that, okay? I'm not sure of the answer right now. So they feed this virus to mosquitoes. They can find it in home mosquitoes at day three after feeding, and it persists for 18 days. Now mosquitoes don't live very much longer than that. So that's a good thing. And it reaches about three times 10 to the fifth focus forming units per mil. They can find the virus in the salivary glands by day seven, persists there for 18 days. And that's important, right? Because it needs to be there for it to be delivered by a bite.

Speaker 4:
[55:09] And these are EDS egypti mosquitoes, I don't know if we mentioned.

Speaker 1:
[55:11] EDS egypti, yes, lab adapted. So this VSV rabies vector proliferates in the mosquito and disseminates in their saliva. Now they say, this is very interesting, minimize potential ecological safety risks. Which is a huge thing, right? Huge. They irradiate the mosquitoes. So these are VSV infected, EDS egypti. They're going to hit them with irradiation to sterilize them. And they say, this is okay, the mosquitoes don't mind this at all. They survive, they have no problem eating. They have no difference in the salivary, vaccine titer. These mosquitoes, these sterilized mosquitoes, do not transmit virus to their mating partners, and they don't transmit virus to their offspring. And they say, this is a very interesting statement, effectively eliminating the risk of environmental virus leakage. I would say you could never eliminate it, right?

Speaker 4:
[56:11] Yeah.

Speaker 1:
[56:11] No matter what your experiment shows.

Speaker 4:
[56:15] I mean, talking about releasing these mosquitoes carrying a lab-engineered virus, going back to Rich is what could possibly go wrong.

Speaker 3:
[56:25] Also, the fact that they say they only live two weeks, but these mosquitoes can actually live up to four to six weeks, and they can travel, normally, Egyptia isn't one of the far traveling, but up to a kilometer a day. And if they're living for a few weeks, that means that they can get pretty far in the wild. I just have to add that.

Speaker 1:
[56:44] Yeah, but the thing is, so they show in this lab experiment that they don't transmit the virus, but who knows what can happen, right? I just don't know. But yeah, the idea is eventually to release these mosquitoes, right? OK, so then they look in pigs. They allow, they take this virus, and they intradermally infect pigs. They don't have any weight loss. They don't find virus in tissues or secretion, but all the animals seroconvert. So apparently, there's some transient replication in the pig, and there's no illness in shedding.

Speaker 3:
[57:22] Well, that's because VSV is naturally a pig virus. I think they're just showing that it's not virulent in its natural reservoir host.

Speaker 1:
[57:29] Yeah. All right. Okay. So then, they're going to look at some experiments in mice. So they use the mosquitoes with two methods of delivery in mice, mosquito ingestion. They're going to feed the mosquitoes to mice, and they're going to allow the mosquitoes to bite the mice. So they sterilize the mosquitoes again by x-ray irradiation. They infect the mice in these two ways. 12 days after blood feeding, the virotiter reaches three times 10 to the fifth FFU per mosquito, and then they use those to immunize the mice. No significant weight loss. These are Balb C mice. By the way, for ingestion, the mice are fed homogenates of five or 20 vaccine carrying mosquitoes. It's a dose response. Then they measure virus neutralizing antibody titers. By day 14, they get a nice increase in neutralizing antibody titers, which are above the minimum needed for saying that you are rabies positive, antibodies positive. Then the mosquito bite group, the mice were exposed twice to 30 vaccine carrying mosquitoes. They have the mouse in a cage. They put the mosquitoes in there and they fly around and bite them.

Speaker 3:
[58:56] Poor mouse. 30 mosquitoes, one mouse.

Speaker 1:
[59:00] Kind of outnumbered. After 28 days after the first exposure, 11 of the 12 mice seroconvert. Then after two exposures, the antibody titers reach a good level. The mice are making antibodies by these two approaches. So they challenged them intracerebrally with the Labadapid rabies virus.

Speaker 3:
[59:23] This was just to show that it is pathogenic in mice and that it's not that it's not doing anything to the mice.

Speaker 1:
[59:29] Also, they want to put it right there and not have to wait for...

Speaker 3:
[59:32] Exactly.

Speaker 1:
[59:35] Then they look at survival for 14 days. All the control mice died. These are mice that didn't get immunized, right? The ones that ingested 5 in 20 mosquitoes, they had 92% and 100% survival rates. So 20 mosquitoes, that's how much you have to eat mouse.

Speaker 3:
[59:52] This makes me think, though, that... Sorry, just like to interject, because in one of the first figures, they're showing that the bite, so like the mosquitoes actually are biting the host, which probably even if there's 30 mosquitoes in one mouse, all 30 are not going to end up biting the mouse. Let's say it's only like five, or who knows how many, right? It's very, it's like stochastic, who knows? But then the actual homogenate, where they're, a homogenate means that they're like crushing it up and giving it to the mice. And also the mice die less with the homogenate, so it just makes me think that there's less viral titer, that there must be less virus if it's 20 to 30, and they die less. If you look at the survival curve, they actually die more. I think it's 42% die with the bite as opposed to with the homogenate, they don't. And it's interesting because when we start looking at it in bats and things like that, we don't see that, I'm wondering if just Balbsea is more sensitive to this than the other species they use because later we can look at hamsters and bats and we don't see the same effect, but I don't know, in that survival curve, the ones that got bit die significantly. I mean, there's no star, but it says they survive 58%, which means that they died 42%, which is not a small amount.

Speaker 4:
[61:00] No.

Speaker 3:
[61:01] Anyway, so I feel like they don't show it. I don't think they showed like a focus forming unit of the homogenate itself, but I'm guessing that it's lower than the actual, like from the saliva.

Speaker 1:
[61:14] Yeah, there is a difference in that Kaplan-Meier curve, for sure. But anyway, it does work to some extent, which is the proof of concept, right? And then you can always tweak it later. Okay, so then, let's see, do we, we're still on mice. Okay, so the challenge we just talked about, now they're gonna look at bats. So they're looking at insectivorous bats, which are the primary reservoirs of rabies. So they use the greater tube-nosed bat.

Speaker 3:
[61:44] I also have qualms, I just have to say I have qualms at this too, because they say insectivorous as if that's like one type of bat, when that's literally 600 species of bats. This is just one of them that lives in Asia. And interestingly, prevalence of rabies, I don't know how high it is in those bats. I tried to look and I couldn't find any, cause there's, but just like as a caveat, I don't know if it's a natural reservoir, especially because I checked to see where they got their bats and they actually caught them from the wild. So these aren't bats in a colony, like in a captive colony, they're actually caught from the wild and they just saw if they were seronegative, which they were.

Speaker 1:
[62:18] Yes, they're seronegative against rabies. And then they give...

Speaker 4:
[62:23] Which actually suggests this species may not be a natural reservoir for rabies, because the ones you happen to catch are seronegative.

Speaker 1:
[62:31] That's interesting. It depends on the percent positivity. It may vary at different times of the year.

Speaker 3:
[62:36] Of course, of course. It's just there was no information on like a reservoir that this is a defined reservoir, is what I mean.

Speaker 4:
[62:42] A good point.

Speaker 1:
[62:44] So two doses of vaccine were given 28 days apart, either by ingestion or bites, mosquito bites. And there's no change in body weight after immunization. And they got neutralizing antibody exceeding this. It's 0.5 IU per mil, which is the level below which you don't have any protection. So it was above that. Okay, so they have they have they challenged these bats with 1000 LD50s of a virus. And so six weeks after vaccination, they intracranially inoculate the bats with 1000 LD50s of this rabies virus. The body weight of bats in both groups remain stable. But with the two vaccinations, but the control group 20 percent weight loss within 18 days, 75 percent survival in the ingestion group, 100 percent in the bite group. And all these all the bats that died had signs of rabies.

Speaker 3:
[63:50] This also makes me want to add, I know I'm being very specific about this, but in South America where they have lots of rabies and in North America and lots of bats, bats that have been caught that are seropositive and things like that, it's not associated with severe disease because the reservoir hosts. So it's very interesting that these bats, when you give them rabies, they're dying. It suggests that they're not adapted to the rabies virus and it's not a virus that would necessarily be within their population, which is maybe good, which is why we should vaccinate them, but it isn't just just also points at the fact that it might not be its natural reservoir.

Speaker 1:
[64:29] Well, it also could be that the glycoprotein of the rabies in bats is different from the one they're using here, which may be different enough to make it. So if you wanted to do this, you really need to do a survey of what's in the area that you want to immunize and see what the glycoprotein sequence is, right? Okay, now we're going to look at an oral vaccination method using this saline attraction. So bats have this mineral seeking behavior.

Speaker 4:
[64:59] As do many animals.

Speaker 1:
[65:02] As do we.

Speaker 3:
[65:04] Do you like salts?

Speaker 4:
[65:06] Salt is actually critical to human history. The trading of salt has been true.

Speaker 3:
[65:11] Without salt, we would die.

Speaker 4:
[65:12] Yeah. But for example, if deer hunters will leave a salt lick out in the woods, and the deer come to it, if you go to a farm, they'll have a salt lick for the horses. So this is a very common behavior.

Speaker 1:
[65:27] So there's this tray where they have the vaccine in the saline, and then there's a mist generator next to it. There's a nice figure showing.

Speaker 4:
[65:38] The mist generator is so the bats will smell the salt water and be able to fly to it.

Speaker 3:
[65:43] It's also propagating the virus just everywhere. If you were to put this in a cave, anyway.

Speaker 1:
[65:49] All right, so they make a... And now this is Nipah virus. I'm sorry, so, right? This is, yeah, this is Nipah virus now. So, because these bats, these frugivores bats don't feed on mosquitoes, so we need to do something else. We use the mineral thing. So, they make... Am I in the right place?

Speaker 3:
[66:12] Okay, no. With the Nipah virus, they actually end up doing the same strategy, which is why I thought it was weird.

Speaker 1:
[66:16] Oh, I jumped ahead. Sorry. You're not on Nipah yet. We're still on rabies.

Speaker 3:
[66:20] Yeah, we're still on rabies.

Speaker 1:
[66:21] So, we want to have a way to immunize bats that's practical because we can't do it the other way. So, they have these bats where the vaccine is present and minerals bats and they have. So, if they first look in mice, oral vaccination with VSV rabies at a couple of doses and they neutralizing antibodies are good after a certain amount of time. In fact, by four months, really good and it's sustained up to six months. And then these mice are intracerebally challenged with 50 LD50s of rabies virus. Six weeks later, the controls all die. The vaccinated mice survive for at least 14 days. So, this is again giving you oral vaccination, right? And so, for bats, they're going to now look in bats. They have a two dose regimen. And all four vaccinated bats are protected against rabies virus challenge. Control group all died. They do a second, they say, because bats probably get infected multiple times, they do a second challenge three months later, and all the vaccinated bats survive that too. They also want to know, could we give a number of doses of this vaccine to bats? So, they orally immunize them every two days for a total of five doses, no weight loss. They don't find any VSV RNA in throat swabs, fecal swabs and all the organs. So, they say favorable safety profile for repeated administration, although they haven't talked to the bats about how they feel, right?

Speaker 4:
[68:05] They haven't taken them to the opera.

Speaker 1:
[68:07] Okay. Now, they're going to do Nipah virus, right? Which we can't use mosquitoes here because these bats don't eat mosquitoes. So, they're going to combine mosquito bites and oral administration. So, they make a recombinant VSV with the glycoprotein of Nipah virus. They make this virus, it works, the glycoprotein is produced, it can infect mosquitoes, and it goes to the salivary glands like VSV. So, they first look at this vaccine in Golden Syrian Hamsters, which is a model for Nipah virus. Two mosquito bite exposures, they make high neutralizing antibodies, or a single oral dose gives good neutralizing antibodies. Then they challenge the hamsters intraparitanninally, the 1000 LD50s. So, an LD50 is the dose that will kill 50 percent of animals. So, they're doing a thousand of those doses, a really high dose. All these vaccinated hamsters survive the challenge. Weight is pretty stable and all the controls die, five to eight. And one hamster survived without being vaccinated. We should study that.

Speaker 3:
[69:17] I was about to say that hamster should be studied.

Speaker 1:
[69:21] Don't sack it, keep it.

Speaker 3:
[69:23] Yeah.

Speaker 1:
[69:25] They also look in M leukogaster with this Nipah vaccine with the same vaccination methods and get hightiters of neutralizing antibodies as well. Okay. Now, the next set of experiments are very interesting. So we mentioned that these insectivore bats eat mosquitoes, and the mosquitoes in turn feed on the bat blood. So they want to see if this actually happens. We know that bats and mosquitoes often live in the same caves, and they have a cave in Guangdong, which they use as their study site. There's a bat species there, Hipposideros larvatus, which is an insectivorous species. And they take fecal samples, and they look at the DNA sequence, DNA present in the fecal samples, and they find that lots of insect DNA from specific families. So the bats are indeed eating insects, and they collect mosquitoes from the same cave, and they can speciate them. And DNA analysis of blood meals from these mosquitoes, you can find bat DNA in it. So bats eat mosquitoes, and mosquitoes feed on bats in the Guangdong cave.

Speaker 3:
[70:48] I think they found three species of bat within one mosquito, like three different species of bat's blood within one mosquito. So obviously the same mosquito is getting around.

Speaker 1:
[71:00] Boom, boom, boom, boom.

Speaker 4:
[71:02] Yeah, and bats commonly share hibernacula with multiple species.

Speaker 3:
[71:05] Yeah, the co-roosting.

Speaker 1:
[71:06] That's a nice word, hibernacula.

Speaker 4:
[71:08] Hibernacula, yes.

Speaker 3:
[71:09] Hibernacula is only when they're hibernating, though.

Speaker 4:
[71:12] Yes, right.

Speaker 3:
[71:12] Now when they're...

Speaker 4:
[71:14] They commonly share lodgings, they room with other bats.

Speaker 3:
[71:17] Roosting site.

Speaker 1:
[71:18] Yeah, it's a roost.

Speaker 3:
[71:19] Yeah, roosting site.

Speaker 1:
[71:19] It's the bat roost. Yeah. All right, so then they can't do field work, right? So they're going to do...

Speaker 4:
[71:30] Well, they can't field vaccinate these. Well, they shouldn't.

Speaker 3:
[71:33] They shouldn't do field work. Not that they can.

Speaker 4:
[71:37] This is not ready for release in the field yet.

Speaker 1:
[71:40] So they're going to do field simulation under laboratory conditions. So they have six insectivorous bats. So they have three leukogaster and three rhinolophus, and they have no antibodies to rabies virus. They're exposed to VSV rabies by biting and ingestion. So after two days, half of the mosquitoes are engorged, and 15 percent were unaccounted for.

Speaker 4:
[72:08] I love that. Yes.

Speaker 1:
[72:10] They were eaten by the bats. They measure neutralizing antibodies and they're there. And then they want to do oral vaccine delivery, so they make these saline traps. The trap is a small humidification device that makes a salt mist and a flat bottom container filled with a vaccine in the saline for oral vaccination. This is cool. They add a tetracycline to the saline, and a week later, they can find tetracycline in 85 percent of bat fecal samples to show that they're actually drinking from this thing. I like that. That's pretty good. You know, this is funny. The saline trap, they mentioned before, but they didn't explain it. Now they explain it later. This is a trend in this paper. It should be at the beginning. It should be before, right? Yeah. All right. So they say bat cave temperatures are like 15 to 25 C, and so they check the stability of the vaccine at 25, and it was okay for a week. So then they do a simulation to look at SARS-CoV glycoprotein in VSV, and they have six bats flying around the saline trap with VSV SARS. They show that the bats are drinking, and by day 28.5, the six bats bat-sera convert. So these are, it's a pretty big space. It's 36 square meters, right? Six by six meters, right? Yeah. And they let them fly around and, you know, they go to this.

Speaker 4:
[73:52] 36 cubic meters.

Speaker 1:
[73:53] Cubic meters, yeah. So what is the, what's the dimension of that then?

Speaker 4:
[74:00] Three by three by three. Three cubed is 27.

Speaker 1:
[74:09] It's not six feet on each side.

Speaker 4:
[74:11] No, it's not.

Speaker 1:
[74:12] So it's less. It's less than six feet.

Speaker 4:
[74:14] Between three and.

Speaker 3:
[74:15] Meters, meters, hmm.

Speaker 4:
[74:17] Well, it's more than, it's more than three meters, which would be nine feet, right?

Speaker 2:
[74:22] I got my scientific calculator out here.

Speaker 4:
[74:25] Yeah, do the cube root of 36.

Speaker 3:
[74:27] It's large enough for them to fly.

Speaker 2:
[74:29] 36 or 3.3.

Speaker 4:
[74:31] 3.3.

Speaker 1:
[74:31] 3.3, so they can fly around.

Speaker 3:
[74:33] That's not that big. That's actually smaller than I thought.

Speaker 4:
[74:36] Nine feet on a side, roughly. Nine, 10 feet, maybe.

Speaker 1:
[74:39] Yeah.

Speaker 3:
[74:39] I mean, these are small bats, though, so for the Ranolophus and the Hippocitoris, they're only about this big. They weigh max 30 grams. They're very small.

Speaker 1:
[74:52] I was at the bat facility in Colorado and for Collins, and it's a 20 by 20 foot room, so it's much bigger than they're flying around.

Speaker 3:
[74:59] Yeah, but Tony has, they have the huge fruit bats, the Jamaican fruit bats. Those are bigger guys.

Speaker 1:
[75:05] Yeah, they made another facility for that, but ones that he showed me were only this big.

Speaker 3:
[75:09] Oh, it's true. He was getting insectivorous small bats, Tony, he told me.

Speaker 1:
[75:12] Yes, that was the beginning. We walked in and they were just flying around. He said, watch out, they'll pee on you.

Speaker 3:
[75:18] And you're like, pee pee pee, please.

Speaker 4:
[75:21] Yeah.

Speaker 1:
[75:22] But I had to wear these big gloves, right, too. I don't know why. Anyway, so this, you know, this vaccine can induce neutralizing antibodies. It's protective, but, you know, they call this a one health approach, right? So the bat vaccine will help both humans and bats, right? The Nipah vaccine helps humans and horses is the same idea. We're all in one world. But what's going to happen with this? Give me your thoughts.

Speaker 3:
[75:57] Like, I think that this is not going to go anywhere, unless it's a specific route so you can put in one of these misting things. But at the same time, like the mosquitoes, I think, is crazy. You can never release mosquitoes. I don't think that should ever be done, because those mosquitoes can, they already said that the mosquitoes can live up to a month, let's say, even if it's just two weeks. They can travel a kilometer a day, so they can get up to, let's say, 10K away or more, where there can be humans that can be bit by these mosquitoes. We have no idea how this virus would replicate in humans. They've never tested that. So obviously, there are people around bats, because bats are everywhere. Like, we're encroaching on wildlife. And also the fact that they said that out of their mist, it lasted for a week was actually worrisome for me. I was like, that's very long, like the stability, meaning that other intermediate hosts that are getting into the cave, other like vertebrates or non-vertebrates could also ingest the vaccine. We don't know how it's going to replicate in them. Like, there's just so many layers of factors that we can't control. So I think it's a nice idea, but I don't think it's very practical, especially for the risk of humans and other like bystander mammals.

Speaker 4:
[77:10] Yeah, they, I mean, you don't know what the mosquito is going to bite either. So you would have to test every possible species in a 10 kilometer radius of the roost.

Speaker 3:
[77:20] And humans, you have to do a human trial then?

Speaker 4:
[77:23] Yeah, exactly.

Speaker 3:
[77:24] Because there's going to be humans around. That's the thing. Sure. Like, there will be humans everywhere.

Speaker 4:
[77:29] They propose some ideas. Well, you could put a fan at the mouth of the cave that would blow the mosquitoes back in and let the bats come out. And it's just not definitely, you know, then the electricity goes off for your fan and the mosquitoes come out and you don't know what else is in the cave. And so I think the mosquito idea is just it's very clever and I'm glad they did it. It's it's fascinating to think about. But I don't see that happening anytime soon.

Speaker 1:
[77:59] Can we make a vector that is not replicating? Why don't we just like deliver an antigen?

Speaker 4:
[78:06] Right. You could you could make a non replicating vaccine if you could get that to last long enough in the mosquitoes.

Speaker 1:
[78:15] I don't even need to use mosquitoes.

Speaker 4:
[78:17] I mean, you could write the saline trap. The saline trap, I think, is a much more viable strategy. To Angela's point, yes, the saline could get around the cave and could get into other species.

Speaker 3:
[78:29] But better than the mosquitoes.

Speaker 4:
[78:30] It's much more contained. It's not going to fly 10 kilometers away. The virus is not going to survive out in daylight for weeks.

Speaker 3:
[78:39] You can put signs up around the cave so humans don't go in, because there are people that go into caves looking for-

Speaker 1:
[78:45] Yeah, sure.

Speaker 4:
[78:46] I mean, you could put a fence across the cave during the week that you've got the saline trap in there. And that could be much more closely monitored and could be delivered kind of like the way you throw rabies baits out of a plane into the wilderness. You don't actually know what all is going to eat those. But that's a very effective and established strategy. So I think that has potential here. The mosquito approach, I think they even mentioned in the discussion, the possibility of genetically engineered mosquitoes.

Speaker 3:
[79:16] Which also is-

Speaker 4:
[79:17] Is a whole other bowl of wax that, yeah, I mean, and I've followed that since people first proposed it. And there have been some test releases and some experiments. And if we get to the point that we're OK releasing genetically engineered mosquitoes, then maybe this is something you could do with them. But that's not anytime soon.

Speaker 3:
[79:41] I still think the current strategy with the baits is much more controlled, because first of all, they're baits that are normally meat based. So only carnivores are going to be eating them. And carnivores are the ones that are carrying most of the rabies. So it's a lot more controlled. There's not going to be like some, I don't know, other animal, like a deer or even though they could also get rabies.

Speaker 1:
[79:59] But it's not the main.

Speaker 4:
[79:59] There is actually evidence that herbivores, including deer, will opportunistically eat meat.

Speaker 3:
[80:05] OK, if they're very hungry, if they have wasting disease or something, maybe.

Speaker 4:
[80:09] You could potentially get this into other animals.

Speaker 3:
[80:11] But a human won't be eating a piece of random meat necessarily in the middle of a fight.

Speaker 4:
[80:16] Well, I've known some humans that might try it, but.

Speaker 1:
[80:20] But like the lady picked up the bait from the dog, right?

Speaker 3:
[80:24] That's true, that's true. So there's always a risk, but I think mosquitoes is like a crazy risk.

Speaker 4:
[80:29] That's over the top.

Speaker 1:
[80:31] By the way, at least for the story we did on TWiV, the bait is actually in a plastic packet, and the animals have to bite it, and it leaks out, and then they get it, so.

Speaker 2:
[80:42] Yeah, and I think it's stamped all over with warnings.

Speaker 4:
[80:46] Yeah. So it's like that chewing gum that we had this when I was a kid. You bite into it, and there is this juice in the inside that came out. Yeah.

Speaker 1:
[80:58] Yeah.

Speaker 3:
[80:59] Anyways, it's a cool idea though. I think it's a very cool idea.

Speaker 1:
[81:03] It's a funny idea, fun to do.

Speaker 3:
[81:04] I also think, I don't know if it would work in fruit bats, because once again, the bats they use, they're insectivorous, and they're looking at Nipah, which is a fruit bat virus, who knows if we'd have to test this in fruit bats if they were gonna want to use it in fruit bats, they'd have to test it in those species first, like the Rosetta's or the Terrapis, but it's cool.

Speaker 4:
[81:23] Fruit bats do probably seek salt.

Speaker 3:
[81:26] Oh, for sure, they could test this. I mean, they could do the same thing, but it's also harder to catch flying foxes, and I don't know if they're allowed to, and they're huge, roosting them. If they only have a three meter enclosure, that's almost the size of flying fox, like open wingspan. So, anyway.

Speaker 1:
[81:45] OK, let's do some emails. Let me take this first one. Chip writes, I've become a huge fan of your work to keep good science in the public conversation. I appreciate your focus on good data and revealing the intricacies of research methodology. Here's my question. You all have been alarmed and dismayed by the rise in measles cases this year. I've been shaking my head about it too and talking to friends about it. I had one challenge me on historical data. Looking at several sites, there seems to be a giant spike in the 1990 timeframe. What the heck caused that? I have a graph here of measles in the US from 62 to 2023, and you can see in the 60s, there were huge spikes of up to 500,000 cases a year. But then it got really low, and then in 1990, there's a little teeny spike less than, I don't know, 50,000 cases, I guess.

Speaker 2:
[82:45] Huge relative to what had become the background.

Speaker 4:
[82:48] Yes.

Speaker 1:
[82:48] The background had been very low, and so it was above that. But this is the reason. There are four reasons for this. First, there was low vaccination coverage in preschoolers, particularly in low-income communities. They were using a single dose strategy at the time of MMR. That was a contributing factor. And so the AAP, the American Association of Pediatrics, recommended the second dose in 1989, but too late for the epidemic. There were budget cuts during the Reagan administration that reduced federal funding towards immunization. And finally, three transmission patterns, predominantly among unvaccinated preschoolers. That was 38% vaccinated school age five to 17, and then unvaccinated and vaccinated post school age persons. So that's the reason. And then after that, it went down. And in 2000, we eliminated it from the US. And it was like that until not too many years ago, when it started circulating again, because people stopped getting vaccinated because of Andrew Wakefield's work. Yeah. Okay. And Alan, can you take a couple?

Speaker 4:
[84:04] Yes, I'll take. So Tom writes, re-TwiV, TWiV 1313. Maybe they're all dementia vaccines. The links between infection and other diseases is getting attention in a good way. Do a quick search for Frederica del Monte, MD, PhD. She is now a professor in medicine in the Department of Medicine, Division of Cardiology at the Medical University of South Carolina, provides a link to a YouTube video. It looks like featuring her, and I have not watched this, but I assume she's talking about what we were talking about on TWiV.

Speaker 1:
[84:35] Yep. Yep. Okay.

Speaker 4:
[84:39] Thank you very much. And Terry writes, hi, I love all of your podcasts. Please give up the great work. I found this in my email and thought you all would find it interesting, especially the response from RFK Jr.'s spokesperson. And this is, what is it? The inadvertent funders of health hoax sites, big medical brands and health organizations are unintentionally funding these sites through, oh, algorithm-driven advertising. Right, interesting, so the anti-vax sites are getting advertising revenue. The algorithms are throwing up ads from actual drug companies that are financing those sites. Those drug companies may want to evaluate how their advertising budget is being spent.

Speaker 1:
[85:31] Interesting, yeah, you can read the article here at this link.

Speaker 4:
[85:34] So who's bringing in the pharma dollars?

Speaker 2:
[85:36] Yeah, so they, I have to point out this one thing here. In response to NewsGuard's inquiry about the study's findings, that the US. Department of Health and Human Services has funded health misinformation, HHS spokesman Andrew Nixon said in an email, quote, Let's be clear, this happened under the Biden administration, etc.

Speaker 1:
[86:04] He's a jerk, he's such a jerk. Angela, please take the next one.

Speaker 3:
[86:10] Yeah. Hi, your discussion of per protocol versus intent to treat was a bit confusing, in part because using this terminology in the context of a synthetic trial is confusing. In a standard perspective clinical trial, intent to treat means you define the cohort at the time of randomization and you analyze everyone who was randomized, whether or not they completed the protocol. Per protocol restricts analysis to only those participants who completed the full protocol. Per protocol analysis can lead to a number of biases. For example, if a drug leads to frequent or serious adverse effects, participants may selectively drop out of the treatment arm but not the control arm. Restricting analysis to those who completed the protocol will underestimate the frequency and severity of adverse events. For drug approval, the FDA requires ITT analysis. In the case of the Synthetic Randomized Trial, people who got the flu shot are more likely to get another flu shot the next year and end up being included in the PP analysis but excluded from ITT. You noted that the study showed stronger effects for vaccination by the mild cognitive impairment criteria compared to a more restrictive Alzheimer's disease diagnosis. It's possible that chronic inflammation leads to mild cognitive impairment even if it does not cause full-blown Alzheimer's disease. On the cause of Alzheimer's disease itself, you mentioned the debated between myeloid versus tau protein accumulation, but a bigger issue is whether amyloid and tau protein accumulation are the cause of neuronal death or a response to other factors that stresses neurons. Monoclonal antibodies such as laconomeb are quite effective at removing amyloid, but only modest effects on a clinical performance, a 27 percent decrease in the rate of cognitive decline. By comparison, high dose versus regular dose flu vaccine did not just slow the rate of progression, but prevented Alzheimer's disease altogether. And this on the top of the effect that standard flu vaccine has only... And this on the top of the effect that standard dose flu vaccine has on risk for Alzheimer's disease. I'm not sure what he means there. But chronic neuroinflammation may be the real cause of Alzheimer's disease, and amyloid protein accumulation may be a secondary response. Best to David. This is David States, MD, PhD. Does anyone know what he meant by on the top of the effect?

Speaker 4:
[88:33] So on top of the effect that standard dose flu vaccine has on the risk of AD.

Speaker 3:
[88:39] Oh, has on the risk of AD. Okay, okay, okay. Sorry. That was... I was lost in the words. It was quite long. And I don't know this PPITT. I did not listen to this.

Speaker 1:
[88:49] This is what we discussed. But this is the way the paper presented it also.

Speaker 2:
[88:53] But I was really happy to hear this discussion of the difference between intent to treat and per protocol. Because I've always assumed that you would want the per protocol data since they completed the trial. But this is a really nice demonstration of how the intent to treat, in fact, is equally, if not more, informative in some cases. I appreciate that. And I should say, we've interacted with, David has written this a number of times and we interacted with him during the COVID pandemic. In particular, I interacted with him in trying to help set up a trial for screening for COVID in Austin. He was working for a local company at the time. So hi, David. Thanks for your email.

Speaker 1:
[89:46] Rich, can you take the next one?

Speaker 2:
[89:48] Brian writes, greetings. Given Vincent's recent interest in physics, I thought that he and the group as a whole might enjoy reading through two short papers that form, at least for me, a model of how to write papers so that both specialists and generalists can get something out of them. As such, I present from 1972, the twin papers around the world atomic clocks predicted and observed relativistic time gains. These papers may be found at, and he gives a couple of links. Unfortunately, these are behind a paywall. Even with my VPN link through University of Florida Libraries, I couldn't get at them because I would like to read them. Both are quite short, two to three pages including endnotes. For me, they do an excellent job of explaining what the expected differences would be, why they would have that value, and why both special and general relativity are involved. For the observations, more than half of the paper consists of error and uncertainty analysis, very important in these results in particular. As a scientist, albeit in astronomy rather than virology, I always appreciate the time and attention you give to research papers, and how careful your discussions are for the understanding of a non-virologist. As an employee of the Space Telescope Science Institute, I am also just thrilled when you have a space-related pick at the end of the episode. Just you wait. This is good. Particularly if it involves JWST, as almost all of my work involves that telescope. Regards from Greenbelt, Maryland, where we have sunny skies at a temperature of 72 Fahrenheit between 22 and 23 C, although the clouds are reported to be on their way later. Brianne. Cool. Yeah.

Speaker 3:
[91:37] These papers are so cool. I just sent you both papers via text message. Or I can send it on e-mail too, but I send it to your iMessage because I have the access through McGill. So now you have them.

Speaker 2:
[91:49] Yeah. Send them to me by e-mail.

Speaker 1:
[91:51] These are so cool. This is the experiment which shows that when you fly above the earth, the clocks are different from the ones on the ground. You use these really high accurate atomic clocks.

Speaker 4:
[92:04] Cesium atomic clocks. And they sent them on commercial airline flights around the world eastbound or westbound to get two different relativistic shifts in the clocks. Very cool.

Speaker 2:
[92:15] I don't understand why there's a, I read the abstract, why there's a difference in the shift eastbound versus westbound.

Speaker 4:
[92:23] Because the earth is turning.

Speaker 2:
[92:24] Okay.

Speaker 4:
[92:24] At about a thousand miles an hour.

Speaker 2:
[92:26] I mean, that's what I figured, but I'm gonna have to read the papers before that really computes.

Speaker 1:
[92:34] Okay. Rodney writes, I, this is about TWiV 1313. I'm a multi-year follower of your stimulating discussions of viruses, political stupidity of our current administration, and the various tangents via Pics of the Week and Followers Letter. Vincent's comments on his visit to Kansas in 1311 and being a resident of this state causes me to comment on his visits to interview science folks whenever they occur on the virus topics as he does. Had he mentioned in advance of his speaking engagement, I would have come being a former microbiology, virology, molecular biology retired faculty member, I would have been able to visit KU. Second suggestion on a great science, great physics books. One quote on its back cover from Anthony J. Leggett, winner of the 2003 Nobel Prize in Physics states, This is an engaging book which situates some of the most important episodes of quantum physics in their historical social context. I too have an interest in physics, especially because it seems to be a major mystery why the classical model and quantum mechanics cannot seem to be married in a grand unified theory. The book by Jim Baggett, The Quantum Story, A History in Forty Moments, he speaks to the individual findings of those who contributed to what we know about the subject from its beginnings to the most recent issues in quantum physics. Each person, moment, he writes about has some biographical information that is engaging informative and illuminating about the findings. At times for the non-physicists, he tells you to skip ahead to continue his narrative, thereby avoiding the mathematics involved.

Speaker 3:
[94:10] Thank you.

Speaker 1:
[94:10] The book has notes and sources for every one of the 40 chapters of bibliography and an index for those like myself who need to go back to something that was in an earlier topic. That's Rodney from Kansas.

Speaker 2:
[94:23] Cool.

Speaker 1:
[94:24] Yeah, I've been reading about the unified attempts in Brianne Green's book and well, they're working on it, right?

Speaker 2:
[94:32] Yeah.

Speaker 1:
[94:34] Well, sorry about the Kansas. I don't usually do it. I mean, I do say on some podcasts, I'm going to Kansas and that's about it, but there's never any advertising. So we have one more and I think Alan, you're next.

Speaker 4:
[94:50] I think that's my turn. Barbara writes, hello, Vincent, a good friend recommended your TWiV podcast to me a few months ago. I have learned so much in just a few months of listening. I was dumbfounded by the double and triple benefits of the shingles, flu, pneumonia, RSV, and COVID vaccines. This information is so valuable. I am hopeful it can be used to persuade the vaccine deniers by extolling the added benefits of lowering dementia and cancer risk by taking these vaccines and keeping them up to date. Maybe the benefits of lowering the risk of cancer and dementia will promote vaccine uptake. This could be tested. This could be tested, I would think. Keep up the good work. Barbara, who adds, PS, the Columbia is my alma mater, PhD in 1983 in nutrition graduate school. Cool.

Speaker 1:
[95:35] Wow. You're a GSAS graduate too, Alan, right?

Speaker 4:
[95:38] I am, yes.

Speaker 1:
[95:41] That's the year after I got here.

Speaker 4:
[95:41] A little later than 1983.

Speaker 1:
[95:43] Yes, indeed. All right, time for some picks of The Week. Angela, what do you have for us?

Speaker 3:
[95:52] I feel like you guys must have done this before, but I couldn't remember if you had or not, but anyway, Nextstrain, which is a website that they defined it as real-time tracking of pathogen evolution. By evolution, I think it's more of an epidemiological website. Have you guys ever heard of this?

Speaker 2:
[96:10] Yeah.

Speaker 1:
[96:10] Yeah. Trevor Bedford, right? He was on TWiV at an ASV a couple of years ago.

Speaker 3:
[96:15] He must have heard of this, but it's very cool for, I think even just the general public, to see, and for anyone, to see different pathogens, like let's say if you want to look at SARS-CoV-2, where there are outbreaks, where there are hotspots. If there's Ebola, you can look to see, and the website is beautiful. The way that it's, like if you click on core pathogens, if I click on dengue, it gives you all, even the phylogenetic trees of like which dengue where, which Ebola where, if it's Ebola there, if it's Ebola X, Y, Z. And I think that the illustrations are really nice and that they're pretty accessible for everyone. And if you want to, you can go deeper into like different visualizations even of the phylogeny. So you can see like rooted versus scatterplot versus, there's different ways to visualize the data, which I think is really nice. Yeah, I just thought it was a really cool website that I had come across the other day. And I was like, I'm sure that you guys have already seen this, but just for the whole TWiV gang.

Speaker 2:
[97:11] Yeah, it's very cool.

Speaker 1:
[97:12] Also during COVID, it was great because they were sequencing everything, right? All the sequences were there.

Speaker 3:
[97:17] But now it's not as COVID centric. It seems like there's tons of other viruses.

Speaker 1:
[97:22] So yeah. Yeah. And also, you know, GISAID, which is another database, they're kind of nasty about sharing data, but this one is nice about it. So this is good. Rich, what do you have for us?

Speaker 2:
[97:34] Okay. I have a pic that was an article that was sent to me by a TWiV listener, Jan, who in fact was even at TWiV 1000. I corresponded with her a little afterwards. She's got a picture of me with her at TWiV 1000. I'm sure there's one of you, Vincent, somewhere as well. The article is... She sent it to me because the article originates from a research organization in Gainesville, Florida. Okay? It's actually not a new article. It's from 2019. But I read it and found it really fun. It's called A Precarious Perch. And it's basically a research study on a bird that spends some time in Gainesville. That's the swallow-tailed kite. That's quite an interesting bird and a really well-written article about how they study these birds and some of their habits. And to me, one of the most remarkable things is that these are migratory birds. And one of the things that they do is to stick, you know, tracking radio transmitters on them and then track their movements, about which they knew nothing before this group started studying them. The article looks at one bird, she went out, the author went out in the field with these guys, and they got one bird that they named Suwannee. And so for the tracking, if you want to see it, I isolated Suwannee's track so you can see what this bird did over a several year period. And the migration pattern goes from Florida across the Gulf of Mexico, the Gulf of Mexico, to Yucatan, and then down follows a land route into South America and Southern Brazil. It's about 5,000 miles, I think, and they do this every year, so they're doing 10,000 miles a year. Interesting, the satellite tracking, they've obviously collaborated with an organization that tracks sea turtles, okay? seaturtle.org. That's a nice collaboration. They are the Avian Research and Conservation Institute that is run by primarily a guy who did a postdoc in Gainesville in the 80s and couldn't leave, stuck around, and it looks like the Research and Conservation Institute runs out of his house, probably, which is about 4 miles from where I used to live. So, I found this an entertaining little dig and I appreciate the heads up, Jen. It's cool.

Speaker 3:
[100:22] Very cool. They're really cute too. They kind of look like birds of prey. They're very cool. They look like seagulls, but then when you look at their face, they have like a very pronounced beak, almost like a little eagle.

Speaker 2:
[100:33] And the way they trap this bird is to put up, effectively, a mist net. And behind the mist net, they put a great horned owl, which is, in fact, their major predator. I would have thought the birds would stay away, but no. These birds are protecting their territory by attacking the owl, and they run into the mist net.

Speaker 3:
[100:52] Oh, wow.

Speaker 1:
[100:54] Alan, what do you have for us?

Speaker 4:
[100:56] So we've been picking a lot of books lately, and I'm going to continue doing that. And it occurred to me, I should probably say, someplace that I found recently to buy books other than Amazon. So, you know, easy to click on Amazon and buy the book, and your hard copy shows up the next day, or you get it on your e-reader instantly. That's very convenient. But then your local independent bookseller goes out of business and you say, gee, that used to be a nice little shop. I wonder what happened to them, and you click on another link to order another book from Amazon. Yes, exactly. Well, you can now have the convenience of Amazon with a completely independent operation that will support your local bookstore. This is bookshop.org. So you go there, you can create a free account, and then you choose a local bookstore that you want to use as your source, basically. Now, bookshop.org has an Amazon size catalog of books, not the self-published stuff that Amazon does, but I'm not interested in that anyway. But all the commercial books are on there. You buy your book, and they'll ship it to you or you get it on an e-reader. There's an app which I found works quite nicely on my phone. So the books that I read in the gym, I now buy this way and load onto my phone. I'm effectively buying them from a place down the road, a cute little bookshop down the road that then gets a profit share from bookshop.org.

Speaker 2:
[102:35] This is excellent.

Speaker 1:
[102:37] It's interesting.

Speaker 3:
[102:37] That is really nice.

Speaker 1:
[102:39] But these are physical books, right?

Speaker 4:
[102:41] You can buy physical books from them or you can buy e-books.

Speaker 1:
[102:44] E-books too.

Speaker 4:
[102:45] I've been buying e-books.

Speaker 1:
[102:46] Oh, that's good. I like that. I prefer that.

Speaker 4:
[102:48] Yeah.

Speaker 1:
[102:49] Very cool. So as you know from the e-mails, I've been trying to learn physics. And when you do that, you inevitably get interested in space because it drives a lot of the questions, the universe and all that. So I found this video on YouTube. It's really cool. The Mysterious 30 Year Journey of Apollo 12. And this is a while ago, but in September of 2002, astronomers found an asteroid in an unusual orbit around the Earth. And this is just drawn in this video. You have to watch it. It's not very long. It goes around the Earth and then it leaves the Earth orbit and goes in another weird orbit near the sun and then comes back. It goes around the Earth and then it does the same thing back and forth. So they looked, they did spectral analysis to figure out what it is, and it came back as titanium based paint.

Speaker 4:
[103:55] It's a spaceship.

Speaker 1:
[103:57] It's the one of the stages of Apollo 12, which is still, I think, maybe the second stage.

Speaker 3:
[104:04] Flying around.

Speaker 1:
[104:05] Which they didn't quite, they meant to park it in an Earth orbit, but something went wrong with the firing, and so it's in this weird orbit.

Speaker 4:
[104:13] The Saturn V third stage.

Speaker 1:
[104:15] Third stage?

Speaker 4:
[104:16] Yeah.

Speaker 1:
[104:16] Oh, so cool. And they could figure out what it is.

Speaker 2:
[104:20] I just absolutely love this, Vincent. This is a great video. Everybody ought to have a look at this.

Speaker 1:
[104:25] It's very nice. Yeah. And I love that they could do the spectral analysis and figure, oh yeah, that's the paint we used on Saturn V, right? So cool. And there are some others too. Like are the orbiters still around the mood from the landers, right? The lunar excursion module, the part, all kinds of videos about that as well. We have a listener pic from Fernando. I'm listening to your closing discussion on Vincent's Brianne Green pic and Alan's point that the equations really matter for understanding makes me recommend the first two volumes of Sean Carroll's series, The Biggest Ideas in the Universe, Space, Time, and Motion, and Quanta and Fields. Yes, they have enough equations to make explanations precise, but all symbols and operations are explained simply. Now, I'm a bit biased because I have a math background, but I feel that with a bit of work, you will get a lot more out of these volumes than from dozens of the other non-equation books on those topics, regardless of who wrote them. Yes, I've read lots of the non-equation books too, because I sometimes want to skim a topic like black holes or quantum entanglement without working too hard. To be honest, most of those readings left little lasting impression, even if they were fun at the time. A few key equations studied conscientiously are worth millions of words. Keep on teaching. Well, I find Brian Greene's not fulfilling. I really don't understand it, because he can make all the analogies that he wants, but I want to know why. I don't get it from that. We talked about this last week. So I will try some of these. One of the problems I have with equations is that people don't understand, don't explain all of the constituents, right?

Speaker 2:
[106:12] This would be very interesting, and I'm sympathetic with the concept here, because I find that when I read science writing about stuff that I'm familiar with, that doesn't go, doesn't do the real stuff, and uses corny analogies and stuff instead, I find that really frustrating or upsetting, because you're not really communicating the real stuff. Let's take the time to communicate the real science at a level that people can understand. So I'm not going to read these, Vincent, but you do it and tell me if it works. This is good.

Speaker 3:
[106:50] Vincent, maybe I can hook you up with my dad or my sister to help explain some of these equations.

Speaker 1:
[106:55] Well, that would be lovely. Your sister was here once, but we didn't have enough time. Now she left New York, so I can't talk about it.

Speaker 3:
[107:03] She's there actually now in sabbatical. So she's actually back and forth between New Haven and New York. So maybe I can set up a meeting between you two and she can explain some things.

Speaker 1:
[107:14] I really have so many questions. But yeah, I thought of her when I was thinking about this because it's really fascinating. I don't know anything about it. I can't figure out the equation.

Speaker 3:
[107:24] So my dad is a math prof. So he can also and he also writes papers in physics and stuff. So maybe and he's your age. Maybe you guys will hit it off. I should I'll put you in contact.

Speaker 1:
[107:35] Okay. Yeah. People then I could fire questions at them. Right. What does this mean? All right. Well, that's what we do on TWiV, Rich. We do more advanced explanation. Right. We don't have just complete vanilla.

Speaker 2:
[107:49] The real thing.

Speaker 1:
[107:51] It's the real thing and it's a little bit hard and that's why we don't have millions of listeners because it's a bit hard. But I think if you can get through it, my philosophy is if you keep listening over and over, eventually you will get the concepts, right? Because we do repeat everything more or less from week to week. Hic, it's been 17 years now. If you've been here from the beginning, you'd really know your virology.

Speaker 4:
[108:19] I've been here from the beginning and I'm really starting to know my virology.

Speaker 1:
[108:23] I do too. I learn a lot and of course, the other podcasts teach me as well and I really enjoy it. I think I love reading papers now more than I used to when I just read polio papers for some reason. I get to read everything. That's TWiV 1315. You can find the show notes at microbe.tv/twiv. If you have any questions or comments or picks of the week, we love to hear from you, TWiV at microbe.tv and if you enjoy these programs, we would love your support. Go to microbe.tv/contribute. Alan Dove is at alandove.com, turbidplac.com. Thank you, Alan.

Speaker 4:
[109:06] Thank you. It's always a pleasure.

Speaker 1:
[109:08] Angela Mingarelli is at McGill University, Immune Vet on Blue Sky. Thank you, Angela.

Speaker 3:
[109:14] Thank you so much. Enjoy the beautiful weather.

Speaker 1:
[109:19] Rich Condit is an emeritus professor, University of Florida, Gainesville. He's currently in Austin, Texas. Thank you, Rich.

Speaker 2:
[109:25] Sure enough. Always a good time.

Speaker 1:
[109:27] 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, Jolene Ramsey for the timestamps, and Ronald Jenkees for the music. You've been listening to This Week in Virology. Thanks for joining us. We'll be back next week. Another TWiV is viral.