Special Omicron Variant Update with Dr Daniel Janies

Down the Wormhole

Episode 95

As much of the US is caught in the grips of yet another wave of COVID-19 infections from the Delta variant, a new, sinister sounding mutation has been making news. The Omicron Variant. What is it? Why is it noteworthy? How is it different from Delta? The answers may surprise you. Frequent guest and expert on the evolution and spread of pathogens, Dr Daniel Janies answers your questions about this new variant as we discuss unknown viral lineages, where this all is going, and what role white tailed deer may have in the future of this pandemic.

Dr Daniel Janies is an American scientist who has made significant contributions in the field of evolutionary biology and on the development of tools for the study of evolution and spread of pathogens. He is The Carol Grotnes Belk Distinguished Professor of Bioinformatics and Genomics at University of North Carolina at Charlotte. He is involved with research for the United States Department of Defense, and has advised multiple instances of the government on methods for disease surveillance.

Colby T Ford, Denis Jacob Machado, Daniel A Janies
Predictions of the SARS-CoV-2 Omicron Variant (B.1.1.529) Spike Protein Receptor-Binding Domain Structure and Neutralizing Antibody Interactions

Jacob Machado, D., White, R., Kofsky, J., & Janies, D. (2021). Fundamentals of genomic epidemiology, lessons learned from the coronavirus disease 2019 (COVID-19) pandemic, and new directions. Antimicrobial Stewardship & Healthcare Epidemiology, 1(1), E60. doi:10.1017/ash.2021.222

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produced by Zack Jackson
music by Zack Jackson and Barton Willis

Transcript

This transcript was automatically generated by www.otter.ai, and as such contains errors (especially when multiple people are talking). As the AI learns our voices, the transcripts will improve. We hope it is helpful even with the errors.

Ian Binns 00:06

So, today we are welcoming back up a frequent guest, our resident expert, all things COVID. He is the University North Carolina or is that UNC Charlotte with me, and he's the Carolina greatness, Belk Distinguished Professor of bioinformatics and genomics. And we are really excited to welcome back to the show, Dr. Daniel Janis. So thank you for joining us again, Dan, we're excited to have you as we are continuing to navigate all of this changing world of COVID. Yeah, thanks for having me. You know, we reached out to you right away of just, Hey, there's this new variant out there. And so we wanted to kind of pick your brain a little bit of what is the Omicron variant? I know, there's been other variants that have emerged, some that emerged that there was nothing about it and others like delta, but what is it about this one that raised concerns that you know, who classified it as something special, I can't remember their categorization but something a variant of concern? So what does that was that mean? Can you what can you tell us?

Dan Janies 01:06

What's interesting about Omicron is it contains 60 mutations with respect to Wuhan virus that emerged late 2019, in Delta contains 46. And what was interesting about Alpha through delta is that you could see them in in a lineage and, you know, nested set of mutations, building, and each one was, you know, incrementally more efficient than the other. What's different about Omicron is, we don't know where it came from. And it's not really in those lineages. And of those 60 mutations. 37 of them are in the spike protein, which is the protein that the virus uses to interact with human cells. So there's a lot of open questions with respect to those, especially those 37 mutations in the spike protein.

Ian Binns 02:04

So like, what, what kinds of questions I mean, what is it that when you saw this and your team and other teams around the world, I mean, what what kinds of things just popped in your head right away of what what you needed to study or questions you want to answer?

Dan Janies 02:17

The main thing is like, what did those mutations do to the conformation of the virus with respect to the antibodies that your body produces, after vaccination and or after infection, and in our early computational predictions, we predict that the antibodies produced by vaccination will be much less efficient in their ability to neutralize Omicron. need

Ian Binns 02:51

exactly what we want to hear.

Dan Janies 02:52

We've already seen this, you know, with with Delta, hence the, you know, the breakthrough in factions. And we, it's so it's, it's, it's more of the same, I mean, we expect more breakthrough infection. We don't know that much about transmissibility yet. What's interesting about Omicron is one of the key mutations that allowed delta to be so much more transmissible in outcompete previous variants is also in our con, but it's in a little bit different. It's in the same position, but a little bit different amino acid change. So the remains to be seen what that means, early data very early data out of South Africa, where this has been going on since mid November shows that Omicron is starting to outcompete Delta, but it's so early that epidemiological data will take some time to know to come in and numbers.

Zack Jackson 03:52

Is there any indication yet of how virulent it is? how dangerous it is?

Dan Janies 03:59

That the South African doctors are saying it's in the vaccinated, you know, they are seeing breakthrough infections, but they're mild cases, just like, you know, Delta, you know, sort of summer cold, so to speak, and hospitalizations, that data even lags, you know, even more, but hopple hospitalizations are not yet up for the unvaccinated. It couldn't be much more severe. We just, we just don't know.

Zack Jackson 04:24

Do you see that as the the eventual trajectory of COVID in general, is it going to go the way of becoming more transmissible but less deadly, so it just kind of settles in our population? Some

Dan Janies 04:36

people think that's the case. It's hard to predict how many more variants there are, since this one was not incremental, so to speak on the others in terms of its evolution, there might be a lot more space, you know, available for code to vary in that the problem is is that we have the tools now you know, least in the in the developed world. Anybody who wants to vaccination can, or two or three can get one. And B, we're not accepting it. So that leaves a pocket of people that delta, or Omicron, in this case, can use to infect and replicate itself and produce new variants. So that's a situation we really found ourselves in.

Ian Binns 05:20

If I, if I may, I'm just curious. I was something I heard the other day on, on someone else was speaking about this. And so I'm curious. The first SARS that was detected, you know, it spread but not wildly around the world like this. Right. And I know we talked in our original episode, we had you on the distinctions here between SARS cov. One SARS, cov. Two. But one of the things I think that the person said, and I can I can't remember the name right now, but what he said was, is that when a virus is more deadly, what that may be one reason why it doesn't spread so much is because orphan acts very quickly and kills a host quickly that doesn't have the opportunity to spread, like one that is not as deadly. Does that make sense?

Dan Janies 06:09

Yeah, yeah. So you're talking about SARS. cov. Oh, some people say SARS cov. One to distinguish it from SARS cov. Two, which we're experiencing now, there was only about 800 cases. And you know, it was much more deadly, but spread less efficiently leaving SARS cov. Two, and that's one of the things one of the Harbinger's of Delta's that it is out competing other viruses, because when it infects you, it's replicating itself so much faster, and it's getting out faster. And it's not causing symptoms as it's getting out of people as people are shedding it. And so people are even walking around more than spreading it more often. It's making so many more copies of it than its predecessors to.

Ian Binns 06:55

Okay, and so that's, that's what makes this one, just SARS, cov. Two in general, from the very beginning, there's one of the reasons why it spreads so quickly is because we don't know we have it in that, right. I mean, if we go back to

Dan Janies 07:08

ever ever more with very nervous. I mean, that's that was good. And

Ian Binns 07:11

now that's even more

Dan Janies 07:12

that was how Delta became so successful is was spreading, what SARS cov, two was spreading naysmith eyston, dramatically, Delta ramped it up.

Ian Binns 07:24

So another question we have for you, is, you know, if if Omicron does indeed show to be a model, milder variant of the virus, you know, with less risk, someone was curious, or, you know, we reached out to listeners, and what they were curious about is that, if that is the case, does it make sense for it to spread throughout the world largely unchecked, like just, this is kind of the whole some, you know, as you said, that there are is a pocket of the population, especially in the US, and the developed in the the world where we have easy access to vaccines, where people do not want to get it for whatever reason, the vaccination. And so is it someone have said, Oh, we should just let it go unchecked? And so I'm just curious, is there

Dan Janies 08:08

Yeah, that was tried in Sweden early on. And conditions are somewhat different there. They have a lot of people who live in their own house by themselves and things like that. But it was a regretted decision, because it was terrible for the for the elderly, you know, you can have most of the population get a cold, but the people that are vulnerable elderly, the immunocompromised people with other underlying conditions, your you're subjecting them to, you know, to a deadly disease in their case. So that was so those of

Ian Binns 08:44

us who can get vaccinated, it's good to do that. So that we slow the potential risk to others who are unable to get vaccinated. That's the whole point of vaccines in anyway. Right, is there are those who are unable to get vaccinated for whatever reason you're medically in any kind of vaccine. And so they rely on those of us who can't get vaccinated to do it so that they can.

Dan Janies 09:04

Yeah, I think it's an interesting choice in medicine, and that you're not only protecting yourself, but you're protecting those around you. And that, that's probably why No, the arguments hard to swallow for a lot of people.

Ian Binns 09:18

Right, right. Yeah.

Zack Jackson 09:20

I mean, if, if it came naturally, to care about your neighbor, then every religion in the world wouldn't have to make it their number one rule. It was just, they would just do it. But it turns out, it's really hard to convince people to think about other people's well being. Yeah, so it seems like we are, it seems like we're getting more variants like like we're just, we just work it up through Delta. I know out here, they're they're still talking about this delta wave. We've just hit the highest number in our in our county in the delta wave. And now we're talking about another variant. Is there an accelerating impact in this? And is that going to mean? Are we going to see more more quickly? Or is this going to make it harder to end this waking nightmare?

Dan Janies 10:15

We just don't know. And the big surprise of Aamir Khan was, it is so different looking. Most of its mutations are not shared by delta. And so, nor any other Coronavirus such that it really made us wonder several things about where it came from. And it's such a surprise, I can't answer your question. You know, maybe a month ago, I would have said something, you know, about the pace of variance. But this really throws a monkey wrench and all that.

Zack Jackson 10:55

Can you can you talk a little bit more about about that. Like how do we get something that is so far out in left field that doesn't that like a long lost cousin that we didn't get? So

Dan Janies 11:06

there is somebody SARS cov two, okay, so it's not short on the virus. There are several speculations. And I'll just preface this by saying there's, there's no data for any of these that I've seen, I'd like to see some data, but much like alpha, which was first called the UK variant. The speculation there was that immune compromised person had been affected with SARS cov two, and the infection sustained itself in their body and was not fought against by their body. And therefore SARS cov to cut can vary within the person. I heard the metaphor the other day, that situations like an evolutionary gym, where in which stars go v2 can try out, get stronger and try out new tricks. So and then it emerged from this hypothetical person. And then there was not much speculation after that for for alpha, and we saw the other variants becoming just, you know, incrementally better alpha, beta, gamma, delta. The interesting thing about Omicron is that it is not connected to any of these lineages evolutionarily deep, you know, very deep in the early emergence of SARS, cov do we can tell it SARS, cov, two and there that brought up other speculations that SARS cov to from people went into an animal animal population, use them as this, you know, metaphorical evolutionary gym and then reemerged into people. And this is not far fetched SARS, cov, two in the Netherlands, for example. And then Denmark, infected from humans, firing minx using the fair trade, and came back out into infect people. We know in the American Midwest, the stars, Kobe to somehow in whitetail deer. They're not farm, they're wild. But they're friendly, and then accustomed to people, especially in the American suburbs. So that is, still remains to be seen any connections there any evolutionary connections, and the third, which I think is more of a, you could say it's a third problem, or kind of an overarching problem, which there's some debate in the surveillance community is that we thought we were doing a great job, you know, sequencing the heck out of SARS, cov. Two cases, but maybe we're just not doing a very good job. And this thing was under the radar. It was first identified in Botswana in a aids lab, but then identified in mass in South Africa. But then, once people had the sequence to Qian and the Netherlands, they found a bunch of cases and travelers returning to Northern Europe, from South Africa. But then they went back into their on yet to be sequence samples. And they found they had early November, mid November cases. So as we go back, we might find more about this. And we just wrote a paper should be out soon, where we'll review that. There are many cases in many countries in the world where even though we're doing a tremendous job and sequencing cases, you can do a back of the envelope calculation that shows we're not doing enough to catch every variant. And so I think this latter scenario of just under surveying, it would be just a Herculean task to survey everything, but under surveying is going to produce these things and that could account For the animal reemergence case and can account for the, the immunocompromised case. So under surveying is a, I think a blanket explanation.

Zack Jackson 15:10

Yeah, I've heard that that was white tailed deer have it in such large numbers in the places for their testing, it was like 75%, or something I read, and that it doesn't, it doesn't kill them. And so it's like, it's like a little, a little playground for them. And if it comes back, and I when I saw that article pop up, that was the first time in the past few years, I felt legitimately hopeless, was on well, it doesn't matter how much we vaccinate if the white tailed deer population, which is all over my garden is is going to be carriers, then what hope do we have?

Ian Binns 15:49

Do you want to address that question, Dan? Or do we just I mean,

Zack Jackson 15:54

if there's no hope to be had,

Dan Janies 15:58

it's speculation when it was discovered in whitetail deer, and nobody was talking about Omicron. So I don't know if there's a real connection there. There's a there's a danger there always.

Ian Binns 16:08

So someone you know, another question that emerged for us was, you know, how does SARS cov to compare to other viruses in terms of how fast it mutates? And I'm sorry, I was looking off. So if this is related to what Zack already asked me, Is there a there's not a set speed or just happen?

Dan Janies 16:24

Yeah, it's it's, it's relatively slow. And the odd thing is SARS didn't SARS. cov two didn't really mutate until mid 2020. I thought sequencing would be quite boring. And then one mutation occurred. And people who pointed that out got quite famous. Because that mutation became fixed. And on subsequent SARS cov. Two cases, in then, we started to realize that mutations were building up. And this whole concept of variants really took off late 2020, early 2021. And then we realized, especially in the UK, that the variants were more efficient in their replication, and thus their transmission. And then it got really interesting to start sequencing variants, but it wasn't a fast process by any means us about comparing to influenza, which is a bit of an apples to oranges comparison, but influenza does not only in its own right, evolve faster, but it's a different genome structure. SARS, cov. Two is just one very long genome. Whereas influenza has eight chromosome like segments to its genome. So those segments, when a person or an animal's co infected with two different lineages, they can reassort it's called, or its kin to shuffling a deck of cards and dealing out different poker hands. So it has not only the mutational avenue to change, but the reassortment Avenue and the we don't see that in SARS, cov. Two now, even though it's theoretically possible could recombine with, but it's not as able to be as it's not segmented, like informed roles.

Ian Binns 18:08

So with the mRNA technology that we have, with at least two of the vaccines that are approved in the US, at least, what can be done with those that technology, the mRNA vaccines to be able to handle this variant or future variants, especially ones that could potentially be much worse?

Dan Janies 18:28

Yeah. Well, the mRNA vaccines are, they can be just, you know, in essence reprinted and the main makers would like to argue that they can just reprint it and reformulate it and have it ready. I think Maderna said by March. So matter of months, the regulators probably want to some in would be wise to do you know, clinical trials before it's used. So, you know, it's really the vaccine productions, you know, almost immediate, but, you know, I think there's going to be a regulatory period as well, they did start to make reformulations of the mRNA vaccines for alpha and delta. But it turned out the vaccines that they that we had, you know, were already approved, or EUA, at least mergency youth authorization. were effective enough. And so the question is, where do you take on a whole new regulatory pathway versus you have something that's still really good? I mean, we're going to talk about going down in efficiency, I think, and in vaccine efficient efficacy, and for me in terms of Omicron and delta, but they're still wildly good. I mean, a flu vaccine some years is only 30% or 50% effective and, you know, nobody, nobody writes home about that. And so if we go from 96%, effective to 75%, effective for SARS, cov, two vaccines, even those directives against wild type Wuhan virus when applied to Delta, or Omicron, we're still, you know, in the black, so to speak, we're still doing pretty good, you know?

Ian Binns 20:09

Right. But they would have to if if something happened, and you know, a variant emerged, and, you know, the current vaccines we have, are not working very well, we need to make something needs to change. Obviously, they would need to go back through that clinical trials process.

Dan Janies 20:28

Again, right, just I believe so I believe they should. Yeah. Okay. I mean, there might be regulatory regimes around the world where they don't but

Ian Binns 20:35

okay. But it's still significantly faster than what anything we've had prior to these mRNA vaccines, like the process is still faster because of the technology that's available to us now,

Zack Jackson 20:46

is that at all possible to anticipate future mutations and create future proofed vaccines?

Dan Janies 20:54

Yeah, I've been thinking about that a lot. I think we're doing great as it is, but I think we could look at the number of possibilities for making a stable, you know, Spike protein and calculate those structures. And, and sort of anticipate the function of them, I think the latter part is the foreign part is easy, we can calculate out our structures, the understanding what they mean is a little harder than the understanding what they mean, you know, biochemically is a little harder, and then the understanding what they mean, epidemiologically is even harder. So, you know, we see this 30% reduction of 36 upwards of 36% reduction of efficiency against current antibodies by Omicron. But we don't know what that means yet, you know, in the real world, so. So, I mean, we could we could make computers run really hard, but it'd be hard to hard to translate that to the real world. That's a great idea, though. I think it's something we should strive for.

Zack Jackson 21:54

Now. I mean, that seems like it would be easier if the viruses were progressing incrementally, like you said, but with something like Omicron, that pops up out of the blue.

Dan Janies 22:04

Yeah, yeah. There are many ways to skin the cat when there might be a very large number of many ways to make an efficient to make an efficient SARS cov. To that, and we have not until Omicron thought that way. Now, we're, you know, when thinking that way for the last two weeks,

Zack Jackson 22:20

how do you? How are there multiple ways to skin cats? Isn't it

Ian Binns 22:26

wondering where that was? Come? Yeah, pull it off.

Dan Janies 22:30

I like the idea here.

Zack Jackson 22:34

Kendra's not here to defend cat giant,

Dan Janies 22:38

often the metaphor of a landscape is used. And so you have a hilly, imagine a landscape with many hills and the hills are optimal viruses, right. And it's, it's sometimes thought it's hard to go from one hill to another, you can kind of like go up the hill a little bit, you can go alpha, up to delta up the hill. And then when you're on the top, you're kind of stuck in one evolutionary space. But you got Omar Khan on this other hill over here. And so it's hard to imagine being less efficient to get more efficient. But what happens, I think, is that there's a set of contingencies, certain mutations happen that allow others to happen, and therefore evolutionary evolutionarily SARS, cov, two starts climbing a new Hill, so to speak. And there may be many hills of deficiency out there of evolutionary peaks. Okay,

Ian Binns 23:30

can we go back to the white that the deer situation? I mean, when we when you learn that emerged, or that it was detected in the deer population? What does that mean? Like for the human population and stuff? I mean, we talked about not really going away. So since it's not, doesn't appear to be deadly to that population. But is it easy for it to jump back to us from them? Or do we know?

Dan Janies 23:54

We don't know. And it's largely dismissed. I mean, the whole notion of zoonosis I think, in general is very important. We don't like to think of reverse zoonosis because we're clean and animals are dirty, but we're just another kind of animal, right? So we just see, we sometimes give bacteria and viruses to animals, and they're not being treated, but by and large, right, so the virus can live amongst them and evolve with them. And yeah, this is true influenza fun, fundamentally comes from birds. We know all these coronaviruses are many, you know, many of them, clinically important ones we're familiar with come from bats. And that's the idea of a reservoir that the virus is in the wild and ever so often infects people and then we pay attention to it.

Zack Jackson 24:40

That that will always stick with me from our first episode that you said the reason why these seem to come from bats, this goes back to have such great immune systems and nothing kills them. And they fly around viruses bounce around. Yeah, and fly around. What have you been thinking about in terms of this? This virus What's interesting to you?

Dan Janies 25:01

I really would like to know where it comes from. I mean, and I really think it's probably under sequencing and how much I'm wondering how much money and effort we're going to spend to deeply survey viruses. I'm not against it, but and we, you know, we can do it. It's just a matter of political Well, yeah, I'm wondering where the political will is gonna take us and a lot of these things, you know, the President's already said, we're not doing lockdowns. I thought that was the state's decision now. But I think this might be Yeah, might be a point where we're going to just decide to live with the pandemic. Unfortunately,

Zack Jackson 25:38

it does seem that way. It does seem like I looked at cases the other day was like, wow, this is nearly the highest single day that we've ever had. And it looks like it did three years ago when I walk into Target. Yeah. And see, I was just talking with a member of my church who is forget her official title, I'm sorry, Amanda. But she's a big wig in the emergency department of the local hospital and asked her how things are going. And she said, it's, it's heartbreaking, Nick, they're, they've lost like 60% of their staff, and the outside world is acting as if nothing is happening inside. And so all these health care professionals are like, they're completely burnt out. And they've lost their faith in humanity. And they're just, they're done. And it seems like Alright, so this is the new normal, we're just going to normalize dying. And

Dan Janies 26:37

yeah, so we can't, we can't live with very Chris, we, you know, we can't make doctors and nurses very fast. That's a lot of training. And it takes the right kind of person. And so maybe that's the response to this, we're just going to live with it. Because we know, we have to have doctors, nurses, and everybody who makes hospitals wrong. So imagine all the ancillary effects. People are not getting their cancer screens not getting their teeth fixed or not getting their surgeries, if the hospitals full well, healthcare effects are going to be tremendous. We have a study here on campus of the adherence to prep treatment for HIV. And we've seen that gone down in in the COVID period as well.

Ian Binns 27:29

I remember when delta started taking off, you know, we used to live in Louisiana, and there was a hospital system down there in Baton Rouge that talked about that the chief medical officer actually said that because the numbers were so out of control there, that they talked about, that we something along the lines of that they were no longer an efficient system or something along those lines. Because their numbers, they were so overwhelmed. That it they were trying to make it clear to people who are unwilling to get vaccinated prior to the emergence of delta, that the even things his car accidents and stuff like that, that they would not be able to be seen, because they were just that overwhelmed. And trying to send the message home to those who were adamantly opposed to vaccinations that the only reason why this is happening because you're not getting vaccinated. Right. And so that's what they were trying to bring home.

Dan Janies 28:25

Yeah, pre COVID. There was already a crisis in rural America, small hospitals were closing in, in, in towns that were not being near big cities. Right. So don't, don't get drawn to me don't get hurt in the country, that's for sure.

Ian Binns 28:42

Yeah. Which was this I remember when that happened with the when delta emerged, and it really took off, and I was here. And then I just kept looking at, you know, my wife and just kind of saying that this is the US like, you don't think of stuff like that. That's not supposed to happen the United States of America, right. And but as you just said, pretty COVID rural hospitals were shutting down and medical care and stuff. But everyone always talks about, you know, we're the greatest and we have all the best medical care and blah, blah, blah, but then we're turning people away, like doctors, which I'm aware that that's not the case. But you know, it just was it was tough to hear, again, to be reminded of the fact that this is not over.

Zack Jackson 29:24

Wealthy people and propagandists say that we have the best health care system in the world. But right. I think most folks would disagree with that. Yeah.

Ian Binns 29:34

But it's just an interesting perspective being shared. And to hear again, you know, chief medical officer saying, we don't have the ability to care for you right now. Yeah, it was very eye opening.

Zack Jackson 29:46

So if you want to give your give your local healthcare provider, a merry Christmas, happy Hanukkah, or Kwanzaa, whatever they celebrate by getting vaccinated. Yeah.

Ian Binns 29:59

When I remember Dan You and I were part of a panel. And it's still funny to think of this. I think it was like February of 2020. Near the end of February and as before things really took off. Yeah. So we know lock downs were in place yet and compared to now very few cases were in the US that we knew of at the time. And we kind of talked about in that panel about, you know, and, and people were asking about, you know, if this gets out of control here in the US, what about lockdowns, all that kind of stuff? We just kind of kept talking about the acceptable level of loss. Like, you know, and then I remember you pulled up a slide talking about the number of flu deaths every year. Yeah. That we were having time. And so we just, that was considered an acceptable level of loss by society, not, you know, into an individual person, obviously. But it sounds like that may be where some are trying to go. Like, you see some just saying, I'm done. I'm not, ma'am. This is over for me.

Dan Janies 30:56

Yeah, I don't think it by design. And I don't think those that's why I showed those slides. And, you know, I don't think people really consider fluid deadly disease, but it is if you're, if the wrong underlying conditions, you know, so now we've got another one that, you know, before we especially before we had the tools, there is some right side, we do have tools now for we've had, you know, influenza vaccines and antivirals now we're getting to the stage where we have, you know, better vaccines than we did for influenza for, you know, for SARS, cov. Two, and there are some new antivirals. I think that will probably be some bright side and the gloomy picture we've been painting that even unvaccinated people can take a regime of these antivirals and less than their illness. Okay, I'm sorry, infection.

Zack Jackson 31:49

Yeah. So thank you so much.

Ian Binns 31:53

Yeah. Thanks. Is there anything else you want to share with us? Based on what you guys you and your teams have been studying the past couple weeks? Um,

Dan Janies 32:01

yeah, I'll send you the I'll send you the paper. One is we we, we predicted the, you know, even though we surveillance looks Herculean right. Now that it's not, we wrote that. And, you know, we predicted time will tell the clinic, but we predict now that vaccines will be less efficient against Aamir Khan than the previous version. So we'll see.

Ian Binns 32:28

Okay. And we can link to that in the show notes. Yeah, be great. All right. Well, thanks, Dan. I appreciate you.

Dan Janies 32:35

Thanks. Thanks for talking again.