The Bioinformatics CRO Podcast

Transcript of Episode 24: Jeremy Kamil

Disclaimer: Transcripts may contain errors.

Razib Khan: [00:00:00] Hey everybody, this is Razib Khan. It is not Dr. Grant Belgard. I am hosting this for now. Some of you may know from my previous appearance on Grant’s show on the CRO Podcast. I am a geneticist who works in the domain of ancestry population genetics. I also have a quite large mouth. You can find me on Twitter at Razib Khan and you can find all of my stuff at razib.com. I talk mostly about ancestry, history, those sorts of things, but I am really, really super interested in genomics. And over the last year, I have gotten super interested in COVID-19 or should I say COVID-19 has gotten super interested in me. Through this process, I have met some people on Twitter which a lot of people denigrate the site and I do too. But I have to say that COVID-19 brought out the best in humanity, even though it was a difficult circumstance. And I got my first shot recently. So hopefully I’m going to put this behind myself personally, although as a culture and as a society will be grappling with the consequences for a while. And so I wanted to have a friend, Dr. Jeremy Kamil at LSU Shreveport, who I have met over the past year through social media and other forums, because he’s a virologist who’s also interested in genomics. Obviously, he’s gotten to be a deal because of the circumstances we find ourselves in. I think Jeremy will probably tell us, like every virologist now, is in much hotter demand than they were in previous years. Jeremy, can you introduce yourself to the audience.

Jeremy Kamil: [00:01:36] Yeah. My name is Jeremy Kamil. I’m at LSU Health Science Center, Shreveport. Not to be confused with Shreveport, the undergrad campus in town, but we’re like a medical school and I’ve been here about a decade. I am now an associate professor. I came here from a finishing a postdoc at Harvard Medical School studying a virus called cytomegalovirus, which I still work on. And until the beginning of the pandemic was basically the exclusive domain of my research. So yeah, I mean, viruses and virus genes are not foreign to me at all. I’m not a genomics whiz next gen sequencing, as they call it, or Illumina sequencing or nanopore sequencing, all that stuff is pretty new to me, although I grasp all the concepts. But yeah, I’ve worked on viruses for a long time, deleting genes, putting jellyfish genes into viruses to watch, what organelle the protein goes to that kind of stuff. Pretty nerdy stuff, outside the realm of what the general public cares about at all. So it’s usually like Battle of the Geeks trying to get some federal dollars to do your research and then battle of the geeks again to publish your research again you know in some journal but then yeah when COVID-19 hit, I started just because I was mostly forced to. They shut our campus down and told us all of our normal virology research had to stop and the only thing we were allowed to help out with was COVID-19.

[00:02:57] And to me that was less research and more just public health work. So it was really my first encounter, like doing public health work, which usually people think that’s utilitarian or maybe even a little bit drowsy. But I found during a pandemic, it’s pretty exciting. The moment we’re in with regard to sequencing the SARS-CoV-2 virus, which of course is the virus that causes COVID-19, that has never been done. No virus, arguably since HIV has been sequenced so much and i think this far eclipses what have been done with HIV. So the amount of sequencing to watch a virus evolve in real time I think been is a colossal achievement for humanity. And it’s been just a stroke of luck that I’ve had pretty close to a front row seat. I won’t say I have a front row seat, but I’ve had pretty close to a front row seat in the auditorium watching this viral observatory or whatever you want to call it. Actually, there’s a lot of politics, of course, that’s always behind the scenes in anything, not just science, but who gets the funding to do stuff? What is the data look like? Who gets to do the work? Who controls the data? All these things have a lot more to do with politics than they do with pure science.

[00:04:06] And I think it’s just really, really fascinating to see a battle of the geeks and the battle of the rarified monkeys that we are fighting over, things that we do. And as you mentioned, it’s a very collaborative moment in humanity, like we all are getting together to solve this problem and come up with vaccines and watch out for new variants and try to understand them. So there’s a lot of people who are genuinely trying to do the right thing and do good. Even if you can consider people who work at a grocery store or still willing to go to work and change a tire and do you know what they do every day? I mean, there’s a heroism when you’re putting your life on the line to do that kind of work that I think also is going unrecognized. It’s not just the scientists who are doing important stuff. It’s like anyone willing to show up to their job takes on an added importance when there’s like a giant spike of cases in your area. So I think we all deserve a pat on the back. There are things to be cynical about at the same time. There’s a lot of funny stuff going on. It’s been interesting just crashing into it at a whole bunch of different levels over the last year.

Razib Khan: [00:05:09] Yeah. So I guess one thing I want to make it clear to the listener is there’s genomics and there’s genomics. So the human genome has about 3 billion base pairs. That’s about the same size as most mammals. I think there are some birds are a little smaller, but that’s the range. So viruses, they’re small, right? Like, can you give us an intuition of how genomics on a viral scale is different?

Jeremy Kamil: [00:05:35] Yeah. I mean, a virus is like a footnote to a footnote to a footnote compared to the human genome. I mean, these are even. Well, there are some new viruses out there like Mimiviruses that are ginormous and have genomes the size of bacterial genomes. But those are really the exception that proves the rule. I had a lecturer at UC Davis where I got my PhD named Martin Privalsky, and he trained with Bishop and Varmus, who won the Nobel Prize for discovering Oncogenes at UCSF. And he I remember to this day his colorful analogy from like some virology class he gave to us. There’s a good size range of genomes for viruses. You have little tiny ones like Circoviruses, and then things like HIV that are about nine kilobases. So that’s 9000 chemical units long, like APGC or AUGC and RNA. So it’s like 9000 letters long, which is obviously a lot smaller than 3 billion base pairs. And his analogy was like, Well, that’s the dude who gets on an international flight with his toothbrush and a handkerchief. And that’s all that person needs to go traveling. And then on the other end of the scale, you have pox viruses and herpes viruses, which are more like 300,000 base pairs in length and they’re double stranded DNA genome. So I can say base pair instead of bases and length. That’s like the virus that pulls up with an RV to the cell. It literally brings the kitchen sink with it, doesn’t trust the cell to do all that much for it, especially a pox virus. Poxvirus encodes its own RNA polymerase, so it doesn’t let the cell do very much for it. It’s still a parasite of the cell, but relative to HIV, it’s a pack rat. There’s nice range there.

Razib Khan: [00:07:09] So actually while you were talking, I decided to be rude and Google SARS-CoV-2. It seems like it’s in the middle of that range. It’s 30,000, which is a good number because, you could just divide it by 3 billion. So I think that’s like, what? Like, like 100,000th or something of a human genome. And so it’s small on an individual scale, but there’s a lot of viral particles out there to sequence. And so this is one of the issues that is going on. So going off memory, I think the original SARS, didn’t it take like two months to sequence it? Like, can you do you remember off the top of your head?

Jeremy Kamil: [00:07:48] I don’t. So that was long before I worked on SARS. So that was around 2003. People in the field called OG SARS and SARS stands for Severe Acute Respiratory Syndrome coronavirus. And yeah, I think gene sequencing then probably was a little slower.

Razib Khan: [00:08:04] I’m looking at the Wikipedia. They isolated it on March 21st. They finished mapping on April 12th, 2003. I think the publication was a little bit later. So yeah, it’s on the order of a couple of weeks to a month or so. And this is just for a single, the consensus sequence of the virus, I’m assuming. Whereas today, can you give us an intuition of how fast the sequencing is happening with the numbers?

Jeremy Kamil: [00:08:32] Well, the sequencing usually happens way slower than it needs to. But if you wanted to go right from a clinical sample to a complete sequence of a nanopore, you could probably get it done in about 12 hours. Mostly what we do is amplicon sequencing now because it’s cheaper, but a lot of our first sequences were all done using hybridization enrichment capture, where basically the same technology used to sequence like DNA from Neanderthal bones and caves. You have a bunch of biotinylated probes that are tiled along the whole genome of the organism you’re interested in. And in the case of Neanderthal cave bones, that’s the entire human genome. And you’re trying to enrich for human genome fragments from cave dust, basically. And there’s a bunch of bacterial garbage around and you don’t want that. So they’re able to enrich for human reads on their NGS preparations. But with SARS-CoV-2, it’s a similar problem in that when you take a swab from someone’s nose, there’s a bunch of other junk in there, a lot of human ribosomal RNA, probably a bunch of metagenomic bacterial stuff. The virus might be fragmented and not super high quality, so it is important to be able to enrich for that. It’s usually cheaper to make amplicons so they have amplicon protocols. But in the beginning, we were using that hybridization capture enrichment and I think that those approaches, some of those would have been possible in 2003, definitely Amplicon sequencing would have been. I don’t think NGS protocols were anywhere near the maturity that they are now. I don’t know when the Illumina first came out with their version zero, but think it must have been around then.

Razib Khan: [00:10:04] I thought the Illumina technology did it too, like 2007 or 2008. But I did actually look at the publication date. The publication date of the sequence was May 1st, so they isolated it on March 21st and they claimed that they had the sequence on April 13th. So it was still pretty fast. So interesting, this is partly a technology issue. So would you say that you’ve been having to deal with this two track parallel issue where there’s the whole science, there’s the virology, which is what you were trained in, and then you had to

learn this genomics stuff and communicate it to the public. Like there’s just two issues the technology and the science.

Jeremy Kamil: [00:10:44] Yeah. And I think you hit the nail on the head that there’s a lot of smoke and mirrors around that, too when people get political with how the work is distributed, how the funding is distributed. The people who want to play games with where the funding goes and who gets to keep ownership of the data, you’ll notice that they always want to talk about metadata standards and they want to keep talking about bioinformatics because what they don’t want to talk about is the fact that these virus samples that are of interest all come from people. And a lot of people don’t have health insurance. A lot of people don’t have access to medical care. There’s this buzzword now about genomic surveillance. And Rick Bright’s leading a really good initiative from the Rockefeller Foundation to amplify the message that we need constant decentralized sequencing of the things that make us sick to make our world more secure. But I would add to that that you can also make the world more fair and more equal by using genomic surveillance. And that may sound rather abstract, but the rich do care about the viruses that are making the poor sick because they can make the rich sick, too. And how are you going to get a stream of data on the viruses that are making people sick in a South African ghetto if you don’t educate those people about what a virus is and you don’t give them medical care. So the poor have an immensely valuable bargaining chip in genomic epidemiology, in viral surveillance.

[00:12:08] But here almost no one talking about this issue. To me, it’s a great opportunity for humanity to give health care to marginalized people, and in exchange, they would provide samples that could be sequenced for viruses or bacteria that are making them sick. And I don’t think that it stops at a transaction. I think you have to give these people, not just the education to understand that they have diamonds under their front lawn, so to speak, but that they should have a connection to those samples forever, like an anonymous code that, hey, you provided this sample. If we get a sequence from it, here’s a code. You can put this into a computer or into your smartphone and see what science has done with your data. And no one’s talking about that and I think it’s a big global opportunity to make the whole world a lot more secure from the next COVID 2024 or whether it’s a really gnarly flu that’s going to come at us in a couple of years. But also to make the world more fair.

Razib Khan: [00:13:03] Yeah. And want to loop back to the politics policy stuff. You’ve kind of gotten involved, I mean arguably involuntarily, because you’re a virologist, you’re a scientist. But I want to loop back to that. But actually first, I want to take a step back because you talked about being trained as a virologist. You were at Davos a little earlier than me, but you were in the microbiology group, I believe. And so you’re a biologist, you’re a legit biologist. I was in the genomics group, so I’m not really a biologist, in terms of I start with the genomics and I go to the organisms. So tell me about what a virus is actually for the listener, because I think SARS-CoV-2 is part of our world. And yet there are still people out there who don’t know what a virus is, what a bacteria is. Can you talk a little bit about the biology and the structure?

Jeremy Kamil: [00:13:47] Yeah, sure. First, I would tell you that I think any biologist would say someone who studies genomics is a biologist of one sort or another. So I would consider you a biologist Razib whether you like that or not.

Razib Khan: [00:13:59] I’ll take it. I’ll take it Jeremy.

Jeremy Kamil: [00:14:00] And so as far as what a virus is like, something around 8% of our genome is like fossil viruses. So viruses are really ancient things. And there’s still a debate out there about what the RNA world was like, the primordial soup that life first came from. So unless you’re a creationist, it’s still not a resolved question in most people’s mind, like what the first life forms were. But viruses probably came pretty darn early. Virus, just by definition, is an obligate intracellular parasite. It’s something that infects a cell, and most viruses are what we call cytolytic, which means they eventually kill the cell even if they go through a latency or something. When they replicate, they turn the cell into a virus factory and it’s basically like harnessing all of its metabolic might into the assembly of de novo virus particles. So all the macromolecular synthesis machinery of the cell to make protein, to make nucleic acid polymers starts to just shift to make polymers that are virally encoded polypeptides or proteins, if you want to call them that. Of course, viral RNAs and depending on what the viral genome is, the viral genome might be a double stranded DNA virus or it might be an RNA virus, but the virus is going to usually encode a replicase or a replication enzyme to copy its own genetic material. There are, of course, viruses like Papilloma or Polyomaviruses that use our own cellular DNA polymerase to copy their DNA genomes.

[00:15:26] So there’s something called the Baltimore Classification Scheme named after David Baltimore, who discovered reverse transcriptase and also NF Kappab. He’s done some pretty important things in science, but one of his contributions was to classify viruses by, I think, seven different groups as to what type of genome they have and what their replication strategy is. So you can get lost in the weeds pretty quick, even trying to transmit the big picture. But a virus is essentially a rogue, self-replicating, selfish gene that takes over your cell and makes copies of itself. Someone called it like a gene wrapped in bad news or whatever. It’s usually got a little lipid envelope or a way of entering your cell. So it’s a really efficient transfection reagent. If you’re a biologist out there like molecular biologists are often interested in putting foreign genes into cells to study them, and viruses are almost like they’re their own transfection reagent too. I mean, they are really good at getting into cells. That’s one of the things that in biotechnology they’re exploited for. We call them viral vectors, like some of the coronavirus vaccines indeed use Adenoviruses. It’s actually an adenovirus vector. It’s like a gutted adenovirus that can’t really replicate and they put a foreign gene in it, in this case, the SARS-CoV-2 spike to send that gene into your cell. So you make spike and then you can mount an immune response against it.

Razib Khan: [00:16:40] You actually anticipated some of the things that I was going to say back to you. So it’s like a selfish gene. So I think a virus holds your cellular machinery hostage. And it does what it needs to do. And a lot of the negative consequences are due to the fact that it just co-opts things and all it cares about its own replication. It doesn’t care about you. Like if you die, whatever it’s going to like go all over the place.

This is what’s happening with SARS coronavirus too. But then we have some viruses I think like MERS have much higher fatality rates, whereas others, I don’t know, there are coronaviruses I believe that cause the common cold. So I think this is called virulence. Is that the technical term?

Jeremy Kamil: [00:17:21] Virulence? Yeah. That’s a very good term.

Razib Khan: [00:17:24] And so it’s basically how harsh it is cause fatality and morbidity. Can you explain how virulence emerges and evolves? Is it just like a random act of God or is there like a logic to this?

Jeremy Kamil: [00:17:39] There’s definitely a logic to it. A lot of the nastiest viruses and infections and I wouldn’t confine myself to viruses here are things called zoonoses, which just means a virus or a bacteria or even a protozoan parasite that ordinary lives in an animal infection cycle. It could have multiple hosts, for instance, like parasites. But when it spills over into a human being, you get problems. So, I mean, there’s a protozoan parasite that’s found in kitty litter called Toxoplasma Gondii and in immune suppressed people, it can get into their brain. I even had a friend I didn’t know he was HIV positive. I met him in Oregon doing forest activism years ago and I found out and I think 2006 that he died of toxoplasmosis and really brilliant, wonderful person. But in a way that’s a zoonotic infection because that parasite, it lives in a rodent cat cycle. And when it gets into people, it causes problems. If you are immunocompetent, you don’t get very ill from it. But if you’re immune suppressed, you have problems. Flu each year in essence is semi zoonotic because that virus evolves in birds and pigs, mainly in birds, and it’s tropism, almost like the coronavirus is determined by its entry glycoproteins and it reliably spills into humans each year and then transmit between humans, sometimes the nastiest. They call them bird flus don’t transmit well between people. They spill from a bird into a human and the human dies. But the virus is not able to transmit from human to human. They like to sequence those. There’s a lot of different perspectives on virulence, and I’m just giving you more of an evolutionary one and not a mechanistic one. But I’d like the evolutionary perspective because it explains a lot. A zoonosis, it has no responsibility to the host, like a really, really super virulent virus, like Ebola.

[00:19:28] It’s easy for that to burn out because if it kills the host very fast and very efficiently, even if it’s rather infectious, people notice when there’s blood coming out your eyes and you’re collapsing on the ground. You don’t get a chance to infect too many people other than the people trying to clean your body or take care of you in the hospital. It’s hard for an Ebola patient to hop on a plane to a different country, walk around, shake lots of people’s hands, go to a bar, do lots of stuff before the disease kicks in. So the original SARS virus wasn’t like Ebola, but the people who were the most ill were the most infectious. So it actually wasn’t until you were hospitalized that you became super infectious with the OG SARS back in 2003, even though it used the same ACE2 receptor and a lot of ways was a similar looking virus, it didn’t have this presymptomatic transmission phase. And so that’s why Tony Fauci got up in the Rose Garden or whatever it was. He gave a warning speech back, I think March a year ago, and he got it wrong. They thought that only people who had fevers or were sick needed to wear a mask. They should have known better by then. How do you think this virus got all over the place so efficiently if there’s not a presymptomatic transmission? But hindsight’s 2020 and in science dogma is the most stubborn and awful force is the arrogance of, Oh, well, we’ve already seen this before, guys. We had a coronavirus looks almost identical from 2003. And so you have all these public health authorities thinking they knew exactly what this meant, but they didn’t.

Razib Khan: [00:21:02] Yeah, yeah. I guess one thing that people have said is that in some ways, SARS-CoV-2 operates in a Goldilocks zone for spread. Its infectiousness is quite high more than the flu. Its virulence is not horrible, but it’s also not great. And then it has this pre-symptomatic spread stage. And so it seems it’s a combination of a lot of different things to make it bad. Now, it’s not like the bubonic plague where one third of Europeans died. So I don’t want to exaggerate how people get mad at me, but case fatality rate, what are we thinking? Like around 1% or so? Like a little higher, a little lower, depending on public health infrastructure? Is it something that is optimized in the modern world? I mean, obviously not consciously. I’m not conspiracy theorist here to just cause havoc because a lot of people aren’t going to take it seriously because you’re not bleeding out your eyes, but you are going to spread it around to people who are going to die.

Jeremy Kamil: [00:22:05] Yeah, that’s I think correct. It does live in the Goldilocks zone for transmissibility. And I think the IFR and the CFR are two different things. So a case fatality rate is when you’ve actually had an encounter with the medical system, the bureaucracy, and you get diagnosed, that’s a case. So it’s a documented case. This person tested positive for SARS-CoV-2, the COVID-19 virus are you going to call it? And what percentage of those people die? And then there’s something called the infection fatality ratio, which is going to be a lot smaller. It’s the number of actual infections that occur in the world, whether or not they are documented by the medical bureaucracy and what’s the rate of death. And I don’t have those numbers off the top of my head. I should look them up. But I think the case fatality rate is somewhere between 0.5 and 1% on average. But if you get up into people who are in their 80s and late 70s, you can have easily 10% of them dying depending on where in the world you are and whether they have access to medical oxygen and steroid treatments and stuff like that. Especially early in the pandemic when physicians didn’t really know how to treat it, it was a higher case fatality rate in those elderly patients. And of course, different populations have different age segmentation. So if a population is full of a lot of younger people and there aren’t a lot of elderly, the infection or case fatality rates are going to be a little bit lower.

Razib Khan: [00:23:30] The next question is, we talk right now and I want to go back to the genomics and the sequencing. We talk about the British variant, the South African variant and all of this stuff, what was it like before sequencing? Like how did people figure out different variants? There are older techniques, whatnot, but how fast was it like, has genomics really transformed our understanding of how these viruses are mutating and diversifying into different lineages in a way that’s actionable and actually is helping us fight the pandemic?

Jeremy Kamil: [00:24:05] Well, that’s a really good question. I think it’s clear that we haven’t realized or harnessed the ability of genomic epidemiology to protect ourselves from the virus or to take public health action. I think that a lot of the stuff about variants is to some degree more of an exhilarating intellectual curiosity than it is something that’s going to protect the average person in India from coronavirus. I mean, quite arguably, and I’m entirely convinced of this, you don’t need to know about new variants to know that if people in India had not been convinced by reading inaccurate information from news organizations that, hey, maybe Indian people are immune naturally to the coronavirus because of their heritage or the spicy food they eat or something, because we expected to see far more deaths earlier and we didn’t see them. I’m guessing people were pretty worried and probably followed precautions early on or something, because I don’t think there’s some magical difference about the variants there that are driving the huge spike in case rates. I’m pretty much assuming that it’s mostly because people stopped being careful. And you there is undoubtedly some role for the increased transmissibility of variants like B117, which clearly is better at spreading. But most of all, it’s people crowding together.

[00:25:31] And once the virus gets into enough people, it’s really hard to stop it. Like it’s exponential growth. That’s something that someone like you can understand really quickly. But a lot of the average public haven’t had enough experience watching a bacterial culture grow and taking the OD and seeing what exponential growth looks like because it is an awesome thing and it’s a scary awesome thing when it’s not an investment making money or something positive that you want. It’s death and fevers and more spread. India has such a high population and also in the urban areas a really high population density. So that’s a recipe for disaster. Back to what you were saying about phylogenetic trees or strains and variants, I think it’s absolutely amazing that we can watch that happen. And it’s crazy to see one spillover event from a bat or some strange animal in a jungle in China or Vietnam or wherever this emerged from turned into basically a family tree. And I like the biblical example of like, Cain and Abel and all this because it’s almost like it was one species. But now that one strain became a tree and now the branches of the tree are competing with each other and you have like B117, like outrunning everyone else, replicating more.

[00:26:51] But there’s also some other rogue variants just trying to eke out a living or to still exist. And so it’s funny because it was one and then it became many and then many are competing with each other. In the past with viruses like dengue, we know there’s different stereotypes and I think before the advent of genomic sequencing and became so inexpensive to deduce the entire genetic code of a virus. And we mostly used serology which is like antibodies to detect a different strain or a different serotype. Because when viruses evolve or change or are different from each other, some proteins won’t change very much and others will. And so the antibodies from a patient from like 1984 that you had in your freezer, they might not recognize all the same proteins that the 1994 variant had, but it’ll still recognize some. And so you’re like, oh, this is a serotype A, because it has this pattern of detection. And then of course when you sequence, you can figure out, Oh, well, these are the genetic sequences that encode these epitopes on these proteins that the antibodies are recognizing.

Razib Khan: [00:27:53] Yeah. That’s one of the interesting things. You bring all these different sciences or scientific disciplines together that have different histories or genomics, which is almost no history comparatively. It’s pretty fascinating. I see this stuff in the media now sometimes, like the California variant, the British variant. Can you tell the listener, I think most listeners are going to be American what the current state of variants in the United States is. I heard Michigan had a massive spike that seems to be declining now. But I heard someone say, well, it could be its own variant. I don’t know, like, what do you know about this stuff? What’s going on right now?

Jeremy Kamil: [00:28:29] I haven’t geeked out over the latest data, but I’ve been looking at it pretty regularly over the pandemic. There’s certainly a ton of B117 here which emerged in Kent and England probably around November, and the first sequences really were collected in October. But the scientific literature says November. So it came out late last year and it’s thought that that came from prolonged infection of like an immunosuppressed person. They don’t have proof of the exact patient who was patient zero for B117. But it’s really thought that infecting immunocompromised people where the virus can live in one host for a long time, allows the virus to adapt to antibodies that the patient comes up with. So an immunosuppressed person usually doesn’t have zero immune system. They just have a weaker one. So it pushes the virus into a corner but leaves the virus enough room to navigate and comes up with some mutant that escapes a major neutralizing response and then it grows a little bit better. And so it accumulates a series of changes within one patient. And that’s really thought theoretically by the people who really understand the mathematics to study viral evolution. They’ve got some pretty compelling models that show one of the key disproportionate drivers of viral evolution for SARS-CoV-2 is infection of immunosuppressed people. And then of course, there is some baseline change in normal infections as well. But when you have an out-of-control pandemic, you end up finding some people who are in immunosuppressed.

[00:29:57] And if you’re in a country like South Africa or sub-Saharan Africa, where there’s a lot of HIV that’s unmedicated and untreated, you have a lot more people who are immunosuppressed who can be infected. And now, as far as the other variants you’re talking about, like the California variant, which has a couple different names depending on what clade system or nomenclature you’re using. I like the Pango lineages, which call it B.1.427 or 429 after that first B.1. And that has some interesting mutations on the spike that are now shown to slightly escape certain neutralizing antibodies. When people say it’s escaping neutralization, it’s hardly ever a complete escape. I think the most concerning one is the one they call the South African variant, which is B.1.351. I’ve seen it in our own data where we collaborated with a guy named Ben Hurley, who’s a professor at Mount Sinai School of Medicine in New York City. And that one really does in our hands. We got some serum from people who are fully immunized using the Sputnik vaccine, the Russian Sputnik vaccine from Argentina. We got their ben-hur’s collaborator in Argentina, Claudia Pedernales. I think that’s how you pronounce her name. Sent us some serum from people who are fully vaccinated. And we saw that that serum really neutralized B117 just fine, but it could not neutralize B.1.351 at all.

Razib Khan: [00:31:21] Jeremy, you’re really reassuring me right now.

Jeremy Kamil: [00:31:24] Yeah, but that’s just neutralization. That’s not T-cells. Like you still have many layers of your immune response. So I think most people should take heart that these vaccines are outstanding. They’re phenomenal vaccines and just being able to be infected is not the same thing as having severe disease. And the most severe disease we know is having bilateral pneumonia, where you end up in the hospital with a risk of dying. And I think these vaccines nearly 100% prevent that outcome even when you talk about infection with variants. And that’s even before we’ve updated the vaccines to incorporate, say, the spike protein of B1351. There’s a guy named Tulio de Oliveira, who’s a Brazilian man who works in South Africa at a place called KRISP. I forget what it stands for, but they’ve discovered B1351, and he has data showing that a patient who recovered from B1351, their serum neutralizes B1351 and neutralizes all the earlier variants. That was an N equals one, but it suggests that we will easily be able to update vaccines to crush this virus. It’s just what does crush the virus really mean? I don’t know if it means driving the virus extinct. I think it means crushing the pandemic in terms of hospitalizations and deaths from COVID-19, very little doubt that we’re going to control the disease. I don’t think it’s going to turn to zero. Even the vaccines are not 100% effective, they’re close to that. But what will happen probably is we have a new pandemic. I hate the word common cold coronavirus because I think that trivializes what all these previous coronavirus that we now call common cold coronaviruses. There is no such thing as the common cold. That is bogus because I took a lot of virology classes. I went to reasonably good schools and I was trained that the common cold is caused by a rhinovirus which looks a little bit like a polio virus, but it can only grow in the upper respiratory tract or the nasal passages because its optimal growth temperature is a little bit below body temperature. So it’s confined to your upper respiratory tract. It can cause you to sneeze and be a little bit uncomfortable. Lots of mucus, lots of keeping the Kleenex company in business, but it’s not that bad. And then someone’s like, Oh, there’s all these common cold coronaviruses, too. I’m like, What are those? No one told me about those before. I mean, unless you really were a coronavirus geek. Even virologists, most of them don’t know about that. So I guess RNA virus, people who study respiratory viruses probably know about them, but I never knew. And those things probably are all the products of previous pandemics, previous coronaviruses that spilled over from nature. And there’s a bunch of veterinary ones and it is a trip, this coronavirus that we get sick with SARS-CoV-2 can also infect mink and cats. It’s obviously has a broad host range. It seems like once you’ve been exposed probably as a child to these common cold coronaviruses, you have a dedicated army of T cells and B cells literally for life.

[00:34:27] They talk about the antibody, the antibodies waning. But that’s, I don’t want to sound too overconfident, but from what I’ve learned about the immune system and I’m not an immunologist, you have memory B cells. They aren’t called memory B cells for nothing. It’s their job to go hide out. Their numbers decrease, but they hide out and they circulate. And then if you get re-infected, dendritic cells, sample antigen from out in tissues and they bring it to the dendritic cell, it’s almost like the station or the station or the cop station, whatever you want to call it, of your body. And then they’re like, they show mug shots of whatever they find to the immune cells. And when one of the memory B cells is like, Oh, I know that dude, that guy got a six, 12 years ago and that that cell just goes, okay, cool. I found my enemy. It’s almost like the Matrix. They make like 4000 copies of themselves. They divide like crazy and then they differentiate into plasma blasts and make antibody that matches that target. Or if it’s a T cell, it clones out and makes a lot of cytotoxic T cells against a specific epitope of a virus. So I have a huge amount, like even if I’m not an immunologist, but what little I’ve learned of immunology from just being a virologist gives me a huge amount of faith in what our body can do to fight a virus.

[00:35:49] And you got to imagine these common cold coronaviruses that kids catch and that adults catch. We probably get infected multiple times in our life by them. And so it keeps a boot camp for our body and it keeps our memory trained on the pathogen. And so that limits the disease. And because the immune system is so dynamic, the immune system generates a response in proportion to the threat. That’s a beautiful thing about it. It doesn’t waste a lot of time making T cells against the virus that’s having an easy time containing. So if there’s a very small amount of disease, you generate a decent response. But it’s not like dominating your pool of memory. So yeah, you can be re-infected a couple of years later, but your immune system ramps up and controls it. So by the time someone’s an elderly person, they probably have a really good trained immune system against all the common cold coronaviruses. And a guy named Steven Goldstein, who trained with a famous coronavirus, just one of the very first ones in the world named Susan Weiss, who’s at University of Pennsylvania. He was saying on Twitter that like, no one really knows how nasty these common cold coronaviruses would be if you were a naive to them, if you grew up on an island and never got infected with one and then got moved into an old folks home and got infected for the first time in your life with one of these, “common cold coronaviruses”. Maybe you’d have pneumonia and die from it, because a lot of what might be keeping us safe from the “common cold viruses” is the fact we have preexisting immunity.

[00:37:14] And if you look at children, they have the least bad infections from this virus. Now, I don’t want to trivialize things like multisystem inflammatory or I forget what it’s called MIS-C. Like there are some really nasty outcomes in a small number of children from this coronavirus. So I don’t recommend people being like, Oh, don’t worry about it at all because kids don’t get sick. I mean, this is a pretty nasty little virus, but I don’t think it’s so, so, so different from viruses that we’ve seen before. Like the measles virus is freaking scary. I mean without a vaccination, you lose 1 in 1000 people and often children, they end up dying of bacterial pneumonia. So that’s a pretty nasty virus and it’s very, very infectious. So people I don’t like the alarmism about this virus.

Razib Khan: [00:38:01] You were going in a positive direction and then you’re talking about people die of measles, at least just in the past.

Jeremy Kamil: [00:38:08] We have a vaccine. That’s a difference, right? Oh, the really scary thing with measles is the brain disease. There’s something called, um.

Razib Khan: [00:38:16] Okay. Jeremy, Jeremy. Talking to a virologist, it’s like Dr. Jekyll and Mr. Hyde. Like, we got these vaccines. We’re super bad all of our technology. And then, like, all of a sudden, it’s like, you want to know a scary disease? No, I don’t want to know a scary disease.

Jeremy Kamil: [00:38:32] Yes, you do. Because it helps people take vaccines. Because I think the scariest thing about coronavirus is that some people think that, oh, I’m going to be fine with no vaccine or vaccines don’t matter. There’s a lot of misinformation out there. And the measles thing is called subacute sclerosing panencephalitis. It’s when measles gets in your brain and it can be like 7 to 10 years after you recover from measles. You have a degenerate brain disease because the virus has evolved inside your body to infect brain cells and not need a receptor anymore. It’s like spike protein, if you will. It’s called F, and it starts to it learns how to enter cells without needing a receptor. Just super scary stuff. And so without the measles vaccine, we’d have a lot more of that. And it’s rare, but it happens. So I think it is important to freak people out a little bit and be like, Look, there’s a bunch of freaky stuff that’s already around. Don’t freak out about it. Like, this is not our first rodeo so to speak. We’re battling, scary things all the time. You just don’t have a powerful enough microscope to watch the horror show. It’s just part of life.

Razib Khan: [00:39:35] Yeah. Yeah, it is part of life. I guess the last question, you’ve been geeking out on science. That’s great. But I do have a question more like policy, politics, communication, which you’ve inadvertently been drafted into over the last year. What do you think about the pause on the J&J vaccine? Like my cards on the table is I understand why they did it to be cautious. But I think part of the issue over the last year is making people conscious of the fact that this is a big deal and there are always trade offs in life, but we need to be a little less cautious because we have something in front of our face right now with the CFRs and the IFRs is that you’re talking about. I felt like the AstraZeneca decision in Europe and the J&J decision indicates a pre COVID-19 mode of thinking. It really confuses people and makes them suspicious because on the one hand, this is horrible and it is horrible even if it’s not the bubonic plague. And we’re trying to convince people of this like this is not just the flu. And then on the other hand, there’s some blood clotting issues. People died. Not a trivial problem. But when you look at the numbers, they were really small. And I’ve told this story before and I’ll tell it again. My best friend from middle school died of a brain bleed due to the anthrax vaccine when he was inducted into the Marines.

Jeremy Kamil: [00:41:01] Wow.

Razib Khan: [00:41:01] This happens every year like he died within an hour.

Jeremy Kamil: [00:41:04] Wow.

Razib Khan: [00:41:05] Why don’t you hear about it? Well, because that’s the risk you take. Like you got to be inoculated against the anthrax vaccine and that happens to some people and they understand that the risks. And so I just think that in terms of cost versus benefit, it was a bad call. And now I’m seeing stuff about how the vaccine uptake drops just on the day of the pause. And other people are saying, well there’s other factors, blah, blah, blah. And I’m just like, okay, but it’s really suspicious that it’s exactly on the day that they announce the pause that the vaccine uptake has dropped. And I recently got the Moderna vaccine, and I was shocked at one how many people were working there compared to how many people were actually getting vaccinated. It just seems that there’s a lot fewer people all of a sudden and other people have said the same thing. They went for their second shot a month later and they’re just like, Wait, what happened? Like, they’re just like, way fewer people. Okay. So a lot of people are immunized. You got the low hanging fruit. But I also think that this was a communication error and it’s part of a general problem of calibrating how our society and our public health communicates.

[00:42:10] What I said recently on Twitter was we have the biotechnology. But one thing we found out is we don’t have the social technology, a place like Taiwan, South Korea, to some extent, Japan, they’ve done really well. And mostly it’s just they were really early and aggressive about certain things like crush and contain. They were not denialists about asymptomatic spread and super spreading events like all of this stuff. They were ahead of the curve. And so I think it really showed some inadequacies in terms of our just social cohesion, social mobilization. And I think the J&J decision is just part of that in terms of after all this years of warning people that you have to take it seriously. All of a sudden some of these downside effects are making the administrators and the regulators be super cautious, which is fine. But now people are just like, well, if you’re going to be cautious, why shouldn’t I be cautious? Why should I take the risk? I don’t know about this mRNA technology. You know what I read on Facebook, which I don’t personally know, but I hear the weirdest things and I’m sure you’ve heard the weirdest things because I’m like, I don’t even know how to respond to this because I have no idea what you’re talking about. But you read it on Facebook. Great.

Jeremy Kamil: [00:43:22] Yeah. They call it an infodemic. It’s like a pandemic of misinformation. And you can almost see like how Russia and countries that are trying to compete with us or they’re not really superpowers anymore, they can use asymmetrical warfare because you can divide Americans against themselves so easily because frankly, our education system sucks. Our public education system is not harmonized well across 50 states. And that’s a really unfair thing. So it’s just like it highlights all these disparities and flaws, some of the virtues of our country, like the independence and freedom we have, are also in some ways weaknesses and some of these countries like Japan or South Korea or Vietnam, there’s a little bit more command and control from the central government to harmonize the message really strictly. I mean, maybe it’s not as totalitarian as place like North Korea, where Kim Jong-il says probably goes.

Razib Khan: [00:44:24] I’ve heard North Korea has no code, never had COVID-19.

Jeremy Kamil: [00:44:27] Yeah, right.

Razib Khan: [00:44:28] That’s what they say.

Jeremy Kamil: [00:44:30] Exactly. Tanzania, too, until the dictator died of it. Right. But what you said about J&J and I think that’s tricky because these things aren’t done on a completely ad hoc basis. I think they did update a lot of policies to fast track the vaccine development and approval to things. But at the same time, the FDA has, I think, preserved its credibility quite well compared to the CBC during this whole pandemic. And they do have guidelines that they put in place ahead of time before they they gave an EUA, the organization. And I don’t work at the FDA, but the sense I have is that they have things that trigger an event and the event is we’re going to have a meeting and we have to gather the data and figure out just how big this problem is because they have a lot of credibility that they don’t want to waste. And if they’re okay, we’re seeing fatal blood clots in women in a certain age group and we don’t know exactly how many of these events that there have been, but we’ve detected this many. We need to stop for just a week or two and figure out what this means and then we’ll issue new guidance. And undoubtedly there probably are people, I went to the post office and it was an older black woman who was the postal clerk and was like, oh, we’re talking. I was like, Are you vaccinated? She’s like, Oh, I was going to get that J&J, but now I don’t know.

[00:45:53] I’m like, Oh, well, you can go to Walmart and get the Moderna or something. And she’s like, Yeah, I probably will. But yeah, I think it did drive hesitancy and probably that hesitancy will no doubt translate to some hospitalizations and probably some deaths. But at the same time, you have to have some kind of a policy for how you’re going to approve vaccines, especially on an emergency basis. I mean, this is like a miracle how quickly these vaccines went from design to first round production to pre-clinical stuff. But if you’re going to commit to that fast tracking, you also have to commit to some safety standards. And if you’re the FDA, you can’t move the goalposts that you agreed to when you decided to emergency authorize this. It was always like, hey, we’re going to emergency authorize this. But the minute we see something weird, we do have to have this meeting and have like a bunch of people who by necessity, are going to be cautious. They’re going to be cautious. And I would argue that, yes, be nice if you could, know the future in advance, but you don’t. And if they knew that it was more than 6 million cases that it was, and it’s limited to women of a certain age and they can just put a black box warning in there and say, hey, if you’re a woman between the ages of 34 and 50, you might want to consider a different vaccine.

[00:47:14] But hindsight is 2020. It’s really easy to criticize them. I think they’ve done a better job than a lot of other parts of the federal government during this thing. But yeah, it’s easy to be Nate Silver on Twitter with your 2 million followers and be like, Oh my gosh, this is such a mistake. Yeah, Like, well, yeah, it’s easy to pontificate and tell people what a mistake is, but it’s their ass that’s on the line when you know someone dies. And if you’re the FDA administrator who just ignores, if it’s someone’s sister who died of a blood clot and it’s clearly thrombocytopenia that looks like it’s related to the vaccine, you’re going to tell her that, oh, no, we’re not going to pause the vaccine for a second because we’re absolutely sure that there is no bigger problem here. We don’t even need to stop. And look, we’re just confident. There’s probably good reasons why they did what they did. And I’m not in a position to second guess them. There’s plenty of other parts of the federal government where I’m happy to second guess how that and even more than that to tell you very clearly that they’re screwing up and they’re screwing you with your own tax dollars in terms of like what they’re doing.

Razib Khan: [00:48:19] So we’ve touched on most of the topics I wanted to talk about. It was a really great conversation. Your infectious enthusiasm for viruses shows through. It’s not virulent at all, just highly infectious. And so I think hopefully the listeners will get that and understand that there’s a reason we got these vaccines, like there’s this huge scientific establishment that pivoted and did this in a year. And it is a miracle. I talked to people last spring who were not as hooked in, but they had worked in the immune system space and immune genetics, and they’re like, oh, this is going to take years. It’s going to take a long time. McNeil was saying, the fastest turnaround had been, what like five years maybe for the mumps vaccine. And so people were freaking out. And so here we are a year later. You’ve been vaccinated for a while. I think a lot of listeners have been vaccinated. I’m still waiting on my second shot, but soon. And so that is the definite positive for all the downsides. It’s a good place to be in to have these gripes.

[00:49:20] And so I don’t want to end on a negative note. I was going to ask about the mRNA technology, but I think we take a lot of your time and listeners can look that up. It’s fascinating. There’s the adenovirus technology, which is kind of older, but there’s new mRNA technology, which I think on the horizon. And maybe someone will do a podcast on this in the future. They’re using it in malaria and other things. So it’s a very, very, very positive development and maybe coronavirus and the pandemic accelerated that, trying to make lemonade out of a lemon here. Finally, I do want to say I didn’t mention your Twitter handle, macrolitter and macro is a macrobiotic, Jeremy Kamil. Dr. Jeremy Kamil, it has been great to have you on. I really enjoy talking to you as always. You’re really good at what you do and I hope people get to hear from you more because you’re clear, you’re concise and you have a definite passion for science. And that’s what I really love.

Jeremy Kamil: [00:50:14] Thank you Razib. I always enjoy hearing you speak as well. You’ve I think much more depth of knowledge than I have about viruses, about human evolution and people and how genes work so admiration is mutual.

Razib Khan: [00:50:25] You are too kind sir.