This podcast is brought to you by the Albany public library main branch and the generosity of listeners like you. What is a podcast? God daddy these people talk as much as you do! Razib Khan's Unsupervised Learning.
Hey, everybody. So I have a friend on today on the unsupervised learning podcast I, I think I will divulge that because sometimes I get a little jocular and familiar with my friends. And I think some of you probably can tell that I know some people better than other people. So I have R. Taylor Raborn on and I've known Taylor, as I call him for a while. And he is a associate principal investigator at NBACC . Taylor, could you say a little bit more about yourself for the listener?
Yeah, so NBACC is an acronym that stands for the National Bio, Defense Analysis and Countermeasures Center. So I started this job. It's up here in sort of Western Central Maryland, and near Fort Dietrich are in Fort Dietrich. I live near Fort Dietrich. And I, for me, I recently started that job. Prior to that I was a research scientist for Mike Lynch out in Arizona. And we'll talk about mostly what what I did out there. But of course, I'm happy to talk about what's known publicly about NBACC and the kinds of things we do.
Mm hmm. Yeah. So I, you know, I wanted to talk to you, I think, in large part, because you were by training. You're an evolutionary geneticist, and, you know, on this podcast, I talk about a lot of things I talk about a lot of things with a lot of different people, you know, like human evolution, I talked recently about a cognitive genomics, just all sorts of random things, right. One thing that, you know, I probably don't talk as much about, but that is kind of a core part of, I think, my mentality, my view on the world, what I'm passionate about, is evolutionary genetics. And some of you might think, like, well, you know, you, you did a podcast with someone who's talking about Denisovans, like, what is that, but evolutionary genetics, and that's fair. But you know, that sort of thing is very, very narrow. It has like paleo, anthropological, Paleo historical relevance. And, you know, there are evolutionary genetic questions that you can investigate, like, you know, like, what is hybridization? Like, how does it work in mammals, species concepts, the role of selection in populations that are relatively small and slow, you know, slow breeding, but it's a very, very narrow purview. evolutionary genetics as a field is much broader. And it's involved with, you know, like changing allele frequencies over time alleles or genetic variants, you know, there's parameters like drift, selection, migration, etc, etc. Okay, so all of this stuff, it's a big catch all. And, you know, nothing in evolution, in my opinion, makes sense. Except in light of evolutionary genetics. It's incredibly important. It's like a Swiss army knife. It's a mental toolkit that you can use to decompose the world around you. And a lot of the people that you guys know that you guys listen to read, that are interested in evolution, like they come out of this background, you know, that they're familiar with Fisher, Sewall Wright, how they these these older 20th century thinkers, and more recently, there have been people like WD Hamilton, probably, you know, Richard Dawkins in hid popular works. And even though he's trainrf as an ecologist, a lot of his stuff is around evolution, genetics. So, you know, Taylor, he, you know, work with evolutionary geneticists. So he was in Mike Lynch's lab. So for those of you who don't know, Mike Lynch is a pretty eminent guy. He has some ideas about the origins of variation in the genome and genome architecture. But also, he has co written two books, genetic analysis, quantitative traits and evolution selection of quantitative traits that are really great if you want to lift with books. They're incredibly heavy.
I don't even have the latest one. So that would be Walsh and Lynch. Volume Two, and it is seriously it's like, yeah, you want to lift it do some curls with its like 45 pounds or something.
Yeah, so I actually have it on. I have the second one on Kindle. The first one. Yeah.
The new weighs about the right size. Yeah,
yeah. Yes, I do have the second one on Kindle. The formating is not that great. But yeah, so this is a joke. But um, you know, I've been I've been talking for a while. Taylor, like, why did you get interested in evolution? Why did you get interested in genetics? Were you interested in evolution? First? Were you interested in genetics first, like, how did you get? You know, you're in Mike Lynch lab as a postdoc like, I mean, how did that happen? Can you talk about your story?
Yeah, my story is, you know, kind of twists and turns in terms of how I got there. But, you know, to start with, I was just always interested in the natural world. You know, if I projected myself forward, based on what I was interested in, like eight years old when I was, so I grew up in Western Canada. I'm an American born in the States. My dad was a faculty member at UNC Chapel Hill, my mom got married. And then I was born shortly after, and my dad was offered a faculty position that with tenure up at the University of Alberta in Edmonton, which is way up there, I mean, shout out to everyone from Alberta. But Edmonton is, you know, it's pretty far north. And it's a long way from Chapel Hill. But we ended up making the move when I was a little guy, and that became my home. And we lived outside of Edmonton. And I just became enamored with the natural world playing outside what we call a crown lands, like public land, behind our house, turning over every rock, trying to characterize all the things that were around, you know, plants, making sketches of leaves, you know, playing with all these bugs, eight years old, I would beg my mom to take me to the library so I could get more books. And that's really how I got started. And, you know, until I was, you know, 13 12 13, that was the thing that I love the most. And biology has always been a love of mine. So when, you know, I got a little bit older, and, you know, socially, I got into sports, and I became, you know, something of an athlete, but always knew that biology and sort of its applications would be something that I would want to do with my career. Went off to Queen's University, which is on the other side of Canada, I guess you call it central Canada, but it's a place called Kingston, Ontario, right on the water there on Lake Ontario and I studied life science. And my first year I got interest I got, I had the opportunity to work during the summertime with Carol Cass and she's a pretty preeminent cancer biologist at the University of Alberta. So I got to live at home and in the summertime and do research for Carol and I just fell in love with the lab, I did three summers with her. And I owe really the beginning of my career to Carol, for supporting me the first year, a couple years later, after that I, you know, I got a fellowship to work there and loved it. And then I really enjoyed my courses at Queen's and when it came time to decide, You know what I was going to do. I started looking into grad school, I didn't really understand that you could have it paid for I think people saw podcast listeners, you know, if you know if you're competitive and if you're in any kind of program worth its salt at least in biology, you're gonna get a stipend may not be very much, but it should cover your room and board and just sort of minimal expenses. You know, I learned that kind of late in the game. But I ended up finding my way out to Iowa City with the deadline I think to the University of Iowa for grad school is like in February, and that was rather than stay in Canada where I enjoyed it there. But I didn't think that the stipends were quite as competitive or the support for grad students was quite as competitive at the time, I decided to apply and I ended up finding a couple places whose deadlines were coming up and one of them was closer to home. University, Montana, one of them was in the middle of the country where I had no relatives and that was the University of Iowa. But you know, I made my way out there. Did my PhD in John Logsdon science lab. And so the reason I was I got into evolutionary genetics was was basically because I did a rotation I was doing different rotations and I I liked the intellectual component of of what John was doing in his lab. And so he studies among other things, sort of the evolution of sex, that is meiosis and asexuality. I think right now he's currently working more on the asexuality side with Maureen Neiman and things like that, but but at the time, he is very interested in evolution of focusing on evolution of sex and and so I you know, really enjoyed that intellectual environment compared with at least in the context where I was, you know, the sort of more, I want to say I just, you know, the medical school, they did some great work, but they really weren't necessarily as interested in ideas for ideas sake.
And you know, every lab has different culture, but I was rotating through labs, and, you know, it was like, could you do this western blot on the first try? And I couldn't right? I mean, you know, I had pretty good hands at the time, but you just, if you're a rotation student, they just drop a protical. So I really liked an intellectual environment in John's lab, and I liked sort of the more fundamental questions they were asking, in the lab, and I, you know, I chose to join John's lab. And so from there, there's sort of all kinds of twists and turns, but I ended up doing what I think was the first bioinformatics mostly bioinformatics PhD, at least in the biology department at the University of Iowa. And I did that just based on where the question was taking me, and we can get into that if you'd like, and some of the details, but, you know, in evolutionary genetics, and I think you did a fantastic job of introducing the topic and what we can talk about some nitty gritty details, but I think your overall, everything you said is, for the listeners that everything that you've said was was bang on in terms of sort of summarizing the topic, but, you know, how did the natural - How did the diverse forms that we see, in around us the biological forms come to be, you know, how do we, how did the changes that give rise to the different forms take place, and all the all of these different questions, you can, you can ask them in various ways. And, and, and, you know, I was very interested in sort of a more molecular aspect of this, where I was really focused on, you know, cis regulatory regions. And I still that that's an intellectual interest of mine, even even though now I don't specifically work on that at NBACC. But we're finishing some work with Mike, where we, you know, where we look at CIS regulatory regions, and for the listener, that these are not coding regions. So you have genes, that if there are protein coding genes, they give rise to protein, you know, they're transcribed into mRNA, and then they're translated. So you have proteins, these little mini machines that are floating around, whereas cis regulatory regions are sort of like, you can almost think of them as switches, but they're necessarily on off switches. In fact, in eukaryotes, that is, you know, they're, they're, in fact, more like dimmers, right. And so I'm interested in these sequences, identifying where they are, and then thinking about sort of how they change and how they evolve. And the work I've done in Mike's lab, which will hopefully come out pretty soon. Talk, you know, that's the kind of thing we focus on. And we use a couple of different model systems for that. But Mike's well known for a number of them, but he has a big project, actually several projects working in daphnia pulex, which is a little water flea. So ironically, I probably looked at Daphnia, excuse me worked. It looked at daphnia a lot in those little prairie slews, when I was growing up, and then I ended up, you know, looking at them in a different way. I was in Mike's lab. So Mike's down, he the way, the way I got into Mike's lab is that I was at IU doing a postdoc with Folkert Randall and I was basically becoming a bioinformatician. At this point, you know, I, he kind of given my union card, so to speak. And in folkers, you know, an exceptional bioinformatician is goes all the way back to us. Sam Carlin and things like that at Stanford. So he, and I was doing work with him. And then I started collaborating with Mike, because, you know, Mike was at IU and he had a big lab, and there's just so many ideas spilling out of his lab, like I wrote a paper with Mike I was able to collaborate with him on some stuff that Folker wasn't funded to do. And then when it was time, of when Mike was recruited to run a center at ASU, which is the center of mechanisms for evolution of evolution. This is a center that's in what's called the biodesign institute, which is kind of like their premier research institute. There it is you and then I got an email. I congratulated him by email and he sent me an email back he said, are you coming with me, is it well, you know, we talked to my wife, but you know, and she's in a different lab. And I, you know, I ended up being able to come I had a good experience with Folker and then I came down eventually about a year after he left, and so that's where I was. until I took this job here in Maryland. So
yeah, twists and turns and and in the process, because you're using different tools, right, I thought I always thought I would just be in the lab, this is what I thought, because I really enjoyed it. This is how biology gets done. And, you know, I had visions of being, you know, continuing the experiences that I had, whether it was in Carol's lab, or whether it was working with John and doing the experiments that I was doing to identify transcription start sites. But But then, you know, I think I could see the kind of ground shifting beneath beneath my feet. And, and then there were some questions that I needed to answer where I just couldn't answer them without, you know, writing code. So I ended up writing a program, which you can find on on Bioconductor, which is called TS architect to identify what are called what we call promoters and promoters are these switches that I was talking about. And they, you know, it's this is where the transcriptional machinery will bind to prior to transcription initiation prior to gene expression, right. And so I wrote a program to identify those on the basis of these different types of data. That that you can generate, you know, that are called TSS profiling datasets. And so your, the listeners may not be aware of this, but, you know, you the listeners that listen to a lot of science podcasts, we know about RNA seek data, right. And so that's been mean, that may or may not be something they're used to. So that this is where you just take all the RNA in the cell and you, you can do different things to reduce it or [uninteligable]. But basically, you get, you get an A library of genes that are turned on, right. But the and this will not include information that allows you to necessarily identify the promoter. And so there's a different type of, of an all of what I'm talking about now is only relevant to eukaryotes, there's whole, whole other things going on in prokaryotes that we can get into. But basically, it's quite complex. And it's not, although there are some interesting things that are happening there. I'm talking about eukaryotes. And so there's this, these types of datasets. And there's this technique called, one of them's called cage. One of them's called rampage, if you want me I can, I can, you can look those things up. But if I can tell you more about them, but then we ended up again, these things are not this is not something I would have planned, but I ended up being involved in developing my own seek method, which is called stripe seek. And basically, Stripe seek is another TSS profiling experiment, and it - and then the innovation with stripe, see, because that allows us to do it with much lower input of RNA. Right. And so the the idea here is, you know, we would talk to collaborators, and they would, we were actually trying to get collaborators to work with us. And I, you know, these are people I was working with it at IU including Gabe Zentner, and Bob Policastro. Bob and Bob is the first author on that paper. And Gabe was the senior author. And both of them are now at one of George Church's startups at in Boston. And they just left recently. But
anyway, we were trying to get people to work with us, or we were trying to get sufficient quantities of RNA. And the amount of RNA that you'd had to provide was sort of was enormous amounts, like five to 10 micrograms, which, for the Lister, that's just a lot of RNA. So and Gabe us a really well, well trained genomic system. He's just like, Well, why can't we use less. And then we ended up you know, really, getting after it and trying to figure out exactly what we could do to make a method like this. I was mostly in the bioinformatics side, but I actually for... normally the movement is one way once you're no longer in the lab, that's it but you once you're a bioinformatician you normally stay there, but actually put the pipette I went back to the pipettes I put the keyboard down for a bit and, for an afternoon or for a week or whatever. And I went back then. So that was fun. And then I brought those tools with me to Mike's lab. And so we did use stripe seek and a whole bunch of things. Really what I'm trying to I was interested in doing and what we're doing now is with my collaborators and like you're doing is to sort of combine molecular genetics with functional genomics. And of course, this has been But with sort of my branch of functional genomics, which was TSS profiling studies, looking at CIS regulatory regions, and you know, that that was the goal. And I can tell, we can talk about sort of some more detail, but that's sort of a high level idea is, you know, how do What are you talking about allele frequency changes and sort of changes in that, you know, that give rise to diversity, but what specifically is happening at the promoter? How do cis regulatory regions evolve, we know that they, there's more bass substitutions there than of course, in in gene sequences. But of course, there are also more highly conserved. If you look at heterozygosity, and things like that, then a number of other regions of the genome so that, you know, there is some conservation. How did the eukaryotic promoter actually evolve? Of course, I haven't answered that question. But these are some important questions that I don't think we know the answers to. And so sort of combining population genetics with my little branch of functional genomics was a goal. And I think we've generated a whole ton of data that we're working on writing up, or we've written up in some form. We're currently do some remapping right now, but you know, we're excited to get these papers out.
Well so, you know, you you got in the weeds, which was great, because this is was what I, you know, had you on? I mean, I think some of the listeners... so, so, here's one thing. You know, I recently did a podcast? Well, I mean, listeners podcast with Alex Young. And I got two responses on that podcast. Well, I got a bunch of- many responses. Many of them were positive, but two of the more negative responses were like, I wish she'd gotten into more technical detail. And then the opposite response was, I have no idea what he said. Right? So um, you know, if some listeners are just like, Whoa, hey Razib, you know, that that was like, I don't know, like, I'm getting my Wikipedia out. That's fine. You know, the this is, this is how science works. And one of the dirty little secrets of science is people go to seminars, and they have no idea what what this person just said, but they kind of got to fake it and ask a question. And, you know, this, this happens, so don't don't feel overwhelmed by what Taylor said. Sure.
Yeah. And the thing is, I you know, it's funny, because to my mind, I was actually, maybe trying to give it at a high level, but I realized, in retrospect, maybe I No, no, it's all good, as well. But yeah, but yeah, but please, you know, happy to kind of smooth over some of those points.
Yeah, well, let's take a step back. Because you said something, which I think a lot of listeners might be like, a little confused by or not. They might not actually, like, understand what's going on here. The evolution of sex? Why would people be interested in the evolution of sex? Like, why is that even a thing? Isn't sex, like a structural parameter in our universe? I mean, I mean, I know it's not, but why don't you like, introduce us to that? Like, why that's even a question.
Yeah. So this is a great question. It, the persistence of sex has been, you know, sort of a long standing question in evolutionary genetics. And, you know, the question is, you know, so So why don't we? Why don't most eukaryotes just reproduce asexually, right? You know, there's a, there's a cost to sex, right? You have to make males. And that's expensive, right? And so, you know, there's, there's just this inherent sort of a cost that comes with doing sex. And when we say sex, there's a sort of cell to kind of cell division that that we're talking about, we're talking, if we're talking about on the molecular side of things, there's sort of a different type of cell division, right, we have mitosis, which is the normal cell division that all of our cells, well, I will say all of our stuff, but, you know, the most vast majority of our cells are are undergoing and then there's this other cell division, which are in our gametes are, take place in our gametes, and that's meiosis, right? And this involves recombination. And, and, you know, it's, it's a, it's a different type of process. And, and this is how we create our gametes. And meiosis is maintained all across eukaryotes, right. You can mean there are some instances where we think sex, ie meiosis, maybe last. But every you know, in almost every case, we look more closely and we find out that it's not been completely lost in this taxa. The one case That's of real. I think potentially. We still haven't said exactly how I think I think the rotifer story was very interesting with Matt Meselson. And you know, he and so he found it that meiosis was taking place in rotifers are just happening in a very different way. I think this paper came out in 2013.
So the rotifers are asexual lineages. Right? Yeah. Well, well, they're No, no, that was asexual lineages.
Right. Right. But it turns out there is there's cryptic sex as I understand it. And but you know, there, there are, there are cases where, of course, you may have heard of, I think it was the condors, right? They, these, this isn't the news. So I'll mention it. The think condors in California, her were found to have done parthenogenesis, right, which is the generation of eggs without fertilization from males, right. And over the input of male material, and the, you know, I'm not doubting this result, but it is probably not obligatory, right. And sex is something that will come in and meet and maintain sort of the genetic diversity. So I didn't mention sort of some of the reasons why we think sex exists. So if you reproduce asexually, then you can introduce different mutations. Of course, mutations exists, regardless of whether one is sexual or asexual. But you don't really have a way to go back to kind of reduce the mutational load. If you're asexual, you kind of just have you only go one way. That is, you can't return to the pre mutated state, right. And this was described in actually another IU person, very famous geneticist, Herman Miller, and Miller tall describes this as this has been coined as Millers ratchet, right, you can only go one way, you can't go back and sort of remove those things. Or it's very unlikely that that would happen statistically. And so what meiosis does, is it allows you to kind of get this genetic diversity with via recombination. And, and so that's thought to be one reason why sex has been conserved sort of over millions of years, all, you know, millions of taxa, right, you know, all over the place. And so and so that's, that's really why it's thought and John has worked on, among other things, sort of trying to establish whether up species given I say tax, so use in as well, whether these species have my arm meiotic. And he, so when I was in his lab, I wasn't working on this stuff, but he was doing developing a toolkit for doing this. And he called it the meiosis detection toolkit, where, you know, he looks at he looks for different proteins, sorry, genes that give rise to rise to proteins that are involved in meiosis, right. And some of the some genes are actually involved in both right the same machinery, but there are some that are only involved in meiosis. And like, for example, DMC1 is involved in repairing these crossover events and things like that. So this was one of his contributions. And then he was very interested in looking in rotifers as well, which is kind of a sort of Holy Grail, I think, because it was thought that rotifers were asexual. And I'm not really sure where things stand I left with no, this left John's lab and then around the time the Matt Meselson's paper came out. So I don't know kind of what's whether the trail has gone cold or there's been established. But there was a very interesting sort of heterodox way that rotifers actually are thought to do meiosis, and I'm saying that at a very high level because I read that paper like seven years ago or something, but
Well, so I, you know, what, we're what we're getting at here, and this is kind of like a recurrent theme of this conversation, which I think is okay, so we have like a high level, abstract idea concept that, you know, would make sense. 200 years ago, 100 years ago. We're talking about sex. Like, you know, dioecious or like dimorphic sex, right? Male, female, and then there's a two fold cost where, you know, obviously, you're diluting your genome by one half by exchanging it with someone else. And then the other cost is like, why are their males like they don't reproduce, right? And so you see these observational patterns. This is across complex organisms or asexual lineages, you know, but the asexual lineages tend to die out what's going on? Why is sex so important? So, you know, there's theories about pathogen coevolution, and whatnot. But over the last, like, you know, 30 or 40 years, we've developed this awesome toolkit on molecular biology. And so you're talking about, okay, meiosis is a concept that comes from Mendelian genetics, right, so it's just recombination across the homologous pairs of variants of alleles, at different genes at different genetic positions. So there's just like swapping, so the genes aren't associated with each other. And now you're but you're talking now, like with sequencing, and modern molecular mechanisms, looking at the biophysical structures of all these things, and what's going on here? And so I think what you're illustrating is that evolutionary genetics started out as this high level conceptual abstract framework, but now you have this. I don't just like Moveable Feast of molecular tools, right? And then with genomics, in the last 20 years, that's taking it to order of magnitude, greater complexity, I would argue,
yeah, I like the term Moveable Feast. That's really nice. Yeah, and I think especially the, the point where I realized that everything was going to change, I think was 2008 or 2009. When labs were starting to publish this sort of, it's a terrible name, everyone, but it's called next generation sequencing data. So this is genomic data, right? And we had, of course, the listeners might say, well, we sequenced the human genome in 2001. Yes, of course, we did. There was such thing sequencing, of course, but Sanger sequencing, which is what it was, and what it's called, it still exists, is just much lower throughput on, I don't have to look at one of those slides that I put up, sometimes, I'm teaching a course but, you know, it's, it's just much lower throughput and much more expensive. And you would literally have you set everything up in the lab, and then you basically do cloning, and do the inserts, there's a whole it was, it was a real experience. And you you'd get, you know, solid data, but it just didn't scale quite the same way. But when you had. So I'll finish that thought by saying, you know, I work with some former Tiger people and Craig Venter Institute people, and they had a whole, the reason they were able to get all this data is they had this whole, almost factory, like, set up, you know, at their office, which I think is down there lab was down in rockville to do all of this stuff. And so, you know, if you're a smaller lab to do sequencing, you can generate sequence data, but, you know, you're just not getting quite the scale. Well, you know, 2007 2008 2009 roll around, and you're getting next generation sequencing data, you know, there are some competitors, but basically Illumina one outs, you had things like solid and other things like that. But Illumina ended up winning that and, you know, this next generation sequencing data, highly, highly parallel data, just completely blew everything open. So I realized that at the time, and I wanted to be somewhere involved in that, even though my, my lab was only doing a little bit of NGS stuff with, you know, I think, as I was graduating, there were some RNA seek data, but I really wanted to be involved in that. And then I realized that that was sort of going to be the way forward. That's, I think that's what partly got me into bioinformatics. But, you know, I realized that sort of this is going to be huge, and it really is, you know, I have I co advise a master's student at ASU still, and she has more data. Right now then, I would say for five PhD students. Now I'm not saying that her thesis is gonna be five times better than than a PhD students was 10 years ago. But what I'm saying is that the amount of data that she has is just incredible. And it's all because of this. NGS data. I mean, we have a we generate, like 2.5 billion reads, in one run. Now, with a nova seek, and thankfully at Jenna and Phoenix has an oversee my actually that's my wife's employer. But we, we don't get a special deal. But we you know, that's where, with ASU we'll send all of our sequencing data. And it's just it's mind boggling. So you're absolutely right. It's a real Moveable Feast. But it's also
there's so much data that you just you need to be able to handle data well, and understand, you know, the, understand at least some, some computing, if you want to be on the side of analyzing it. And the good news is that there's a lot of tools online to help you learn. And I, you know, initially was self taught, there weren't quite as many tools online, I actually went to library and got a book and just started learning, and it was really painful. But, you know, now you can go to YouTube videos, you can, you know, just talk to someone, if you if you know, anyone in bioinformatics, and I'm sure they'll be able to help help point you to thing, but one place to go is, is Biostar. It's a really good forum. I haven't actually answered that many questions. So I'm not like the best Biostar person, but that there are a lot of there's, you know, questions and answers. And actually, I think a handbook they sell there for people that want to get into bioinfoqmatics. So I'm not a member of, you know, I don't, I'm not like a member of the Chamber of Commerce or anything like that. But I am a bit of an evangelist, because it helped me It helped my career to get in that way. But you know, it for me, it was, it was all about answering some of these questions, and I kept tugging at that thread. And the thread, you know, kind of led me across the country a couple of times. But bioinformatics and genomics is really exciting. And it will continue to be. And it's not just the things that I've talked about, but it's a lot more to, and plenty of different types of data out there that you can generate, you can combine them. And then you can use those data it for me what motivated me. And was was to be able to answer some questions relating to evolution. But of course, you can do the same thing to answer questions relating to, you know, whatever other another problem, you're interested in development, you know, some sort of disease if you have a model system for it. My wife's actually working on a couple of things, multiple myeloma right now, but right before COVID hit, she was working on a project on lung diseases. And so that was actually not a bad move for her. Because she got on a few papers, big people on regarding COVID, right. Yeah. Which is kind of neat. Yeah, thatwas crazy.
Well, so um, you know, to recap here, I want to, you know, just draw attention to the listener. Okay. So evolution is this big picture concept. You didn't have a theory of inheritance. And originally, that really worked. Mendelism and Mendelian genetics. So this conceptual idea of district discrete particulate inheritance shows up in the early 20th century, Fisher fuses it with, you know, evolutionary biology, you get evolutionary genetics, population genetics, really, in the 1920s. And 1930s, was Fisher's tool, right? Haldy and few other people. Okay, so you got all this, right, yeah. And then you got the modern synthesis, you got DNA emerges. And so now you're at a situation where, okay, there's these molecular tools, molecular methods, and we're starting to understand the molecular biophysical basis of inheritance of DNA. And so where we are right now, what you're talking about, is this massive fusion of, you know, these intellectual traditions that go back to Darwin, but also go back to, you know, Crick was trained as a physicist, these sorts of biophysical model based understandings of, you know, like how DNA is as a macro molecule. And, you know, evolution works through the the mediating, you know, influence of these of these molecular structures. And so, I guess the point that I'm trying to get out there is okay to understand evolution, you need to understand its bio molecular basis and to understand its bio molecular basis. I mean, what what do you want to do you want to read the sequence, that's the first thing you mentioned, RNA, obviously, DNA translates into RNA, RNA turns into proteins is the central dogma for those of you with biological science background and those of you without, that's what it is. There's all these like, proxies, and these like things going on in your body, in the cells, and in your development and across your lifetime. And this is all shaped by evolution, and does shape evolution. And so yeah, like you have Origin of Species and you can imagine dinosaurs and stuff like that, but really to understand evolution today, I feel like you know, you you need to think like a molecular biologist, like the genomsist, and then work your way backwards. But you know, maybe that's my My own bias, maybe that's your bias, you know?
Well, you know that that's certainly my bias, but I don't want to take anything away from you know, the, the, the many other parts of evolutionary genetics where it may be more ecology based, they may be looking at, you know, at different traits that they give them, you know, in, in nature where, and then or they bring back their study organism, and then they look at it that way. Or, also, of course, um, you know, a lot there a lot of theoreticians who do sort of simulations, and an incredible amount of important work that's done. And I'm friends with still friends of people at IU and some of them are doing things like that Matt Han's lab does a great job of a kind of, I wouldn't say they're exclusively a theory lab, but they're kind of there on that side of things. Of course, Mike works on theory as well. So there's a lot of cool things you can do, I like to work with genomic data, and then like you said, work backward. Of course, you know, this, we all we need to have sort of a starting point, you know, set of ideas, that sort of...that we can test our data against. And so, you know, there are some still some controversies out there, you know, Mike is on.... So, there's a cons, there's some controversies, I don't want to a may or may not, you may or may not want me to get into them. But of course, there's, you know, the idea of neutrality versus selection and things like that. But there's still these controversies out there. And, and Mike's actually kind of branching into kind of solidifying a new field. And so that's really interested in sort of what he has in mind. And he's written papers on this. And I think he's got a book that he's going to be publishing at some point. But he wants to, he wants to kind of wants people to coalesce around a field called evolutionary cell biology. So now we're looking at sort of traits of the cell, and how did how did they evolve? And so what are some fundamental scaling laws of the cell? And things like that? And so I, I don't know how Mike does it, he must, he must have more hours in the day than the average person. But, you know, this is the kind of thing he's he's also interested in. One of my lab mates at ASU is Paul, he's a fellow from the Netherlands and he was working on some of these scaling principles, you know, just looking at, okay, how long is the flagellum and looking at all the different flagella all over, you know, in different taxa, and different things like this, and sort of trying to kind of come up with sort of a set of us come up with some understanding as to kind of what gave rise to these flagella, which I think we know, sort of what are the limitations in terms of energy? Because you know, everything that we we have to power these things using ATP and sort of like, what are the limitations are, so he, you know, there's all kinds of really interesting work that's being done. But I, you know, I'm biased, I think it's interesting to kind of use genomic data to interrogate some of these things. And thankfully, you know, even though I'm doing other things that I'm back, you know, this work continues with my collaborators and sort of my, my evenings and weekends with this getting these papers out.
Yeah, really appreciate you spending time on this podcast, cuz I know you're busy. So I love it. Yeah. So NBACC You mentioned a couple times. So you know, when I first knew you, I think when we first started talking, you were at Indiana, I think doing a postdoc, I you and you're you're an evolutionary genetics guy. That's what that's how I know you. And then you went with Mike Lynch, who, you know, you're doing more bioinformatics, but really, Mike Lynch says he's an evolutionary guy, a genomic sky. Yeah. Okay, so that's what you're doing, you're in academia. And now you're kind of in a different place. So talk about that a little bit for the listener. And I know there are people out there who are in graduate school who are probably going to listen to this, or you know, their postdoc King and tell us about how you got where you are, and I know you're, you're pretty happy where you are, but can you just tell us about that journey? Tell us what you're doing and maybe talk a little about your work there.
Of course, yeah. So yeah, so eventually NBACC and I will read out spell out with the acronym stands for so it's the national bio defense analysis and countermeasures center, and so NBACC and so I actually, so it what its role is and you can you can look this up so, it's reading from their, their mission statement. So it's a one of a kind facility dedicated to different fending the nation, ie the United States against biological threats. Its work supports intelligence assessments, preparedness, planning, response, emerging threat characterization, and bio and bio forensic analysis. A lot of maybe buzzwords in there. But I'm happy to for the listener, I'm happy to clarify anything. But so basically, we stand up sort of defense, and against potential bio weapon threats or other biological threats. And it's run by the Department of Homeland Security. And it's, but interestingly enough, it's actually on Fort Dietrich in Maryland. So Fort Dietrich is the headquarters of the bio defense apparatus in United States, and it's about an hour, hour and a half north west of Washington, DC. And I see hour and a half people who know DC might recognize that there's a lot of traffic to get up to Frederick. So yeah, so that's what we do there. And I'm a principal investigator in bioinformatics. So there's some I can talk about in a high level what I do there, but you know, of course, a lot of what we do is, is either classified or business sensitive, or however you want to call it. So. But you know, I am involved in kind of making sure that sort of our, what we do there, you know, the work that we do is I support the bioinformatics side of things. So, we have, for example, some kind of threat that comes in, we need to have software that allows us to detect it, and most of the time, you know, at least, like what I do, we're dealing with genomic related data sequence related data, right? I think that's, you know, that's fair to say, but, you know, we have a number of other capabilities that I won't get into, but you know, what my job is to sort of work with our really talented analysis team to make sure that sort of our, we can sort of do analysis for our agency partners when a threat comes in. And we can also sort of help stand up some of the software that, you know, that, that we, we build that and the pipelines that we build, so that we can prepare ourselves for different potential threats. And, you know, this is we work together with no actually really collegial group at NBACC. And it's, it's been fun so far, I've been there in just over five months. And so far, so good. I worked remotely for a little bit and then was able to, we drove across the country in August. So that was a big drive. That's the kind of thing we do. I'm talking on a kind of very high level. But basically, if, you know, heaven forbid, if there's like an anthrax attack, I hope that never happens. But if if something like that were to happen, and there have been instances where anthrax was, was used as a threat, or as a weapon, you know, in sort of a small scale, but also in I think, early on a more large scale. So that's the kind of thing that we would respond to in terms of being able to detect it and try and track it down. And actually, that was one of the reasons why I'm NBACC came into being is that there was an anthrax attack in 2001. And we wanted to have that the federal government wanted to have a place where this work could be done. That is responding to this quickly that it would they actually were contracting out with another lab to respond to that. And they realize, well, we need a facility to do that. And so that's NBACC was born. And it's been around I think, about 16 years or so.
Yeah, you know, world men now we remember the anthrax attacks. I think some of the Zoomers listening in probably don't know what you're talking about, but that's okay. Okay, so, you know, we had a little bit of a chit chat before you got on. And you mentioned that you'd be willing to talk about like, what happened in February 2020. You know, we're as we're recording, okay, you know what, I've been saying this for six months, podcast, as we're recording, we're at the tail end of the COVID 19 pandemic, but we're at the tail end of the COVID 19 pandemic, okay.
Yeah, speak it into existence. Yeah.
So but um, you know, it started in February 2020. Actually, like, you know, both of us were, I think on the alarmist side, you know, we were paranoid early, so whatever, like we knew what was coming like what happened And with our government's response, do you know like, can you tell us something, I can shed some light on this?
So, first of all, you know, I speak for myself and not NBACC or anyone else. And my opinions about this reformed before. NBACC was even a glimmer in my eye when I start the application process sort of while before I joined, but an interview process but yeah, so just so the listeners even I were kind of talking online about how this is going to be a big deal. And like, people in in the United States, as I saw it, okay, in February, and March, sorry, January, February, were largely oblivious to it, which is there, right. I mean, we didn't know, I don't think most people predicted it to be as catastrophic as it has been. But you know, both you and I Razib were pretty worried about it. For different reasons, I think familiar reasons. Right. So for me, my wife's Vietnamese American, and she had gone back home for Tet, which is the lunar festivals is the same, celebrated in the same day as a Chinese New Year. And so she had been she was gone, I was actually writing an r1, with a colleague of mine at the time, still a friend Jeremy Weidman at ASU and he, she was gone. And, and I remember just being glued to everything that was happening and watching it very carefully. And we ended up buying, I think, the last few masks that were there in early February that were at the CVS there in Tempe. And I remember saying, like, you better be really careful. I remember having to reroute my wife out of Shanghai. And instead of flying through Shanghai, she flew through Seoul. And it was a really close run thing to make sure that she got back, okay, because she got back kind of towards the end of February. But it has become, I wouldn't say an obsession for me to figure out what happened in terms of our federal sort of response to this. And I and but it's been something that I'm very interested in. And I had been looking up online in kind of trend to reading articles. Thankfully, there have been some articles on this. But my view is that I think this is a pretty fair consensus view is that we didn't really know what we didn't know. Right? We we didn't have the testing stood up at that time. And that is the at the time is the response... And it may still be the responsibility of the CDC. And I'm not criticizing everyone at the CDC. But there was a particular lab, I think that the respiratory diseases lab, respiratory viruses lab, they were supposed to be you know, I say standing up, but you know, creating this this test, right, the PCR test that I'm sure every single one of my listeners has, has subjected themselves to right. And they had a lead time, remember that the viral genome sequence was published, I want to say like the 16th of January, it was early. Yeah, yeah, it was pretty early. And, and so from, you know, that time until the end of February, there really was no working test. And my mom's from the south. So I would just say, bless your heart, you know, those people messed it up. And yeah, that's, it was a real, it really bothers me. But basically, what it came down to is, they're just some, as far as I can tell, so I've read, there's a really good, I think, ProPublica article about that, and you can if you Google it, and I can give this to you after our interview, but basically, they made some bad decisions, they decided to actually sequence the or generate the, the, the positive control in house. Okay, so to back up in a test, you have to have a negative control, so that you know, it doesn't work, right. And these types of things. And then you have your regular samples right from you or me, whoever yours and then you have to have positive control. So if if nothing actually lights up, when you're doing this, you have to have a positive control. That actually works great. So you know that the experiment, the test itself was working, it just didn't detect what you were looking for. So and they were actually generating this in house, this positive control
And what that means is that you have all of this oligonucleotide, these are just short sequences of DNA or RNA that they had that were getting that were contaminating the sample, right. And so you were having some positive control, I think was, was contaminating some of the other samples. So the negative control was lighting up, I think, at some point. And I don't know if we know for sure, but at some point, there was virus can have viral contamination. So the negative control was lighting up, I think they made some mistakes with designing these primers. And I used to know as primers are these short sequences that helped get the reaction started all these things. And so I don't want to say it was a comedy of errors, but certainly they were able to generate a working test. And so other places had to pick up the slack. And so for a while, I think the premier testing agency in the United States was actually the Fred Hutchinson or the University of Washington virology department. And, you know, there are some other interagency issues, as far as I can tell, but I think that story needs to be told someone needs to write sort of the definitive book on that, because I'm convinced that if had we known about this in the middle of February, our response to this pandemic would be much different. Yeah. And this is my personal view. You know, I've had this view, long before I joined my career where I was, I was actually watching this, horrified about it. But what I will say is that he kind of, you know, my, when I watched what was happening, I, you know, I didn't want to just be someone who was, you know, flapping his gums about something and complaining, I saw myself if I have an opportunity to be in a situation, or contribute to kind of, you know, the, this type of thing protection against threats. I, I'll take it. That's what I told myself. And it turns out that I know that that's, you know, I'm at a place like this. Now, we have different, we have a different purview, a different mission, or role is not the same as the CDC. But we, you know, there are other threats that we face. And so I want to make sure that we that I do my job, because I really am frustrated by that response. And I actually think it would be helpful not to kind of, I'm not going to say the person's name it's public knowledge to the lab head there at CDC. It sounds like he has been punished internally there. But you know, I think it would be really helpful if just, you know, instead of having political squabbles, although those will continue. I'm sure. If there was some sort of commission that just looked at what happened in the early part of 2020. And focusing, I think, on the testing, because, you know, this is this kind of thing allowed Trump to say, I'm not picking on him, per se, but I'm just saying I allowed him to say, well, there are only 25 cases, or however many there were at the end of February, well, no, there weren't. That was just how many there had been positively detected, because we didn't have, you know, a really good testing regime at the time. And so that, that's still bothers me, Chris has been many other problems of not saying this is the only reason that that this country has not had, I think the kind of COVID response that we can be proud of overall. Now, you know, I think there are things we can be proud of, for example, getting these vaccines out the door. That's incredible. And some of the things but you know, but this just the way that it all unfolded. So that's my little spiel about what I think. But, and I focused on the testing, because I just think if we if we knew about what was happening, if we knew the real numbers in, for example, New York, Seattle, then we would have stopped everything about a couple of weeks earlier. Yep. And that would have made a big difference. And then all the other things would have, could have would have fallen into place. I don't think it's fair to actually model this. I've actually talked to some epidemiologists like, what, you know, what can we can we model this and say, well, that's Imagine we started, we had testing and we found it at this point. And they said, You really shouldn't make those assumptions. So I've actually not I haven't been able to come up with any number. And again, that's a little bit outside of my expertise anyway. But yeah, it is something that animates me because because people just didn't know and we, you know, we were what was the the US consumed with at that time Razib? was it impeachment? When I was that was Yeah.
It was in the wake of impeachment. Look, I mean, we're both on science, Twitter. Yeah, I remember I remember being at the gym, checking my Twitter and seeing that people were dunking on Richard Dawkins for being a eugenicist. I mean, and I remember thinking
I'm only laughing because like, Richard Dawkins gets dunked on a lot. And it's it's not always I mean, sometimes it's for for things that are that are less dunk worthy. I mean, sometimes he kind of walks into it. Yeah. I don't remember exactly the tweeting questions. So don't cancel me. But
well, so if February 17 Got to The Washington Post. "Eugenics is trending: That's a problem. scientist Richard Dawkins sparked controversy when he tweeted that aside from moral problems, eugenics would work in practice". So that tweet was on to its loading. This is this is this is sausage getting made guys, February 16 2020. And for the next two days, my timeline was filled with, you know, self righteous scientists. I mean, it's dumb tweet, whatever. But I was starting to get super worried. I really phased out my interactions with people after the 20th. And yeah, I did. I was like, super confused as to what people's priorities were.
I was I think, at that point, I was telling you, and you were telling me to go to Costco and get a lot of food. Yeah. And I think I already I think that was right around the time my wife got back. So I was yeah,
Yeah a lot of us were, I mean, I had gone in the first week of February, kind of seeming kind of silly, but I think I was telling you and we there's a bunch of us, right? We were talking and not just me. Other people who have told me privately, yeah, they went in the middle of February, but they didn't tell anyone. By the middle of February, I think I think we started worrying. That stuff was happening. Like Iran, Iran really kicked off.
Italy is what scared me. Yeah. And I again, it's not it's just because I was like, I was watching it. And the numbers, like the case fatality rates looked like they were close to 10%. And I was like, if it 10% CFR, you know, you're starting to see society breakdown at that point in my and it turns out my, my uncle, by marriage ended up flying out there, too. I think the hardest hit cities - the I forgotten which what the name of the city is, but one of the hardest hit cities in the Piedmont area of Italy. And he was dead set up, he was with an organization where they set up like a field hospital, right there outside the hospital, because the hospital is completely full. So this was actually kind of really, it felt. It almost felt like a movie. It felt like, I don't know, pandemic or some one of these movies. And but it was really scary. And I was worried for everyone. And, you know, we of course, it turns out that the CFR is 1/10 of that, but it's still awful. Right? And yeah, you know, the things that that the knock on effects of that. So I, you know, hopefully we've learned we can learn from this. It's, it's a hell of a way to, to have to learn, but you know, to learn, and, you know, the dominant paradigm at the time, and I'll say this was like, don't panic, that that was the dominant paradigm. And there, I'm not gonna say his name, but you know, your listeners can Google pretty well, there was a Canadian infectious disease doc. Fortunately, he's also from Alberta. So, you know, I hope you don't hold that against Alberta. But he he wrote this Facebook post that was shared 2 million times on Facebook. That's a lot of people. Sharing a lot of boomers sharing Facebook, right. It's not just boomers. I don't want to pick on I'm pro Boomer. Yeah. Or prozoomer. I like
Boomer subscribers out there. I love you know, I I disavow with Taylor just that about you?
Well, no, I'm just saying like, you know, Facebook sharing that's a you know, that's right in the wheelhouse there but, but, and I saw friends share this. And it turns out basically the article is like, I'm not afraid of COVID Like, don't be scared. I'm a infectious disease doc. I've seen lots of bad diseases. And, you know, infamously in my view said like, when COVID gets here, I don't - I expect it won't do much damage. So he was he was mainly worried. It sounds like from us. He's basically saying Don't panic, you know, can you imagine it might cancel We might have to cancel the Olympics as though, that, you know, and this was shared too many times, that was the dominant paradigm. And I'm you know, and now he's something of a of like a COVID splitter up in Canada, like the CTV interviews of all time, and I just can't believe it. Like, and not only that, that was that article that is if want to call it an article that post was actually publishes articles in a bunch of like, medium sized to small papers in the US and Canada. So I say that just to say, like, No, we don't want anyone to panic, I think everyone thinks PANIC IS is a bad thing, right? But it's, you know, to have in that situation with something is... has a potential to grow exponentially, I think you need to be careful. And you and you may mean that you may want to think about maybe giving up the Olympics, if it comes to that, because the alternative is much worse. And I'm, you know, I'm a former athlete, I like I love watching Olympics, but you know, I'm willing to give it up if it means protect, you know, our, our societies from this type of thing. So I think there's kind of a serious that seriousness that at the time that we lacked, and maybe it was just because we didn't, had never experienced anything like this sort of the memory of sort of the social memory of these kinds of pandemics had kind of faded, and we didn't really have that so called sort of social immune system, but kind of, as I said, as a hell of a way to deal with it. So that that's a little bit of a rant. But, you know, I do think, you know, we need to, we need to prepare ourselves for the future. And be able to, to, kind of, as a society, as a country, and as an international community also just like protect ourselves against threats like this. And, you know, it's awful. I'm really hoping that we can kind of move into the future with where we will probably have to live with COVID to certain extent, but all the mitigation measures that we've been taking, and vaccines and all that stuff.
Yeah, yeah. So I mean, you know, on that cheery note,
sorry, everyone, and you can cut this.
No, I know, I'm not gonna cut it. But, uh, yeah, I mean, you know, this is the world this is the world as it is, and you know, I want to talk to you, Taylor, just to give the listeners just a sense of what, you know, a life in science can be how it winds, the use of the turns, you know, and your experience is not that atypical, I think, you know, you start out with an interest in evolution, you get into molecular biology, all of a sudden, this thing, bioinformatics shows up, you can develop some skills. Next thing, you know, you're working at NBACC, you're thinking of like, you know, like diseases and, you know, bio terror attacks like this stuff happens. So, you know, biology news, you can use, you know, building a better century, you know, we're going to talk about genetic engineering, and all these other things the next 10 years. So, it's great to have, like, all the skills and the tool sets that you have. And, you know, I think one thing we share is, you know, whatever, whatever you have to do for your bread and butter. And it's super important. And I'm not denigrating it any way, there are these big questions of evolution of the meaning of life and like, why life is diverse, and all these things that are still with us, and that we're still exploring that we're still learning in the 21st century with the tools of evolutionary genetics, which are manifold and very, very diverse and wide ranging now.
Yeah, exactly. And I should say this, that I put into practice, all of the things that I well, I will say all of them, but many of the things that I learned, sort of, you know, in undergrad and grad school, as a postdoc that I in life isn't in my life in academic science, at NBACC right in the day to day basis. And I'm still doing, you know, I can't talk about the projects, but I have some, some projects there. And I'm, I'll start up a research program there. But, but I put them into practice. And so it's different in the sense that I, you know, I can't during the day, I can't, I do.... Okay, you know, we because of our security, I don't do you know, I'm not on talking about science during the day on Twitter, which I by no means think is bad. I think it's I mean, that's Twitter's been very helpful for me in science. But just because of our security, I don't do that. But I I, you know, we're not an academic environment. But we, we put a lot of these things into practice. We we do invite speakers, we have a seminar series that's going on, I'm involved in recruiting people for and, you know, so So it's there, there are other positions outside of the traditional sort of academic path. I didn't necessarily expect to that I would that would come here but I once I learned more about this position. I thought it was really Nice and a really good opportunity. And it was something that I was 100% behind at least putting my hat in the ring. And, and so, you know, and then I and I'm still on a couple of committees and doing some work. You know, and I didn't mention this during early part of the podcast, but we're actually working on with some collaborators at MTSU on a project, looking at sort of promoter use in Alzheimer's disease. So you know, kind of a little bit further afield from my my background in evolutionary genetics, but certainly something that's of societal interest and things like that. But But yeah, there are jobs in industry, of course, and also in government. And I think I'm kind of I would, I'm more on the government side, I don't work directly for the government, I work for a contractor. But But yeah, there are jobs there. And they're fulfilling, and, you know, we need really talented people to fill those roles. And you don't, you don't have to have a PhD. There are other roles for people that may have an undergraduate degree or a master's degree or something like that. So so keep your ear to the ground. And, and, of course, and I think industry is actually has been booming, I think biotech is growing a ton and we have a really good biotech base in this country. It's one of the reasons that I decided to come down here for grad school, in addition to the fact that I've finally done here, and I'm American as well, so
yeah, you're American and Canadian, the best of both worlds, right? .
Although not a hockey player, but I'm a big Edmonton Oilers fan so I gotta put a shout out for them.
All right. Um, it was great talking to you Taylor and I will see you online man.
All right. We'll take care Razib and thanks to the listeners for for the opportunity. I know that for sure.