Lex Fridman Podcast - #216 – Vincent Racaniello: Viruses and Vaccines

Starting point is 00:00:00 The following is a conversation with Vincent Reckanielo, professor of microbiology and immunology at Columbia. Vincent is one of the best educators in biology and in general that I've ever had the pleasure of speaking with. I highly recommend you check out his this week in Verology Podcast and watch his introductory lectures on YouTube. In particular, the playlist I recommend is called Virology Lectures 2021. To support this podcast, please check out the sponsors in the description.

Starting point is 00:00:33 As a side note, please allow me to say a few words about the COVID vaccines. Some people are scared of a virus hurting or killing somebody they love. Some are scared of their government betraying them. Their leaders blinded by power and greed. I have both of these fears, and, too, I'm afraid, as FDR said, of fear itself. Fear manifests as anger, and anger leads to division in the hands of charismatic leaders, who then manufacture truth and quotes that maximize controversy and a sense of imminent crisis that only they can save us from. And though I'm sometimes mocked for this, I still believe that love, compassion, empathy is the way out from this vicious downward spiral of division.

Starting point is 00:01:25 I personally took the vaccine based on my understanding of the data, deciding that for me the risk of negative effects from COVID, short-term and long-term are far worse than the negative effects from the mRNA vaccine. I read, I thought, I decided, for me. But I never have, and never will, talk down to people who don't take the vaccine. I'm humble enough to know just how little I know, how wrong I have been, and will be on many of my beliefs and ideas. I think dogmatic certainty and division is more destructive in the long term than any virus. The solution for me, personally, like I said, is to choose empathy and compassion towards all fellow human beings, no matter who they voted for.

Starting point is 00:02:15 I hope you do the same. Read, think, and try to imagine that what you currently think is the truth may be totally wrong. This mindset is one that opens you to discovery, innovation, and wisdom. I hope my conversation with Vincent Rakeniello is a useful resource for just this kind of exploration. He doesn't talk down to people, and he's the most knowledgeable virologist I've ever spoken to. He has no political agenda, no desire to mock those who disagree with him. He just loves biology and explaining the fundamental mechanisms of how biological systems work. That's a great person to listen to and learn from with an open mind. I hope you join me in doing so and no matter what, try to put more love out there in the world.

Starting point is 00:03:06 As usual, I'll do a few minutes of ads now, no ads in the middle. I try to make this interesting, so hopefully you don't skip, but if you do, please still check out the sponsor links in the description. It is in fact the best way to support this podcast. I use their stuff and enjoy it, maybe you will too. This show is brought to you by a new sponsor, Privacy. I love these guys. It's a brilliant idea, brilliant implementation. I can't believe this hasn't already been done, especially as well as they have done it. So the idea is they generate a virtual card

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Starting point is 00:07:13 And right now, they're offering $90 off for your first four deliveries, including free shipping on the first box. When you go to sunbasket.com slash Lex and enter code Lex. That's sunbasket.com slash Lex and enter code Lex. This show is sponsored by the information. They do in depth data driven investigative journalism in the world of technology. The information was actually the first place when I realized that good journalism cost money. I don't always agree with the writing they do or with certain aspects of the articles they put out, but I think they are all exceptionally well researched and I always learn something.

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Starting point is 00:09:56 That's athleta-greens.com-slash-lex. This is the Lux Friedman podcast, and here is my conversation with Vincent Ruckin-Yellow. You mentioned in one of your lectures on biology that there are more viruses in a leader of coastal seawater than people on earth. In the Nature article titled, Markobiology by Numbers, it says there are 10 to the 31 viruses on Earth. Also, it says that the rate of viral infection in the oceans stands at 10 to the 23 infections per second. And these infections are moved 20 to 40% of all bacterial cells each day. There's a war going on.

Starting point is 00:11:00 Do you, what do you make of these numbers? Oh, why are there so many viruses? So the numbers are quoting it. They're in my first virology lecture, right? Because people don't know these numbers and they get, wow, they get wowed by them. So I love to give them. So the way to start to interrupt, as I was saying offline, you have one of the best introductory lectures on virology that I've ever seen. Introductory lectures, periods, I highly recommend people find you on YouTube and watch it

Starting point is 00:11:32 if you're curious at all about viruses. Yeah, there's a lot of times throughout watching it, I felt like, whoa. Yeah, that's my goal, is to work. And that's when my students tell me one student once that every day, after every lecture, I could go home and tell my roommate something she didn't know and blew her away. So the number of viruses is really an amazing number. So that number, 10 to the 31, is actually just the bacterial viruses in the ocean. So there are viruses that infect everything in the ocean. And so 10 to the 31 is from basically particle counts

Starting point is 00:12:07 of seawater all over the world. So there are more viruses than 10 to the 31, but just in the ocean. And that number is so big, first of all, the mass exceeds that of elephants on the planet by a thousand fold. And if you lined up those viruses and to end, they would come to you First of all, the mass exceeds that of elephants on the planet by a thousand fold.

Starting point is 00:12:26 And if you lined up those viruses and to end, they would go 200 million light years into space. It's so big a number. It's amazing. And then, yes, 10 to the 20-some infections per second of these viruses killing bacteria and releasing all this organic matter. And that's part of this what we call the biogeochemical pump, cycling of material in the ocean, the bacteria die.

Starting point is 00:12:55 They start to sink and then they get metabolized and converted to compounds that are needed. A lot of it gets released as carbon dioxide and so forth. So these are actually really important cycles that are catalyzed by the virus. Well, it's so well that nature has developed a mechanism for mass murder of bacteria. That's one way to look at it, but it's just what happened, right? It's interesting. I mean, I wonder what the evolutionary advantage of such fast cycling of life of like such fast cycling of life, is it just an accident of evolution that virus is so numerous? Or is it a feature, not a bug? So the fast is, it does not all fast, not all viruses are fast. Some are 20 minutes per cycle, some take weeks per cycle. But that's just per second.

Starting point is 00:13:48 There's so many viruses in the ocean that that's what you get per second, no matter how fast the cycle is. But I look at it this way, viruses were probably the first organic entities to evolve on the planet. Long ago, billions, billions years ago, just as the Earth cooled and organic molecules began to form. I think these self, we call them self replicators. They're just short things that today would look like RNA, which is the basis of many viruses, right? They evolved and they were able to replicate. Of course, they were just naked molecules. They had no protection. And it was just RNA-based. And that's tough because RNA is pretty fragile in the world. And it probably didn't get very big as a consequence.

Starting point is 00:14:39 But then proteins evolved, and I'm skipping like hundreds of millions of years of evolution proteins evolved, maybe without a cell, maybe with a cell. But then to make a cell, there probably were some RNA-based cells early on, but they were pretty simple. But the cells that we know of today, bacteria and single cell, eukaryotes, they have very long DNA genomes, and you need a lot of DNA to make a complicated cell. And so we think at some point the RNA became DNA.

Starting point is 00:15:13 And probably one of the earliest enzymes that arose is the enzyme that could copy that RNA into DNA, which we now know today as reverse transcriptase, which my former boss, David Baltimore, and Howard Teman that co-discovered. And that ends, I'm a rose and copied RNA to DNA, and then you could build big cells with the, because DNA can be millions and millions of bases in length. And RNA, the longest RNA we know of is 40,000 bases, not much bigger than the SARS-CoV-2. What would you say is the magic moment along that line? I saw it was one or two billion, maybe three billion years it took to go from bacteria to complex organisms. It seems like Earth had a very long time like not a very long time without life Mm-hmm, and then a very long time with very primitive life

Starting point is 00:16:13 Maybe I'm discriminating calm back to your primitive life. Yeah people would object to you But it seems like complex organist when he starts becoming something like I It seems like complex organist starts becoming something like I don't know what's a good not animal like but More complexity than just like a single cell What what do you think is the magic there? What's the hardest thing if you were trying to engineer earth and build life and Build the simulations that obviously we're living in a video game what this is so if you're trying to build this video What's the hardest part? so bacteria video game, what this is. So if you're trying to build this video, what's the hardest part without long-savolution? So bacteria are mostly single cells. They do make colonies. They get together in biofilms, which are really important. But they're all single bacteria in that. And the key is making an organism where cells do different things. We have skin cells and eye cells and brain cells.

Starting point is 00:17:05 And bacteria never do that. And the reason is probably energy. Bacteria can't make enough energy to do that. And so there was another cell existing at the time, the archaea. And the idea is that a bacteria went into an archaea and became the modern day mitochondria, the energy factory of the cell. And that now let that cell develop into more and more complicated organisms like we have

Starting point is 00:17:34 today. It was all about energy. So the mitochondria, the energy, the mitochondria is the magic thing. I think so. Actually, not my idea. It's Nick Jones. Have you heard of Nick Jones? He's an evolutionary

Starting point is 00:17:45 biologist in the UK. And he's done experimental work on this. And it's his idea that the defining point was the ability to make a lot of energy, which a mitochondria can do. It's basically a whole back theory inside of a bigger cell. And that becomes what we now call eukaryotes and that they can get more and more complicated. So let me be back to the viruses. I want to finish that story. Yeah, which points of viruses come along? So we remember we have these precellular, they're called precellular replicons, right?

Starting point is 00:18:15 And so we have a precellular stage where we have these self replicating molecules and cells arise. And then the self replicating molecules invade the cells. self-replicating molecules and cells arise and then The self-replicating molecules invade the cells be why because it's a hospitable environment I mean they didn't know that they just went in and it turned out it was beneficial for them So it stuck and they replicate inside the cell now where they have pools of everything they need They get more and more complicated and then they steal Proteins from the cell to build a protective shell. And then they can be released.

Starting point is 00:18:49 As virus particles, they're now protected. They can move from host to host. And because they're at the earliest stages of cellular evolution, they can diversify to infect anything that arises. And that is why I think there's so many of them. And everything on the planet is infected because the ancestor of everything was infected many years ago. So it's easier to steal than to build from scratch. So it's easier to sort of break into somebody else's thing and steal their proteins. Yes. My colleague Dixon, D. Pomadek, calls viruses safe crackers.

Starting point is 00:19:31 Safe crackers. So it's just from an evolution perspective, it's, yeah, it's, it's easier to steal because you can select, but then you have to figure out mechanisms for stealing for breaking into, for cracking the safe. Well, you don't have to figure out. It just happens, right? Because molecules are so diverse that a molecule gets into a cell and if there's a protein that sticks to it, it's going to stick and that gives an advantage. There's no, you know, there's no planning, there's no thinking about it, right? It just happens. Oh, we'll return to that. What up, but these numbers are crazy. So what, as these more complex organisms evolved, let's take us humans as an example, should

Starting point is 00:20:12 we be afraid of these high numbers? Should we be worried that there are so many viruses in the world? But to a certain extent, I mean, they have, it's twofold. They're good and bad, right? Viruses are no, there's no question they can be bad. We know that because they've infected cause disease throughout history, but we're also, you and I are full of viruses that don't hurt us

Starting point is 00:20:32 at all and probably help us and every organism is the same. So they are clearly beneficial as a consequence. So I think, so every living thing on the planet it has multiple viruses, in fact, everything you can see. And most of them, I think we don't worry about because they can't infect us. They're unable. In fact, now you can actually take your feces and send them to a company and they will

Starting point is 00:21:00 sequence your viruses in your feces for you, your fecal viral, right? And the most common virus in human feces is a plant virus that infects peppers. It's called pepper model mosaic virus. And that's because people eat a lot of peppers. And it just passes right through you. Cabbage is full of viruses from the insects that walk on the cabbage and the fields. We eat them. They just pass us. So I think most of the viruses we don't need to worry about except when we're talking about

Starting point is 00:21:32 species that are closest to us mammals. Of course, I think the most numerous ones are the most concerning. Their viruses like bats, bats are 20% of mammals, and rodents are 40% of mammals. And we humans live nearby, right? Yeah. And we know throughout history, many viruses have come from bats and from rodents to people. No question about that. So there's a proximity in terms of just living together in a proximity genetically too,

Starting point is 00:21:59 so it's more like the virus will jump from a bat and a rodent. And birds too. Birds can give us their viruses that happen. Influenzo viruses come from birds mainly. So I think those are the three species. I'm not species. It's higher than species, obviously. But those are the three I would worry about in terms of getting their viruses.

Starting point is 00:22:19 And we don't really know what's out there, right? We have very little clue about what viruses. And I, for years, wanted to capture wild mice in my backyard and see what viruses they have, because no one knows. And it's an easy, we can't ask them. So you mean map, like, is there a word? It's asking them. Yeah. No, I have to, it would have to sacrifice them and take tissue and then bring it in the lab and do genome sequencing. So you can do a thorough sequencing to determine your viruses. Is there a sufficiently good categorization of viruses where you be? That's a very good question.

Starting point is 00:22:53 So whenever you do sequence, right, you get some environmental sample and you extract nucleic acid and you sequence it. What you do is you run it past the database. The gold standard is the GenBank database, which is maintained here in the U.S. and you see if you get any hits. And then you can say, ah, look, this sequence is similar to this virus and you can classify all the viruses you see. The problem is 90% of your sequence is dark matter. It doesn't hit with anything. It's probably a lot of it is unknown viruses and that's going to be hard to figure out because someone's going to have to go

Starting point is 00:23:30 after it and sort it through. So yes, you can find a lot of viruses and the numbers you get are astounding. You can find thousands of new viruses just by looking in various life forms but there are many more that we don't pick up because they're not in the database. Maybe this is a good time to take a quick tangent. What do you think about alpha fold two? I don't know if you've been paying attention to that. Well, the deep mind solving the protein folding problem and then also releasing first of all open sourcing the code which is for me as a software person that I love and then second of all also making Like 300,000 predictions or something like that for different protein structures and releasing that data

Starting point is 00:24:15 Yeah So on the side of because you make you're saying there's dark matter, right? Is there something? What first what are your general thoughts, level of excitement about their work and second, how can that be applied to viruses? Do you think we'll be able to explore the dark matter of virology using machine learning? Yeah, absolutely. Because in all this dark sequence, you can translate it and make a protein. You can see what a protein looks like. It has what we call an open reading frame, right? A start and a stop.

Starting point is 00:24:48 And right now, it's just a bunch of amino acids. But if we could fold it, maybe the fold would be like something we already know, some protein fold, which gives you a lot of clues, because there are only so many protein folds in biology, and that dark matter is probably one of them. So I think that's very exciting because for years I followed structural biologists for years and you know in the beginning we couldn't even solve structures of viruses. They're too big. We could do small molecules like myoglobin like that was the first one done,

Starting point is 00:25:21 took years to do that. And then as computational power increased, then they could start to do viruses, but it took a long time. X-ray crystallography, depending on getting crystals of the virus, right? And now we can do cryo-electron microscopy, which is much faster. You could solve a spike of SARS-CoV-2

Starting point is 00:25:41 was solved in two months by Jason McLelland here in Austin actually at the beginning of the pandemic, but you're limited. You can't do huge proteins. You can only do moderately sized ones. So, or actually, you can do viruses, but you can't do small proteins. So that's speeded it up, but it's still too fast to solve, you get a new protein, you want to solve its structure. So if we could predict it, and I know from talking to structural biologists, this has been their holy grail from day one, they want to be able to take a sequence of a protein, put it in a computer, and have the structure put

Starting point is 00:26:16 out without having to do all the experiment. So that's why this is very exciting that you can predict it. That mean it's not finished obviously, and there's more to do. But I think that will be a day where you could take any amino acid sequence and predict what it's gonna look like. See, but like our structure of bowel is gonna get greedy. So once you have that,

Starting point is 00:26:35 don't you wanna go more complicated than? Don't you wanna go? Cause that's just the first step, right? To go from amino acid to the structure. Then there's like multiple protein interactions. Like, how do you get to the virus? Well, so that's what the ultimate goal of getting a structure is that then you can do experiments and figure out what the structure means, right? So many, in the old days, structural biology was a career in itself. You worked with people who had a system and just solved proteins for them, and then you moved on to another one. You didn't really do any experiments. The other people got to

Starting point is 00:27:08 do all the interesting experiments. Now, young structural biologists are multifaceted. They solve the structure, and then they say, what happens if we change this amino acid? Oh, look, it blocks binding to the receptor. This must be the receptor binding interface. So that's the exciting stuff. Absolutely. It's doing the experiment. I wonder if you can do some kinds of simulations of different proteins or multi-protein systems going to war against each other. Like, to try to figure out, reinforcement learning is used in Alpha Zero, for example,

Starting point is 00:27:49 to learn chess and go, and that's using the self-play mechanism where the thing plays against itself. Sure. And learns better and better. Yeah. Whether you can, I wonder if you can simulate almost evolution in that way for primitive biological systems. Sure.

Starting point is 00:28:04 Have them in simulation fight each other and see what comes out. Like a super dangerous virus comes out or super like Chuck Norris type of thing that defends against the super dangerous virus. And it's all in simulation. So an example would be, we have all these variants of SARS-CoV-2 arising, right? Which looked to be selected by immune responses. But we now, we know what amino acids are changing in the spike and how they block antibody bonding. You could simulate that. You could say, what is the antibody looking at? These are where antibodies bind on proteins are called epitopes, right? You could map them all and change them in a simulation one by one and go back and forth between the antibody and the virus. So all these evolution is what we call

Starting point is 00:28:50 an arms race, right? The virus changes and then it evades the host and then the host can change. The host takes longer to change though, unfortunately, it takes geological time, but it can and then the virus can change and it can go back and forth and we can see evidence of this in genome sequences of both viruses and their hosts. And so you can take a protein in a host that is a receptor for multiple viruses and you can see all the impacts of virus pressure on it and you could simulate that for sure. And that's just one thing that you could do. You could simulate changes in, say, an enzyme that makes it resistant to a drug and predict all the drug resistance. But the problem

Starting point is 00:29:33 is people like me, the experimental virologist, don't know how to do any of that. So we need to collaborate with people, I guess, with all the other do that we do that, but with People from a field that were not used to like I suppose people who would it be AI? I suppose yeah machine learning people machine learning people and you would say look This is the biological problems. They're a way we can use your tools to attack it the problems those people are Anti-social introverts that have a place like this and try to hide from other people in the world. Very difficult to find in the wild. and produce five, I would say, related podcasts, including my favorite this week in virology, also this week in parasitism, this week in microbiology and so on. So, you're a good person to ask, what are the categories of small things, small biological things in this world that can kill you?

Starting point is 00:30:41 Kill us us humans. Let's look, you said like most viruses are friendly or at least not unfriendly, but let's look at the unfriendly ones, viruses and bacteria and those kinds of things. When you look at the full spectrum of things that can kill you, can you kind of paint a brief picture? Yeah, I think the big picture is that the things that can kill you are a minority of everything that's out there. And we're talking about molecules. So we have in us proteins that can kill us. Yeah. Preons that are just it's a protein in us. And if it misfolds, it makes all of its other copies misfold. And then then you die of a neurological disease. Yeah.

Starting point is 00:31:25 That's pretty rare. So there are proteins, there are viruses. As I said, only certain ones can kill us. But even though if we get those from animals, it's not straightforward. If you look at SARS-CoV-2, right, this is probably a once-in-a-hundred-year pandemic, I would say, equivalent to 1918 in its devastation. And in between there have been smaller pandemics of other viruses, but it doesn't happen all that often.

Starting point is 00:31:53 So we have a lot of viruses. We have a lot of bacteria of various sorts that can cause infections in us. And there's a limited number, right? You're strapped to cacao and staflo caca and claustridia, we can go on and on. But we know how to handle those, as long as we have anti-microbials,

Starting point is 00:32:12 it's just that we abuse them and we get resistance. So that can be a problem. Then we have fungi, not mushrooms, but much smaller fungi that multiply sub-microscopic or just at the microscopic level, they can, you know, and dry climates of the U.S. you can inhale their spores and they can grow in your lung if you're immunosuppressed and so forth. So those are the tiny guys. And then we have parasites, which we do this week in parasitism, where single cells, even worms of various

Starting point is 00:32:42 sorts, can invade you and cause all sorts of problems. How kind of terrified to listen to that podcast, what's it like? What you learn is that you can, you travel somewhere and you can get infected and bring it back home. Yes. Here in the US, we do have certain kinds of parasites, but because of our lifestyle, we more or less have avoided them. For example, there is a parasite called toxoplasma, which is infected most of the world, actually,

Starting point is 00:33:17 because a lot of people like to eat raw meat, and you would get it from raw meat. And we're not as fond of that here in the US. We like to cook our meat, but that could be a consequence of eating raw meat. Is that what leads to what is it called taxoplasmosis? Yeah, so taxoplasmosis, it's mainly a big issue is if you're pregnant and you get toxic, so then your fetus is going gonna be very badly malformed.

Starting point is 00:33:46 It's gonna have brain defects and so forth. And animals can get it as well. So there are a lot of parasites of that nature which you often acquire by food, eating food of different sorts. And it usually happens elsewhere. We just, on this weekend parasitism, we do a case. So the anagryiffin is our resident

Starting point is 00:34:07 physician. He's a doctor, a real doctor, right? And every month he comes up with a case. Okay, this is a person I saw. And last month this young lady had traveled somewhere and she ate raw fish. She was somewhere Southeast Asia or something. and she ended up with red bumps all over her skin and it turned out it was a parasite from the fish that moved around in her. And very easy to cure. We have the right doctors and the right drugs you can cure all these. What about diagnosis? Like connect the red spots to the fact that it's a parasite.

Starting point is 00:34:42 Very easy to, if you have the right diagnostics. Now Daniel often goes to parts of the world where they don't have diagnostics and he has to use other mechanisms. He may have to take a bit and look at it under a microscope. And then he may not be able to get the drug depending on where he is. But if these, but often he sees patients who come back to the US and they get diarrhea or they have a fever and he said, where have you been? And he can put two and two together. And so we let our listeners do that and they all send in guesses and it's wonderful to hear them go through this.

Starting point is 00:35:11 So there are a lot of parasites. So the puzzle and solve the case. That can get you. You have to be careful about eating when you go overseas. And water too. Water as well. And you know, in parts of Africa, there are parasites in the lakes. And if you go swimming, they can invade you.

Starting point is 00:35:25 And in fact, I can go into your hair follicles and burrow in and get into your bloodstream. That's exciting. So Daniel is interesting because he's very adventurous and he's not afraid of any of this. So there's a famous lake in Africa, Lake Malawi, which harbors a lot of these parasites. And he said, oh, yeah, yeah, I just make sure I towel off vigorously when I get out. And get rid of them. And that was a name of an episode. But you know, food is, you know, sushi, you can, you can get worms from sushi.

Starting point is 00:35:56 And the solution is to freeze it. And many sushi restaurants now have liquid nitrogen. They snap freeze their sushi and that kills all the parasites. And a study was actually done in Japan showing that freezing does not alter the taste of sushi because it's up to you to see a big industry. That's brilliant. That's brilliant. Yeah, I was thinking about, you know, I'm so boring and bland that especially when I'm now in Texas here and I've been eating quite a bit of barbecue

Starting point is 00:36:27 I realize that really haven't explored the culinary world and I've been curious to travel and taste different foods Is there something you can say by way of advice? You know channeling Daniel, I guess if you were to travel in the world, if eating is the thing that gets you the parasites, what's a good advice for eating in strange parts of the world? Mongolia, India, China. Is there something you could say by way of advice? I think Daniel would say, make sure your food is cooked, right?

Starting point is 00:37:01 Cooked, but that's so boring. Yeah, it's unfortunate. He would agree with you because, you know, many vegetables are delicious. Salads even are delicious, not cooked, but they can have parasites in them. Meats, fish, people like to have uncooked fish. So if you want to be really safe and boring,

Starting point is 00:37:19 just make sure everything is cooked. And now we have a case this week on Twip, of a young man who went, I forgot where he went, but he stayed in a hotel. I think he, oh, Wahaka, Mexico, stayed in a hotel. And he said that he came back with diarrhea and fever. And he said, that, I don't know where I stayed in the hotel. I just ate hotel food, lots of vegetables and fruits. And probably they weren't washed with clean water. You know, we got something from that. The bottom line is most of these

Starting point is 00:37:51 infections with parasites can be diagnosed, and you can be treated, and you'll be fine. So, if you really want to experience the cuisine, I don't think you should worry about it. That's what Daniel would say. Let's return to the basics. We can then jump around all over the place. What are the basic principles of virology? Maybe a good place to start is what is a virus? That's great. I mean, I talk in my first lecture for 20 minutes before I get to that, but and I wonder if I should put it up front, but it's kind of a boring definition. So if you do that, first people will turn off. So first you tell them about all the millions and billions of viruses around. So a virus, we have a very specific definition because

Starting point is 00:38:36 it's different from everything else on the planet. Because first of all, it's a parasite. It takes, a parasite means you take something from someone else. And we have human parasites who take money from others, right? But in biological terms, a parasite takes something from the host that, the host would otherwise use energy or some building block or something.

Starting point is 00:38:59 There's never really a symbiotic relationship between a virus and a host. Well, there can be. So that's the dichotomy I think, is that we define them as parasites. Yet, I just told you 20 minutes ago that many viruses are probably beneficial. So I think what it means is we, at some point, we're going to have to change our definition, right? Because after all, definitions we make are just constructs that make it easy for us to study that not necessarily represent what's right.

Starting point is 00:39:30 Yeah, like Pluto was a planet first and not a planet anymore and a lot of people very upset. But it's only according to us there may be another race living somewhere else who thinks it's a planet right. Well, maybe that's why viruses are attacking humans. They're very angry. They weren't calling them parasites. So right now our definition includes parasite because a virus cannot do anything without a cell. If this mug were full of viruses, it would not do anything for years. It would eventually probably lose its infectivity, but it's not going to reproduce here.

Starting point is 00:40:04 It needs cells. And to the first people who discovered viruses, that was astounding that they didn't just reproduce, divide on their own bacteria. So the virus needs to get inside of a cell, inside the cell. It can't just hang around on the surface. It needs to get in in order to make more of itself. And so we call it an obligate intracellular parasite, because it needs to get in a cell, and then it takes things from the cell in the form

Starting point is 00:40:31 of all kinds of molecules and processes and energy and so forth to make new viruses. A obligate means it's obligated to be inside the cell. Absolutely. It will not reproduce outside of the cell. So this mug of viruses is can in no way be living in my opinion. However, once it gets inside of a cell now the cell is a virus infected cell. It's alive. So a virus in my view has two phases, right? It's this non-living, particular phase that everyone is used to. I'll send you, you need a virus for your table. I'll send you a nice model. I think it would look good here.

Starting point is 00:41:09 Yes, definitely. You don't have to go with all this other stuff. Well, these are all mechanical, there's no biology here. So you wouldn't want a virus here? No, I'd want a virus, of course. I'll send you one and then you can look at it. Because now that we have the three-dimensional structures solved by structural biologists, we take the coordinates and we put it in a 3D printer and you can make amazing models, right? Of any virus.

Starting point is 00:41:32 And so there's a huge variety of viruses. Huge. That we know of, which is only a fraction of what's out there. What's the category? So there's RNA, there's DNA viruses. What are those? What's DNA and RNA? Two broad categorizations.

Starting point is 00:41:47 RNA and these are genetic material. Can be two different chemicals. So RNA, everything else on the planet besides viruses is all DNA based. You and I are DNA based. Everything on the planet today is DNA based except some viruses are RNA based. And that's because, as I mentioned earlier, the first life that arose on the planet was RNA based. Yeah. So these are like old school viruses.

Starting point is 00:42:13 So old school, we call relics, yeah, relics. And this has got a name called the RNA world, which I think is great. Is it big, though, or are they are the relics dying out? Oh, no, the relics, in my opinion, are the most successful viruses, the RNA viruses in the SARS-CoV-2 is an RNA virus. We can talk about why they're so successful. But you have broadly speaking viruses with RNA genetic information, which are relics, of course, they're contemporary. They have adapted to the modern world and the modern organisms living in it.

Starting point is 00:42:44 And then we have DNA based viruses, which are extremely conservative and slow. They're very successful. You know, everyone has a Herpes virus infection, but they don't get the news like the RNA viruses do. The HIV's and the influenza viruses and the SARS-coronavirus, they get all the press and they're RNA-based because RNA lets you change more so than DNA. So they evolve much faster, aren't they, viruses? Much faster.

Starting point is 00:43:12 And in fact, when I have an electron evolution, I don't know if you've listened to that when you should, it's really, I think it's really interesting. RNA viruses exist at their error threshold, which means they can't make any more mutations when they reproduce otherwise they're dead. They would go just think they're they're evolving at their error threshold. DNA viruses are hundreds of times lower than their error thresholds. And we know this we can do an experiment to find that out. Now why that is is a good question, but that's the reason why RNA viruses are far more successful.

Starting point is 00:43:53 They, in fact, many more hosts, and they're very, I would say, slippery. They can change hosts really quickly because in any animal harboring in RNA virus, like let's say a bat in some cave somewhere, it's not just one genome, it's millions of different genomes, all kinds, all within the framework of say, coronavirus, but they're all different. And one genome in there might just be right for infecting a person if it ever encountered that person.

Starting point is 00:44:21 I mean, that's the thing that... Well, there could be a large number. This is a tiny fraction, but a large number of them. And they're all operating at the threshold of error. That's right. That's fascinating. It's like, little like, uh, it's like startups, little entrepreneurs, like, I start up worlds. Yes, and many of them fail. Yeah, many of them change. And then there's the DNA virus that are like the IBM and the exactly the big corporations that the Compton conservative with the bureaucracies and all that kind of stuff. So a lot of baggage.

Starting point is 00:44:49 Yeah, yeah, it's expensive for them to reproduce. Yeah. And they don't move quickly. Yes, the already viruses are the fast moving members. So that's what a virus is. We call them, obviously, the intracellular parasites. And then I told you there's DNA and RNA. But then let's go further.

Starting point is 00:45:06 The nucleic acid is not naked because naked nucleic acid in the world isn't good. I mean, it existed in the precellular world, but it probably weren't a lot of threats to it then. Naked nucleic acid doesn't last long in the environment. So they're covered. The nucleic acid doesn't last long in the environment. So they're covered, the nucleic acid is covered. It can be covered with a protein shell, a pure protein shell, or it can have a membrane around it, which would be lipids from the host cell.

Starting point is 00:45:36 So lipids, it's fatty membrane. Fatty membrane. So our cells are coated with fatty membranes, right? Our cells, the outer platylo membrane, right? That's the same. Revires can be too. So they're kind of like cells, but without the ability to do the mitochondria stuff. Some are. Some, they don't have nuclei, they don't have mitochondria. But they do have a nucleic acid, they have a membrane, and then of course there's spikes in the membrane that allow them to attach to cells. And so that completes our two different kinds. So they have, they all have like Of course, there are spikes in the membrane that allow them to attach to cells.

Starting point is 00:46:05 So that completes our two different kinds. So they all have attachment mechanisms, like ways to keys into the cells. They all have to get into cells. There are a couple of exceptions though. There are viruses of fungi and plants. So let's do the fungi. Fungi would be like yeast. The virus, the yeast cell wall is pretty hard to get through. So viruses typically don't attach to a yeast and get inside. Rather, they just live in the

Starting point is 00:46:37 yeast forever. Yeah. And they multiply as mostly nucleic acids and as the yeast divide, they go into the daughter cells. And that's how they exist. The plant viruses, also the plant cell wall, would be very hard to get across with a, by binding a protein. So plant viruses get into plants either by pests that inject them in, they're sucking sap out, and they inject virus at the same time, or farmers, they have contaminated farm equipment and they roll over the plants and introduces viruses. So those fungi and plant viruses, they don't have this specific receptor binding to get them into the cell. But everything else, the virus binds to something on the surface, very specific.

Starting point is 00:47:19 It's taken into the cell because that's what cells do. When things bind their exterior, they take it in. Because in most cases, it's good. It's something they need. And so the virus slips in, I guess you'd call that a Trojan horse, right? Trojan horse. It's so hard to not at the purmorphizes whole thing. It is hard. So obviously they don't know any of this. It's not an actual Trojan horse. So they, they're not getting actually tricked in the way humans trick each other.

Starting point is 00:47:48 No, it's well passive. It's just, so many years of evolution, you select something that works and it continues. And what survives then goes on with a perhaps a slightly different approach. I love this idea of passive. Of course, according to Sam Harris, so for my sufficiently intelligent alien civilization observing humans, our behavior might seem passive too, because they understand fully exactly what we're doing.

Starting point is 00:48:14 And then there's no free will. And we're all just operating in the same way. It could be cell does, but just a much higher level of complexity. Yeah. So I love the distinction between active and passive. I mean, the point is, I think anthropomorphizing through a certain extent is fine because it helps people understand. But when you start to say, I think the virus is doing that because then you're putting a human lens on it and you may be wrong. Yeah. Because you don't know why things happen for a virus. So right now we have variance emerging

Starting point is 00:48:47 and people say, well, I think it's because the antibodies are selecting for variance. That's a good idea, but it may not be the only thing that's good. Well, you started imagining them coming to the table negotiating, yeah, you get the trouble with that. That's why I tell my students, be careful about the anthropomorphizing because

Starting point is 00:49:06 You're gonna apply your values to a virus and you have different value you're human and you have What you think is the reason for this outcome may not be right. That's all just be open-minded Yeah about it in both directions I actually one of the things that push back on is in the space of robotics people most people in robotics try to not anthropomorphize. For example, they don't give a gender or a name to robots. They really try to see as a machine. To me, that makes sense in one way, but it totally doesn't make sense to another.

Starting point is 00:49:39 If that robot is to interact, operate in the human world and interact with humans, we have to anthropomorphize it in order to understand as an engineering problem, how should it operate in a human world. Now the difference with viruses, the scale of operation, it doesn't make sense to treat them as human-like, because the scale of operation is much small, but robots, you're in the same time scale, the same spatial scale. Of course, in the movies, they always give them names and personalities. Yeah. Well, yeah, that's the, but that's my argument is we should do the same when you're trying

Starting point is 00:50:17 to solve the engineering problem of robotics too. It's not just for the movies. Well, let me ask you this, because you've said controversially, not really, that viruses are not living, defend yourself. So viruses alive or not? So I've seen many people say, oh, they have to be, they have nucleic acids,

Starting point is 00:50:38 they evolve, they mutate. That's all true, but they don't do it on their own. The particles in my mug are just not doing any of that unless they get into a cell. So a virus in fact, it's a live. I totally agree with that because in fact, when a virus gets into a cell, it converts it into a virus making factory, if you will.

Starting point is 00:50:58 There's no longer a cell. It's a, some people call it a viral cell. I don't really like that, but it's fine. So that's what I'm talking about. The particle is not alive. You can have your virus infected cell as alive, but the particle it just would not do anything Forever without getting inside of a cell. Well, once it's into cells It is alive then, but it's no longer a particle. It's taken apart and New glycacid is moving around the cells, making proteins. Eventually, it makes new particles, and then those particles released from the cell,

Starting point is 00:51:29 they're not living anymore. So it's kind of, I think it's kind of like a spore, a spore of a or a seed. Although the seed doesn't work because the seeds, the cells in the seed have the ability to make their own energy and so forth. But a bacterial spore, and it's the same thing, doesn't do anything unless you add water and nutrients, and that starts to divide, but it doesn't need to get into a cell. It's very different from a virus. So that's why the particle, and when people think of virus, they're always thinking of the particle, and that's why I say it can't be alive because the particle can't do anything

Starting point is 00:52:04 on its own. But if you think of a virus as an organism with a particle phase in a part in a cell then it makes sense to be alive And by the way when you say particle you're referring to that structure that you've been mentioning some Basel membrane and not that that's that's been called what is a viral particle? Some very what you should have here I'll send you one and then you can refer to it. What's the sexiest one to have like what in terms of particles to have on a table? Well, fortunately, the ones that you can 3D print, they're not going to be. They're the ones that we know the structures of, right?

Starting point is 00:52:40 So someone sent me last year a 3D model of SARS-CoV-2, and it's beautiful. It's actually cracked open so you can see the RNA and the spikes are sticking out. And they even put some antibody sticking onto the spikes. And that's cool. I mean, when I show this on a live stream, people love this. They go, my God, this is beautiful. It is. It's absolutely gorgeous. I have that.

Starting point is 00:53:00 I have my virus that I worked on most of my career polio virus. I have a 3D model of that Which I actually just had made. It's gorgeous and you can have it made in any color you want right? What would you say is the most fascinating? terrifying surprising beautiful virus to you so you evolve the viruses you looked at Sometimes when you just sit late at night with a glass of wine looking over the sunset, which viruses do you think about? So fulfilling all of those adjectives is hard, right?

Starting point is 00:53:35 Fascinating, exciting, terrifying. Well, the terrifying is an optional one, I think, because maybe that puts a lot of pressure. I see, terrifying to me, I'm not terrified because I think we can handle. As most viruses, as you see with this brand new one that emerged a year ago, we can handle it. From a virology perspective. Yeah, I mean, the human perspective is a different story, right? That's always an issue. So I think there are a couple of different categories of virus.

Starting point is 00:54:09 So we could do the terrifying. And I think rabies is a terrifying virus because unless you're vaccinated, 100% certainty you're going to die. So you get bitten by a rabid raccoon or bat or dog, whatever. bitten by a rabid raccoon or bat or dog, whatever. And you know, and there's still 70,000 deaths a year of rabies throughout the world, because there are a lot of feral dogs running around that are infected. Unless you're vaccinated, you're going to die. There's nothing we can do. But we do have a vaccine, which we can actually give you even after you've been bitten, which is the only vaccine that works that way. It's a therapeutic, right? It will treat your illness because the disease takes so long to develop. Eventually, you get what kinds of neurological issues and paralysis and so forth,

Starting point is 00:54:57 but it takes time and you can be vaccinated. It will prevent that in the meanwhile. So people always say, what's the most lethal virus? Is it Ebola? I said, no, it's actually rabies, unless you're vaccinated, and you know, we'll kill you. Maybe it's good to linger, because we'll talk about vaccines a few times today. It's good to linger on cases where vaccines have clearly undoubtedly helped human civilization. And it seems like rabies is a good example.

Starting point is 00:55:29 Oh, rabies is great because everyone knows what happens when somebody gets rabies, right? You have fear of water, hydrophobia. Your body becomes spastic and stiff and shirks around and you lose consciousness. You can't, you know, no more. It's not a fun ride to death. It's horrible. It's a horrible way to die. So I think most people know that. It's been popularized enough in media, right? So that nobody would probably object to getting, oh, I was just bit by this raccoon and it ran off. Okay, well, we should assume it's rabid. We should immunize you and most people are okay with that.

Starting point is 00:56:09 Yeah. Because they know the consequences. And it's also pretty rare, right? It's not like something that you're trying to get into the arms of, you know, 250, 300 million Americans. That's hard. But the few thousand every year, it's easy. So the transmissibility is difficult.

Starting point is 00:56:27 Right. It has to always not, it's not airborne. So it's not your board. It's just, you have to be, you have to be bitten. Well, though some, some people claim you could walk into a cave and the bats, you know, breathing out rabies, virus could infect you, but I don't really think that's well, that's well substantiated. I think it's a bite.

Starting point is 00:56:47 How would you do a study on that? Yeah, it's very hard to do. You'd have to collect the vapors in the cave and show that they're infectious, which, and by the way, someone emailed me the other day, you'll like this. They say, why can't we just immunize all the bats in the world against these viruses? And I said, well, how would you do that? There are caves everywhere, right? Yeah.

Starting point is 00:57:07 He said, well, maybe you could just go and aerosolize that. Yeah. It's pretty dangerous. And then all the bats should have vaccine passports to make sure that they're. Yeah. And so you have to get their consent before you do it. But we do immunize wildlife against rabies.

Starting point is 00:57:25 We have rabies vaccines for wild animals. They're a whole bunch of them that get rabies. And we put it in bait and drop it from helicopters in the woods and it drops down the incidence of rabies and people. Wow. You know, people hiking, getting bitten and so forth, it drops the incidence.

Starting point is 00:57:41 So we can do that. I didn't know that. I was wondering how much medical care we're doing for animals in the wild because every season they become more and more aware that animals are living in extreme poverty. You think natural, it's great. When animals are living in a farm, it's terrible, but you also have to compare to like, what life is like in the, or like the zoo, you have to compare what life is like in the wild.

Starting point is 00:58:12 Well, life in the wild is very tough, I think. I mean, most animals have to, well, the carnivores anyway, they have to catch their food every day, right? And then there's the viruses there. They have viruses as well. So the rapeseed immunization is the only one I'm aware of for wild animals.

Starting point is 00:58:31 We do immunize lots of other animals. So we immunize chickens and pigs and cows, even fish. Farmed fish, we pick each fish up and give it an injection. And when it's a small fish But that's mostly So that the farmers get a good yield. We don't really care about the animals, right? We want a good yield for Market and then there's some examples where we Immunized animals to prevent spillovers into people So there's a disease called hendra in Australia, which was discovered in the 90s. It turns

Starting point is 00:59:11 out there's a there are bats, fruit bats that have this virus. The bats are fine, but sometimes they flying at the horse stalls, and the horses get infected. And these are in Australia, it was initially race horses, which are very expensive, right? The horse has gotten infected and they died and the humans who would take care of them would die also. So now they immunize the horses to prevent the, well, the save the horses. Probably that's the motivation because these horses are hundreds of thousands of dollars,

Starting point is 00:59:37 right? And then the people don't get sick because the horses don't get sick. You don't want to immunize all the people because it's too rare. But that approach is called one-world health approach, which means everything's connected on the planet. And we have to think of everything in the grander scheme, not just us. Yeah, so you can immunize some things along the trajectory that a virus would take. Exactly. So it's something, some living beings. Yeah. And the Arabian Peninsula, they have a merged coronavirus issue every month.

Starting point is 01:00:06 There are a couple of cases where a camel will infect the human and the human can get very sick. It's respiratory disease, very much like COVID. And so, camels are very common there. They're used to race, they're used as pets, they're eaten. So there's a lot of human camel contact. But the number of cases are rare to a month. So you don't want to immunize all the humans. So the idea would be to immunize the camels. So I like it. So okay. So you put rabies, but Ebola also is a famously

Starting point is 01:00:42 deadly one. What is it? It kills like, I't know 50 60% of it's 50 to 90 but That's in Africa where the health care isn't great What you saw when they when it cases of Ebola came to the US? We're we could take care of it. We didn't take care of it. We had fancy hospitals and so forth and now we have a vaccine so we can and the vaccine is really good so forth. And now we have a vaccine. So we can, and the vaccine is really good, but there are many governments in Africa who are suspicious of us and they don't want to use our vaccine. So there's a vaccine for Ebola. There is. Yeah. And the effectiveness and safety of it to how much is understood. So this is difficult because there's not a lot of Ebola, right?

Starting point is 01:01:27 It's not a continuous ongoing thing. There are sporadic outbreaks here and there of a few thousand people at most, at most, usually a few hundred. And the biggest ever, in fact, this is why we didn't for years have an Ebola vaccine. The US military together with Canada developed an Ebola vaccine for service people, right? They wanted to say, well, we're sending people into these Ebola areas. We want a vaccine for them. So they had developed it through all the preclinical, which means before it goes into people. And that stopped because there was no money to do a phase one and a phase two and a phase three.

Starting point is 01:01:59 In fact, for a phase two and three, you need to have infections going on because you're looking at how well the vaccine prevents infections, right? So then there was a West African outbreak in 2015, 2013, 2015. The most cases ever, 25,000. So they got the test of vaccine. But they only put it in a few thousand people. It's not like it's been in hundreds of thousands of people, like the COVID vaccines has been. So it looks like it has high efficacy, but we'd like to have more data. Side effects may be are not so great, there are a couple of different available vaccines,

Starting point is 01:02:37 some have been tested more than others. I would say this would probably not be widely accepted in the US. But then neither would be something over 50% deadliness of a virus. Now, I think if you were, in fact, many physicians work in countries that have Ebola, so they get vaccinated because they understand the choice. Yeah, right. It's always about the choice. So then one more thing to answer the interesting,

Starting point is 01:03:06 what are some of the viruses you really are fascinated by? There are a number of viruses that have clearly been shown to alter host behavior, and that's how they spread. I think those are fascinating. For example, there are some viruses of plants that are spread by aphids. And the aphid bites the plant, the virus reproduces in the plant.

Starting point is 01:03:32 And it somehow engineers the plant to give off volatile organics to attract more aphids, which will spread the virus. Isn't that amazing? Yeah. So that's altering the ater. Because somehow the virus infecting the plant cells gives off these organics and attracts aphids. And furthermore, somehow the when the aphid bites, it tastes horrible. So they immediately leave with the virus, they've just picked up and go to another plant to spread it. So they're attracted and then repulse at the same time.

Starting point is 01:04:07 And obviously you don't want to anthropomorphize this like a strategy they're taking on somehow this worked out. It worked out this way. It just evolved. And you know, evolution is sometimes hard to trace, right? Like Darmun famously said, he could never figure out how an eye evolved from a single cell, right?

Starting point is 01:04:23 But it did. The more complicated complex, the holistic organism is that the virus invades the less able it is to control that organism, right? So I wonder if there's viruses that can control human behavior, you know, to induce more spread of the virus. Well, I don't see why not. There's not enough humans I supposed to like evolve through. Well, we can't do the experiment, the test, right?

Starting point is 01:04:52 We have to observe and that's always hard when you're observing because there's so many things that can confound about your look at that. Yeah, change human behavior, yeah. I mean, there's so many things that impinge on our behavior, but yeah, I think it's possible. I think it's highly possible. If it does it in a plant, why not change some other organisms behavior?

Starting point is 01:05:14 I think it's fine. Anyway, those are fascinating. There are lots of examples of those that are fascinating and how they work. People are trying to figure out, but there's not a lot of money to work on, you know, insect and plant viruses unless you're going to the USDA, so they don't get a lot of work moving forward. What is there, if you understand some of those viruses, is that transferable to human viruses that understanding?

Starting point is 01:05:37 I think some of it could be, sure, I think the general principles, for example, how does the virus cause volatile organics to be made? It must be turning on some genes, and you could learn principles from that. How the virus might do that? Sure. I think everything is broadly applicable. So to say, it's not useful to study viruses of insects and plants. It's just wrong.

Starting point is 01:06:02 Because in science, you probably know this, maybe in your field, it's the same. If you're curious, you're going to run into interesting things that you never planned on, right? That's what people, like, you can criticize, why do we want to go on Mars? Why do we want to colonize Mars? Well, it's like, why do you want to go to the moon? The reality is when you do really difficult things, engineering things like all these inventions along the way I created It's kind of fascinating. How basically just pick a Pick a thing that everyone can agree is kind of cool and it's really hard and do that And then you'll have like thousands of inventions have nothing to do with the thing. That's right. I think you should let

Starting point is 01:06:44 Curious science just just follow what they're interested in to a certain extent. You can, you know, in science, we say we have translational research where we say, okay, here's some money, go cure cancer or diabetes or heart disease, whatever, right? And that's fine. But that often doesn't work out very well. What works better is to say, you're, you have a good lab, you have a good track record. Here's some money

Starting point is 01:07:07 Something and that's where PCR CRISPR Recombinant DNA all that stuff which is made the field explode That's all it came from not from people saying I want a cure genetic diseases by gene editing But by saying what are these repeated things in this bacteria? I'm doing yeah Can I ask you a big philosophical question? So, there's these deadly viruses that are not very transmissible. You ball of babies. And then there's these less deadly viruses that are very transmissible.

Starting point is 01:07:39 Like COVID, I guess, kind of borderline. But why isn't there super transmissible, super deadly viruses? I think if you compare SARS-1 and 2, you get somewhat of an answer, right? SARS-1 was more deadly. In fact, over half of the time when people were infected, they ended up in the hospital, because they were that sick. And then the peak of virus shedding from them happened long after they went to the hospital,

Starting point is 01:08:13 so it's easy to contain the infection when you're in a hospital, right? There was not much pre-symptomatic or asymptomatic shedding with SARS-1. And shedding means you're becoming infectious. So in a respiratory virus, you inhale the droplets with a virus, and they produce in your upper respiratory tract, what we call the nasopharynx, right? The nose and going back to that little cavity just above your mouth. So the virus reproduces really well. And then as you talk, and sneeze and cough,

Starting point is 01:08:43 you expel droplets and then those are inhaled by other people. And then they reproduce. And for SARS-2, we now know there's a lot of reproduction just before you feel anything if at all. So there's a lot of shedding and transmission before you get symptomatic. And many people don't ever get symptomatic, right? So they spread really easily. So that explains why some viruses can transmit a lot better than

Starting point is 01:09:10 others. And if one happens to knock you out, then you're never gonna transmit because you're in the hospital like SARS-1. But why can't you have both? Why can't you just wait a while before knocks you off or when knocks you out? It really kills you. That's that is a philosophical question, right? Because we could talk about why we haven't observed it. I mean, one issue is that if you're killed too quickly by a highly lethal virus, you're not going to transmit it very well, right? So Ebola can kill you quite rapidly. And most of the transmission occurs when people are being cared for at home or in hospitals. Doctors and nurses get virus. But people walking around, you're not walking around when you have Ebola, you're too sick. You know,

Starting point is 01:09:58 you have black bloody diarrhea, you're vomiting, you're bleeding from your skin and mucus membranes, and not walking around, not going to parties. So I think that's part of it that if the infection is too lethal, you're simply not a good transmitter. And I think transmission is probably one of the most powerful selection forces for viruses because a virus always has to have find a new host. If it doesn't, it's a start up that fails, right? If it doesn't find a new host, it's gone. And so anything that makes the virus transmit better is going to help it. And if killing you, being less lethal is part of that, that works too. So there's a strong selection

Starting point is 01:10:43 pressure against being lethal. I So there's a strong selection pressure against being lethal. I think there's a strong selection pressure, pressure against being lethal and being more transmissible. Those two seem to work in opposite ways. And now we don't have a lot of data to support this. This is kind of a thought experiment, but there is one experiment done in Australia many years ago. I don't know if you know this, but in the 1800s the hunters in Australia imported a rabbit from Europe so they could hunt it because the native rabbit in Australia was too fast for them. They couldn't shoot them. So they were out in this European rabbit and they reproduced out of control within a couple of years. They were everywhere millions of rabbits and all the watering holes.

Starting point is 01:11:27 And now they had a problem. So they decided to use a virus to get rid of these excess rabbits. And they used a virus, a pox virus called mixoma virus, which is a natural virus of a different kind of rabbit. But for these European rabbits, it was quite lethal. And it's spread by mosquitoes. So they said, okay, let's release this virus. And the first year, 99.2% of the rabbits were killed, but that 0.8% that were left had some form of resistance. They were variants. You know,

Starting point is 01:11:59 every organism, not just viruses, makes mutants. And there were some variants of the rabbits that could survive infection. And then in subsequent years, the virus became less lethal. And then the mosquitoes had a better shot of transmitting it from one rabbit to another if the rabbit lived longer. That's the selection probably. And so in the end, the rabbits lived on. The virus was there and evolved to be more transmissible and less lethal. So that's amazing. That's the only data. It is. It is. If you take the time to look at it and see what's happened,

Starting point is 01:12:33 it is amazing. It's also humbling that it just makes you realize humans are just a small part of the picture. Of course. And we're wrecking it, aren't we? Well, I mean, that's not really, I mean, viruses are wrecking it some ways. Part of this, we're not really wrecking anything. It's all part of it. But you know, when the ways that human exists encourages viruses, to infect us, right? When we were hunter-gatherers, living in bands of 100 people,

Starting point is 01:13:02 very few viruses, because it was hard for the virus to go from one band to another. And perhaps a hunter would, one of these humans would get an animal and bring a virus into camp, and some people would die, but it would never spread to another. And then when we started to congregate in cities, we figured out agriculture and so forth and how to harvest animals, then we could get bigger and bigger populations, and the viruses went crazy. And they went from animals to us. So measles went from cows to humans when humans learned to domesticate cows and started gathering in big cities. Yeah, but now that humans are able to communicate and travel globally, the viruses become more

Starting point is 01:13:42 and more dangerous, transmissible. If you look at Earth as an organism, thereby pushing humans to be more innovative, create alpha-fold two and three and four and five, create better systems, and eventually there's rockets that keep flying from Earth, and eventually the virus is becoming super dangerous and threatening all of human civilization,

Starting point is 01:14:03 will force it to become a multi-planetary species, and this organum starts expanding. So I think it's a feature, not a bug. I don't know. Well, I think that we have, are early, probably the most of the, what we're studying viruses since 1900, right? Most of that time was because of diseases they caused. The first virus is discovered, yellow fever, virus, smallpox, polio virus, influenza virus. Those were all because people got sick and they said, oh, this is a virus that's associated with it. And so we got good at learning how

Starting point is 01:14:41 to take care of these, in fact,, making vaccines and so forth over the years. And it's only in the last 20 years that we recognize that there are more viruses out there that are far more interesting, perhaps. But we've learned how to deal with the bad ones, for sure. So we talked about what is a virus. We talked about some of the most dangerous and deadly viruses. Can we zoom in and talk about COVID-19 virus? Sure. I don't know what your preferred name is, but the virus is SARS-CoV-2, which is hard, it's long, right?

Starting point is 01:15:12 And then COVID-19 is the disease. So you could say the virus of COVID-19, that's fine. Yeah. The virus of COVID-19. But for the purpose of this conversation, well, every once in a while, just say COVID. It's fine. Problem. What is this virus from, I don't know how many ways we can talk about it, I think from

Starting point is 01:15:30 a basic structural, like the variant structure, biological structure perspective, what is it, what are its variants, can you describe the basics, the important characteristics of the virus? So viruses are classified by humans just to make it easier to keep track of them, right? So this is a coronavirus, which is because when they were first discovered, I think the first ones were animal coronaviruses. They looked at them in the electron microscope and it looked like the solar corona and that's all there is to it and I have to say that early in the outbreak the place with the highest seropositivity in the US for a while 68% was a working class neighborhood in New York City called corona

Starting point is 01:16:19 Can you can you beat that right? That's crazy. Yeah, so the coronaviruses they have membr that, right? That's crazy. Yeah. So, coronavirus is they have membranes, right? We talked about memories. They have spike proteins in the membrane, so they can attach to cells. And inside, they have RNA. And they are the viruses with the longest RNA that we know of. No, none other comes close. For some reason, they're able to maintain 30,000,

Starting point is 01:16:43 so SARS-CoV-2 RNA in a 30,000 basis of RNA and some of the other coroners are even longer, 40,000. This is a, uh, coronas are family viruses that included the, what, the, the one you mentioned before, version one. So SARS-CoV-1, yeah. CoV-1, and I guess other ones is. So the first, we first learned of them in animals, a lot of animals pigs and cows and horses

Starting point is 01:17:10 have coronaviruses. And then in the 60s, we discovered a couple of human coronaviruses that just coals, very mild coals that you wouldn't even think twice about, right? And then suddenly in 20, there's this outbreak of severe respiratory disease in China. And you know, it started in November

Starting point is 01:17:35 and it didn't tell the world until February. And that was really bad because it was already spreading by the time they told people about it. But this went to many, 29 different countries. Only 8,000 people were infected and then it stopped. And that was the first time we saw an epidemic coronavirus. And what they did afterwards is they said, okay, it looks like it came from the meat markets. They have live meat markets in Guanzhu in the south of China Where you can go and pick out an animal and the guy will

Starting point is 01:18:09 slaughter it for you and give it to you and then of course there's blood everywhere and that's how they got infected and they figured out that There's this animal called a palm civet That was the source of virus the palm civets are shipped in from the countryside and they the palm civet Somehow in the countryside got it from a bat So they went looking in caves in the countryside and they found in one cave all the viruses that could make up SARS-1. And that was 2000. And I would say took about 5, 8 years after that outbreak. So that was the first hint that bats have corona viruses that can infect people and cause problems, right?

Starting point is 01:18:46 And after that, we should have been ready. So didn't they already start developing vaccines after then? So some people started making vaccines. They tested them in mice, but they never got into people and some people started working on antiviral drugs. Nothing ever came of them because, you know, industry, there's no, there's no disease. It's gone.

Starting point is 01:19:11 Why should we make vaccines and drugs? And NIH in the US, you submit a grant and they say, this is too risky. There's none of this virus around. So people were really short-sighted because I always say, we could have had antivirals for this. Absolutely. Absolutely. Yeah.

Starting point is 01:19:26 For sure. No question. In fact, one, the one antiviral that's in phase three, it's called molnupiravir. It's the only one that you can take orally. It's a pill. It looks really good. That was developed five years ago, but never taken into humans.

Starting point is 01:19:41 It could have been ready. So we dropped the ball and then the next decade, 2012, MERS coronavirus comes up in the Arabian Peninsula. This comes from camels and infects people, but probably the camels got it from bats originally some time ago. But that never transmits from person to person, very rarely. Every new little outbreak is a new infection from a camel.

Starting point is 01:20:09 So that was 2012. And now here we are, 2019, a new outbreak of respiratory disease in China. And this one really goes all over the world. We're SARS-1 could not. It's a coronavirus. It's different enough from SARS-1 that it has very different properties. But it still has a membrane, it still has a very long RNA in the middle, and then it still has the spike proteins. That's right. What are the things that are, what are the

Starting point is 01:20:36 little unique things that make it that much more effective? That make it cause a pandemic of millions of people as opposed to SARS-1. Well, the genome is 20% different from SARS-1, say. And in those bases, there's some, there are things that make it different from SARS-1. It binds the same receptor, ACE2, on the cell surface. That's remarkable. It has a lot of the same proteins. They look similar. Like if you look at the structure

Starting point is 01:21:05 of the spikes, they look similar, but there's enough amino acid differences to make the bile. And what it is, we don't know because how do you figure that out? You need to study animals because you can't infect people. And the animal models aren't great. You know, for first... So the way you figure that out is you figure out how those differences, what functional, like how the difference in the amino acids lead to functional differences of the virus, like how it attaches, how it breaks the cell wall... Exactly. And how the hell do you figure that out? Like, I guess there's models of interaction.

Starting point is 01:21:43 So you need to, first you need an animal of some kind to infect, right? You can use mice, people have used ferrets, guinea pigs, nonhuman primates, all of the above of nonhuman primates are very expensive, so not many people do that. And then you can put the virus in the respiratory tract, but in fact, none of them get sick like people do. Many people with COVID get a mild disease, but 20% get a very severe longer-lasting disease, and they can die from it, right? No animal does that yet. So we have no insight into what's controlling that, but if you just want to look at the very first part of infection and the shedding and the transmission, you can do it in any one of

Starting point is 01:22:26 several animal models. Ferris are really good for transmission. They tend to have nasal structures like humans and they, you could put them in cages next to each other and they'll transmit the virus really nicely. So you can study that. But the other thing that's important that we should mention But the other thing that's important that we should mention is how do you manipulate these viruses? So these are RNA viruses. You can't manipulate RNA. We don't know how to do it. But we, DNA, because of the recombinant DNA revolution that occurred in the 70s, we can

Starting point is 01:23:01 change DNA anyway we want. We can change DNA anyway we want. We can change the single base, we can cut out bases, we can put other things in really easily. And if I may give it a personal aspect, when I went to MIT as a postdoc in 1979, David Baltimore said, here's what I want you to do. The moratorium on recombinant DNA experiments on viruses

Starting point is 01:23:27 has just been lifted. I want you to make a DNA copy of polio and see if you put that in a cell, whether it will start an infection. It's okay. So I made a DNA copy of polio virus. It's only 7,500 bases. It's much smaller than corona. And I took that DNA and I put it in a piece of DNA from a bacteria called a plasmid. And you can grow plasmids in many, many bacteria make lots of them and purify the DNA really easily.

Starting point is 01:23:58 And I took that DNA. And I sequenced it because we wanted we didn't know the genome sequence of polio at the time. That took me a year, by the way, because the techniques we had were really archaic. Nowadays, you could do it in 15 minutes. It's amazing. I took the DNA and put it into cells and out came polio. So that's the start. Now, since then, everybody has taken that technique and used it for their virus, you can now do it with SARS-CoV-2.

Starting point is 01:24:26 You make a DNA copy of any RNA virus. You can modify it and you put it back into cells and you get your modified virus out. So that's an important part of understanding the properties of the virus is saying an animal by changing the virus. You're changing a DNA copy. You're making the virus then and putting it into the anode. Can you clarify, so even in the RNA virus, you can take and turn it into DNA.

Starting point is 01:24:51 Yes. And then that allows you to modify it. Yes. So what's that mapping? Well, no, no, what's the process of going from RNA to DNA? Reverse transcription. That's the reverse transcription. Also, you actually go through the process of reverse transcription to do this. Yes.

Starting point is 01:25:08 Remember David Boltsmore and Howard DeVon? Yes. I discovered this enzyme in the 70s. They got the Nobel Prize for that. And when I went to David's lab at MIT, he had the enzyme in the freezer. He said, here, take this and make a DNA copy of Poli. Yeah, I didn't make the connection that you can use that kind of thing for an RNA virus. And so that's. And then modify it. See, any DNA virus already exists as DNA. So you can modify it.

Starting point is 01:25:32 That's no, but for RNA viruses, it was difficult. And so then from that point on, for influenza, every other RNA virus and coronaviruses, people made DNA copies. And that's what they use to modify and ask questions about what things are doing, right? What's this gene doing? What if we take it out? What happened?

Starting point is 01:25:51 Can you do the same thing with COVID? It's on A. And then in fact, in January 2020, as soon as the genome sequence was released from China, the lab is all over. We're synthesizing this 30,000 base DNA and getting around. What can you figure out without infecting anything, just turning into, with reverse transcription, turning into DNA and modifying stuff and then putting into a cell, what can you figure out from that?

Starting point is 01:26:21 Well, you could, let's say you can cut out a gene. You see some genes in the sequence. I don't know what these genes do. Let's cut them out. And then you could cut them out of the DNA. You put the DNA in cells and maybe you get virus out and you go, oh, clearly that gene's not needed for the virus to reproduce, at least in cells, right?

Starting point is 01:26:41 Or maybe you take the gene out and you never get any virus. So it's lethal. Is there a nice systematic way of doing this? The people kind of automated? Absolutely. And we, I mean, the problem with SARS, the COVID virus is it's 30,000 bases with a lot of stuff there. Yeah. And what makes it more difficult is that you have to, it's been classified as a BSL-3 agent, biosafety level 3. And so not everyone has a lab that's capable of doing that, so it limits the number of people who can do experiments. You know, we're lucky to have a few in New York City, but not every place has them. So you cannot work with the virus just out on the bench like we do with many other viruses, you have to wear a suit and have to have special procedures and containment and

Starting point is 01:27:30 so forth. So it makes it difficult to do basic experiments on the virus. But it's a pandemic, there's a lot of money, there's a lot of incentive to work on it harder. So I know, so you don't need to work on the virus. You can take bits of it and work, you could take, say, just the spike, right? And say, can we make a vaccine with just the spike? Because that doesn't require BSL3. So yes. So, like, building a vaccine requires you to figure out how, or antiviral drugs, how to attack various structural parts of the virus and the functional parts of the virus.

Starting point is 01:28:00 Right. You have to decide on a target. Yeah. Like, I'm going to make an antiviral, what am I going to target in the virus? And there are a few things that make more sense than others. Usually, we like to target enzymes. I don't know if you remember any, your biochemistry, but you know, enzymes are catalytic. You don't need a lot of them to do a lot of things. So, they're typically in

Starting point is 01:28:25 low concentrations in a virus in fact, it's also easier to inhibit them with a drug. And the coronas have a couple of enzymes that we can target. So you've figured that out ahead of time, and decide what to go after. And then you can look for drugs that inhibit what you're interested in. It's not that hard to do. There's just something beautiful about biology, about the mechanisms of biology. And I kind of regret falling in love with computer science so much that I left that biology textbook on the show and left it behind. But hopefully we'll return to it now, because I think one of the things you learn, even in computer science, that studying biology and certainly neurobiology,

Starting point is 01:29:13 you get inspired. Here's a mechanism of incredible complexity that works really well, is very robust, is very effective, efficient. It inspires you to come up with techniques that you can engineer on the machine. So that's what drives the field forward when people improvise and come up with new technologies that really make a difference. We have a bunch of those now. What's the difference between the coronavirus family and the other popular family and fluenza virus family.

Starting point is 01:29:47 I mean, if I were, because you mentioned, we should have done a lot more in terms of vaccine development, that kind of thing for coronavirus. But if I were back then, from my understanding, the thing we should all be afraid of is influenza, like some strong variants coming out from that family, that seems like the one that will destroy human civilization or hurt us really badly. I don't know if you agree with this sense, but maybe you can also just clarify what to use the difference between the families. So it's an interesting difference. They both have membranes, right? So then they have spike proteins embedded in them

Starting point is 01:30:31 for different spikes. In fact, for influenza, there are two main ones. They're called the HA and the NA. But what's inside is RNA, but it's very different RNA. And here we have to explain that. So viruses with RNA can have three different kinds of RNA. They can have what we call plus RNA. They can have minus RNA, or they can have plus minus,

Starting point is 01:31:03 actually, two strands hybridized together. The plus RNA simply means that if you put that plus RNA in a cell, you know, your cell has ribosomes in it that make the proteins that you need. The ribosomes will immediately latch onto the plus RNA and begin to make proteins. A minus RNA is not the right strand to make proteins, so it has to be copied first. Then the plus minus is both together. The SARS, all the coronaviruses have plus RNA. So as soon as that RNA gets in this album, it starts an infectious cycle. Same thing with polio virus, by the way, which I worked on.

Starting point is 01:31:45 Influenza viruses are negative stranded. So they cannot be translated when they get in the cell. So that's tough for the virus because the cell actually cannot make plus RNA for minus RNA. It doesn't have the enzyme to do it. So the virus has to carry it in inside the virus particle. And then when the minus RNA is in the cell, the virus enzyme makes plus RNAs and those get translated. That's a big difference. And then in the influenza virus,

Starting point is 01:32:16 it's not only is it minus RNA, but it's in pieces. It's in eight pieces. We call that segmented, whereas the corona is in one long piece of RNA. So what is that? Is that they're like floating separately? Yeah. So the genes are on separate pieces. They're all packaged inside that virus particle of influenza virus, but they're in pieces. And why that's important is because if two different influenza viruses infect the same cell, the pieces as they reproduce can mix

Starting point is 01:32:47 and out can come a virus with a new resortment of pieces. And that allows influenza virus to undergo extremely high frequency evolution. That's why we get pandemics. When we have a new flu pandemics, it's because somewhere in some animal, two viruses have re-assorted and made a new virus that we hadn't seen before. So you're talking about biological characteristics, but what am I incorrect in my intuition that from the things I've heard that the influence of a family of viruses is more dangerous? Like what makes it more dangerous to humans? Well, it depends on the, there are many flavors or ventages of influenza virus. Some are dangerous

Starting point is 01:33:33 and some are not, right? It depends on which one. Some like the 1918 apparently was, was very lethal, killed a lot of people. But more contemporary virus is we had a pandemic in 2009 of influenza. That wasn't such a lethal virus. We don't know exactly why, but it didn't kill that many people. It transmitted pretty well. That's it. The bird flu one. They're all they're all deriving. That one was called swine influenza. Swine. Thatine influenza. It seemed to have started in a pig, but it had bird It had RNAs from bird influenza viruses. These viruses are all Reassortments of different viruses from pigs and birds and humans But influenza can cause pneumonia and can kill you as does

Starting point is 01:34:22 SARS-CoV-2 so So it depends on the virus. So there is another influenza virus that's currently circulating. So right now we have the 2009 pandemic virus. That's still around. And then the 1968 pandemic virus, which was the one before 2009, that one is still around too.

Starting point is 01:34:41 And that's more lethal. And depending on the season, some seasons, the 2009 virus predomin season, some seasons, the 2009 virus predominates, some seasons, the 1968. And when the 68 is around, you get more lethality. So we're living with the influenza family. We haven't exterminated them. Right, we never will. Never exterminate them. Why? Because every shore bird in the world is infected with them, you know, gulves and turns and ducks and all sorts of things. But why can't we develop strong vaccines

Starting point is 01:35:11 that defend against? Oh, we could do that, sure. But that would not eliminate them from humans. Even if you had the best vaccine, you would never get rid of it in people because there would always be someone who's not vaccinated or in which the vaccine didn't work You know, no, but no vaccine is a hundred percent right so well you just contradict yourself You had the he said the perfect vaccine so

Starting point is 01:35:35 Imperfect imperfect but you then you said like even if you had the perfect Yeah, some people wouldn't get vaccinated, but I understand what you mean So but I actually was asking how difficult is it to make vaccines like that for it seems like it's very difficult to do that for the influenza virus. So it's really easy to make an old school vaccine. So the way the first influenza vaccines were made was actually Jonas Salk worked on them in the 40s. He just grow lots of virus and you grow it in eggs, by the way, chicken eggs. Nice.

Starting point is 01:36:10 Literally, wait, wait. Yeah, chicken, embryo needed. So they get fertilized and there's a 10 or 12 day embryo in it and you put virus in it and it grows up and then you harvest it. You get about 10 MLs of fluid. And then you take that, you treat it with from aldehyde or formalin,

Starting point is 01:36:25 and it inactivates the virus, so it's no longer infectious. And you just inject that into people. And that was the first flu vaccine that was made for the U.S. Army, actually. And then it got moved over to people. We still use that old school tech today. So you're taking, can you help me out here? Okay, so this is a good time to talk about vaccines. Okay, so you're talking about, you're taking the actual virus. Right. You put it in an egg, you let it grow up.

Starting point is 01:36:55 It's very funny that you put it in an egg. It's very poetic. And then how do you make it not infection, not effective or whatever? Not infectious. Not infectious. Is that the right term here? Yeah. So how do you make it not infectious?

Starting point is 01:37:12 You can treat it with any number of chemicals that will disrupt the particle so it no longer infects. So that step of disrupting the particle is that very specific to a particular variant particle? No, the same collection of chemicals you can use for all kinds of interaction. And our which have been used for SARS-CoV-2 vaccines also. So, same technology. Okay, so what are the several things to ask? So you call it old school in a way that's slightly dismissive, like people talk about Windows 98 or something. slightly dismissive like people talk about Windows 98 or something.

Starting point is 01:37:48 So is there risks involved with it? Or is it just difficult to produce large amounts? No, it's a lot of eggs. It's very easy. We could do it in cells and culture, but eggs were convenient. And in the 1940s, we didn't have cells and culture. We didn't have to do that. So we had to use something else. It's easy to do, but the process of inactivating the virus with a chemical makes it not the best vaccine you can make.

Starting point is 01:38:13 The flu vaccines that we have today, which are mostly based on this inactivation. It's called inactivated virus vaccines. Also like the kind of thing it presents to the immune system to train on is not close to the actual virus. Yes, that's what we think. So that's why probably the flu vaccines are just not very good. You know, 60% efficiency at the best, right?

Starting point is 01:38:42 Which is not really good. What does the measure of efficiency for a vaccine? Well, it how it does in the general population at preventing influenza. At preventing illness, not infection. We usually don't measure infection when we're testing a vaccine. We just measure sickness. That's really easy to score, right? You do a trial and you say, if you feel

Starting point is 01:39:06 sick, give us a call. We'll tell you what this is. So yeah, I mean, what's what sickness sickness is the presence of symptoms? So this is good time to say what a symptom is, okay, a symptom is what you only can feel, only you can feel an upset stomach or a sore throat or that sort of the lived experience or something. Or as a sign is something that someone could measure and tell that you're in fact that like virus in your nasa pharynx or something else, right? Signs and symptoms.

Starting point is 01:39:41 And so in a vaccine trial, they tell you, if you have any of these symptoms, they give you a paper with the exact symptoms listed to make sure you're picking them up, right? So for flu, it would probably be fever, sore throat, cough. You call them and then they will do a PCR, make sure you've got flu and not some other virus that makes similar symptoms. And then they would say, are you a vaccine or non-vaccine arm and count up all the infections and see how the vaccine did, basically. That's so fascinating because the reporting, so symptom is what you feel. Yes, for sure.

Starting point is 01:40:18 And certainly the mind has a ability to conjure up feelings. Oh, yes, absolutely. And so, like culturally, you know, maybe there was a time in our culture where it was looked down upon to feel sick or something like that, like tough enough kind of thing. And so then you probably have very few symptoms being reported.

Starting point is 01:40:43 Absolutely. And then now is like much more, I don't know, perhaps you're much more likely to report symptoms not as fast as any, because then it changes. Oh, it is definitely a perception because for, you know, your symptom may be nothing to me or vice versa, right? And so when you're doing this,

Starting point is 01:41:01 it's a little bit of an imprecise science because in, and even it's a little bit of an imprecise science because, and even it's a cultural thing, and some countries, something that would make us feel horrible, they wouldn't even bother reporting. No, I didn't have any symptoms. So it's a little bit imprecise, and it clouds the results. So if you can measure things, it's always better. But you start out with a symptom.

Starting point is 01:41:21 And if you say, if someone tells you this virus, 20% of the people are asymptomatic, they don't report symptoms. That number is probably not as a constant. It depends where you did the study. It could be different in China versus South America, Europe, etc. Yeah. I was trying to fix it. So I took two shots of the Pfizer vaccine. I had zero symptoms. Wow. So and I was wondering, we'll see, but that's my feelings, right? This is not because I felt fine. I was waiting. Did you have pain at the injection site? No, it's kind of pleasant. Did you felt nothing the next day? No, nothing. No, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no And those I was out all next day, like exhausted for some reason. So that gave me like a sense like, okay, at least sometimes I can feel shitty. That's good to know. Sure. And then what the vaccine, it didn't, but the question is like, how much does my mind come into play there? The expectations of symptoms, the expectations of not feeling well, how does that affect

Starting point is 01:42:53 the sort of the self-reporting the symptoms? I think it's definitely a variable there, but there's certainly many people that don't feel anything after the vaccine. And there's some that have a whole range of things like soreness and fever, et cetera. Yeah. So, OK. You were talking about the old school developments

Starting point is 01:43:10 at the egg. Right. What's better than that? What's more? So then the next generation of vaccines, which arose in the 50s, were what we call replication competent, where the virus you take and it's actually reproducing in you.

Starting point is 01:43:27 Yeah, that sounds safe. And it can be somewhat problematic, yes, as you might imagine, because once you put that virus in you, you have no more control, right? It's not like you have a kill switch in it, which actually would be a great idea to put in. Like nano-bots, what can possibly put something in there? If you added a drug, you would, you would, you would shut it off, right? And people are thinking about that because now we're engineering viruses to treat

Starting point is 01:43:56 cancers and other diseases. And we may want to put kill switches in them just to make sure they don't run away. Oh, which things? So you can like deploy a drug that binds to this virus that would shut it off in the body, something like that. Something like that, yeah. That would be the idea. You'd have to engineer it in.

Starting point is 01:44:13 Anyway, these were, the first one was yellow fever vaccine. That was made because that was a big problem. And this virus, and the way you do this, back in the old day was empirical. So Max Tyler, we did the yellow fever vaccine, he took the virus, which is a human virus, right? And he infected, I think he used chick embryos. And he went from one embryo to another

Starting point is 01:44:40 and just kept passing, he did that hundreds of times. And every 10 passages, he would take the virus and put it in a mouse or a monkey, whatever his model was. And then eventually he got a virus that didn't cause any disease after 200 and some passages. And then that was tested in people. And it became the yellow fear of vaccine that we used today. He selected for mutations that made the virus

Starting point is 01:45:04 not cause disease, but still making immune response. So those are called replication component. We now have the polio vaccine, which was developed in the 50s after the yellow fever, then we had measles, mumps, gubella, those are all replication component vaccines. And you mentioned, that's a good idea. They are all safe vaccines. The only one that has had an issue is the polio replication-competent vaccine. It was called Sabin vaccine or oral polio virus vaccine.

Starting point is 01:45:39 Because you take it orally, it's wonderful because you don't have to inject it. This is the perfect delivery. because you take it orally, it's a wonderful because you don't have to inject it. This is the perfect delivery, either intranasal for respiratory virus or orally for polio, it goes into your intestines, it reproduces and it gives you wonderful protection against polio. However, you do shed virus out.

Starting point is 01:46:02 And that virus is no longer a vaccine. It's reverted genetically in your intestine. So you can infect others with polio? You could take that virus and put it into an animal and give it polio. And in fact, the parents of some kids in the 60s and 70s who were immunized, got polio from the vaccine. The rate was about one and a half million cases of polio from the vaccine. The rate was about one and one and a half million cases of polio. So it's called vaccine-associated polio. And I always argue that we may not have picked the right

Starting point is 01:46:33 vaccine. There was a big fight in the US and other countries between the inactivated polio and the infectious polio vaccines, which ones we should be using, because we found out that the infectious vaccine actually caused polio. And eight to ten kids a year in the U.S. alone got polio from the vaccine, which looking back is really not acceptable in my view, although the public health community said it was to get rid of polio. So now we're close to eradicating polio globally. But this vaccine, the right polio is a problem. So now we have to go back to the an activated vaccine, which is tough

Starting point is 01:47:13 because it's injected. So, okay, so the the basic high level, you know, how vaccines work principle is, uh, you want to deploy something in the body that's as close to the actual virus as possible, but doesn't do nearly as much harm. That's right. And there's like a million, not a million, but there's a bunch of ways you could possibly do. So those are two ways. And now, of course, we have modern ways.

Starting point is 01:47:36 We can make mRNA vaccines, right? What are the modern ways? Do you want to look at mRNA vaccine? That's one of the, that's the most modern. But even before mRNA vaccines, we learned that we could use viruses to deliver proteins from a virus that you want to prevent. And so the Ebola vaccine, we took the spike gene of Ebola virus and put it in a different virus. And we deliver that to people. And that's called a vector vaccine. And some of the COVID vaccines are vectors of different kinds.

Starting point is 01:48:09 The most famous are adenovirus vectors carrying the spike gene into the cell. Can you explain how the vector vaccine works again? So we have, we take a virus that will infect humans, but will not make you sick. In a case of adenovirus, the years and years of people studying, it has told us what genes you could cut out and allow the virus to infect the cell, but not cause any disease. So instead of doing selection on it, you, you, you actually genetically modify it. Yes.

Starting point is 01:48:41 You modify the vector. Yeah. So you can be much more precise about it. You're very precise. And then you splice in the gene for the spike. And then you use that to deliver the gene. And it becomes produced as protein. And then you make an immune response. And vectors the term for this modified. Right. So we're now using viruses at our bidding,

Starting point is 01:49:01 we're using them as vectors, not just for vaccines, we can cure monogenic diseases. That is, if you have, if you're born with a genetic disease, you have a deletion or mutation in a gene, a single gene, we can give you the regular gene back using a virus vector. So, but cancers too. We can cure cancers with vectors. Wow. Really? Interesting. Yeah. I think in 10 to 15 years most cancers will be treatable with viruses. Yeah. Wow. And not only can we put things in the vector to kill the tumor, we can target the vector to the tumor specifically in a number of ways. And that makes it less toxic, right? It doesn't infect all your other cells. But it takes time to develop a vector for particular thing

Starting point is 01:49:48 because it requires a deep understanding. Yeah, in fact, we have about a dozen different virus vectors that have been studied for 20 years. And those are the set of vaccine vectors that we're using. So it includes adenovirus, the secular stomatitis virus, which is a cousin of rabies, but doesn't make people sick.

Starting point is 01:50:09 Influenza virus is being used as a vector in many, even measles virus. So we're familiar with how to modify those to be vectors and those are being used for COVID vaccines. And then of course, we have the new, the new is just the nucleic acid vaccines. So years ago people said, why can't we just inject DNA into people? Take the spike and put it in a DNA and inject it. So people tried many, many different vaccines.

Starting point is 01:50:38 And in fact, there's there are no human license of vaccines that are DNA vaccines. Although there is there are no human license of vaccines that are DNA vaccines. Although there is a, there is a West Nile vaccine for horses. That's a DNA-based vaccine. So if you have a horse, you can give it this vaccine, but no human. So can you clarify, does a DNA vaccine only work for DNA viruses? No, it can work for DNA or RNA,

Starting point is 01:51:00 because remember, for an RNA virus, we can make a DNA copy of it. Right. And it will still, when you put that DNA in a cell, it goes into the nucleus. Okay. Right. So it's, you're just stepping up. You get proteins. Our name, vaccines. Yeah. You're giving, okay, I got it. So those didn't work for human vaccines. And there were many HIV, AIDS, vaccine trials that used DNA vaccines didn't work. And then the number of years ago, people

Starting point is 01:51:27 started thinking, how about RNA, RNA vaccines. And I first heard this. I saw what? I've worked with RNA my whole career. It's so fragile. If you look at it, the wrong way it breaks. I mean, that's, that's being facetious, right? But you have to be very careful because your hands are full of enzymes that will degrade RNA. So I thought, how could this possibly work injecting it into someone's eyes? An example of, I was skeptical and I was wrong. It turns out that if you modify the RNA properly and protect it in a lipid capsule, it actually works as a vaccine. And people were working on this years before COVID came around.

Starting point is 01:52:10 They were doing experimental mRNA vaccines, and there were a couple of companies that were working on it. And so at the beginning of 2020, they said, let's try it. And I was skeptical, frankly, because I just thought RNA would be too labile, but I was wrong. So this is, as we're saying offline, one of the great things about you is you're able to say when you're wrong

Starting point is 01:52:34 about intuitions you've had in the past, which is a beautiful thing for scientists. But, you know, I still think it's very surprising that something like that works, right? I am surprised. So you're just launching RNA in a protective membrane. Yeah. And then now, one thing is surprising that the RNA sort of lasts long enough, right,

Starting point is 01:52:57 for the in its structure. But then the other thing is, why does it work that's a good training ground for the immune system? Is that obvious? Well, I don't think it's obvious to most people, and it's worth going into it, because it's really interesting. I mean, first of all, they wrap the RNA in fats and lipid membranes, right? And the particular formulation, they test for years to make sure it's stable, you know, it lasts a long time after it's injected and the two companies that make the current COVID vaccines, right? Moderna and Pfizer, they have different lipid

Starting point is 01:53:38 formulations to get to the same. So that's a real part of it. And it's not simple. There are quite a few different lipids that they put into this coating and They test to see how long they protect the RNA after it's injected say into a mouse how long is it last and the way it works is These apparently these lipid nanopartus they get injected into your muscle they bump into cells and they get taken up. So lipid fat is sticky. It's greasy. We like to say. And so your cells are covered with the greasy membrane. Also, so when these lipid nanoparticles bump into them, they stick and they eventually get taken up and they figured this out right at the beginning. If we put RNA in a lipid nanoparticle and they eventually get taken up and they figured this out right at the beginning. If we put RNA in a lipid nanoparticle, will it get taken up into a cell and the answer

Starting point is 01:54:29 was yes, it was just, let's try it and it worked. So it's basically experiment. It's not like some deep understanding of biology. It's experimentally speaking. It just seems to work. Yeah. Well, they had some idea that lipids would target this to a cell membrane. And remember, there's no, there's no receptor involved.

Starting point is 01:54:47 Like, the virus has a specific protein that attaches to a receptor. It's not efficient enough to just bump around and get into a cell. That's what these things are doing, and they probably optimize the lipids to get more efficient uptake. But it's not as efficient as a virus would be to get it into a cell. You have no specific, I mean, which is why it's surprising that you can crack into the safe with a hammer or with some fat. I mean, that's kind of surprising. It's kind of amazing that it works. So maybe let's try to talk about this.

Starting point is 01:55:31 So one of the hesitancies around vaccines or basically around any new technology is the fact that mRNA is a new idea. And it's an idea that was shrouded in some skepticism, as you said, by the scientific community. Because it's like, it's a cool new technology, surprising that it works. What's your intuition? I think one nice way to approach this is try to play devil's advocate and say, both sides. One side is why your intuition says that it's safe for humans. And what arguments can you see if you could steal man and argument why it's unsafe for humans or not unsafe for humans, but the hesitancy to take an mRNA vaccine is justified.

Starting point is 01:56:28 So many people are afraid because it's new technology and they feel it hasn't been tested. I mean, in theory, what could go wrong? The nice thing about mRNA is that it doesn't last forever. As opposed to DNA, which doesn't last forever, but it can last a lot longer, and it could even go into your DNA, right? So mRNA has a shorter lifetime, maybe days after it's injected into your arm than it's gone. So that's a good thing because it's not going to be around forever. So that would say, okay, so it's sticking around for your lifetime is not happening. But what

Starting point is 01:57:12 else could happen? Well, let's see, the protein that's made could that be an issue? And again, proteins don't last forever. They have a finite longevity in the body and this one also Last perhaps at the best a few weeks. No, this is a protein that's made after the RNA gets into the cell. Yeah, so the lipid nanoparticles taken up into a cell and the mRNA is translated and you get protein And there's also a question. I'm sorry to interrupt, where in the body, because it's not well targeted, or I don't know if it's supposed to be targeted, but it can go throughout the body.

Starting point is 01:57:53 That's one of the things that's been said. So it's injected deep into your deltoid muscle, right here, shoulder. And the idea is not to put it in a blood vessel, otherwise it would then for sure circulate everywhere. So they put it in a blood vessel, otherwise it would then for sure circulate everywhere. So they go deep in a blood vessel, and it's locally injected. And they did, before this even went into people,

Starting point is 01:58:14 they did experiments in mice, where they gave them a thousand times higher concentrations and they would ever give to people. And then when you do that, it can go everywhere, basically. You can find these nanoparticles in every tissue of the mouse. But that's at a thousandfold higher concentration, right? So I think at the levels that we're using in people, most of it's staying in the muscle, but sure, small amounts go elsewhere.

Starting point is 01:58:39 And it's because there'd be a lot of harm caused if it goes elsewhere? And like, let's say, ridiculously high quantities. I'm trying to understand what is the damage that can be done from an RNA just floating about? So the RNA itself is not going to be a problem. It's the protein that is encoded in it, right? This is a viral RNA, which has no sequence in us. So there's nothing that it could do. It's the protein that I would say

Starting point is 01:59:06 you could ask, what is that going to do? And the one property we know about the spike is that it can cause fusion of cells. That's how the virus gets in in the beginning. The spike attaches to the cell by this H2 receptor, and it causes the virus and the cell to fuse. That's how the RNA gets out of the particle. But so, wait, I'm a bit confused. So, with this mRNA vaccine with lipids and the RNA, there's no spike, right? The mRNA codes for the spike. Oh, the mRNA codes, so it creates the spike.

Starting point is 01:59:49 It creates a spike. And so that spike could cause fusion of cells. Yes, except they modified the spike so it wouldn't. Got it. They made two amino acid changes in the spike so it would not fuse. So they understand enough which amino acids are responsible for the fusion. That's right. Interesting. So they understand enough which amino acids are responsible for the fusion. That's right. Interesting.

Starting point is 02:00:06 So they could modify. So now it's not going to cause fusion, so that's not an issue. It's called the pre-fusion stabilized spike. Cool. So the spike when it binds ACE2 that top falls off and the spike, and the part of the spike that causes fusion is now exposed. And that doesn't happen in this mRNA vaccine. So those are the things that could have happened, but I think they're ruled out by what we've just said. But there's no better test than putting it into people,

Starting point is 02:00:35 right? And doing phase one, phase two, and phase three, and increasing numbers of people and asking, what do we see? Do we have any concerns? And so now it's been in many millions of people and we don't see most of the effects you see in a vaccine. You see in the first couple of months things like the myocarditis with some of the vaccines, the clotting issues with the AstraZeneca vaccine, Guillain-em Barre, you see those relatively quickly. And we've seen small numbers of those occur, but other things we haven't seen, and you know, you never say never, right? Right. So, I mean, this is fascinating, right? It's like, I, I put Splenda in my coffee and has supposedly no calories, but it tastes really good. And despite what like rumors and blogs and so on, I have not seen good

Starting point is 02:01:40 medical evidence that is harmful to you, but it's like it tastes too good. So I'm thinking like there's gotta be long-term consequences. But it's very difficult to understand what the long-term consequences are. And there's this kind of like distant fear or anxiety about it. Like this thing tastes too good, it's too good to be true, there's no free launch in this world. This is the kind of feeling that people have about the long-term effects of the vaccine. That you mentioned that there's some intuition

Starting point is 02:02:18 about near-term effects that you want to remove the diffusion of cells and all those kinds of things. But they think, okay, this travels to other cells in the body, it travels to neurons or that kind of stuff. And then what kind of effect does that have long term that's yet to be discovered? What do you make, I mean, for this vaccine,

Starting point is 02:02:38 but in general in science about making statements about long term negative effects? Is that something that weighs heavy on you? Is that something we can kind of escape through just large-scale experimentation with animals and humans? Well, if you're really, if you're concerned about long-term, then you have to do a long-term experiment, right? And maybe you don't see something for 50, 60 years. So if someone says to you, there are no long-term effects of the COVID vaccines, they can't say that because they haven't done the long experiment, right?

Starting point is 02:03:14 There's always the possibility, but you have to weigh it. It's always, there's no free lunch, right? There's always a risk-benefit calculation you have to make. You can have the study that goes for for 50 years, and then decide. But I guess what you're doing is just like we said, I forget with which one, with polio, with rabies, I forget, but you're weighing the side effects or the vaccine versus the effects of the virus.

Starting point is 02:03:44 And like both of them, you don't know long-term effects. But you're building up intuition as you study, which what are the long-term effects? Like, there's a huge number of people like that have like, I don't want to say experts, because I don't like the word, but people have studied it long enough to where they build up intuition. They don't know for sure. There's basic science being done, there's basic studies. We start to build up an intuition of what might be a problem done online and what is not

Starting point is 02:04:22 biologically speaking. And so given that map, considering the virus, there seems to be a lot of evidence for COVID having negative effects on all aspects of the body, not just even respiratory, which is kind of interesting. So the cognitive stuff, yes, terrifying kinds of systems above. Yes. And then you look at the same thing with the vaccine, Yes, terrifying. All kinds of systems above. Yes. And then you look at the same thing with the vaccine,

Starting point is 02:04:46 and there seems to be less of that. But of course, you don't know if it's some kind of dormant thing that's just going to... You won't know. It's you have to make a judgment and for a lot of people they can't, right? Because they don't have the tools to make the judgment. I totally understand that.

Starting point is 02:05:03 And we have let people down a few times in medicine, right? And I know two very specific examples. The first polio vaccine ever made. The Salk vaccine was released in 1955. Immediately, within months, a few hundred cases of paralysis and kids who got it because it was not properly inactivated. Now you have to understand parents were dying for a polio vaccine because kids were getting paralyzed every summer, 30,000 kids a year and so they went and took it. They took the word of the medical establishment that it was safe, and it wasn't. Big letdown. Never gonna forget something. Although I think a lot of people today

Starting point is 02:05:48 don't aren't aware of that. I think that was a big problem that several last thing. Then the attenuated vaccine that we talked about, the infectious causing polio, yet parents continued to bring their kids to be vaccinated because they were said, this is the right thing to do. I have to say, I was involved in several lawsuits where parents of a kid who got paralyzed

Starting point is 02:06:12 from the polio vaccine decided to sue the manufacturer and get some money for their kid. So they got mad and and I think you could not The the first Issue could have been prevented Could have been prevented by and activating it properly. I think the company just did the wrong thing The second we had evidence for and we should probably have not used that vaccine any longer But I think that destroys public confidence, but those are not long to minority of cases. This is a minority. This is a very rare event. Yeah. But nevertheless, science is an institution. Didn't make corrections in that case. No, they didn't. And so what do you

Starting point is 02:06:56 make of that? I mean, it's very unfortunate that those few things can destroy trust. But I don't think that lasts till today. I think today is a different era, right? And most people don't know about those stories. I already tell them to you because that's what could happen. I think it could happen today. If you look at the history of the polio vaccine, the US Public Health Service wanted kids to be vaccinated.

Starting point is 02:07:25 So they did things that probably weren't correct to get the vaccine back online, right? But they did it and they pushed it through. So the question is, what do we do today? So I can look at, as we just said, I can look at what might happen and I can make reasonable Decisions about the likelihood of them happening and I can also say I don't want to get COVID of any kind because I've seen how Nasty it can be and I decide I'm taking the risk at whatever small of a long-term effect I'm gonna take the risk my family took the risk and many other people did. Oh, the vaccine. Of getting vaccinated, because I think it's very small. But I understand where people can't make that decision

Starting point is 02:08:10 and that begs the question, what would they need to make a decision? So if you're concerned about an effect in 40 years, we're not gonna know for 40 years. Yeah, so I think if I were to speak, because I spoke, so I talked to, like I mentioned offline to Joe Rogan and his podcast yesterday I talked to him all the time about this. I think the concern is less about

Starting point is 02:08:37 the long-term effects like on paper. It's more about the the like people like Anthony Fauci and people at the top are simply misrepresenting the data or like are not accurately being transparent, not collecting the data properly, not reporting on the data properly, not being transparent, not representing the uncertainties, properly not being transparent, not representing the uncertainties, not openly saying they were wrong two months ago, like in a way that's not dramatic, but revealing the basic process of science when you have to do your best under uncertainty, just also just being inauthentic.

Starting point is 02:09:19 There's a sense, especially with a younger generation now, there's a certain way on the internet, like the internet could smell bullshit, much better than previous generations could. And so they see there's a kind of, you know, authenticity that comes with being, like, representing authority. Like, I am a scientist. I'm an expert of a PhD. I have four decades of work. Therefore, everyone should listen to me. And somehow that maps to this feeling of, what are they hiding? If they're speaking for my authority like this, if everyone is an agreement like this, that means they all have emails between each other. They said, we're going to tell this. This is the message we're going to tell the public.

Starting point is 02:10:05 Then what is the truth, the actual truth? Maybe there's a much bigger uncertainty. Maybe there's dead people in the basement that they're hiding from bad mRNA vaccine experiments. Maybe they're, and then the conspiracy theory starts to grow naturally when there's this kind of mistrust of that. So it's less about kind of like a deep concern about long term effects. It's a concern about long term effects. If we find out that there's some secret stuff that we're not being told, it all runs on

Starting point is 02:10:42 that. So what the, I mean, I put the blame not on the data, but basically on the leaders and the community, the communicator of the science at the top. Well, to that, I would say all the data, as far as I know, are made public. So you can dive into it. And I know a lot of people ask me questions, and I just say, it's right here in the data. And I know a lot of people can't do that. They can't dive into it. But that's one solution for people who are able. It's, and now you could argue, well, maybe they've left data out.

Starting point is 02:11:17 Well, then not even I can help, because then they're hiding it from me too. And I think that's highly unlikely. I think for the most part, the FDA requires the release of all the clinical trial data, right? So, okay, so this clinical trial data, that's one thing. So that's the data that we should be focusing on, right? So there's a lot of different data sets here. So there's pre-clinical data, which is everything that was done in the lab before this vaccine ever went into a human arm. It's all the cell culture work that we talked about a little experiments and animals All of that is

Starting point is 02:11:50 publicly accessible most of it gets published and then there's the initial drug filing which is huge The books of diet you can get that and look at right this is me sort of asking sort of difficult questions here, okay So there is a there's a lot of money to be made by makers of the vaccine. So for these companies, obviously there's a distress of those folks too. They've done a lot of really good things in this world, but the incentives are such that you want to sweep stuff under the rug if you're not 100% pure in your ethics. And how hard is it for that data to be fabricated, manipulated? Like, what's your intuition for the pretrial stuff? I think when you start fabricating, then you get inconsistencies, which are pretty easy to pick up.

Starting point is 02:12:47 When you talk about some large scale things of this nature. Because then you can look through the data very, you're going to, I mean, we require looking very carefully, but you'll see inconsistencies from one trial to another. And that might ring a bell that something's been done. Yeah. It's like the moon landing thing. I think sometimes like going to the moon is easier than faking. Right. In the sense it might be easier to do a large scale trial and get an effective vaccine

Starting point is 02:13:18 versus faking. But you know, when you brought up the for-profit issue, I think that is always been an issue. I have always felt that having your health depend on for profit industry may not be the best solution. And I don't know how else to do it. People tell me I'm a dreamer that thinking that, you know, all medicines could be nonprofit, but I also think that the world should have one health system that takes care of everyone, right? Because there are some countries that can't and other countries have an excess like us. So I wish we could do that.

Starting point is 02:13:53 Well, the argument is the speed of which the vaccines for COVID were produced would never happen in a nonprofit system would never happen in a non-capitalist system? Oh, I could set up a vaccine production institute in the US that would get the vaccines done because you just need to put money into it. That's what made these vaccines get done money. They poured billions of dollars and they got it done quickly. But if I set up a nonprofit institutes of vaccines throughout the US, staffed with really talented people, pay them well, keep them motivated. You'll get your vaccine. No, but that's the thing with capitalism is that the selection of who to hire, when you say good people, the capitalist has a machine that fires people who are not good

Starting point is 02:14:42 and selects people who are good, coming from the Soviet Union, the dream of communism is similar to what you're saying, broadly defy. It certainly doesn't work, and the broads, the question whether it works in the healthcare space. You know, there is some aspect to the machine of capitalism being the most effective way to select for good people and to effectively produce the thing. And but then of course, a lot of people argue the current, even the current healthcare is not with like regulations.

Starting point is 02:15:16 There's some weird mix where there's a lot of opportunities for inefficiencies. There's a lot of opportunities for bureaucracy. So you have like the worst of all world. Can't there be some intermediate that works? Because the other issue that we have mentioned is that politics gets thrown into this. That really messes up and it should never be mixed with healthcare. But it is because a lot of funding comes from the government. So that's another confounding factor.

Starting point is 02:15:43 But I really think I could make a vaccine institute that if someone didn't do well, I'd fire them. No, you're not going to stay if you can't do your job and do it well. You don't give them incentives, but it doesn't have to be the two extremes, I think. It has to be a solution that people don't have this mistrust for a company making huge profits off of a drug. But you know what, it's funny. It seems that vaccines and antivirals bear the brunt of this criticism, yet there are many other pharmaceuticals that people rely on of all sorts.

Starting point is 02:16:18 They don't seem to question and have issues with those and they have far more side effects than vaccines. It's a very strange how we're picking that way, but I should also say that when, you know, if you have one big vaccine institute, one of the other like sets of vaccine conspiracies, I mean, I would say they're a little farther out into the into the wild set of ideas, but it's you know There's one way to control the populace is by injecting substances into them right people. I mean part of that

Starting point is 02:16:57 Funding enough is probably has to do with needles versus something you put in your mouth Yeah, but there's something about the government, especially when it's government mandated injection of a substance into you. I don't care what the science says if it's 100% effective, 100% safe, there's a natural distrust of what, like even if this is effective and safe, giving the government power to do this. Aren't they gonna start getting ideas down the line for, you know, I think that they can barely govern.

Starting point is 02:17:33 I don't think they're gonna do that, but you don't have to take, unless you're a federal employee, you don't have to take a COVID vaccine. Yeah, but that largely has to do. Not largely, but there is an individualistic spirit, you know, to the American people. There's this like, you're not gonna take my gun away from me. Sure.

Starting point is 02:17:59 You're not going and I think that, you know, that's that's something that makes America what it is. It's coming from the Soviet Union. There's a power to sort of resisting the overreach of government. That's quite interesting because I'm a believer, I hope that it's possible to have, to strive towards a government that works extremely well. I think at its best, a government represents the people and functions in a similar way the year you're mentioning, but that like push back, even if it turns into conspiracy theory sometimes, I think is actually healthy in the long arc of history.

Starting point is 02:18:39 It can be frustrating sometimes, but that mechanism of pushing back against power, against authority can be healthy. I agree. I think it's fine to question the vaccines. What I have issued with is that many people put out incorrect information, and I'm not sure what their motivations are. And it's very hard to fight that because then it's my word versus theirs. And I'm happy to talk with people about any of their concerns. But if you start getting into the stuff that just isn't true, then we

Starting point is 02:19:12 have a problem. The thing I struggle with is conspiracy theories, whatever language you want to use, but sort of ideas that challenge the mainstream, quote unquote, narrative, given our current social media and internet, like the way it operates, they can become viral much easier. There's something much more compelling about them. Like, I have a secret that about the way things really work. That becomes viral and that's very frustrating because then you're not having a conversation on level ground. When you're trying to present scientific ideas and then there's conspiracy theories, the conspiracy theories become much viral much faster and then you're not just having a

Starting point is 02:19:57 discussion on level ground. That's the frustrating part that it's not an even discussion. Can I just say one more thing? I mean, the internet is here to stay, so we can figure out how to deal with it, right? But from my perspective, I was skeptical that these mRNA vaccines, that any COVID vaccine would be ready within a year, that's amazing. Plus, the way I look at the mRNA vaccine as a scientist, it's GWIS to me. It's amazing that it worked. And I love to think the data are great, so I want it. Well, as a scientist,

Starting point is 02:20:34 I want it. One of the really sad things again with me too, as a scientist or as an admirer of science is, I don't know if it's politics, but one of the sad things to me about the previous year is that I wasn't free to celebrate the incredible accomplishment of science with the vaccines. I was very skeptical that's possible to develop a vaccine so quickly. So it's unfortunate that we can't celebrate how amazing humans are to come up with this vaccine. Now this vaccine might have long term effects. That doesn't mean this is not incredible. Why couldn't you celebrate?

Starting point is 02:21:19 Like, because I would love to inspire the world with amazing things science can do. And, you know, when you say something about the vaccines, they're not listening to the science. A lot of people are not listening to the science. What they hear is, oh, you're, um, you're a Republican or you're a Democrat and you're social signaling us, doing some kind of signaling. No, I think that the vaccine you're talking about injecting something into you. And maybe you're right that the rhetoric is like you better take this or your dumb. You know, it's not the right approach.

Starting point is 02:21:52 Actually, it's kind of interesting. I think both sides kind of imply that. So the people who are against the vaccine are dumb for not trusting science and the people who are for the vaccine are called dumb for trusting science, the scientific institutions. And they both kind of have a point. Like because you can always, it's like a glass half full or half empty because you can always look at like science from a perspective of certain individuals that don't represent are perhaps the not greatest leaders, almost like political leaders. There's a lot of, you know, I've yesterday went on a whole rant. Again, I said a lot of positive things about Anthony Fauci before I went on a rant

Starting point is 02:22:48 against it. Because ultimately, I think he failed as a leader, and I know it's very difficult to be a leader, but I still wanted to hold them accountable for that as a great communicator science and as a great leader. But what do you think he didn't do right? I'm curious. So the core of the problem is the several characteristics of the way he was communicating to the public. So one is the general enough entity. Two is a thing that is very hard to put into words,

Starting point is 02:23:28 but there are certain ways of speaking to people that sounds like you're hiding something from them. That sounds like you're full of shit. That's the authenticity piece. Like it sounds like you're not really speaking to the full truth of what you know and that you did some shady shit in your past that you're trying to hide. So that's a way of communicating that I think the internet and people in general are becoming much better at detecting. And as I said, they're good BS detectors.

Starting point is 02:24:02 Yeah, good BS detectors. But contributing to that is speaking from authority, speaking with authority and confidence where neither is deserved. So first of all, nobody's an authority on this new virus. We're facing a deadly pandemic and especially in the early stages, it was unclear how deadly it would be. It was unclear, probably still unclear,

Starting point is 02:24:33 fully how it's transmitted. The full dynamics of the virus, the full understanding of which solutions work and not, how well masks of different kinds work, how easy or difficult it is to create tests, how many months or years it's going to take to creative vaccine, how well in history or currently do quarantine methods or lockdown methods work, how, you know, what are the different data mechanisms that are data collection

Starting point is 02:25:03 mechanisms that are being implemented. What are the clear plans they need to happen? What the epidemiology that's happening? What is the uncertainty around that? Then there's the geopolitical stuff with China. Like what, I personally believe there should have been much more openness about the origins of the virus, whether a leak from a lab or not, I think communicating that you're open to these ideas

Starting point is 02:25:34 is actually the way to get people to trust you, that you are legitimately open to ideas that are very unpleasant, that go against the mainstream. Showing that openness is going to get people to trust you when you finally decrease the variance in your uncertainty, like decrease uncertainty. We still have a lot of uncertainty, but this is the best course of action. Vaccines still have a lot of uncertainty around them. mRNA is a new technology, but we have increasing amounts of data. And here's the data sources, and like laying them out in a very clear way, of this is the best course of action that we have now. We don't know if it's the perfect course of action,

Starting point is 02:26:17 but it's by far the best course of action. And that would come from a leader that has earned the capital of trust from people. I mean, I think in recent history, the worst pandemic is 1918 flu, right? But that's mainly because we didn't know what to do. We didn't have many tools that are disposal. And those tied up with World War I. That's right. That's right.

Starting point is 02:26:42 So the leadership there, I mean, I... But I don't know what is a lot of deaths, right? And any one person is someone's family. So to them, it's a lot, right? But that logic, we don't apply that logic generally because there's a lot of people suffering and dying throughout the world and we turn Turn the other way all the time and that's the story of history. So saying saying you all of a sudden Well, bothers me though. I mean personally, I don't like anyone dying anywhere turn the other way all the time. And that's the story of history. So saying, saying you all of a sudden, well, bothers me though.

Starting point is 02:27:06 I mean, personally, I don't like anyone dying anywhere. But especially considering what technology we're able to muster, yet we still kill each other. It's just dichotomy to me. Yeah, but I mean, this is the, what is the Paul Farmer? There's these great stories. I mean, that's the burden of being in healthcare of being a doctor is you have to help,

Starting point is 02:27:36 you can't help but help a person in front of you, who's hurting. Sure. But you also are burdened by the knowledge that you helping them, you spending money and effort and time on them means you're not going to help others and you cannot possibly allocate that amount of time to everybody.

Starting point is 02:27:53 So you're choosing which person lives and which person dies. And you're doing so, the reason you're helping the person in front of you is because they're in front of you. And so the reason right now, we care a lot about COVID is because the eye of the world has turned to COVID, but we're not seeing all the other atrocities going on in the world. They're not necessarily related to deaths, they're related to suffering, human suffering, which you could argue is worse than death, prolonged suffering. Of course. There's all there's all these questions and the fundamental

Starting point is 02:28:27 question here is are we overreacting to COVID in our policies? So that this is the when we turn our eye and care about this particular thing and not other things, are we dismissing the pain that business owners who've lost their businesses are going to feel and then the long Talking about long COVID the long-term effects economic effects on the millions of people that will suffer that suffer Financially, but also suffer from their dreams being completely collapsed So a lot of people seek gain meaning from work and if you take away that work, there's anger that can be born There's pain. And so what does that lead to that can lead to the

Starting point is 02:29:13 Rising up of charismatic leaders that channel that anger towards destructive things. That's been done throughout history So like you have to balance that with the policies that you have in COVID. And then, I mean, very much my main opposition to Fouci is not on the details, but the final result, which is, I just observe that there's a significant decrease in trust and science as not the institution, but the various mechanisms of science. I think science is both beautiful and powerful, and the reason why we have so many amazing things in such a high quality of life. And distrust in that, the thing we need now to get out of all the troubles we're in,

Starting point is 02:30:00 continue getting out of the troubles we're in is science, the scientific process, broadly defined like innovation, technological innovation, scientific innovation, all of that, distrust in that is totally the wrong thing we need. And so anybody who causes a distrust in science to me, you know, carries the responsibility of that and should be, and because the response, I mean, should be fired, should be, should be, or at least openly have to carry the burden of that, of having caused of that kind of level of mistrust. Now it's maybe unfair to place it on any one individual, but you have to, I think in your pockets, the book stops at the top, like the leaders tend to care.

Starting point is 02:30:51 No, no, there's a clear leader here. Yes, absolutely. So even if it's not directly his fault, you know, he has to carry, carry the price of that. Do you think we should, at this point, say, okay, we have vaccines. You can decide whether you take them or not. Let's move forward. Maybe you can help me understand this because it seems like why is that not the right solution? Completely open society. The vaccines, at least in the United States, as I understand, are widely available. So, this is the American way. You have the decision to make. If you have conditions that make you worried to get COVID and go to the hospital, then you should get vaccinated. Because here's the

Starting point is 02:31:40 data that shows that it's much less likely for you to die. If you get vaccinated, if you don't want to get vaccinated because you're worried about a long-term effects of vaccine that you don't have to, but then you know, suffer the consequences of that. And that's it. So here's what I think is driving. I think it's all about kids.

Starting point is 02:32:04 Because they're going to go back to school in the fall and many of them can't be vaccinated. Right. So if they get infected, they do have less frequency of disease, but it's not zero. They do get sick and they can have long-term consequences. And at that age, it would be a shame, right? And not even their choice. They can't decide to get vaccinated or not because they can't have access to it. So I think that would, that's what would drive my

Starting point is 02:32:32 efforts to try and get more people at least in schools vaccinated, but I might be wrong. It may not be that. Can you kind of dig into that a little bit? So there's, But so there's, so you're saying that there should be an effort for increased vaccinations of kids going to school, just not for societal benefit, but for the benefit of each individual kid, right? So right now, kids under 12, right? You're not yet vaccinated, is that correct? Yeah, I think so.

Starting point is 02:33:03 And it's gonna be, it's not gonna be in time for school opening that they get vaccinated. Is that correct? Yeah, I think so. And it's going to be, it's not going to be in time for school opening that they get vaccinated. And then, I mean, I suppose the teachers are all going to be vaccinated. Makes sense for them to do that. But I'm just worried the kids are going to be transmitting it amongst them. And many states don't allow mask mandate in school.

Starting point is 02:33:22 So I think that's what's driving the larger narrative in the US to protect kids. It's kind of what I hear from Daniel Griffin because increasing numbers of kids are being admitted to hospitals now because they're the they're becoming the major unvaccinated population. They're hanging out over the summer and that's just going to get worse in the fall. And so you could have a lot of kids with long COVID and disabled their entire lives, right? So. And of course, hearing from people who are vaccine hesitant, I hear exactly the kids statement, but they're saying they don't want the long vaccine, the long term effects of the vaccine to affect the kids.

Starting point is 02:34:06 That's the of the code of this new vaccine. Which I would say is, as I said before, you can't say never, but we do know that long COVID exists. We don't know for how long because we've only looked out six or eight months. We know that exists and the frequency is increasing. It certainly exists in young kids and we have no idea about long vaccine effects. So I think they have to make their decision based on that. But, yeah. But your question is why don't we just open up society? Say here we have these vaccines if you want to protect yourself.

Starting point is 02:34:44 I think it's mainly the school that's driving the whole narrative. That's my opinion in which direction not to open up or to open up, but to try and get, you know, their efforts at the federal level to get people vaccinated, right? But see, how higher the risk for kids? I mean, as my understanding was, it's, I mean, yes, it's non zerozero, but very low. But what is the numbers? Now 70,000 hospitalizations so far in kids as of last week.

Starting point is 02:35:13 So yes, it's low, but polio was low. Polio was 20, 30,000 kids a year paralyzed. And many people have actually argued that that vaccine was a necessary, you know That wasn't a substantial enough health problem. But paralyzed is different than hospital So what does hospitalize mean? What but it's the long COVID question. I mean, this is the open question It was long COVID in kids. What is that? So well There's a lot of the same issues, cognitive issues, motor issues, respiratory GI dysfunction.

Starting point is 02:35:51 How long we don't know? I mean, it could end in a year or, as you know, there are other post-acute infectious sequelae that we know about, you know, chronic fatigue, MECFS is thought to be a post-infectious sequelae, which has gone for many decades now and many millions of people. This could be another one of those. So I'm just saying it might be worth airing on the side of not letting the kids getting factored.

Starting point is 02:36:19 Yeah, well, I'm trying to keep an open mind here and appreciate you doing you doing the same. Of course I lean on definitely not requiring people to get vaccinated, but I do think getting vaccinated is just the wiser choice, looking all the different trajectories before us. Getting vaccinated seems like from the data, it seems like the obvious choice, frankly. But I'm also trying to keep an open mind. There's some things in the past that seemed obvious, which turn out to be completely wrong. So I'm trying to keep an open mind here. So for example, one of the things I'd love to get your thoughts on this is antiviral ideas. So ideas outside

Starting point is 02:37:07 of the vaccine. So Iver Mectin, something that Brett Weinstein and a few others have been talking about, there's been a few studies, some of them have been shown not to be very good studies, but nevertheless, there seems to be some promise. And I wanted to talk to Brett about this particular topic for two reasons. One, I was really bothered by censorship of this. That's a whole nother topic. I'm bothered by censorship.

Starting point is 02:37:39 This is a gray area, of course. But it just feels like that should not have been censored from YouTube, like discussions of Ivermectin. We can set that aside. The other thing I was bothered by the lack of open-mindedness, unexploring things like Ivermectin in the early days, especially when at least I thought the vaccine would take a long time. I mean, it's not just I have a mech then. It's really seriously at a large scale, rigorously exploring the effectiveness of masks and the big one for me is testing. Like the fact that that wasn't explored aggressively to lead to mass manufacturing like May 2020 is absurd.

Starting point is 02:38:25 Anyway, so I was bothered by the solutions not being explored and not by now having really good Ivermectin studies. So can I talk about Ivermectin? Yeah, I would love that. Sure. So full disclosure, my wife worked on Ivermectin at Merck for 20 years.

Starting point is 02:38:40 Okay, so they just want people to know, but I didn't, I don't talk to her all the time about it. Anyway, she hasn't been at Merck for a long time. As you know, Ivermectin is a very safe drug used to treat certain parasitic infections. Right? And it is approved. It's amazing.

Starting point is 02:39:01 You can take one dose a year and be protected against river blindness in Africa and certain parts of Africa. It's remarkably effective. And so it's quite a safe drug at the doses that are approved. Now early last year, a study was done, I believe in Australia, which showed in cells in the lab, if you infect with SARS-CoV-2 and put Ivermectin in, it would inhibit the virus production substantially. It was quite clear, right?

Starting point is 02:39:29 But the concentrations they were using were rather high and could not be achieved by the approved dosing. So you would need to do a dosing study to make sure it's safe. The reason is that Ivermectin binds to receptors in your brain, and it can have high doses. A lot of some people take high doses inappropriately, and they have neurological consequences. So if you needed 10 times more eye ver mech, then you'd have to make sure it would be safe in people.

Starting point is 02:39:59 So there's a question of safety, too. Right. So I think it has always been the case that it should have been properly studied, but it wasn't. There are lots of trials here and there are lots of improperly controlled trials where someone would just treat some patients

Starting point is 02:40:14 and say, hey, they all did fine, but have no control arm. And there were some controlled trials, but they were very small. So right now, 4,000 person trial is enrolling to test in a randomly controlled trial setting, whether it works or not. There's still plenty of cases that you can do that, so you can ask whether in there, whether there are any side effects. I think that's completely

Starting point is 02:40:37 fine. And if it says it works, then we should use it. In the meantime, I always tell people, if you want to use Ivermectin, you can do it off label. It's FDA approved. And if your physician says, I'm going to give you this off label, I don't have any objection, but I don't know if it's going to work. Now, a friend of ours, last week in New Jersey got COVID. He went to his local hospital and their regimen was Remdesivir Dexamethasone Ivermectin. It's written that's what they do for every COVID patient. They just give it to them automatically and

Starting point is 02:41:15 Well, so he's he recovered so who's to say it was or we're not was not Ivermectin right so I Don't have any strong ideological opposition. I just think it should be tested for what you want to use it for. And that's being done, and I think that's fine. Is it strange to you that Ivermectin or other things like it weren't tested aggressively in the beginning? From a broad scientific community aspect, you aspect, I can be a little bit conspiratorial. This is what people talk about with Evermechton. Yeah. It's with the vaccines, there's quite a lot of money to be made. With Evermechton,

Starting point is 02:41:57 there's not as much money to be made. Is that too conspiratorial? Like, why didn't we try more solutions in the beginning? Well, all the money was put into vaccines, right? Very little was put into antivirals, because the decision was made at a very high level, probably involving Dr. Fauci. We're gonna put 24 billion into vaccines, right? And I think part of the reasoning is,

Starting point is 02:42:21 they give you years worth of protection, whereas an antiviral works, and you have to keep dosing and so forth. But I've ever methen is not trivial. And I agree it should have been tested early on, but we had a really bad experience with hydroxychloroquine, which we can talk about too. I have ever methen is very hard to synthesize. Most drugs you synthesize chemically. You devise a formulation in a synthesis and they do it, they scale it up and it's fine. I remember Mechton's really hard. And so what they do

Starting point is 02:42:52 instead is they take the culture of the bacterium that makes it and they grow it up and they ferment it and then they purify it. And Merck owns the bacteria. A number of years ago, two employees of Merck stole it and left the company and tried the market and they were arrested and they got put in jail. So they protected very carefully. So she can't just make it. If you do, it's incredibly expensive. And now India is very cheap apparently. They use it quite liberally there. And I don't know how they're they're making it. Maybe they've licensed it from American, so forth. But that's why it hasn't been tested more widely, I think. There's complexities in terms of getting a lot of it and manufacturing a lot of it. Yes.

Starting point is 02:43:39 Okay. So what was the hydrochloric? Hydroxychloric was also shown early on to inhibit virus in cell culture. And that's not surprising. Hydroxychloric, and of course, is used from malaria. And what it does when your cell takes up things from the plasma membrane, including viruses, it goes through a pathway called the endocytic pathway, which involves a vesicle moving through the cell.

Starting point is 02:44:07 And as it moves through the cell, it's pH drops. And that lets a lot of viruses out, actually, and hydroxychloroquine blocks that. So it blocks infection with a lot of viruses. So the problem with those early studies that were published is that they were done in kidney cells and culture, where the only way the virus can get in is through the endosome. And in hydroxychloroquine inhibits that, and that's why it inhibits in kidney cells and

Starting point is 02:44:37 culture. But lung cells and respiratory cells of humans where the virus reproduces can get in two different ways. It can get in from this endocytic pathway, which is inhibited by hydroxychloroquine, or it can get in at the cell surface, which is not inhibited by hydroxychloroquine. So when you treat patients, it has no effect in the lung because the virus can just bypass it. And all the usage initially were based on the studies done in kidney cells and culture. So that was just wrong, scientifically incorrect, yet it drove a lot of.

Starting point is 02:45:15 And today many people still think they should be taking it, but... So like that, not panning out, kind of resulted in loss of optimism about other similar things. Well, that and many other drugs, repurposed drugs were tried, right? And a lot of HIV antivirals were tried. I think the problem with hydroxychloroquine influenced the Ivermectin narrative, right?

Starting point is 02:45:39 People thought that data was being hidden about hydroxychloroquine. So they said, well, they must be doing the same thing with Ivermectin, but with hydroxychloroquine. So they said, well, they must be doing the same thing with ever maximum. But with hydroxychloroquine, it just scientifically could not work as an antiviral. The other problem that is more broad that is important to point out is that when you have COVID and you need an antiviral, it's usually because you can't breathe and you go in a hospital. Because if you're mildly ill, you're never going to go to your doctor and ask for an antiviral. And the problem is when you can't breathe, it's no longer a viral issue.

Starting point is 02:46:13 It is now an inflammatory issue and no antiviral in the world is going to help you. So if that's why REM DESIVIR doesn't work very well, because it's mainly given intravenously to people who go in a hospital. If you get biver mectin in the hospital, it's not going to do anything for reducing virus because by that time you have very little virus to begin with. You have an inflammatory problem that you need to treat in other ways. So this is why a lot of the antivirals failed because they're used too late. What you need is a pill you take on that first positive test when you have a scratchy throat. You get a PCR in 15 minutes, I'm positive, take a pill, boom, that's gonna inhibit it.

Starting point is 02:46:56 If you wait till you can't breathe, and that's why the monoclonal's even, don't work if you're in hospital that well, because it's too late and the approach now is, if you're in a high risk group, if you're in hospital that well because it's too late and that the approach now is if you're in a high risk group, if you're over 65, if you are obese or have diabetes or any other comorbidities, your first sign of a scratchy throat positive, you get monoclonals. Then they might help you, but if you wait till you go to the hospital, it's too late because the viral curve drops after that first symptom within three days, you're no longer shedding enough virus to transmit.

Starting point is 02:47:33 Drops really quickly. That's the reason a lot of these antivirals failed because they were tested in hospitalized patients. And we have nothing but Remdesivir now, unfortunately. So it was the wrong approach. We should have been giving it to people who just tested positive from the start. Or it's you and for preventative and see.

Starting point is 02:47:51 You could do that too. But I have to say the other issue is, this monopere of here is the drug in phase three now. It's an oral antiviral, it looks good. If we go ahead with just one, we're gonna get resistance within a few months, and it will be useless. We need to have at least two or three drugs that we can give in combinations. And we know that because that's what took care of HIV, that's

Starting point is 02:48:15 what took care of HCV, hepatitis C virus. It really reduces the emergence of resistance. Joe Rogan got quite a bit of heat recently about mentioning a paper and a broader idea, which I didn't, I don't think is that controversial, but maybe we can expand on it. And the idea is that vaccines create selective pressure for a virus to mutate and for variants to form. First of all, from a biological perspective, can you explain this process and from a societal perspective, what are we supposed to do about that? So let's get the terminology right. So as we talked about earlier, viruses are always mutating.

Starting point is 02:49:07 So no vaccine or no drug makes a virus mutate. But that's the wrong perspective in which you look at it. Right. What the immune response is putting pressure, selection pressure on the virus. And if there's a one particle with the right mutation that can escape the antibody, that will emerge. Right. So that's what happens with influenza virus, right? We vaccinate every year, and there are not a lot of people that get infected, so they get natural immunity. And then virus is incredibly varied. It mutates like crazy. And there's in some person somewhere, there's one variant that escapes the antibody, which has been induced either by infection or vaccination. It can be both.

Starting point is 02:49:52 And that drives the emergence of the new variants of the next year we need to change the vaccine. So I would say both natural infection and vaccination sure select for variants. Absolutely. There's no question because they're inducing immunity. Now, what happened last year was at the beginning of 2020, very few people in the world were immune as the virus first started spreading. But you can see in the sequences of those isolates from the beginning of 2020, you can see in the sequences of those isolates from the beginning of 2020. You can see all of the changes that are now present in the variants of concern. It's very, very low frequencies. They were already there, but there was no selection for them to emerge until November, when we now had many millions of people who had mostly been infected, but also some vaccinated.

Starting point is 02:50:43 Then we saw the alpha variant that merged in England, probably because of immune selection. Now, the virus that had the change that evaded the antibody had an advantage, and that virus drove through the population. So that's what we're seeing. We're seeing all these variants are simply antigenic selection. This is the variants, the mutations that are at the core of these quote unquote variants, there were always there all along the vaccine or the infections did not create

Starting point is 02:51:13 them. No, they didn't create them. They're selected. It's like the vaccine wipe out a lot of the variants, right? And then by making a body immune to them. And so, but some of them survive. Yeah. And then there's another tree that's built. And it's unclear what that tree leads to. I mean, it could make things much worse or much better. We don't know. Well, with flu, we see year after year, the virus changes, we change the vaccine, we deal with it, we change it again, there's an unending. But see, that's a very different story. If do you think, do you think COVID will be with some likelihood, like the flu, whereas basically variants will never be able to eradicate it.

Starting point is 02:52:06 It will never eradicate it in any case, ever. Well, come up with a vaccine that makes you immune to enough variance to where there's not enough evolutionary like room. Well, if you cut down the number of infections, then you reduce the diversity. Sure. Yes. Right. The problem is, if let's say you're a cynic and you say, well, vaccination is just selecting for variance. So let's stop it. But then you're going to have infection. And that's going to select for variance. And there, the more you're more likely to get very sick because we know the vaccines are really good at preventing you from dying. So that's why it still makes sense to use vaccines because they prevent you from dying. That's the bottom line.

Starting point is 02:52:51 But can we ever make a vaccine that deals with all variants? Absolutely. And the reason I say that is because people who get naturally infected with SARS-CoV-2, they develop COVID, they recover. If you give them one vaccine dose, they make an immune response that handles all the variants that are around right now. All of them, much better than people who've gotten two doses of vaccine. For some reason, their immune response is suddenly broadened after the infection vaccination, and they can handle all the variants that we know of so far. So that tells me we can devise a strategy to do the same thing with a vaccine that makes

Starting point is 02:53:38 a really broad vaccine that'll handle all the variants. Well, you actually on the virology blog, I don't know if you're the author of that, but I guess. I guess. Oh, the blog, yes, but there's a particular post that's talking about reporting on a paper that makes a match strategy. Oh, yes, that's one of my co-writers, Trudy Ray, yeah.

Starting point is 02:53:57 Yeah, that's an interesting idea that there's some early evidence now that mixing and matching vaccines, like one shot of Pfizer and one of like Moderna or something that creates a much better immunity than those two shots of Pfizer. I think that's worth exploring. Absolutely. And this is relevant.

Starting point is 02:54:20 What we're doing with influenza, you know, instead of having to vaccinate people every year, why can't we devise a vaccine which you'd get once in your lifetime or maybe once every 10 years? Okay. So the spike of influenza, it's a long protein, kind of like the spike of SARS-CoV-2. It's stuck in the virus membrane and the very tip, that's the part that changes every year. This is where the antibodies bind. But the stem doesn't change. And if you make antibodies to the stem, they can also prevent infection.

Starting point is 02:54:55 It's just that when people are infected or with the current vaccines, they don't make many antibodies to that stem part. But we're trying to figure out how to make those and we think they would be broadly protective and you'd never be able to or more rarely be able to have a variant emerge that escaped it. And I think we can do the same thing with with coronavirus to for sure. Can I ask you about testing?

Starting point is 02:55:21 Sure. Sure. Sure. The mentioned PCR, what kind of tests are there? The antigen tests? What are your thoughts on each? Maybe this is a good place to also mention viral load and the history of the virus as it passes through your body in terms of what's being tested for and all those kinds of things? So the first tests that were developed were PCR, polymerase chain reaction,

Starting point is 02:55:53 they're basically nucleic acid amplification tests. And they were very first ones, they stuck the swab all the way up into your brain almost. And I had that done a couple of weeks ago, oh my gosh, it's really nasty. But now they do an interior nary swab. They get a bunch of cells and some mucus, which has virus and parts of virus,

Starting point is 02:56:16 stick it in a test tube, and then they run a reaction, which by the way involves reverse transcriptase, because it converts the viral RNA to DNA and then you amplify it and you can specify what part of the viral RNA you want to amplify and then a machine will detect it and it can be done in 15 minutes. But you're detecting pieces of RNA not infectious virus, so we're measuring viral RNA loads, right? And a common mistake that many people who should know better, you know, physicians and scientists of all kinds, they think that indicates how much virus you have. It doesn't. It's a diagnostic of whether you

Starting point is 02:57:00 have bits of RNA in you, and it probably means you're infected, but you can't use it to shed light on what's going on and I'll tell you why in a bit, but first we have to explain some other things. So until you get to about a million copies of RNA, so you can measure the copy number in this test, this PCR test. It's a number called CT or cycle threshold. The test, the way the machine works, it goes through cycles and every cycle it amplifies what you put in. And the more cycles you need to see something, that means there's not a lot of RNA there. So if you see, if you do a test and you have a cycle threshold of 35,

Starting point is 02:57:44 you have very little RNA in you Contrary if you have a cycle threshold of 10 you have a ton of RNA. You only took 10 cycles to detect it And you can extrapolate from that number the number of copies you have per sample say per swap and if you don't have a million You're not infectious. You're not going to infect anyone. So in the early days, no matter what PCR result you had, they would quarantine you. And that was wrong because you're not shedding. You don't need to be quarantined, but wasn't thought through properly, right?

Starting point is 02:58:16 That's where you had like 14 days or something like that. Like, 14 days. Which is now we know it's too long because you don't shed for that long in a normal infection. Now it's 10 days should be fine. So what happens is you get infected, you don't know it, of course. The virus starts to grow very quickly and within four or five days you reach a peak of shedding. You're making a lot of RNA

Starting point is 02:58:40 and you may be asymptomatic. You're shedding. You can affect others and then you may or may not have your symptom onset. So you shed for a couple of days before symptom onset, and then within three days, four days, the viral RNA crashes, and you're no longer shedding, you're no longer transmitting. So that's the one kind of test we have. It can tell you if you're infected at the moment,

Starting point is 02:59:01 but it won't tell you if you're going to be infected tomorrow, right? Because if you're negative today be infected tomorrow, right? Because if you're negative today, you could be positive tomorrow. You just might be in a different part of the incubation period, right? So that's one test. Been used the most. You can now get 15 minute versions of them in a walk-in or whatever finds. Then their antigen tests, which look for the proteins that the virus is making. So as it's reproducing in your nose, it's not only making genomes, it's making proteins. So these you can buy in the drug store.

Starting point is 02:59:33 These would have been great if they had Michael Minna last year had the idea that if we could make a little stick, a little piece of paper that you would suck on and it would tell you if you're infected or not, if this could cost less than a buck, everybody could test them. Which they can cost less than a buck, by the way. Yeah, but they were never made, right? They're never mass manufacturers. So his idea is to do like daily tests. Yeah, daily and then the kids go into school. He's positive or she's positive. Well, if it's cheap enough, you just take another test because they have a certain

Starting point is 03:00:06 error frequency. If it's positive, twice you stay home and the next day you try again. And this, I think this would have revolutionized because the PCR tests are more expensive at the time and they're take longer to do and so forth. But it never happened. But now we do have $20 buy next now and others that you can buy and people buy them and see, but that can still happen, right? And this is the very first thing to me because I'm worried about variants, but I'm also worried about future much more deadly pandemics. Like, I know we kind of said, yes, COVID and lots of deaths, but like it could be a lot worse too. And so I'm thinking

Starting point is 03:00:47 what is going to be the right response for the future pandemic of its kind. And what's the right response for continued number of variants and some of the variants might be deadlier or more transmissible? Well, we can, the the antigen tests will pick up the variants. That's not a question. The PCR may be influenced by changes, but you can quickly adapt the primers that you use. But that's what I mean. Like to me, all these discussions about vaccines and so on,

Starting point is 03:01:17 vaccines, we got very lucky that they took so little time. Right. And, and you have to be aware, no matter what, that there's hesitancy with the vaccines in this country before. I mean, yeah, if that's a reality, you can't just be like magically saying that you're going to overcome that. And I don't think there's any hesitancy and cheap tests at home.

Starting point is 03:01:37 I agree. I think if someone, so the question is, if someone tests a positive, would they stay home? That's the question. What if their job depends on them going in? I mean, that's, well, you have to look at sort of aggregate. Yeah. How many people would decide? And I think, um, again, a lot of that is in leadership, but I think a lot of them, I would say most people stay home.

Starting point is 03:02:00 I think that Minna had the idea and it would have changed the whole situation for sure. If it could have been made, when we talked to him last spring, I think, or summer, we would have gotten around a lot of the issues that we were in today because I think people would have stayed home and not transmitted. And I think it's still valuable to this day. In the fall, if we don't have vaccine uptake, we could just test kids every day and get it and keep them home when they're infected. It cuts, it's, and we don't have it.

Starting point is 03:02:31 But I think, and I'm not privy to what was going on, but I don't think a lot of emphasis was put on testing early on. You know, the CDC developed the first one. It was flawed. They had to recall the kids. I mean, as if he asked, they should have had 100 companies making the tests initially, right? So for the future, I think what we have learned is we need to have a rapid antigen test right off the bat that's doable. You can't do it in a day like you can for PCR because

Starting point is 03:03:01 you need to make antibodies to the protein that you're looking for, and you need to do those in animals, but you can do it in weeks, and we should be ready for that. Yeah, because, I mean, to me, that's obvious. That's obviously the best solution. Second to that, if we understood how well masks work. Like, maybe let me ask you this question. Let's put masks aside. How will do we understand how COVID is transmitted? There's droplets of different sizes, aerosols, tiny, tiny droplets.

Starting point is 03:03:40 It seems like that's a very difficult thing to understand thoroughly. So, it seems like it's transmitted in both ways. It's unclear how exactly. So, how much do we understand and why is it so difficult to understand it fully? I think it's clear that it's transmitted through the air, mostly. It's not touching. We thought initially it would be a lot of touch, but very little of that. It's through the air. And when you talk, mainly when you talk, you you expel a lot of droplets, right? Even the

Starting point is 03:04:11 closives that your foam thing here are meant to pee, right? That you send out little sprays and those have viruses in them. And the big drops fall to the ground and the little ones can go a hundred feet or more, right? But the little ones also have less virus in them. So I'm not sure what we certainly do not know how much virus you need to be infected, but it's probably at least several thousand particles, if not more. And it could be that for most people, the tiny droplets don't have enough virus to infect someone else. But there's one observation about this virus. It's really interesting.

Starting point is 03:04:53 And that is that 80% of transmissions are done by 20% of the people, of the infected people. Not every infected person transmits. That's been born out in multiple studies. In fact, there's a study at University of Colorado where they quantified the viral RNA loads and all the swabs that had been done of students for like a six month period. And most of the infectious virus,

Starting point is 03:05:22 most of the RNA copies were found in 15 to 20% of the people. The rest had really low and they probably, that's probably why they don't transmit. So those are the ones that might get by enough virus in the tiny droplets to be able to infect someone at a distance. And I think that's entirely possible. Why is it hard to study? You can't do it in real life because you don't know who's infected, and if you do, there's not a controlled environment to measure droplets and so forth. You'd have to do it in a laboratory situation.

Starting point is 03:05:56 If you use an animal, you just don't know what the relevance of that is to people. You'd have to use human and do challenge experiments, and you know, we don't do that at this point at least not for this virus So that's why it's hard to know what's going on. So we have to make inferences from epidemiological Associations where you're studying say transmission in a household where people are stuck in the same rooms together and you can get an idea of What kind of droplets were involved?

Starting point is 03:06:23 So that makes it much harder to if you're if you're leaning on epidemiological stuff as opposed to like biophysics or something like the mecanology. Very hard. So that makes it really hard to then develop solutions like masks to ask the question how well the masks work, because then to answer that question you can lean on epidemiological stuff again, like looking at populations that wear masks, or she's don't wear masks.

Starting point is 03:06:50 As opposed to actually saying, like from an engineering perspective, like what kind of material and what kind of tightness by which amount decreases the viral load that's received on the other end. But some experiments have been done with masks and just droplets with no virus in them, right? Yes. And you can measure the efficiency of different mask materials at keeping those in. So if I say that this mask stops 70% of this or larger size droplet, that leads to this percent decreased transmission.

Starting point is 03:07:33 And also on both the generation and the receiving end and the giving end. So how well do masks protect you, from others? How well do you do mask protect others from you? Like all of those things seem like they could be more rigorously studied. There's no doubt about it. And now is the time because once this is over, nobody's going to do it. Nobody's going to care. Right. But it seems like to me, so test is one thing, but masks, like, the good mask, whatever the good means, whatever that means, like some level of a quality of material on your face, if it's shown to actually like thoroughly shown to work well. That seems like an obvious solution to reopen society with if you have a good understanding of how well they work. Because if you don't have a good understanding,

Starting point is 03:08:33 if there's a lot of uncertainty, that's when you get, and you have people speaking from authority, that's when you start getting the politicization of the solutions. Of course. No, the data, there are some data, mostly epidemiological, and they show some effect in some countries, right? But they could be way better. Yeah. And, but the fact that they're not perfect, then people take advantage of and say,

Starting point is 03:09:00 well, look, they don't work that well, so I'm not gonna wear it. I think, as you said, people can use it as an excuse. But even if it works, so Daniel always says that a mask will cut down transmission by 50 to 60 percent, and then distance will do another 30 percent. Those numbers I made up though. I mean, they're not made up, but they're estimates. Absolutely. And many of them are made based on models, right? We make this model and let's say the mask cuts down this much. What's what will be the effect on it?

Starting point is 03:09:31 I mean, yeah, they're models. And it's for the same reason, I don't believe the transmission of the variants because it's all based on statistical models as well, not biological experiments done in the lab. So that in that sense, vaccine data is much better than mask data. For sure. For sure. So my problem with the mask day, which I always thought was fascinating, I stopped talking

Starting point is 03:09:52 about it. I was in a paper about masks. I stopped talking about it because what was started happening is mask created assholes on both sides. The people that were like in Silicon Valley, the friends of mine, they were watering masks. The way they look at others who don't is like, that's a whole another issue. But that's what that, that's happens when you don't have solid science. Understood. They now start judging you like you're a less a human being. You're not only a dumb, but you're just, you're almost like evil. You're doing

Starting point is 03:10:25 bad for society by not wearing a mask. And then the people looking in the other way are seeing you for the asshole that you're being for judging them unrightly. So they almost want to say, F you by not wearing the mask. And there's this division that's created that that was heartbreaking to me because masks like testing is a solution that was available early on and if understood well, it could be deployed in a mass scale and it seems like there's some historical evidence for other viruses where it does Yes, very well. That's correct. So like the fact that this was politicized Yeah, it was a little bit heartbreaking. You can find in the literature studies mostly of healthcare workers in influenza, where you can actually, because you see the people every day, they can sample them, you can actually

Starting point is 03:11:12 see what masking does, and some of them show an effect, and others do not, and that's the problem. Like anti-trial, sometimes if it's not big enough, and then people latch onto that C, it doesn't really work. But I think the main issue is that in January, both CDC and WHO said masks don't work, they'll use them. That was the kiss of death for masks because when they then changed their mind, they didn't say we screwed up. They just said wear masks. If they had said we made a mistake, we were wrong. I think more people would have worn masks, but they didn't. And like you said,

Starting point is 03:11:51 admitting you're wrong is like a real big part. And I also think almost the better way is not just saying you're kind of saying you're wrong, but in January saying, like revealing the uncertainty end of which we operate, like actually, like reveal what was done with the Spanish food at the beginning of the previous century. Because there's a lot of mass controversy then too. It went back and forth. And that was actually the source of a lot of distrust there too. So, and then look at influenza, like, how is it effective with that? And just reveal this word, we don't know. But with some probability, this is the best option we got, currently. And then in a month or two, I just did saying that, you know what, our uncertainty decreased a little bit. We have a better idea.

Starting point is 03:12:43 That was an incorrect estimate, but reveal that you're struggling. It's not like this weird binary clock that goes one direction or the other, you're struggling with uncertainty. And like trusting, maybe criticize me sometimes of this, but I think most people are actually intelligent. Like trusting the public to be intelligent, if you have transparent and give them information in a real authentic way, don't look like you're hiding something.

Starting point is 03:13:13 I think they're intelligent enough to use that data to make decisions. It's the same thing as with the testing. If you put that power in the people's hands to know if they're second-ought, they're going to make unmasked the right decision, I think. It's that, the masks and the testing has been a bit heartbreaking.

Starting point is 03:13:31 I think it's a good point though, that most people don't seem to have an objection to testing. It's a good point. Yeah. And then obviously, Mucka Meena makes that point brilliantly. And still, there's very little excitement around that. But he said he was going to do it.

Starting point is 03:13:48 I don't understand. I mean, I haven't spoken to him since then. So I don't know what he's pushing it. Well, I mean, but he can't do it alone. He has to get, so one of the resistance is FDA doesn't like cheap things. Yeah. They don't want to approve it.

Starting point is 03:14:03 So it makes the mass manufacturer, like with the emergency exceptions, all those kinds of things very difficult. And then there's not much money to be made on it without that. I don't know. I think there's just economic pressures against it. And because so much investment was placed on the vaccines. And obviously there's an incentive mechanism there where the company's lobbyists and all those, there's this machine that says, arguing for tests is difficult because a thing that's worked for most severe viruses

Starting point is 03:14:39 in the past is vaccines. Now we have vaccines, why the hell would you need tests? At that time, why the hell do you need tests? At that time, like, why the hell do you need tests when we can be working on vaccines? It seems like the obvious thing to be working is the vaccines from their perspective, but it's not obvious at all to me. I think you should have both.

Starting point is 03:14:57 I think you have vaccines and good testing, and that covers you really well, because you're always gonna have people who don't get vaccinated. I don't get vaccinated. I don't know if you've been paying attention to this. There's a guy named Wienstein. There's a guy named Sam Harris. They have good representation. I would say of of two sides of a perspective on the vaccine. So from Sam Harris's perspective, it's obvious that everybody should get vaccinated and it's

Starting point is 03:15:29 irresponsible to not get vaccinated. I think he represents a lot of people's belief in that. And then Brett talks a lot about hypermectin, but also talks about hesitancy towards the vaccine for people who are healthy, who are people who are younger, that kind of thing. And saying we should consider long-term effects of the vaccine in making this calculation. What do you make about this conversation? Some of it happens on Twitter, some of it happens in the space of podcasts. Do you pay attention to this kind of thing? What's your role in this? What do you hope

Starting point is 03:16:13 is the way to resolve this conversation? Do you think it's healthy? Well, a conversation is always healthy, but to make definitive statements is not because it suggests you have information that you don't have. So, you know, we talked about long-term effects. I think you need to balance those versus long-term effects of the disease and you can make your decision. I don't think you need to tell everybody to get vaccinated. I think you need to present the case. You say, here, we made good vaccines, here, the safety profile, here's the risk-benefit balance, and you the case. You say here we made good vaccines here, the safety profile. Here's the risk benefit balance and you should decide. You're a smart person, you should decide.

Starting point is 03:16:51 Now, companies are going to do differently, right? Companies may say you have to be vaccinated to work here. My employer, Columbia, said we have to be vaccinated to work in the fall. And if you want to be a student, you have to be vaccinated. So you decide whether you want to go or not. But the idea that you should make a decision based on long-term effects, there is no evidence, right? So how can you make a decision when we don't have evidence, whereas we do have evidence that there are long-term effects of getting COVID. So I don't think that's a fair argument, and it just makes people scared to say that.

Starting point is 03:17:26 But on the other hand, for some of the states, it's a no-brainer and to denigrate people for not being vaccinated. That's not the approach either because they're gonna dig in and say, I'm not doing this because you tell me too, right? I think the middle ground is to say, take a bit of both and say, hear the potential issues and hear

Starting point is 03:17:47 the benefits. And this is what I would do. And you have to just decide on your own. I'd leave it to them. I say, you decide. And if you don't want to, you know, it's up to you. You don't have to get vaccinated. And you'll probably get infected at some point. And maybe you'll be okay. Well, here's the best available data. And it looks like the vaccines are pretty damn smart solution. They seem to work. I think you tell people what you did and present both sides calmly.

Starting point is 03:18:15 And I think digging in, you know, as like in a debate, I don't think that's terribly useful. Yeah. So that's my view. I mean, people come to me all the time and ask me What I'm worried what should I do and I say what are you worried about? Let's talk about and go through it calmly and if they want to still take Iver Mech then I said it's fine It's your choice and I'll problem with that. I love that I love that's the way you think people should definitely listen to this week in virology

Starting point is 03:18:47 And follow your work as brilliant. I've been really enjoying it lately. It's like it's my favorite way to stay in touch with the the happenings of COVID. Obviously you put in a lot of other stuff in there, but we used to do other viruses before COVID. It was quite interesting. And I'm trying to slip other viruses in because I think they're informative in many ways and we're going to do more and more of that. But I have to say I canceled usually a record on Tuesday and Friday and I canceled today so I could be with you. You're a huge honor. I appreciate that. No, no, it's fine. I think a couple of other people were going to be away anyway. So,

Starting point is 03:19:23 so I do a lot of different pods. They're all on YouTube, but I also do a live stream on Wednesday nights on YouTube, which you can find. And that's where people can come and ask questions. We don't have an agenda. We just start and by 30 minutes in, there's 700 people with questions that I can't even get through because there's so many of them. And I'm actually astounded that so many people have really good questions. Most of them are reasonable and they

Starting point is 03:19:51 come back every week. So it's a great, it's turning into a great forum to have a nice discussion. And the YouTube channel is called What? So you could search for my name, which is Vincent Racken Yellow. It'll turn up or my handle on YouTube is prof VRR, PR-OF VRR. Have you read the plague by Kamu Bay and Chance? Years ago. Years ago. I have to read it again. That's really relevant. Well, let me sort of ask you a question about it.

Starting point is 03:20:24 It describes a town that's overtaken by a plague. It's blocked off from the rest of the world. It kind of reveals the best, the worst of human nature. It's like how people respond to that. Sort of the encroaching that their own mortality, their own death and the horizon. I think what are the messages in the book that ultimately my love for others. So like a lot of people want to become isolated and they hide from each other, but ultimately the thing that saves you is love, which is one of the things I've just watched in this pandemic, you know, with the distance, with the masks, that's all fine. But there's a distancing from people of that, that, that, that tension, the breaking of the common humanity between people.

Starting point is 03:21:12 That's one of the reasons I, when I came to Austin earlier this year, just to visit, I fell in love with the city because even with the masks and the distance, there were still a camaraderie, like, I don't know, just the love for each other, just a kindness towards each other. And that's why I took away from the plague. Mostly it's told to the story of the doctor who basically gives in and just gives himself as a service to others. And that love is the thing that liberates him from his own conception of mortality. The fact that he's here, he's going to die.

Starting point is 03:21:51 What do you think about this defect of the virus? We talked a lot about biology, but the effect of the virus and the fabric of the common humanity that connects us. the fabric of the common humanity that connects us. Well, that's what a pandemic does. It really cuts that, right? Because small outbreaks are local. They don't have global effects. But when you have something this big, where pretty much nobody escapes,

Starting point is 03:22:20 and not just making people sick, it changes your life, right? People lose jobs, they change jobs, they move somewhere else. They have all kinds of disruptions. Kids can't go to school, really shows you. I mean, I always like to say a tiny virus can bring earth to its knees.

Starting point is 03:22:44 A tiny virus that you can't even see them, that most people don't even think about most of the time. And the real effect is not just sickness. It's what it does to people because in the end, we are animals and most animals like each other and they interact, they have great social structures and that makes them do well. And I guess the exception is people in AI, right? They could be on their own. Well, that's why you build robots that you fall in love with. That's right. And so I think when a real story is what it does to society for sure, which has ramifications

Starting point is 03:23:21 way beyond the number of people dying in the vaccines and the tests and all of that. And this one has really made a big rupture. And you could tell, not now so much, I think, being out and about now things look pretty normal except, you know, for some people wearing masks. You would never know. I mean, the airport this morning was completely jammed. People go in, and they're all in vacation, well, wearing shorts, right? So they're back to normal. It's August. But last year, it's really different in New York, where you're used to lots of people on the street. It was eerie. It was just quiet. But, you know, under at all, people are still, most people help each other when they have to, right? Most people are willing to,

Starting point is 03:24:04 Most people help each other when they have to, right? Most people are willing to, if something happens to someone to reach out and help them, you know, they're always exceptions where people are mean and that's, you know, that's just the way animals are. We're not the only ones that can be mean to our own species. But I think most of the motivation for everything that was done is to help other people. I mean, I do think that the vaccine manufacturers, maybe not the leaders, but the people working in the labs really wanted to get this out quickly and help people, right? Yeah.

Starting point is 03:24:36 I think at every level, people who are contributing really wanted to help other people and feel proud that they're able to do that. So there's, I view it as, you know, we're never going to be 100% good because animals are not evolution made us. I mean, we're lucky. We somehow rose above by having incredible brain and so forth, but a lot of our base instincts are animals and, you know, they chase each other and and have alpha males and all that stuff. And we always have a little bit of that in us. But we do have some humanity that this really ripped up. It really did.

Starting point is 03:25:14 And I think for me, someone who studied viruses for over 40 years, it's just amazing that invisible thing can do that, right? It goes back to the thing you found fascinating, which is a virus affecting human behavior, or behavior of the organism. Yes. So, you know, humans can make weapons and do harm, and you can see that, but this you can't even see. Yeah. You can't, and look what it has done, and it'll do it again. There'll be more, I just, I wish we would be more prepared because we know what to do. We know we should be making antivirals, vaccines, masks, testing masks, making test modalities that we can really quickly redesign.

Starting point is 03:25:59 But after SARS-1, all that went out the door. People didn't do anything. And that's why we're in this situation. So people ask me this all the time, are we gonna be ready for the next one? And I always say, we should be. We have all the information we need to know what to do. But somehow I think people forget. That said, sometimes we really step up when the tragedy is right in front of us.

Starting point is 03:26:28 We do. On the catastrophic. So I don't know. Somehow humans have still survived. The fact that we had nuclear weapons for so many decades and we're still not blowing each other up, whether by terrorists or by nation is quite surprising. That's always after reading the Pentagon papers, it's even more amazing, right? So I don't know how we do it.

Starting point is 03:26:48 I tend to believe it's, there's that, you know, at the surface, you notice the greed, the corruption, the evil, but the core of human nature, the human spirit is one in the scientific realm of curiosity and more deeply is kindness, compassion, and wanting to do good for the world. I believe that desire to do good outpowers all the other stuff by a large amount, and that's why we have not yet destroyed ourselves. There's a lot of bickering, there's a lot of wars on the surface,

Starting point is 03:27:24 but underneath it all, there's this ocean of love for each other. I mean, I think there's a evolutionary advantage to that. And it would be a good explanation why we still have and destroy it ourselves. Oh, we had so many opportunities. If you look at all the wars and history, so many. Yeah. That was just, my son was telling me about the Ottoman Empire, right? I mean, it's just, you know, war after war, and then other countries splitting up countries with no regard to who's living where, right? It's just how can these people do this? Yeah. It's fascinating. Human history is fascinating, and we're still young as a species

Starting point is 03:28:07 We have a lot they're very young. Yeah more time to go and a lot More wasted to store ourselves. Do you have advice? Like you said you have many decades of research and incredible like career and life Do you have advice for young people about? career about life people in high school, people in college of how to live a life that can be proud of? So what I like to do is tell people, don't plan it because I didn't plan anything. Everything I did was one step at a time.

Starting point is 03:28:38 You don't have to plan. I just found things that were interesting to me. So, my father was a doctor, and he wanted me to be a doctor, but I was not interested in taking care of people. I learned that. But I couldn't say no to him, so I was a biology major in college and I graduated and I didn't have anything to do. So I liked science, so I got a job in the lab. And it was very exciting and that led

Starting point is 03:29:13 to everything else that I've done one step at a time. And I think the most important thing you can do, whether two important things, you can be really curious all the time. You mentioned curiosity. I think curiosity is essential. You have to be curious about everything. And if you are, you're never going to be bored. And so people who say they're bored, I say, you're not curious. You should just think about things and say, look at something and say, how does that work or what

Starting point is 03:29:41 is it doing and how did they get there? And you'll never be bored. And the other thing is when you find something which may take time, it's fine. You have to be passionate about it. You have to put everything into it. And that's what I did with viruses. So I think they're amazing. And I tell my classes, I love viruses. They're amazing and people think I'm morbid

Starting point is 03:30:06 because obviously they kill people and I shouldn't love something that, but that's not the point. That's not what I mean. I love them in the way they have emerged and how they work and so forth and all that we don't know about. So you need to be curious and passionate and don't plan too much.

Starting point is 03:30:21 And just find something that you don't call a job because someone said on the live stream last week, I wish I had a job. I like this much as you. I said, it's not a job. I never looked at it as a job. It's my vocation. It's my passion. If it's a job, then you're not going to like it.

Starting point is 03:30:39 Yeah. Something that doesn't feel like a job. So you said viruses are kind of passive non-living you could say or even cells are passive and humans are kind of active. We seem to be making our own decisions. So let me ask you the why question. What do you think is the meeting of this life of ours? Oh, there's no meaning. It just happened. It's an accident. I think there's no life elsewhere because this is just a rare accident that happened in the right conditions. I mean, people all think I'm wrong because there are billions and billions

Starting point is 03:31:15 of stars out there, right? So there's a lot of opportunity. There's no meaning. It's just a, what do they call it, a perfect storm of events that led to molecules being formed, and eventually, I mean, it took a long time for life to evolve, right? But it's just driven by conditions. If something emerged that worked, it would then go on to the next step.

Starting point is 03:31:40 There's no meaning other than that. The only difference is that we, I think many other animals can probably, we have the ability, we're sentient, right? We can influence what happens to us. We can take medicines, right? We can alter what would normally happen to us so we can remove some of the selection pressure. But I think everything else on the planet just goes, you know, looks for food and give a lot of offspring so you can perpetuate. It's just a natural biological function.

Starting point is 03:32:12 Yeah, they're much more directly concerned with survival. I think humans are able to contemplate their mortality. We can like see that even if we're okay today, we're eventually going to die and we really don't like that. So we try to come up with ways to push that deadline farther and farther away. Well, we have really, I mean, we used to die in our 30s, right?

Starting point is 03:32:34 And now it's 70s, 80s. Almost always used to die in the first few weeks. That's true. Yeah, infant death. I always tell people the only thing that's 100% is death. That's the only thing in the world that's 100. Do you think about your own mortality? No, I never think about it. I'm just enjoying day to day. And I don't really.

Starting point is 03:32:56 You work on viruses. You don't contemplate your own mortality given the deadliness of the viruses around it. your own mortality given the deadliness of the virus. No, I never thought COVID would kill me. No, I never was afraid of that, not at all. I mostly feared for other people getting sick, especially people who could die of it and want that to happen to them. But I always thought that it's obviously not a realistic viewpoint not to be worried because many people are. But I've been relatively healthy. They should sequence my genome because it works really well and have a good immune system. Maybe you'd be the first immortal person. I don't think so.

Starting point is 03:33:39 I don't think so. I think that biologically you just can't, you know, the ends of our chromosomes keep getting shorter and shorter, and that's eventually what kills us. So you just can't keep going on, but that's fine. I don't need to. I understand from the vampires, it's not good to live forever. I guess make the most of the time you got, that's the bacteria live a much shorter time.

Starting point is 03:34:07 So we got that on bacteria. Bacteria are just, you know, little bags of chemicals that split. So they have no, they have no stake in the matter at all. It doesn't bother. I think you have to go a long ways before you get into some kind of consciousness. But yes, we're that this bag of chemicals has a stake in the matter. Like our human body is consciousness is a weird thing. Not just in us, but they make half of the oxygen on the planet.

Starting point is 03:34:37 20% of the oxygen comes from bacteria. And they made in the beginning of Earth, they made enough oxygen to start oxygenation, going life, going. I mean, they have an incredible world. There's all in accident. Just happened. Well, Vincent, like I told you, I'm a huge fan. It's a big honor that you were talking to me today.

Starting point is 03:35:00 Thank you so much for coming down. Thank you for spending so much time with me. And thank you for everything you do in terms of educating above viruses, above biology, microbiology and everything else. I can't wait. Everybody should check out Vincent's YouTube, watch his lectures, listen to the podcast, it's truly incredible. Thank you so much for talking to David. Hey pleasure. Thanks for listening to this conversation with Vincent Rakaniello. To support this podcast, please check out our sponsors in the description. And now, let me leave you with some words from Isaac Asimov.

Starting point is 03:35:34 The saddest aspect of life right now is that science gathers knowledge faster than society gathers wisdom. Thank you for listening and hope to see you next time. you

Lex Fridman Podcast - #216 – Vincent Racaniello: Viruses and Vaccines

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