Vincent Racaniello: Viruses and Vaccines | Lex Fridman Podcast #216
the following is a conversation with vincent raqueniello 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 virology 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 as a side note please allow me to say a few words about the coveted 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 two i'm afraid as fdr said a fear itself fear manifests as anger and anger leads to division in the hands of charismatic leaders who then manufacture truth in 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 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 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 raqueniello 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 this is the lex friedman podcast and here is my conversation with vincent raqueniello you mentioned in one of your lectures on virology that there are more viruses in a liter of coastal seawater than people on earth in the nature article titled microbiology by numbers it says there are 10 to the 31 viruses on earth also it says that the rate of viral infection in the ocean stands at 10 to the 23 infections per second and these infections remove 20 to 40 percent of all bacterial cells each day there's a war going on do you uh what do you make of these numbers why are there so many viruses so the the numbers you're quoting they're in my first virology lecture right because people don't know these numbers and they get whoa they get wowed by them so i love to give them so the way they decide to interrupt as i was saying offline you have one of the best introductory lectures on virology that i've ever seen introductory lectures period so i highly recommend people find you on youtube and watch it if you're curious at all about viruses it it um yeah there's a lot of times throughout watching it i felt like whoa yeah that's my goal is to and that's what my students tell me one student once said i every day after every lecture i could go home and tell my roommate something she didn't know yeah and 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 on the planet including bacteria there's a lot of bacteria in the ocean and so 10 to the 31 is from basically particle counts of seawater all over the world so they're 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 end 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 they start to sink and then they get metabolized and converted to compounds that 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 it's so wild that nature has developed a mechanism for mass murder about 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 like such fast cycling of life is is it just an accident of evolution that viruses are so numerous or is it um is it is it a feature not a bug so the the fast is it rain it does not all fast not all viruses are fast some are 20 minutes per cycle some take weeks per cycle um but that's just per second 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 billion 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 that's tough because rna is pretty fragile in the in the world and um it probably didn't get very big as a consequence 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 even bacteria and single celled 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 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 tement co-discovered and that that enzyme arose and copied rna to dna and then you could build big cells with because dna can be millions and millions of bases in length and rna the the longest rna we know of is 40 000 bases not much bigger than the sarsko v2 what would you say is the magic moment along that line i saw it was uh one or two billion billion maybe three billion years it took to go from bacteria to to like complex organism like it seems like earth had a very long time like not a very long time without life and in a very long time with very primitive life um maybe i'm discriminating calling bacteria affirmative life yeah but people would object to you yeah doing that for sure but it seems like complex organ when you start becoming something like um i don't know what's a good uh not animal like but more complexity than just like a single cell um what what do you think is the magic there what's the hardest thing if you're trying to engineer earth and build a life and build the simulations obviously we're living in a video game what this is so if you're trying to build this vehicle what's the hardest part about long-term evolution 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 you know we have skin cells and eye cells and brain cells and bacteria never do that and the reason is probably energy bacteria don't 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 today it was all about energy so the mitochondria the energy uh the mitochondria is the magic thing i think so it's actually not my idea it's nick jones have you heard of nick jones he's an evolutionary biologist in the uk and he's 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 bacteria inside of a bigger cell and that becomes what we now call eukaryotes and uh that they can get more and more complicated so let me bring you back to the viruses i want to finish that story yeah which points the viruses come along so remember we have these pre-cellular they're called pre-cellular replicons right and so we have a pre-cellular stage where we have these self-replicating molecules and cells arise and then the self-replicating molecules invade the cells why because it's a hospitable environment and 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 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 like it's easier to sort of break into somebody else's thing and steal their proteins yes my colleague dixon de pombiere calls viruses safe crackers safe crackers so it's just uh from an evolutionary 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 from crack in the states 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 uh but these numbers are crazy so what as these more complex organisms evolved let's take us humans as an example uh should we be afraid of these high numbers should we be worried that there's 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 and caused disease throughout history but we're also you and i are full of viruses that don't hurt us 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 has multiple viruses infecting 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 could actually you can actually take your feces and send them to a company and they will sequence your viruses in your feces for you your fecal firearm 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 in 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 species that are closest to us mammals of course i and i think the most numerous ones are the most concerning they're 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 it there's a proximity in terms of just living together in a proximity genetically to so it's more likely that a virus will jump from a bat in the road and birds too birds can give us their viruses that's happened you know influenza viruses come from birds mainly so i think those are the three species not species it's higher than species obviously but those are the three i would worry about in terms of getting their viruses and we don't really know what's out there right we have very little clue about what viruses and i've for years wanted to capture wild mice in my backyard and see what viruses they have because no one knows wait and it's you can't ask them so you mean map uh like is there a way to ask them yeah no i have to would have to sacrifice them and take tissue and then bring it in the lab and do genome sequences so you can do a thorough sequencing to determine which viruses is there a sufficiently good categorization of viruses where you'd be that's a very good question 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 with 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 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 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 too i don't know if you've been paying attention to that well the them uh 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 yeah so on the side of because you make you're saying there's dark matter right is there something um what first what are your general thoughts level of excitement about their uh 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 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 and right now it's just a bunch of amino acids but if we could fold it maybe the fold would recognize like something we already know some protein fold which gives you a lot of clues right 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 and that was the first one done 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 it depended on getting crystals of the virus right and now we can do cryo-electron microscopy which is much faster you could solve the spike of sars cov2 was solved in two months by by jason mcclelland 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 out without having to do all the experiment so that's why this is very exciting that yeah you can predict it i mean it's not finished obviously and there's more to do but i think it will be a day where you could take any amino acid sequence and predict what it's going to look like see but yeah like aren't structural biology is going to get greedy so once you have that don't you want to go more complicated then don't you want to go because that's 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 you solved proteins for them and then you moved on to another one you didn't really do any experiments the other people got to do all the interesting experiments right 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 it blocks binding to the receptor this must be the receptor binding interface so that's the exciting stuff absolutely is doing the experiment i wonder if you can do some kinds of like simulations of like you know different proteins or multi-protein systems going to war against each other like to try to figure out you know reinforcement learning is used in alpha zero for example 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 us for primitive biological systems have them in stimulation fight each other and then 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 cov2 arising right which which look 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 what is the antibody looking at you 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 and go back and forth between the antibody and the virus so all these evolution is is what we call 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 a an enzyme that makes it resistant to a drug and predict all the drug resistance but but the problem 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 oh with other humans we do that we do that okay but with people from a field that we're 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 problem is there a way we can use your tools to attack it the problem is those people are anti-social introverts that that have a place like this and try to hide from other people in the world very difficult to find in the wild um okay so outside of doing amazing brilliant lectures online you host and produce five i would say related podcasts including my favorite this week in virology also this weekend 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 kill us humans let's let's look you said like most viruses are friendly or at least not unfriendly right but let's look at the unfriendly ones and 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 the big picture is that the things that can kill your minority of everything that's out there and we're talking about molecules so we have in us proteins that can kill us yeah prions that are just it's a protein in us and if it misfolds it makes all of its other copies misfold and then you you die of a neurological disease yeah that's pretty rare um so there are proteins there are viruses and 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 sarsko v2 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 other viruses but it doesn't happen all that often 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 this it's a limited number right your streptococci and staphylococci and clostridium we could go on and on but we know how to handle those as long as we have antimicrobials 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 submicroscopic or just at the microscopic level they can you know in 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 we do this week in parasitism where single cells even worms of various sorts can invade you and cause all sorts of problems how um i was like kind of terrified to listen to that podcast what uh what's it like i mean 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 has is infected most of the world actually because a lot of people like to eat raw meat and you would get it from from raw meat and we're not as fond of that here in the u.s 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 toxoplasmosis it's mainly a big issue is if you're pregnant and you get toxo then your fetus is going to be very badly malformed it's going to 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 week in parasitism we do a case so daniel griffin is a resident physician he's a doctor a real doctor right and he 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 just somewhere southeast asia or something and she ended up with with with red bumps all over her skin it turned out was a parasite from the fish that moved around in her and and they're very easy to cure we have you have to write doctors and the right drugs you can cure all these what about diagnose like connect the red spots to the fact that it's a parasite it's 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 so there are a lot of parasites puzzle and solvent 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 that if you go swimming they can invade you and in fact it can go into your hair follicles and burrow in and get into your bloodstream that's exciting so um daniel is interesting because he's very adventurous he doesn't he's not afraid of any of this so there's a famous lake in africa lake malawi where 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 yours get rid of them and that was the name of an an episode but you know food vigorously you know sushi you can uh you can get worms from sushi yeah 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 oh wow except you see a big industry yeah that's brilliant that's brilliant yeah um i i was thinking about you know i'm so boring and bland that especially when i am now in texas here and i've been eating quite a bit of barbecue i realized i 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 uh 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 good advice for eating in uh 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 but that's so boring yeah it's unfortunate and 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 just make sure everything is cooked 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 oaxaca mexico stayed in a hotel and he said to dan he came back with diarrhea and fever and he said 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 he got something from that the bottom line is most of these 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're gonna 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 it's different from everything else on the planet um because first of all it's a parasite it takes a parasite means you take something from someone else you know 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 there's never really a symbiotic relationship between a virus and a host well there 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 easier for us to study that not necessarily represent what's right yeah right like uh like pluto was a planet at first and now it's not a planet anymore and a lot of people are 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 uh calling them parasites so right now our definition includes parasite because a virus cannot do anything without a cell if i 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 it needs cells and you know to the first people who discovered viruses that was astounding that they didn't just reproduce divide on their own like bacteria so a 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 of all kinds of molecules and processes and energy and so forth to make new viruses 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 particulate phase that everyone is used to yeah 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 yes you have to go with all this other stuff yeah well these are all mechanical there's no biology here so you wouldn't want a virus here no i'd want to buy of course i'll send you one and look at that you can look at it because now that we have the three-dimensional structures solved by structural biologists we take the coordinates so we put it in a 3d printer and you can make amazing models right of any virus and so there's a huge variety of viruses huge that we know of yeah which is only a fraction of what's out there what's the categories so there's rna there's dna viruses what what are those what's dna and rna two two broad categorizations rna and these are genetic material it 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 they're old-school these are we call relics yeah they're relics and this has got a name it's called the rna world which i think is great is it big still or they are the relics dying out oh no the relics in my opinion are the most successful viruses the rna viruses and the source cov2 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 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 they don't get the news like the rna viruses do the hivs and the influenza viruses and the um sars coronaviruses they get all the press and they're rna-based because rna lets you change more so than dna so they they've evolved much faster rna viruses much faster and in fact when i i have an electron evolution i don't know if you've listened to that one 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 don't extinct 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 uh that's that's the reason why rna viruses are far more successful they infect many more hosts and they're very i would say slippery they can change hosts really quickly because in any animal harboring an rna virus like let's say a bat in some cave somewhere it's not just one genome it's it's millions of different genomes of all kinds with 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 i mean that's the thing that well there could be a large number this is a tiny fraction but a large number of uh of them and they're all operating at the at the threshold of error that's right that's fascinating it's like a little like uh it's like startups little entrepreneurs like a startup world yes and many of them fail yeah many of the changes and then there's the dna of ours that are like the ibm and exactly exactly big corporations it's very good conservative with the bureaucracies and all that kind of stuff so there's a lot of baggage yeah yeah it's expensive for them to reproduce yeah and they don't move quickly yes the rna viruses are the fast-moving members so that's what a virus is we call them obligated intracellular parasites and then i told you there's dna in rna but then let's go further the the nucleic acid is not naked because naked nucleic acid in the world isn't good i mean it it existed in the in the pre-cellular world but there probably weren't a lot of threats to it then naked nucleic acid doesn't last long in the environment so they're 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 uh lipids from the host cell so lipids so it's a fatty membrane fatty membrane yeah so our cells are coated with fatty membranes right our cells the outer plasma membrane right that's the same viruses can be too so they're kind of like cells but without the ability to do the mitochondria stuff some some are some they don't have nuclei they don't have mitochondria yeah but they do have a nucleic acid they have a membrane and then of course there are 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 attachment mechanisms like ways to like keys into the into the city they all have to get into cells there are there are a couple of exceptions though uh there are viruses of fungi uh and uh plants so let's do the fungi fungi would be like yeast the virus 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 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 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 yeah the virus binds to something on the surface very specific 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 frozen horse it's so hard to not anthropomorphize this whole thing it is hard so obviously they don't know any of this it's not an actual trojan horse so that they they're not getting actually tricked in the way humans trick each other no it's all passive and it's just through so many years of evolution it's you select something that works and it continues and what survives then goes on with the uh perhaps a slightly different approach i love this idea of past of course according to sam harris uh so from a sufficiently intelligent alien civilization observing humans our behavior might seem passive too because they understand fully exactly what we're doing and then there's no free will and we're all just operating in the same way it could be a cell does which is a much higher level of complexity yeah so i love the distinction between active and passive i mean the point is i think anthropomorphizing to 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 variants emerging and people say well i think it's because the antibodies are selecting for variants that's a good idea but it may not be the only thing that's going on you start imagining them coming to the table negotiating yeah you get into trouble with that that's right that's why i tell my students be careful about the anthropomorphizing because you're going to 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 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 it as a machine and to me that makes sense in one in one way but it totally doesn't make sense in another if that robot is to interact operate in the human world and interact with humans we have to 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 operations is much smaller but with robots you're on the same sure time scale the same spatial scale of course in the movies they always give them names and personalities yeah well yeah that's the move but that's my argument is we should do the same when you're trying 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 uh viruses are not living um defend yourself so are viruses alive or not so i've seen many people say oh they have to be they they have nucleic acids 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 infected cell is alive i totally agree with that because in fact when a virus gets in a cell it converts it into a virus making factory if you will it'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 as alive but the particle it just would not do anything forever without getting inside of a cell well once it's in the cells it it is alive then but it's no longer a particle it's taken apart and nucleic acid is moving around the cell it's making proteins eventually it makes new particles and then those particles released from the cell 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 just 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 then it 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 on its own but if you think of a virus as an organism with a particle phase and 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 so right membrane and not that that's that's been called what is a viron particle or something so what you should have here i'll send you one and then you can refer to what's the sexiest one to have like what what in terms of particles to have on the table well unfortunately the ones that you can 3d print oh they're not going to be so they're they're only they're the ones that we know the structures of right so someone sent me last year a 3d model of source cov2 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 antibodies sticking onto the spikes and that's i mean when i show this on a live stream people love this thing oh my god that's beautiful it is it's absolutely gorgeous i have that 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 of all the viruses you looked at sometimes when you just sit late at night with a glass of wine looking over the sunset which virus do you think about so fulfilling all of those adjectives is hard right 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 where we can handle it from a virology perspective yeah i mean the human perspective is a different story right that's always an issue but um so i i think there are a couple of different categories of virus so we could do the 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 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 you know eventually you get all kinds of neurological issues and paralysis and so forth 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 it will 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 uh rabies is a good example oh rapist is great because everyone knows what happens when somebody gets rabies right you have fear of water hydrophobia your body becomes and stiff and jerks around and you lose consciousness you can't no no more 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 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 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 three 250 300 million americans that's hard but yeah the the the few thousand every year is easy so the transmissibility is difficult right it has to oh it's not it's not airborne so now you're bored it just has to be you have to be bitten although 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 yeah i think it's a bike 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's caves everywhere right yeah he said well maybe you could just go and aerosolize that yeah it's pretty dangerous and then and then all the bats should have vaccine passports to make sure that they're yeah so you have to get their consent before you do it but you we do immunize wildlife against rabies we have rabies vaccines for wild animals there are a whole bunch of them that get rabies and we put it 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 get bitten and so forth it drops the incident so we can do that i didn't know that i always wondered how much medical care are we doing for animals in the wild because i've recently become more and more aware that animals are living in extreme poverty right like you don't know you think like natural it's great um you know like uh like when animals are living on a farm it's terrible but then you also have to compare to like what life is like and or like the zoo you have to compare what life is like in in the wild 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 yeah right and then there's the viruses there and viruses as well so the rabies immunization is the only one i'm aware of for wild animals um we do immunize lots of other animals we immunize chickens and pigs and cows even fish farmed fish we pick each fish up and give it an injection you know 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 immunize animals to prevent spillovers into people so there's a disease called hendra in australia which was discovered in the 90s it turns out that there are bats fruit bats that have this virus and the bats are fine but sometimes they flying into horse stalls and the horses get infected these are in australia it was initially race horses which are very expensive right the horses got 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 to save the horses probably that's the motivation because these horses are hundreds of thousands of dollars 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 something some living beings in the arabian peninsula they have a mers coronavirus issue every month 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 very much like covid and so camels are very common there they're used they're raced they're used as pets they're eaten so there's a lot of human camel contact but the number of cases are rare two 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 uh also is a famously deadly one right what is it it kills like i don't know 50 60 percent of it could be 50 to 90 but that's in africa where the health care isn't great what you saw when they when cases of ebola came to the u.s we were we could take care of it we knew how to take care of we had fancy hospitals and 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 that are suspicious of of us and they don't want to use our vaccines so that they so there's a vaccine for ebola there is yeah and uh the effectiveness and safety of it to how much is understood so this is difficult because there's not a lot of ebola right 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 pre-clinical 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 in fact for 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 to test the 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's it looks like it's it has high efficacy um but we'd like to have more data side effects may be are not so great there are a couple of different available vaccines some have been tested more than others i would say this would probably not be widely accepted in the u.s but then neither would be something over 50 uh deadliness of a virus no i think if you are 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 um so so then one more thing to answer the interesting 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 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 behavior altering because somehow the virus infecting the plant cells gives off these organics and it contracts 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 repulsed at the same time 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 darwin famously said he could never figure out how an eye evolved from a single cell right but it did the more complicated complex the 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 um 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 to test it right we have to observe and that's always hard when you're observing because there's so many things that can confound what you're looking at change human behavior yeah i mean there's so many things that impinge on our behavior but um yeah it's i think it's possible um i think it's highly possible if it does it in a plant why not change some other organisms behavior i think it's fine anyway those fascinate me 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 uh work moving forward well is there if you understand some of those viruses is that transferable to human viruses that understanding i think some of it could be sure i think the general principles for example how the 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 is just wrong 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 why people like you can criticize uh why do we want to go on mars why do we colonize mars well it's like why do you want to go to the moon the the reality is when you do really difficult things yeah engineering things like all these inventions along the way are created it's kind of fascinating how basically just pick a pick a thing that everyone can agree it's kind of cool and it's really hard and do that and then you'll have like thousands of inventions that have nothing to do with the thing that's right i think you should let curious scientists just follow what they're interested in to a certain extent you can't 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 here you're you have a good lab you have a good track record here's some money or something and that's where pcr crisper recombinant dna all that stuff which has made the field explode that's all it came from not from people saying i want to cure genetic diseases by gene editing but by saying what are these repeated things in this bacterium doing yep can ask you a big philosophical question so there's these deadly viruses they're not very transmissible ebola rabies and then there's these less deadly viruses that are very transmissible um like uh like covid is i guess kind of borderline but uh why isn't there super transmissible super deadly viruses i think if you compare stars one and two you get somewhat of an answer right sars one 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 in the hospital so it's easy to contain uh the infection when you're in a hospital right there was not much pre-symptomatic or asymptomatic shedding with sars1 and shedding means you you're in you become infectious so in a respiratory virus you're you inhale the droplets with virus and they they reproduce 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 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 others and if one happens to knock you out then you're never going to transmit because you're in the hospital like sar as one but why can't you have both why can't you just wait a while before he knocks you out but when it 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 one issue is that if you uh 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 the doctors and nurses get virus but people walking around you're not walking around when you have ebola you're too sick you know you have black bloody diarrhea you're vomiting you're you're bleeding from your skin and mucous membranes you're not walking around not going to parties so i think that's part of it that if 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 of ours always has to have find a new host if it doesn't it's a startup 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 pressure against being lethal i think there's a strong selection of 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 brought in this european rabbit and they they reproduced out of control within a couple of years they were everywhere millions of rabbits and all the watering holes 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 let's uh release this virus and the first year 99.2 of the rabbits were killed but that point eight percent that were left had some form of resistance they were variants you know 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 it evolved to be more transmissible and less uh lethal so that is amazing that's the only data that's amazing it is it is if you take the time to look at it and see what's happened 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 that we're not really i mean viruses are wrecking it some way it's 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 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 at the 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 and started gathering in big cities yeah but now that humans are able to communicate and travel globally the viruses become more and more dangerous transmissible thereby 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 uh the virus is becoming super dangerous and threatening all of human civilization will force it to become a multi-planetary species and this organism starts expanding so i think it's a feature not a bug i don't know um well i think that we have our early probably the most of the when we're studying viruses since 1900 right most of that time was because of diseases they caused the first viruses discovered yellow fever virus smallpox poliovirus influenza virus those were all because people got sick and they said oh look this is a virus that's associated with it and so we got good at learning how to take care of these infections 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 covin-19 virus sure i don't know what your preferred name is but well right the virus is cov2 which is hard it's long right and then covet 19 is the disease so you could say the virus of covet 19 that's fine it's a virus of cova-19 but for the purpose of this conversation we'll every once in a while i'll just say kovid it's fine no problem what is this virus from uh i don't know how many ways we can talk about it i think from a basic structural like the the varian 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 corona virus 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 the place with the highest cereal positivity in the u.s for a while 68 was a working-class neighborhood in new york city called corona can you can you beat that right that's crazy yeah so coronaviruses they have membranes right we talked about membranes they have spiked 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 thirty thousand so sars cov2 rnas thirty thousand bases of rna and some of the other coronas are even longer 40 000. this is a coronas our family of viruses that included the what the the one you mentioned before version one cesares kovi one yeah kobe one and i guess other ones so the first we first learned of them in animals a lot of animals pigs and uh cows and horses have coronaviruses and then uh in their 60s we discovered a couple of human coronaviruses that just caused colds very mild colds that you wouldn't even think twice about right and then suddenly in 20 2003 there's this outbreak of severe respiratory disease in in china and you know they it started in november and they 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 it what they did afterwards is they said okay it looks like it came from the meat markets they have live meat markets in guangzhou in the south of china where you can go and pick out an animal and the guy will 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 civ 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 saurus one and that was 2000 and well i would say took about five eight years after that outbreak so that was the first hint that bats have coronaviruses that can infect people and cause problems right and after that we should have been ready so didn't they already start developing vaccines yes so some people started making vaccines they tested them in in mice but they never got into people and some people started working on anti-viral drugs nothing ever came of them you know industry there's no there's no disease it's gone why should we make vaccines and drugs and nih in the u.s you submit a grant and they say it's too risky there's no none of this virus around so people were really short-sighted because i always say we could have had antivirals for this absolutely yeah for sure no question in fact one the one antiviral that's in phase three it's called molnu pyravir 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 it could have been ready so we dropped the ball and then the next decade 2012 mers coronavirus comes 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 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 where sars one could not it's a coronavirus you know it's different enough from sars one that it has very different properties but it still has a membrane 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 little unique things that make it that much more effective to make it cause a pandemic of millions of people as opposed to sars one yeah well the genome is 20 different from source one say and in those bases there's some there are things that uh make it different from soros one it binds the same receptor ace2 on the cell surface so that's remarkable it has a lot of the same proteins they look similar like if you look at the structure of the spikes they look similar but there's enough amino acid differences to to make the biology 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 the animal models aren't great you know for for 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 difference 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 you need uh first you need an animal of some kind to infect right you can use mice people have used ferrets guinea pigs non-human primates all of the above and non-human primes are very expensive so not many people do that um and then you can put the virus in the respiratory tract but in fact none of them get sick like people do you know many people with with kovid get a mild disease but 20 percent 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 several animal models ferrets are really good for transmission they tend they have nasal structures like humans and they you can 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 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 change dna any way we want we could change a 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 the moratorium on recombinant dna experiments on viruses 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 poliovirus it's only 7500 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 and many many bacteria make lots of them and purify the dna really easily and i took that dna and i i sequenced it because we wanted we didn't know the genome sequence of polio at the time and that took me a year by the way because the techniques we had were really archaic and nowadays you could do it in 15 minutes right it's amazing and i took the dna i 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 source cov2 you make a dna copy of any rna virus you can modify it and you put it back into cells and you'll get your modified virus out so that's an important part of understanding the properties of the virus as say in an animal by changing the virus you're changing a dna copy you're making the virus then and putting it into the end can you clarify so even in the rna virus you can take and turn it into dna yes and then that allows you to modify it yes what's that what's that uh mapping well no no what's the process of going from rna to dna reverse transcription that's reverse transcription right oh so you actually go through the the process of reverse transcription to do this yes oh remember david baltimore and howard yes had 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 paul 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 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 and ask questions about what things are doing right what's this gene doing what if we take it out what happened can you do the same thing with uh kovid uh is it takes rna and then of course and in fact in january 2020 as soon as the genome sequence was released from china the labs all over we're synthesizing this 30 000 base dna and getting what can you figure out without infecting anything just uh turning into with the reverse transcription turning into dna modifying stuff and then putting it into a cell what can you figure out from that oh 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 or maybe you take the g now and you never get any virus so it's lethal is there a nice systematic ways of doing this do people kind of automate it absolutely and we i mean the problem with sars the covid virus is it's thirty thousand basis a lot of stuff there yeah and what makes it more difficult is that you have to it's been classified as a bsl3 agent biosafety level three 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 some we were 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 a have to have special procedures and containment and so forth so it makes it difficult to do basic experiments on the virus but well it's a pandemic there's a lot of money there's a lot of incentive to work on it harder and also 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 if uh 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 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 low concentrations in in a virus-infected cell so it's easier to inhibit them with a drug and the coronas have couple of enzymes that we can target so it's you have to figure that out ahead of time and decide what to go after and then you can look for drugs that inhibit what 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 um 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 uh you you get inspired here's a mechanism of incredible complexity that works really well is very robust it's very effective efficient it inspires you to come up with techniques that you can engineer in the machine so that's that's the what drives a field forward when people improvise and come up with new technologies that really make a difference we have we have a bunch of those now what's the difference between the coronavirus family and the uh the other popular family influenza virus family is um 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 coronaviruses 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 uh or hurt us really badly i don't know if you agree with this sense but maybe maybe you can also just clarify what to use the is the difference between the families so it's an interesting difference they both they both have membranes right so then they have spike proteins embedded in them for and they're different spikes in fact for influenza there are two main ones they're called the h a and the n a 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 could have plus minus 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 on to 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 and then the plus minus is both together so the sars coronaviruses all the coronaviruses have plus rna so as soon as that rna gets in the cell boom it starts an infectious cycle same thing with poliovirus by the way which i worked on influenza viruses are negative stranded so they cannot be translated when they get in the cell so that that's tough for the virus because the cell actually cannot make plus rna from 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 it's a big difference and then in the influenza viruses 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 it 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 and out can come a virus with a new assortment 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 is because somewhere in some animal two viruses have reassorted and made a new virus that we hadn't seen before so so you're you're you're talking about kind of biological characteristics but what am i incorrect in my intuition that or from the things i've heard that the influence of family viruses is more dangerous like what what makes it more dangerous to humans well it depends on the there are many flavors or vintages of influenza virus some are dangerous 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 viruses we had a pandemic in 2009 of influenza and 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 is that the bird flu one they're all they're all deriving that one was called swine influenza swine it seemed to it started in a pig but it had bird it had rnas from bird influenza viruses these viruses are all reassortance of different viruses from pigs and birds and humans um but influenza can cause pneumonia and can kill you as does sorrows covey too so it depends on the 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 and that's more lethal and depending on the 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 well because every shore bird in the world is infected with them you know gulls and turns and ducks and all sorts of things why can't we develop strong vaccines that defend against oh we could do that sure um but that would not eliminate them right 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 but you then you said like even if you had the professor 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 the way the first influenza vaccines were made was actually jonas salk worked on them in the 40s you just grow lots of virus and you grow it in eggs by the way chicken eggs nice literally wait wait yeah chicken embryonated so they get fertilized and there's a 10 or 12 day embryo in it and you put virus in it it grows up and then you harvest it you get about 10 ml of fluid and then you take that you treat it with formaldehyde or formalin 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 it was made for the the us army actually and then it got moved over to people we still use that old school tech today so you're 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 it's very funny that you put in an egg it's very um it's very poetic and then uh how do you make it not um infection uh not effective or whatever not infectious not infectious is that the right term here yeah so how do you make it not infectious you can treat it with any number of chemicals that'll disrupt the particles so it no longer so that that step of disrupting the particle is that very specific to any a particular variant particle no the same collection of chemicals you can use for all kinds of action and which have been used for sars cov2 vaccines also same technology okay so what are there's several things to ask so you called it old school in a way that's uh slightly dismissive like people talk about windows 98 or something uh so there 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 i mean you could do it in cells and culture but eggs were convenient and in the 1940s we didn't have cells in culture we didn't know how 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 not the best vaccine you can make the flu vaccines that we have today which are mostly based on this inactivation this is called inactivated virus vaccines oh so like the kind of uh thing it presents to the immune system to train on not right it's not it's not it's 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 which is not really good what does it mean what is the measure of efficiency for a vaccine well it's 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 sick give us a call we'll tell you so uh yeah i mean what's what's 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 okay so the sign is something that someone could measure and tell that you're infected like a virus in your nasopharynx or something else right signs and symptoms 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'd probably be fever sore throat cough you call them and then they will do a pcr make sure you 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 um the reporting so symptom is what you feel yes 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 uh looked down upon to to feel sick or something like that like toughen up kind of thing yes and so then you probably have very few symptoms being reported absolutely and then absolutely and now is like much more um i don't know perhaps you're much more likely to report symptoms now it's fascinating 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 so when you're doing this it's a little bit of a imprecise science because in in and even it's a cultural thing in 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 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 et cetera yeah i mean i was trying to figure so i took two shots of the fisa vaccine i had zero symptoms wow so and i was wondering well see but that's my feelings right this is not because i i felt fine i was waiting did you have pain at the injection site uh no it was kind of pleasant yeah you felt nothing the next day no nothing okay no no no tightness no exhaustion no um but see like i have an insane sleeping schedule i already put myself through crazy stuff that said maybe i was expecting something really bad like i was way and therefore didn't feel it then but i also got um allergy shots and those i was out all next day like exhausted for some reason so that that gave me like a sense like okay at least sometimes i can feel shitty that's good to know sure and then then with the vaccine it didn't but the the question is like how much does my mind come into play there are the expectations of symptoms uh the expectations of not feeling well how does that affect the sort of the self-reporting the symptoms i think it's definitely a variable there but um there's certainly many people that don't feel anything after the vaccines and there's some that have a whole range of things like soreness and fever etc yeah so okay you were talking about the old-school development inside the egg right what's uh what's what's better than that what's what so then the next generation of vaccines which arose in the 50s were what we call replication competent where the virus you're taking it's actually reproducing in you yeah that sounds safe and it can be somewhat problematic yes as you might imagine because you know 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 like nano nano bots what composition no you could just put something in there if you added a drug you would do it shut it off right and people are thinking about that because now we're engineering viruses to treat cancers and other diseases and we may want to put kill switches in them just to make sure they don't run away oh interesting so you can like deploy a drug that binds to the this 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 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 who 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 and just kept passing it did that hundreds of times and every 10 passages he would take the virus and put it in a 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 fever vaccine that we use today he selected for mutations that made the virus not cause disease but still make an immune response wow so those are called replication competent we now have the polio vaccine which was developed in the 50s after the yellow fever then we had measles mumps rubella those are all replication competent vaccines and you mentioned is that's 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 because you take it orally it's a wonderful because you don't have to inject it this is the perfect delivery you know either intranasal for a respiratory virus or orally for polio goes into your intestines it reproduces and it gives you wonderful protection against polio however you do shed virus out and that virus is no longer a vaccine it's reverted genetically in your intestine so you can infect others with poor 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 got 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 vaccine there was a big fight in the u.s and other countries between the inactivated polio and the and the infectious polio vaccines which ones we should be using because we found out that the infectious vaccine actually caused polio and 8 to 10 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 are we're close to eradicating polio globally but this vaccine derived polio is a problem so now we have to go back to the an activated vaccine which is tough 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 that's right 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 we can make mrna vaccines right what's what are the modern ways i did you want to look uh mrna vaccine that's so 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 vectored vaccine and some of the covid vaccines are vectors of different kinds of most famous or adenovirus vectors carrying the spike gene into the cell can you explain how the vector vaccine works again so we have we take a a virus that will infect humans but will not make you sick in the 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 uh you you actually genetically modify it yes you modify the vector yeah so you'll be much more precise about it 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 then you make an immune response and vector is the term for this modifying right so we're now using viruses at our bidding 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 a mutation in a gene a single gene we can give you the 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 affect all your other cells but it takes time to develop a vector for a particular thing 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 vesicular stomatitis virus which is a cousin of rabies but doesn't make people sick influenza viruses being used as a vector and many even measles virus so we're familiar with how to modify those to be vectors and those are being used for for covid vaccines and then of course we have the 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 and in fact there's there are no human licensed 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 can you clarify uh does a dna vaccine only work for dna viruses no it can work for dna or rna 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 just essentially you get you get proteins 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 a number of years ago people started thinking how about rna rna vaccines and i first heard this i thought 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 it's 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 they're doing experimental mrna vaccines and there are 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 uh as we're saying offline one of the great things about you is you're able to say when you're wrong about intuitions you've had in the past which is a beautiful thing for scientists uh but you know i still think it's very surprising that something like that works right yeah i am surprised so you're just 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 for the uh in its structure but then um the the other thing is why does it work that that that's a good training ground for um for the immune system is that is that obvious i don't think i don't think it's obvious to most people and it's worth going into because it's really interesting i mean first of all they they wrap the rna in in fats in 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 covet vaccines right moderna and physio they have different lipid 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 coding and they test to see how long they protect the rna after it's injected say into a mouse how long does it last and the way it works is these apparently these lipid nanoparticles 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 mem 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 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 was yes it was just let's try it and it worked so 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 like the virus has a specific protein that attaches to a receptor right 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 to get more efficient uptake but it's not as efficient as a virus would be to get into a cell you have no specific i mean which is why it's surprising that uh you can crack into the safe with with a hammer or with some fat i mean that's a that's kind of surprising it's kind of amazing um that that it works but so maybe let's try to um talk about this 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 but it's the scientific community because it's like it's a it's a cool new technology surprising that it works what's your intuition i think one nice way to approach this is um 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 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 this is 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 then 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 else could happen well the 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 lasts perhaps at the best a few weeks now this is a protein that's made after the 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 made and there's also a question i'm sorry to interrupt where where in the body so because it's not well targeted or i don't i don't know if it's supposed to be targeted but it can go throughout the body that's one right so it's injected deep into your deltoid muscle right your shoulder and the idea is not to 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 it's locally injected and they did before this even went into people they did experiments in mice where they gave them a thousand times higher concentrations than they would ever give to people and then when you do that it can go everywhere basically you can find this these nanoparticles in every tissue of the mouse but that's at a thousand-fold 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 small amounts go elsewhere could there be a lot of harm caused if it goes elsewhere in like let's say ridiculously high quantities i'm trying to understand what is the damage that could 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 a protein 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 you 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 right 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 and that's how the rna gets out of the particle but so wait uh i'm a bit confused so with this mrna vaccine with the lipids and the rna there's no spike right the the mrna codes for the spike oh the mrna codes so it creates the spike it creates a spike 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 this is so they could modify it so now it's not going to cause fusion so that's not an issue it's called the pre-fusion stabilized spike um the spike when it binds ace2 that 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 right right and doing phase one phase two and phase three in increasing numbers of people and asking what do we see do we 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-barre you see those relatively quickly um and we've seen small numbers of those occur but um other things we haven't seen and you know you you never say never right right so i mean this is fascinating right it's like uh i i drink uh i put splenda in my coffee and has supposedly uh no calories but it tastes really good and i this despite what like rumors and blogs and so on i have not seen good medical evidence that is harmful to you but it's like it tastes too good so i'm thinking like there's got to be long-term consequences but it's very difficult to understand what the long-term consequences are uh like that 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 got to be 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 about near-term effects that you want to uh uh remove like 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 uh 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 but in general in science about making statements about long-term uh negative effects is that something that weighs heavy on you is that something we can kind of escape through just large-scale experimentation with human 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 right is 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 50 years and and then decide but i guess what you're doing is you just like we said um i forget with which one with polio with rabies i forget but you're weighing the side effects yeah the vaccine versus the effects of the virus 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 there's a huge number of people like um 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 in this basic studies we start to build up an intuition of what might be a problem down the line and what is not biologically speaking and so given that map you then 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 right so the cognitive stuff that's terrifying all kinds of systems of autism yes and then you look at the same thing with the vaccine 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 and we have 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. and immediately within months 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 going to forget something although i think a lot of people today don't don't aren't aware of that i think that was a big problem that's everlasting 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 and i have to say i was involved in several lawsuits where parents of a kid who got paralyzed from the polio vaccine decided to sue the manufacturer and get some some money for their for their kid and so they got mad and and i think you could not 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 aren't they're not long minority of cases this minority this is a very rare event yeah but nevertheless science is an institution uh didn't make corrections in that case no they didn't so what do you 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 yeah and most people don't know about those stories i tell them to you because that's what could happen i think it could happen today if you look at the history of the the polio vaccine the u.s public health service wanted kids to be vaccinated so they did things that probably weren't correct to get the vaccine back online right but they they did it and they pushed it through um so where 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 covet of any kind because i've seen how nasty it can be and i decide i'm taking the risk whatever small of a long-term effect i'm going to take the risk my family took the risk and many other people did of a vaccine of getting vaccinated because i think it's very small but i understand where people can't make that decision 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 going to know for 40 years yeah so i think if i were to speak because i suppose as 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 the uh long-term effects like on paper it's more about the the ins like um people like anthony fauci and people at the top are simply misrepresenting the data or like are are not accurately being transparent not collecting the data properly not reporting on the data properly not being transparent not representing the uncertainties not us openly saying they were wrong two months ago like in a way that's not like dramatic but uh revealing the basic process of science when you have to do your best under uncertainty just also just being inauthentic there's a there's a sense especially with like a younger generation now there's a certain way on the internet like the internet can smell much better than previous generations could and so they they see there's a kind of um inauthenticity that comes with being uh like representing authority like i am a scientist i'm an expert i have a phd i have four decades of work therefore everyone should listen to me got it and somehow that maps to this feeling of well what are they hiding if they're speaking from authority like this if everyone is in 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 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 from bad mrna vaccine experiments maybe they're and then and then the conspiracy theories start to grow uh naturally when there's this kind of mistrust of the 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 that so what what the heck i mean i so i put the blame not on the data but basically on the leaders and the community communicators 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 now you could argue well maybe they've left data out 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 what so this clinical trial data that's one thing so that's the data that we should be focusing on right is it so there's there's a lot of different data sets here so there's preclinical 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 in animals all of that is publicly accessible most of it gets published and then there's the initial drug filing which is huge the books of dot you can get that and look at it right this is me sort of asking sort of difficult questions here right okay uh so there is a there's a lot of money to be made by makers of the vaccine so for these company obviously there's a distrust of those folks too they've done a lot of really good things in this world but they've there's the incentives are such that you want to sweep stuff under the rug if if you're not 100 pure in your ethics and how hard is it for for that data to be fabricated uh manipulated like what's your intuition for the the pre-trial stuff i think when you when you start fabricating then you get inconsistencies which are pretty easy to pick up when you talk about some large-scale things of this nature because then you can look through the data very you're gonna i mean we require looking very carefully but you will see inconsistencies from one trial to another and uh that might ring a bell that something's been done yeah it's like it's like the moon landing thing i think sometimes like going to the moon is easier than faking it right in the sense it might be it might be easier to do a large-scale trial and get an effective vaccine versus faking it but you know when you brought up the for-profit issue i i think that is always been an issue i've 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 non-profit 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 well the argument is the speed of which the vaccines for covet were produced would never happen in a non-profit system would never happen in a non-capitalist system oh i could set up a vaccine production institute in the u.s 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 non-profit institutes of vaccines throughout the u.s 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 uh the selection of who to hire like good when you say good people yeah the capitalist has a machine that still fires people who are not good and selects people are good coming from the soviet union the dream of communism is is similar to what you're saying broadly defined it certainly doesn't work in the broad the question whether it works in the healthcare uh 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 would argue the current even the current healthcare is not with like regulations 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 the world can't there be some intermediate that works because i mean the other issue that we haven't mentioned is that politics gets thrown into this and that really messes up and it should never be mixed with health care but it's it is because a lot of funding comes from the government so that's another confounding factor but i 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 there 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 yeah of all sorts they don't seem to question and have issues with those and they have far more side effects than vaccines it's 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 uh 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 that's one way to con control the populace is by injecting substances into them right people i mean part of that funny enough is probably has to do with needles versus uh something you put in your mouth yeah but there's something about the government especially when it's governor mandated injection of a substance into you i don't it doesn't 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 yeah aren't they going to start getting ideas down the line for you know uh i i think that they can barely govern 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 covet vaccine right yeah but that's that largely has to do not largely but there is an individualistic uh spirit you know to them to the american people there's this like you're not going to take my gun away from me sure you're not going and i think that you know that's that's that's something that makes america what it is just 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 i hope that it's possible to have to strive towards a a government that works extremely well i think at its best a government represents the people and functions in the similar way that you're you're mentioning but that like pushback even if it turns into conspiracy theories sometimes i think is actually healthy in the long arc of history it can be frustrating sometimes but that mechanism of pushing back against power against authority can be healthy i i agree i think it's fine to question the vaccines what i have issue 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 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 sure 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 the you know 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 discussion on level ground it's um that that's the frustrating part that it's not an even discussion can i just say one more thing so i mean the internet is here to stay so we're gonna have to figure out how to deal with it right but from my perspective i was skeptical that these mrna vaccine that any coveted vaccine would be ready within a year yeah that's amazing me too plus these the way i look at the mrna vaccine as a scientist it's g whiz to me it's amazing that it worked and i think the data are great so i want it well as a scientist i wanted one of the really sad things again with me too as a scientist or as a 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 i wasn't free to celebrate the incredible accomplishment of science with the vaccines i was very skeptical as possible to develop a vaccine so quickly so it's unfortunate that we can't celebrate how amazing humans are to to come up with this vaccine now this vaccine might have long-term effects that doesn't mean this is not incredible why why um why couldn't you celebrate um because i would love to inspire the world with the 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 of 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 you're or you're dumb you know it's not the right approach i've seen actually it's kind of interesting i think both sides kind of imply that so the 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 nobody wins yeah and they both kind of have a point like because because you can always it's like a glass half full or half empty because you can always look at um like science from a perspective of certain individuals that don't represent uh perhaps not greatest leaders uh almost like political leaders there's a lot of you know i've yesterday went on a whole rant um against i said a lot of positive things about anthony fauci before i went on a rant i guess uh because ultimately you know i think he failed as a leader and i know it's very difficult to be a leader but i still wanted to hold him accountable for that as a great communicator of science and as a great leader what 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 inauthenticity uh two is a thing that it's very hard to put into words 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 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 in your past 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 it's like you said they're good bs detectives yeah good bs detectors uh then but contributing to that is speaking from authority speaking um with with uh with authority and confidence where neither is deserved so first of all nobody's an authority on on this new virus right we're facing a deadly pandemic and threatens especially in the early stages it was unclear how deadly it would be it was unclear probably still unclear fully how it's transmitted the full dynamics of the virus the full 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 is going to take to create a 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 mechanisms that are being implemented what are the clear plans they need to uh happen what the epidemiology that's happening what is the uncertainty around that um then then there's the geopolitical stuff with with china you know like what uh uh i you know personally believe there should have been much more openness about the the origins of the virus whether a leak from a lab or not i think communicating that you're open to these ideas is actually the way to get people to trust you that you're 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 and have 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 but it's by far the best course of action and that would that would come from a leader that has earned the capital of of trust from people i mean i think in recent history the worst pandemic is 1918 flew right but that's mainly because we didn't know what to do we didn't have many tools at our disposal and that was tied up with world war one that's right that's right so the the leadership there i mean but i don't know what 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 what bothers me though i mean personally i don't like anyone dying anywhere but and especially considering what technology we're able to muster yet we still kill each other it's just a dichotomy to me yeah but i mean this is the what is the paul farmer uh there's these great stories i mean that's that's the that's the um that's the burden of being in health care being a doctor is you have to help 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 so you're choosing which person lives and which person dies sure and you're doing so the reason you're helping the person in front of you because is because they're in front of you and so the reason right now we care a lot about kovid is because the the eye of the world has turned to covet but we're not seeing all the 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 so there's all there's all these questions and and the the fundamental question here is are we overreacting to kovid in our policies so the the 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 rising up of charismatic leaders that channel that anger towards destructive things that's been done throughout history it's like you have to balance that with the policies that you have and covid and then i mean uh very much my main opposition to uh fauci is not on the details but the final result which is i just observe that there's a significant decrease in trust in science as a not the institution but the various sort of mechanisms of science i think sciences is both beautiful and powerful and the reason why we have so many amazing things and such a high quality of life and distrust in that that the thing we need now to get out of all the troubles we're in 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 is uh is totally the wrong thing we need and so anybody who gets in who uh causes a distrust in science to me um um you know um carries the responsibility of that and uh should be in because the response means should be fired should be should be or at least uh openly have to carry the burden of that of having caused of that kind of level of mistrust now it may be unfair to place it on any one individual but you have to uh i think in your pocket the the buck stops at the top like the leaders dude no no there's there's a clear leader here yes absolutely so even if it's not directly his fault you know he has to carry uh uh 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 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 uh conditions that make you worried to get coveted and go to the hospital then you should get vaccinated because here's the data that shows that it's much less likely for you to die uh right if 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 suffered the consequences of that and that's it so i here's what i think is driving the i think it's all about kids right because they're going to go back to school in the fool 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 efforts to try and get more people at least in schools vaccinated but i might be wrong it may not be that so can you kind of dig into that a little bit so there's um see you're saying that there should be an effort for increased vaccinations of 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 and it's going to be it's not gonna be in time for school opening that they get vaccinated um and then i mean i suppose the teachers are all gonna be vaccinated it makes sense for them to do that but i'm just worried the kids are gonna be transmitting it amongst them and many states don't allow mass mandate in school so i think that's what's driving the larger narrative in the u.s 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 mid 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 covered 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 that's the of the co of this new vegetable 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 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 no to open up but to try and get you know their efforts at the federal level to get people vaccinated right but see how high are the risk for kids i mean as my understanding was it's i mean yes it's non-zero but it's very low for but what is the numbers now 70 000 hospitalizations so far in kids as of last week so yes it's low but i i polio was low polio was 20 30 000 kids a year paralyzed and well many people have actually argued that that vaccine wasn't necessary you know that wasn't a substantial enough health problem but paralyzed is different than hospital so what does hospitalized mean but this is the long covered question i mean this is the open question it was long covered in kids what is that so well a lot of the same issues cognitive issues motor issues respiratory gi dysfunction how long we don't know i mean it could end in a year 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 another one of those so i'm just saying it might be worth airing on the side of not letting the kids get infected yeah but well i'm trying to keep an open mind here and i appreciate you doing you're doing the same of course i uh lean on definitely not requiring people to get vaccinated but i do think getting vaccinated is just um the wiser choice if looking uh all the different trajectories before us getting vaccinated this um seems like from the data it seems like the obvious choice frankly but i'm also trying to keep an open mind because some things in the past that seemed obvious would 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 uh antiviral ideas so ideas outside of the vaccine so ivermectin something that uh 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 other topic i i just i'm bothered by sensors there's a gray area of course um but i it just feels like that should not have been censored from youtube like discussions of vibramectin we can we can set that aside the the other thing i was bothered by the lack of open-mindedness mindedness on exploring things like avermectin in the early days especially when at least i thought the vaccine would take a long time i mean it's not just ivermectin it's um 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 as absurd anyway so i was bothered by these solutions not being explored and not by now having really good ivermectin studies so can i talk about ivory mechanics yeah i would love that yeah sure so full disclosure my wife worked on ivermectin at merck for 20 years 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 merc for a long time as you know ivermectin is a very safe drug used to treat certain parasitic infections yes right and it is approved it's amazing 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 um it's quite a safe drug at the doses that are that are approved now uh early last year a study was done i believe in australia which showed in cells in the lab if you infect with source cov2 and them and put ivermectin and it would inhibit the virus production substantially it was quite clear right but the concentrations they were using were rather high and could not be achieved by uh the the approved dosing so you would need to do a dosing study to make sure it's safe and the reason is that i have a mechanic 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 ivermectin you'd have to make sure it would be safe in people so this is a question of safety too right so my 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 lots of improperly controlled trials where someone would just treat some patients 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 a four thousand person trial is unroll 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 their whether there are any side effects i think that's completely 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 a any objection but i don't know if it's going to work now i a friend of ours last week in new jersey got covered he went to his local hospital and their regimen was rem deservier dexamethasone ivermectin it's written that's what they do for every coven patient they just give it to them automatically and um wow so he's he recovered so who's to say it was or were 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 yeah and that's being done and i think that's fine is it strange to you that um ivermectin or other things like it weren't tested aggressively in the beginning like from a broad scientific community aspect you know i can be a little bit conspiratorial and this is what people talk about with ivamectin yeah is with the vaccines there's quite a lot of money to be made a with then there's not as much money to be made is is that too conspiratorial like why didn't we try more solutions in the beginning well um well all the money was put into vaccines right very little was put into antivirus because the mission decision was made at a very high level probably involving dr fauci yeah we're going to put 24 billion into vaccines right yeah and i think part of the reasoning is they give you years worth of protection whereas an antiviral works and you have to keep dosing and so forth but vermectin is not trivial and that's i i agree it should have been tested early on but we had a really bad experience with hydroxychloroquine which we can talk about too um ivermectin 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 hypermectin is really hard and so what they do 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 to market and they were arrested and they got put in jail so they protect it very carefully so you can't just make it if you do it's incredibly expensive and now india it's very cheap apparently they use it uh quite liberally there and i don't know how they're they're making it maybe they've licensed it from merc and 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 okay so what was the other the hydrocarbon hydroxychloroquine was also shown uh early on to inhibit virus in cell culture and that's not surprising hydroxychloroquine of course is used for malaria and what it does when you're when your cell takes up things from the from the plasma membrane including viruses it goes through a pathway called the endocytic pathway which involves a vesicle moving through the cell and as it moves through the cell its 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 in culture where the only way the virus can get in is through the endosome and hydroxychloroquine inhibits that and that's why it inhibits in kidney cells and 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 uh the the studies done in kidney cells and culture so that that was just wrong scientifically incorrect yet it drove a lot of and today many people still think they should be taking it but so like the that not panning out kind of resulted in a loss of optimism about other similar things well that and many other drugs repurposed drugs were tried right a lot of hiv antivirals were tried i think the problem with with hydrox i think hydroxycork would influence the ivermectin narrative right people thought that the data was being hidden about hydroxychloroquine so they said well they must be doing the same thing with hydromaxim 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 when you have covet and you need an anti-virulence usually because you can't breathe and you go in the 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 it is now an inflammatory issue and no antiviral in the world is going to help you so if that's why rem deserver doesn't work very well because it's mainly given intravenously to people who go in a hospital if you get ivermectin in the hospital it's not going to do anything for 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 going to inhibit it if you wait till you can't breathe and that's why the monoclonals even don't work if 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 into hospital it's too late because the viral curve drops after that first symptom within three days you're you're no longer shedding enough virus to transmit drops really quickly so that's the reason a lot of these antivirals failed because they were tested in hospitalized patients and we have nothing but rem deserve here now unfortunately so it was the wrong approach we should have been giving it to people who just tested positive from the start or just even for preventative and see you could do that too yeah but i have to say the other issue is this monument is a drug in phase three now it's an oral antiviral it looks good if we go ahead with just one we're going to 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 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 uh create selective pressure for a virus to mutate and for variance to form what um 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 so no vaccine or no drug makes a virus mutate right that's the wrong perspective which you look at what the what the immune response is 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 the 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 and that drives the emergence of the new variant so the next year we need to change the vaccine so i would say both natural infection and vaccination sure select for variance 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 all of the changes that are now present in the variants of concern at 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 then we saw the alpha variant emerge in england probably because of immune selection now the 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 so so the the variance the mutations that are at the core of these quantum core variants they were always there all along the vaccine or the infections did not create them no infections don't create they're selected it's like the vaccine wipe out a lot of the variants right and then um by being immune by making your body immune to them and so but some of them survive yeah exactly and 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 don't 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 um with some likelihood uh like the flu whereas basically variants will never be able to um eradicate it it will never eradicate it in any case ever well come up with a vaccine that uh 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 they're 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 yeah that's the bottom line 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 psoriasis 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 a really broad vaccine that'll handle all the variables well you actually uh on the virology blog i don't know if you're the author of that but i am yes oh the blog yes but there's a particular post that's talking about reporting in a paper the mix-and-match strategy oh yes that's one of my co-writers trudy ray yeah yeah that's a it'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 modern or something that creates a much better uh immunity than uh does two shots of laser i think that's worth exploring absolutely and this is relevant 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 the spike of influenza it's a long protein kind of like the spike of saurus cov2 it's stuck in the virus membrane and the very tip that's the part that changes every year that's where the antibodies bind but the stem doesn't change and if you make antibodies to the stem they can also prevent infection it's just that when people are infected or with the current vaccines they'll 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 that escaped it and i think we can do the same thing with with coronavirus too for sure can i ask you about testing sure sure so you mentioned pcr what kind of tests are there the antigen test uh what what are your thoughts on each maybe this is a good place to uh to also mention like viral load and um the history of the virus as it passes through your body in terms of the okay what's being tested for and all those kinds of things so the the first tests that were developed were pcr polymerase chain reaction 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 you know 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 little they get a bunch of cells and some mucus which has virus and parts of virus 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 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 it's a diagnostic of whether you 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 it's it's a number called ct or cycle threshold the test the way the machine works it goes through cycles in 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 a if you do a test and you have a cycle threshold of 35 you have very little rna in you contrary if you have a cycle threshold of 10 you have a ton of rna it 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 ct whatever 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 but wasn't thought through properly right that's where you had like 14 days or something like that which is now we know is 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 and you may be asymptomatic you're shedding it can affect others and then you may or may not have your symptom onset so you shed for a couple of days before symptoms 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 but it won't tell you if you're going to be infected tomorrow right because if you're negative today you could be positive tomorrow you just might be on 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 fine then there are 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 and so these you can buy in the drugstore and these would have been great if they had you know 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 which they can cost less than a buck by the way yeah but they were never made right right uh they're never mass manufactured so his idea is to do like daily tests so yeah daily and then the kid's going to school he's positive or she's positive well if it's cheap enough you just take another test because they have a certain 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 take longer to do and so forth but it never happened but now we do have twenty dollar binax now and others that you can buy and people buy them and see but that can still happen right and this is a very frustrating thing to me because i'm worried about variance but i'm also worried about future much more deadly pandemics like i know we kind of said yes covey lots of deaths but like it could be a lot worse too and so i'm thinking 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 we can the antigen tests will pick up the variance that's not a question the pcr may be influenced by changes but you can quickly adapt the primers that you use that's what i mean like to me all these discussions about vaccines and so on 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 right you're going to overcome that and i don't think there's any hesitancy and cheap tests at home i agree i think if someone so the question is if someone tested positive would they stay home that's the question what if their what if their job depends on them going in i 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 mo i would say most people stay home i think that mina 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're 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 yeah and get them and keep them home when they're infected it cuts it's and we don't have it 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 kits i mean there's a fiasco 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 you need to make antibodies to the protein that you're looking for and you need to do those and 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 uh 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 covet is transmitted there's there's droplets of different sizes uh aerosols tiny tiny droplets it seems like that's a very difficult thing to understand thoroughly uh so it seems like it's transmitted both ways it's unclear how exactly so how how how much do we understand and why is it so difficult to understand hopefully 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 plosives that your foam thing here is 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 100 feet or more right but the little ones also have less virus in them so i'm not sure well we certainly do not know how much virus you need to be infected right 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 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 borne out in multiple studies and 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 fire most of the rna copies were found in 15 to 20 percent of the people the rest had really low and they're 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 this there's not a controlled environment to measure droplets and so forth you'd have to do it in a laboratory situation 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 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 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 the mechanic very hard so that makes it but that makes it really hard to then develop solutions like masks to ask the question how will the masks work because then to answer that question you can lean on epidemiological stuff again like looking at populations that wear masks versus don't wear masks as opposed to actually saying uh 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 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 percent of this or larger size droplet that leads to this percent decreased transmission um and also on both the the generation and the the the the receiving end and the giving end sure so how will the mask protect you from others how well do you do mass protect uh 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 gonna do it nobody's gonna care no 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 uh to reopen society with if you have a good understanding of how well they work because if you don't have a good understanding 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 most they're 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 well look they don't work that well so i'm not going to wear it i think as you said people can use it as an excuse but even if it works so daniel always says it a mask will cut down transmission by 50 to 60 percent and then distance will do another 30 yeah those numbers are 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 yeah we make this model and let's say the mask cuts down this much what's what will be the effect on i mean yeah they're models and it's for the same reason i i don't believe the transmission uh var 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 masks for sure for sure so my my problem with the mask date which i always thought was fascinating i stopped talking about it i was in the paper about masks i stopped talking about it because what what started happening is mass created on both sides the people that were like in silicon valley friends of mine that were wearing masks the way they look at others who don't is like that's that's a whole other issue right that's yeah but that what that i understand that's happens when you don't have solid science understood they that now start judging you like you're less a human being you're not only uh dumb but you're just you're almost like evil you're doing bad for society by not wearing masks and then the people looking in the other way are seeing you for the that you're being for judging them uh unrightfully so they almost want to say fu 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 and so like the fact that this was politicized um yeah was a little bit heartbreaking you can find in the literature studies mostly of healthcare workers and influenza where you can actually because you see the people every day they can sample them you can actually see what masking does and some of them show an effect and others do not then that's the problem that's like any trial sometimes if it's not big enough and then people latch on to that see it doesn't really work but i think the main issue is that in january both cdc and who said masks don't work don't 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 yeah and like you said admitting you're wrong is like a real big part of it i 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 under which we operate like actually like uh reveal what was done and with the spanish food at the the beginning of the previous century uh 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 uh look at influenza like how is it effective with that and just reveal this we don't we don't know but uh with like with some probability this is the best option we got right currently and then and then in a month or two adjust it saying that you know what our like uncertainty decreased a little bit we have a better idea like that was a 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 in with uncertainty and like trusting people maybe criticize me sometimes with this but i i think most people are actually intelligent like trusting the public to be intelligent uh with if you give them if you have transparent and give them uh information in a real authentic way like don't look like you're hiding something i think they're intelligent enough to use that data to make decisions it's the same thing as with the testing is if if you put that power in the people's hands to know if they're sick or not they're going to make unmask the right decision i think it's uh that the masks and the testing has been a bit heartbreaking i think it's a good point though that most people don't seem to have an objection to testing that's a good point yes yeah and then obviously makamina makes that point brilliantly and still there's very little excitement around that but he said he was going to do it i don't understand i mean i haven't spoken to him since then so i don't know why he's pushing it well i mean but he can't do it alone he has to get so one of the one of the resistances fda doesn't like cheap things yeah they don't want to approve it so it makes the mass manufacturer like uh 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 uh placed on the vaccines and obviously there's an incentive mechanism there where the companies sure you know lobbyists and all those because there's this machine that says um arguing for tests is difficult because the thing that's worked for most severe viruses in the past is vaccines now we have vaccines why the hell would you need tests at that time like why the hell do you need tests when we could be working on vaccines it seems like the obvious thing to be working is the vaccines from from their perspective but it's not obvious at all to me i think you should have both i think you have vaccines and good testing and that covers you really well because you're always going to have people who don't get vaccinated i don't know if you've been paying attention to this there's a guy named brett weinstein there's a guy named sam harris they have good representations i would say of uh of two sides of a perspective on vaccines so from sam harris's perspective it's obvious that everybody should get vaccinated and it's irresponsible to not get vaccinated i think he represents a lot of people's belief in that and then uh brett is talks a lot about ivermectin but also talks about the hesitancy towards the vaccine for 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 um do you pay attention to this kind of thing what's your role in this what do you hope 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 um 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 should decide you're a smart person you should decide 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 fallen if you want to be a student you have to be vaccinated so you decide whether you want to go or not but the 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 covet so i don't think that's a fair argument and it just makes people scared to say that yeah but on the other hand for someone to say it's a no-brainer and to denigrate people for not being vaccinated that's not the approach either because they're going to 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 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 but here's the best available data and it looks like the vaccines are pretty uh a pretty damn smart solution they seem to work i think you tell people what you did and present both sides calmly 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 i mean people come to me all the time and ask me i'm worried what should i do and i'd say what are you worried about let's talk about it and go through it calmly and if they want to still take ivermectin i said it's fine it's your choice and i have a problem with that i love that i love that's the way you think uh people should definitely listen to this week in virology and follow your work is brilliant i've been really enjoying it lately it's 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 covert 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 i record on tuesday and friday and i canceled today so i could be with you huge honor i appreciate that no no it's fine um i think a couple of other people were going to be away anyway so 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 are have really good questions most of them are reasonable and and they come back every week so it's a great it's turning into a great uh forum to have a nice discussion and the youtube channel is called what so you could search for my name which is vincent dracquiniello it'll turn up or my handle on youtube is prof vrr p-r-o-f-e-r-r have you read uh the plague by kamu by any chance years ago years ago i have to read it again that's really relevant well let me just sort of ask you a question about it it describes a town that's overtaken by a plague and it's blocked off from the rest of the world and it kind of reveals the best the worst of human nature that's like how people respond to that sort of the encroaching that their own mortality their own death on the horizon i think what are the messages in the book that ultimately like love for others so it's like a lot of people want to become isolated and they hide from each other but ultimately the thing that saves you is is love which is one of the things i've just watching 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 um the tension the breaking of the common humanity between people 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 in the distance there were still um a camaraderie like a like a i don't know just a love for each other just a kindness towards each other and uh that's what i took away from the plague mostly it's told the story of the doctor who basically gives in and uh just gives himself as a service to others and that 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 what do you think about this the effect of the virus we talked a lot about biology but the effect of the virus and the the 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 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 you know kids can't go to school it really shows you i mean i always like to say a tiny virus can bring earth to its knees tiny viruses 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 a.i 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 uh when a the real story is what it does to society for sure which has ramifications 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 now never know i mean the airport this morning was completely jammed people go and they're all on vacation or wearing shorts right so they're 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's just quiet but you know under it all people are still most people help each other when they have to right most people are willing to uh if something happens to someone to reach out and help them you know there are 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 yeah but i think most of the motivation for everything that was done is to help other people i mean i 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 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 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 and i think for me someone who studied viruses for over 40 years it's just amazing that an invisible thing can do that right it goes back to the thing you found fascinating which is a virus affecting human behavior yes or uh 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 mode modalities that we can really quickly redesign but after sars one all that went out the door people didn't do anything and that's why we're in this situation so i you know people ask me this all the time are we going to 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 uh that said sometimes uh we we really step up when the tragedies run in front of us we do on the catastrophe 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 amazing it's quite surprising so always after reading the pentagon papers it's even more amazing right so i don't know how we do it i i tend to believe as there's uh there's that you know at the surface you notice the greed the corruption the the evil but the core of human nature of the human spirit is is uh one in the scientific realm is curiosity and more deeply is kindness compassion and like wanting to do good for the world like i i believe that desire to do good out powers all the other stuff uh by a large amount and that's why we don't we have not yet destroyed ourselves we kind of there's a lot of bickering there's a lot of wars on the surface but underneath it all there's there's this ocean of uh love for each other i mean i think there's a evolutionary advantage to that and uh it would be a good explanation why we still haven't destroyed ourselves oh we had so many opportunities yeah if you look at all the wars in history so many yeah i was just my son was telling me about the ottoman empire right 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 we have a lot very young yeah more time to go and a lot more ways to distort ourselves do you have advice like you said you have many decades of research and an incredible like career in life you have advice for young people about career about life people in high school people in college of um how to live a life that can be proud of so i 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 you don't have to plan i just found things that were interesting to me and so i 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 you know i was a biology major in college and i 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 to everything else that i've done one step at a time and i think the most important thing you can do well they're two important things you could 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 yeah and so people who say they're bored i say you are not curious you should just think about things and say look at something and say how does that work or what what is it doing and how do 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 i think they're amazing and i tell my classes i love viruses they're amazing and people think i'm morbid because obviously they kill 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 and so forth and all that we don't know about them so you need to be curious and passionate and don't plan too much and just find something that you don't call a job [Music] because someone said on the live stream last week i wish i had a job i liked as 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 yeah something that doesn't feel like a job so you said uh viruses are kind of um passive non-living you could say uh or even cells are passive and humans are kind of active we seem to be making our own decisions so uh let me ask you the why question what do you think is the meaning of this life of ours oh there's no meaning it just happened it's an accident um i think there's no life elsewhere because this is just a rare accident that happened and the right conditions i mean people all think i'm wrong because there are billions and billions 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 yeah but it's just driven by conditions if something emerged that worked it would then go on to the next step there's no meaning other than that the only difference is that we and i think many other animals can probably we we have the ability we're sentient right we can influence what happens to us and 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 uh give a lot of offspring so you can perpetuate it's just a natural biological function yeah they're much more directly concerned with survival i think sure 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're we really don't like that so we try to come up with ways to uh push that deadline farther and farther away well we have really i mean we used to die in our 30s right now it's 70s 80s well most of us used to die in our in the first few weeks that's true yeah infant death i i always tell people the only thing that's 100 is death it's the only thing in in the world that's a hundred percent you think about your own mortality yeah i never think about it i'm just enjoying day to day and i don't really you you work on viruses you don't contemplate your own mortality given the the deadliness of the virus i i around i never thought covert would kill me no i never was afraid of that not at all i um i mostly feared for other people getting sick especially people who could die of it i didn't 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 that's got to be at first so i don't think so i think that uh biologically you just can't you know the ends of our chromosomes keep getting shorter and shorter and that's eventually what kills us um so you just can't keep going on but um that's fine i i don't need to i understand from the vampires that it's not good to live forever i guess make the most of the of the time you got that's the uh bacteria live a much shorter time so we got that on bacteria bacteria are just you know little bags of chemicals that that split so they have no they have no stake in the matter at all it doesn't doesn't bother and i think you have to go a long ways before you get into some kind of consciousness but it's weird that this bag of chemicals has a stake in the matter like our human body is uh consciousness is a weird thing not just in us but they make half of the oxygen on the planet 20 of the oxygen comes from bacteria um and they made in the beginning of earth they made enough oxygen to start oxygenation going life going i mean it's they have an incredible role it's all an accident just happened well vincent like i told you i'm a huge fan it's a big honor that you were talking with me today thank you so much for coming down thank you for spending so much time with me um and thank you for everything you do in terms of educating about viruses about 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 davidson my pleasure thanks for listening to this conversation with vincent raqueniello to support this podcast please check out our sponsors in the description and now let me leave you with some words from isaac asimov 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