Transcript
00:00:00 The following is a conversation with Vincent Recaniello,
00:00:03 professor of microbiology and immunology at Columbia.
00:00:08 Vincent is one of the best educators in biology
00:00:10 and in general that I’ve ever had
00:00:12 the pleasure of speaking with.
00:00:14 I highly recommend you check out
00:00:16 his This Week in Virology podcast
00:00:19 and watch his introductory lectures on YouTube.
00:00:22 In particular, the playlist I recommend
00:00:24 is called Virology Lectures 2021.
00:00:28 To support this podcast,
00:00:30 please check out the sponsors in the description.
00:00:33 As a side note, please allow me to say
00:00:35 a few words about the COVID vaccines.
00:00:38 Some people are scared of a virus hurting
00:00:41 or killing somebody they love.
00:00:43 Some are scared of their government betraying them,
00:00:46 their leaders blinded by power and greed.
00:00:50 I have both of these fears.
00:00:52 And two, I’m afraid, as FDR said, of fear itself.
00:00:57 Fear manifests as anger and anger leads to division
00:01:01 in the hands of charismatic leaders
00:01:03 who then manufacture truth in quotes
00:01:06 that maximize controversy and a sense of imminent crisis
00:01:10 that only they can save us from.
00:01:13 And though I’m sometimes mocked for this,
00:01:15 I still believe that love, compassion, empathy
00:01:20 is the way out from this vicious downward spiral of division.
00:01:24 I personally took the vaccine
00:01:26 based on my understanding of the data,
00:01:28 deciding that for me, the risk of negative effects
00:01:30 from COVID, short term and long term,
00:01:33 are far worse than the negative effects
00:01:36 from the mRNA vaccine.
00:01:38 I read, I thought, I decided, for me.
00:01:43 But I never have and never will talk down to people
00:01:47 who don’t take the vaccine.
00:01:49 I’m humble enough to know just how little I know,
00:01:52 how wrong I have been and will be
00:01:55 on many of my beliefs and ideas.
00:01:58 I think dogmatic certainty and division
00:02:01 is more destructive in the long term than any virus.
00:02:04 The solution for me personally, like I said,
00:02:07 is to choose empathy and compassion
00:02:09 towards all fellow human beings,
00:02:12 no matter who they voted for.
00:02:14 I hope you do the same.
00:02:16 Read, think, and try to imagine
00:02:19 that what you currently think is the truth
00:02:22 may be totally wrong.
00:02:24 This mindset is one that opens you to discovery,
00:02:27 innovation, and wisdom.
00:02:30 I hope my conversation with Vincent Racanello
00:02:33 is a useful resource for just this kind of exploration.
00:02:36 He doesn’t talk down to people
00:02:37 and he’s the most knowledgeable virologist
00:02:40 I’ve ever spoken to.
00:02:42 He has no political agenda,
00:02:43 no desire to mock those who disagree with him.
00:02:47 He just loves biology
00:02:49 and explaining the fundamental mechanisms
00:02:51 of how biological systems work.
00:02:54 That’s a great person to listen to
00:02:55 and learn from with an open mind.
00:02:58 I hope you join me in doing so,
00:02:59 and no matter what,
00:03:01 try to put more love out there in the world.
00:03:04 This is the Lex Friedman Podcast
00:03:06 and here is my conversation with Vincent Racanello.
00:03:11 You mentioned in one of your lectures on virology
00:03:14 that there are more viruses
00:03:16 in a leader of coastal seawater
00:03:17 than people on earth.
00:03:20 In the Nature article titled Microbiology by Numbers,
00:03:25 it says there are 10 to the 31 viruses on earth.
00:03:29 Also it says that the rate of viral infection
00:03:33 in the ocean stands at 10 to the 23 infections per second.
00:03:39 And these infections remove 20 to 40%
00:03:42 of all bacterial cells each day.
00:03:45 There’s a war going on.
00:03:47 Do you, what do you make of these numbers?
00:03:49 Or why are there so many viruses?
00:03:52 So the numbers you’re quoting,
00:03:54 they’re in my first virology lecture, right?
00:03:57 Because people don’t know these numbers
00:04:00 and they get, whoa, they get wild by them.
00:04:02 So I love to give them.
00:04:04 So the way, sorry to interrupt.
00:04:06 As I was saying offline,
00:04:08 you have one of the best introductory lectures on virology
00:04:12 that I’ve ever seen, introductory lectures, period.
00:04:14 So I highly recommend people
00:04:16 find you on YouTube and watch it
00:04:18 if you’re curious at all about viruses.
00:04:20 It, yeah, there’s a lot of times throughout watching it,
00:04:24 I felt like, whoa.
00:04:26 Yeah, that’s my goal is to work.
00:04:28 And that’s what my students tell me.
00:04:29 One student once said, every day after every lecture,
00:04:33 I could go home and tell my roommate something
00:04:35 she didn’t know and blew her away.
00:04:38 So the number of viruses is really an amazing number.
00:04:42 So that number 10 to the 31 is actually
00:04:45 just the bacterial viruses in the ocean.
00:04:48 So there are viruses that infect everything
00:04:50 on the planet, including bacteria.
00:04:52 There are a lot of bacteria in the ocean.
00:04:54 And so 10 to the 31 is from basically particle counts
00:04:58 of seawater all over the world.
00:05:00 So there are more viruses than 10 to the 31,
00:05:02 but just in the ocean.
00:05:04 And that number is so big.
00:05:06 First of all, the mass exceeds that of elephants
00:05:10 on the planet by a thousand fold.
00:05:12 And if you lined up those viruses end to end,
00:05:15 they would go 200 million light years into space.
00:05:19 It’s so big a number.
00:05:21 It’s amazing.
00:05:23 And then yes, 10 to the 20 some infections per second
00:05:27 of these viruses killing bacteria
00:05:30 and releasing all this organic matter.
00:05:32 And that’s part of this, what we call
00:05:35 the biogeochemical pump, cycling of material in the ocean.
00:05:39 The bacteria die, they start to sink
00:05:42 and then they get metabolized
00:05:45 and converted to compounds that are needed.
00:05:48 A lot of it gets released as carbon dioxide and so forth.
00:05:50 So these are actually really important cycles
00:05:52 that are catalyzed by the virus.
00:05:54 Well, it’s so wild that nature has developed
00:05:56 a mechanism for mass murder of bacteria.
00:05:59 That’s one way to look at it,
00:06:00 but it’s just what happened, right?
00:06:02 It’s interesting.
00:06:03 I mean, I wonder what the evolutionary advantage
00:06:06 of like such fast cycling of life is.
00:06:10 Is it just an accident of evolution
00:06:13 that viruses are so numerous
00:06:16 or is it a feature and not a bug?
00:06:20 So the fast is, it’s not all fast.
00:06:25 Not all viruses are fast.
00:06:26 Some are 20 minutes per cycle.
00:06:28 Some take weeks per cycle, but that’s just per second.
00:06:33 There’s so many viruses in the ocean
00:06:35 that that’s what you get per second,
00:06:36 no matter how fast the cycle is.
00:06:39 But I look at it this way.
00:06:41 Viruses were probably the first organic entities
00:06:46 to evolve on the planet.
00:06:48 Long ago, billion years ago,
00:06:50 just as the earth cooled
00:06:52 and organic molecules began to form,
00:06:55 I think these self, we call them self replicators.
00:07:00 They’re just short things that today,
00:07:02 would look like RNA, which is the basis of many viruses.
00:07:07 They evolved and they were able to replicate.
00:07:09 Of course, they were just naked molecules.
00:07:12 They had no protection and it was just RNA based.
00:07:16 And that’s tough because RNA is pretty fragile in the world.
00:07:20 And it probably didn’t get very big as a consequence.
00:07:24 But then proteins evolved and I’m skipping like hundreds
00:07:28 of millions of years of evolution.
00:07:30 Proteins evolved, maybe without a cell, maybe with a cell.
00:07:35 But then to make a cell,
00:07:38 there probably were some RNA based cells early on,
00:07:40 but they were pretty simple.
00:07:42 But the cells that we know of today,
00:07:43 even bacteria and single celled eukaryotes,
00:07:48 they have very long DNA genomes.
00:07:50 And you need a lot of DNA to make a complicated cell.
00:07:54 And so we think at some point, the RNA became DNA.
00:07:59 And probably one of the earliest enzymes that arose
00:08:04 is the enzyme that could copy that RNA into DNA,
00:08:06 which we now know today as reverse transcriptase,
00:08:09 which my former boss, David Baltimore
00:08:11 and Howard Temin co discovered.
00:08:14 And that enzyme arose and copied RNA to DNA.
00:08:19 And then you could build big cells with DNA
00:08:22 because DNA can be millions and millions of bases
00:08:24 in length and RNA, the longest RNA we know of
00:08:27 is 40,000 bases, not much bigger than the SARS CoV2.
00:08:32 What would you say is the magic moment along that line?
00:08:36 I saw it was one or two billion,
00:08:39 maybe three billion years it took
00:08:43 to go from bacteria to complex organism.
00:08:49 It seems like Earth had a very long time,
00:08:52 not a very long time without life,
00:08:54 and then a very long time with very primitive life.
00:08:59 Maybe I’m discriminating, calling bacteria primitive life.
00:09:03 People would object to you doing that for sure.
00:09:06 But it seems like complex organism
00:09:07 when it starts becoming something like,
00:09:11 I don’t know what’s a good, not animal like,
00:09:13 but more complexity than just like a single cell.
00:09:17 What do you think is the magic there?
00:09:20 What’s the hardest thing?
00:09:21 If you were trying to engineer Earth and build life
00:09:23 and build the simulations,
00:09:25 obviously we’re living in a video game, what this is.
00:09:27 So if you were trying to build this video game,
00:09:29 what’s the hardest part along this evolution?
00:09:32 Bacteria are mostly single cells.
00:09:36 They do make colonies.
00:09:37 They get together in biofilms, which are really important.
00:09:41 But they’re all single bacteria in that.
00:09:43 And the key is making an organism
00:09:46 where cells do different things.
00:09:49 We have skin cells and eye cells and brain cells.
00:09:51 Bacteria never do that.
00:09:53 And the reason is probably energy.
00:09:55 Bacteria can’t make enough energy to do that.
00:09:58 And so there was another cell
00:10:02 existing at the time, the archaea.
00:10:06 And the idea is that a bacteria went into an archaea
00:10:10 and became the modern day mitochondria,
00:10:13 the energy factory of the cell.
00:10:14 And that now led that cell
00:10:17 develop into more and more complicated organisms
00:10:19 like we have today.
00:10:20 It was all about energy.
00:10:21 So the mitochondria, the energy,
00:10:24 the mitochondria is the magic thing.
00:10:26 I think so.
00:10:27 It’s just actually not my idea.
00:10:28 It’s Nick Jones.
00:10:29 Have you heard of Nick Jones?
00:10:30 He’s an evolutionary biologist in the UK.
00:10:33 And he’s done experimental work on this.
00:10:36 And it’s his idea that the defining point
00:10:39 was the ability to make a lot of energy,
00:10:41 which a mitochondria can do.
00:10:43 It’s basically a whole bacteria inside of a bigger cell.
00:10:46 And that becomes what we now call eukaryotes
00:10:48 and that they can get more and more complicated.
00:10:51 So let me bring you back to the viruses.
00:10:53 I wanna finish that story.
00:10:54 Yeah, which points of viruses come along?
00:10:56 So remember, we have these precellular,
00:10:58 they’re called precellular replicons, right?
00:11:01 And so we have a precellular stage
00:11:05 where we have these self replicating molecules
00:11:08 and then cells arise.
00:11:10 And then the self replicating molecules invade the cells.
00:11:15 Why?
00:11:16 Because it’s a hospitable environment.
00:11:17 I mean, they didn’t know that.
00:11:19 They just went in and it turned out
00:11:20 it was beneficial for them, so it stuck.
00:11:23 And they replicate inside the cell now
00:11:25 where they have pools of everything they need.
00:11:27 They get more and more complicated.
00:11:29 And then they steal proteins from the cell
00:11:31 to build a protective shell.
00:11:34 And then they can be released as virus particles.
00:11:36 They’re now protected.
00:11:37 They can move from host to host.
00:11:39 And because they’re at the earliest stages
00:11:43 of cellular evolution, they can diversify
00:11:46 to infect anything that arises.
00:11:48 And that is why I think there’s so many of them
00:11:52 and everything on the planet is infected
00:11:54 because the ancestor of everything
00:11:56 was infected many years ago.
00:11:57 So it’s easier to steal than to build from scratch.
00:12:01 So it’s easier to sort of break into somebody else’s thing
00:12:05 and steal their proteins.
00:12:06 Yes.
00:12:07 My colleague, Dixon de Palmier, calls viruses safe crackers.
00:12:11 Safe crackers.
00:12:12 So it’s just, from an evolutionary perspective,
00:12:15 it’s easier to steal because you can select.
00:12:20 But then you have to figure out mechanisms for stealing,
00:12:23 for breaking into, for cracking the state.
00:12:25 Well, you don’t have to figure out.
00:12:26 It just happens, right?
00:12:28 Because molecules are so diverse
00:12:30 that a molecule gets into a cell
00:12:33 and if there’s a protein that sticks to it,
00:12:35 it’s gonna stick and that gives an advantage.
00:12:39 There’s no planning.
00:12:41 There’s no thinking about it, right?
00:12:43 It just happens.
00:12:44 Oh, we’ll return to that.
00:12:46 Ha ha ha ha ha.
00:12:48 What, but these numbers are crazy.
00:12:50 So what, as these more complex organisms evolved,
00:12:55 let’s take us humans as an example,
00:12:58 should we be afraid of these high numbers?
00:13:01 Should we be worried
00:13:02 that there’s so many viruses in the world?
00:13:05 Well, to a certain extent.
00:13:06 I mean, they have, it’s twofold.
00:13:08 They’re good and bad, right?
00:13:09 Viruses are no, there was no question they can be bad.
00:13:12 We know that because they’ve infected
00:13:14 and caused disease throughout history,
00:13:15 but we’re also, you and I are full of viruses
00:13:17 that don’t hurt us at all and probably help us
00:13:20 and every organism is the same.
00:13:22 So they are clearly beneficial as a consequence.
00:13:25 So I think, so every living thing on the planet
00:13:31 has multiple viruses infecting everything you can see.
00:13:35 And most of them I think we don’t worry about
00:13:39 because they can’t infect us.
00:13:41 They’re unable.
00:13:42 In fact, now you can actually take your feces
00:13:45 and send them to a company
00:13:47 and they will sequence your viruses in your feces for you,
00:13:49 your fecal virome, right?
00:13:52 And the most common virus in human feces
00:13:57 is a plant virus that infects peppers.
00:14:00 It’s called pepper model mosaic virus.
00:14:03 And that’s because people eat a lot of peppers
00:14:05 and it just passes right through you.
00:14:06 Cabbage is full of viruses from the insects
00:14:09 that walk on the cabbage in the fields.
00:14:10 We eat them, they just pass us.
00:14:13 So I think most of the viruses we don’t need to worry about
00:14:16 except when we’re talking about species
00:14:19 that are closest to us, mammals, of course.
00:14:23 And I think the most numerous ones
00:14:25 are the most concerning, they’re viruses like bats.
00:14:28 Bats are 20% of mammals and rodents are 40% of mammals.
00:14:33 And we humans live nearby, right?
00:14:37 And we know throughout history,
00:14:38 many viruses have come from bats and from rodents to people,
00:14:41 no question about it.
00:14:42 So there’s a proximity in terms of just living together
00:14:44 and a proximity genetically too.
00:14:46 So it’s more likely that a virus will jump
00:14:48 from a bat and a rodent.
00:14:49 And birds too.
00:14:50 Birds can give us their viruses that’s happened.
00:14:53 Influenza viruses come from birds mainly.
00:14:57 So I think those are the three species,
00:15:00 not species, it’s higher than species obviously,
00:15:02 but those are the three I would worry about
00:15:04 in terms of getting their viruses.
00:15:05 And we don’t really know what’s out there, right?
00:15:09 We have very little clue about what viruses,
00:15:12 and I’ve for years wanted to capture wild mice
00:15:16 in my backyard and see what viruses they have
00:15:18 because no one knows.
00:15:20 And it’s an easy.
00:15:21 We can’t ask them, so you mean map,
00:15:23 like is there a way?
00:15:24 I can’t ask them, yeah.
00:15:25 No, I would have to sacrifice them and take tissue
00:15:27 and then bring it in the lab and do genome sequencing.
00:15:30 So you can do a thorough sequencing
00:15:32 to determine which viruses.
00:15:33 Is there a sufficiently good categorization of viruses
00:15:37 where you’d be?
00:15:38 That’s a very good question.
00:15:40 So whenever you do sequence, right?
00:15:42 You get some environmental sample
00:15:44 and you extract nucleic acid and you sequence it.
00:15:47 What you do is you run it past the database.
00:15:49 The gold standard is the GenBank database
00:15:52 which is maintained here in the US.
00:15:54 And you see if you get any hits.
00:15:56 And then you can say, ah, look,
00:15:58 this sequence is similar to this virus.
00:16:01 And you can classify all the viruses you see.
00:16:03 The problem is 90% of your sequence is dark matter.
00:16:09 It doesn’t hit with anything.
00:16:11 It’s probably a lot of it is unknown viruses.
00:16:14 And that’s gonna be hard to figure out
00:16:16 because someone’s gonna have to go after it
00:16:17 and sort it through.
00:16:18 So yes, you can find a lot of viruses
00:16:21 and the numbers you get are astounding.
00:16:22 You can find thousands of new viruses
00:16:25 just by looking in various life forms.
00:16:28 But there are many more that we don’t pick up
00:16:30 because they’re not in the database.
00:16:32 Maybe this is a good time to take a quick tangent.
00:16:36 What do you think about Alpha Fold 2?
00:16:38 I don’t know if you’ve been paying attention to that.
00:16:40 With them DeepMind solving the protein folding problem
00:16:44 and then also releasing, first of all,
00:16:47 open sourcing the code, which is for me
00:16:49 as a software person, I love.
00:16:52 And then second of all, also making like 300,000 predictions
00:16:57 or something like that for different protein structures
00:17:00 and releasing that data.
00:17:01 Yeah.
00:17:03 On the side of,
00:17:04 because you’re saying there’s dark matter.
00:17:06 Right.
00:17:07 Is there something, first, what are your general thoughts,
00:17:12 level of excitement about their work?
00:17:15 And second, how can that be applied to viruses?
00:17:19 Do you think we’ll be able to explore
00:17:20 the dark matter of virology using machine learning?
00:17:24 Absolutely.
00:17:25 Because in all this dark sequence,
00:17:26 you can translate it and make a protein.
00:17:29 You can see what a protein looks like.
00:17:31 It has what we call an open reading frame, right?
00:17:34 A start and a stop.
00:17:35 And right now it’s just a bunch of amino acids,
00:17:37 but if we could fold it,
00:17:39 maybe the fold would be like something we already know,
00:17:43 some protein fold, which gives you a lot of clues, right?
00:17:46 Because there are only so many protein folds in biology
00:17:49 and that dark matter is probably one of them.
00:17:52 So I think that’s very exciting because for years,
00:17:55 I’ve followed structural biologists for years
00:17:59 and in the beginning,
00:18:01 we couldn’t even solve structures of viruses, they’re too big.
00:18:04 We could do small molecules like myoglobin,
00:18:06 that was the first one done, took years to do that.
00:18:09 Then as computational power increased,
00:18:13 then they could start to do viruses,
00:18:14 but it took a long time.
00:18:16 X ray crystallography,
00:18:18 depending on getting crystals of the virus, right?
00:18:21 And now we can do cryo electron microscopy,
00:18:24 which is much faster.
00:18:26 You could solve,
00:18:27 the spike of SARS COVID 2 was solved in two months
00:18:29 by Jason McClelland here in Austin actually
00:18:32 at the beginning of the pandemic,
00:18:34 but you’re limited, you can’t do huge proteins.
00:18:38 You can only do moderately sized ones.
00:18:41 So, or actually you can do viruses,
00:18:45 but you can’t do small proteins.
00:18:47 So that’s speeded it up, but it’s still too fast to solve.
00:18:50 You get a new protein, you wanna solve its structure.
00:18:52 So if we could predict it,
00:18:53 and I know from talking to structural biologists,
00:18:55 this has been their holy grail from day one.
00:18:58 They wanna be able to take a sequence of a protein,
00:19:00 put it in a computer and have the structure put out
00:19:03 without having to do all the experiment.
00:19:05 So that’s why this is very exciting
00:19:06 that you can predict it.
00:19:08 That mean it’s not finished obviously,
00:19:10 and there’s more to do,
00:19:11 but I think it will be a day
00:19:12 where you could take any amino acid sequence
00:19:15 and predict what it’s gonna look like.
00:19:17 See, but like aren’t structural biologists
00:19:19 gonna get greedy?
00:19:20 So once you have that,
00:19:21 don’t you wanna go more complicated then?
00:19:24 Don’t you wanna go,
00:19:25 because that’s just the first step, right?
00:19:27 You go from amino acid to the structure,
00:19:29 then there’s like multiple protein interactions.
00:19:32 Like how do you get to the virus?
00:19:34 Well, so that’s what the ultimate goal
00:19:37 of getting a structure is that then you can do experiments
00:19:39 and figure out what the structure means, right?
00:19:42 So many, in the old days,
00:19:44 structural biology was a career in itself.
00:19:48 You worked with people who had a system
00:19:50 and just solve proteins for them,
00:19:51 and then you moved on to another one.
00:19:52 You didn’t really do any experiments.
00:19:54 The other people got to do all the interesting experiments.
00:19:57 Now, young structural biologists are multifaceted.
00:20:02 They solve the structure,
00:20:03 and then they say,
00:20:04 what happens if we change this amino acid?
00:20:06 Oh, look, it blocks binding to the receptor.
00:20:09 This must be the receptor binding interface.
00:20:11 So that’s the exciting stuff, absolutely,
00:20:13 is doing the experiment.
00:20:14 Well, I wonder if you can do some kinds of like simulations
00:20:18 of like, you know, different proteins
00:20:22 or multi protein systems going to war against each other,
00:20:27 like to try to figure out, you know,
00:20:31 reinforcement learning is used in alpha zero, for example,
00:20:35 to learn chess and go,
00:20:37 and that’s using the self play mechanism
00:20:39 where the thing plays against itself
00:20:41 and learns better and better.
00:20:42 Whether you can, I wonder if you can simulate
00:20:45 almost evolution in that way
00:20:46 for primitive biological systems,
00:20:49 have them in simulation, fight each other,
00:20:52 and then see what comes out,
00:20:53 like a super dangerous virus comes out
00:20:55 or super like Chuck Norris type of thing
00:20:58 that defends against the super dangerous virus,
00:21:00 and it’s all in simulation.
00:21:01 So an example would be,
00:21:03 we have all these variants of SARS COVID 2 arising, right?
00:21:07 Which look to be selected by immune responses,
00:21:13 but we know what amino acids are changing in the spike
00:21:17 and how they block antibody binding.
00:21:19 You could simulate that.
00:21:20 You could say, what is the antibody looking at?
00:21:24 Where antibodies bind on proteins are called epitopes, right?
00:21:28 You could map them all and change them in a simulation
00:21:30 one by one and go back and forth
00:21:32 between the antibody and the virus.
00:21:33 So all these, evolution is what we call an arms race, right?
00:21:38 The virus changes and then it evades the host
00:21:41 and then the host can change.
00:21:43 The host takes longer to change though, unfortunately.
00:21:45 It takes geological time, but it can.
00:21:47 And then the virus can change
00:21:49 and it can go back and forth.
00:21:50 And we can see evidence of this in genome sequences
00:21:54 of both viruses and their hosts.
00:21:56 And so you can take a protein in a host
00:22:00 that is a receptor for multiple viruses
00:22:02 and you can see all the impacts of virus pressure on it.
00:22:05 And you could simulate that for sure.
00:22:07 And that’s just one thing that you could do.
00:22:09 You could simulate changes in say an enzyme
00:22:13 that makes it resistant to a drug
00:22:15 and predict all the drug resistance.
00:22:18 But the problem is people like me,
00:22:21 the experimental virologists
00:22:22 don’t know how to do any of that.
00:22:24 So we need to collaborate with people, I guess.
00:22:27 Oh, with other humans.
00:22:29 We do that, we do that.
00:22:31 But with people from a field that we’re not used to,
00:22:35 I suppose people who, would it be AI, I suppose?
00:22:39 Yeah, machine learning people.
00:22:40 Machine learning people.
00:22:41 And you would say, look, this is the biological problem.
00:22:44 Is there a way we can use your tools to attack it?
00:22:46 The problem is those people are antisocial introverts
00:22:51 that have a place like this
00:22:55 and try to hide from other people in the world.
00:22:57 Very difficult to find in the wild.
00:23:00 Okay, so outside of doing amazing brilliant lectures online,
00:23:04 you host and produce five, I would say, related podcasts,
00:23:09 including my favorite, This Week in Virology,
00:23:13 also This Week in Parasitism,
00:23:16 This Week in Microbiology, and so on.
00:23:18 So you’re a good person to ask,
00:23:21 what are the categories of small things,
00:23:23 small biological things in this world that can kill you,
00:23:27 kill us humans?
00:23:30 Let’s look, you said like most viruses are friendly
00:23:33 or at least not unfriendly.
00:23:35 But let’s look at the unfriendly ones.
00:23:38 And viruses and bacteria and those kinds of things.
00:23:42 When you look at the full spectrum of things
00:23:43 that can kill you, can you kind of paint a brief picture?
00:23:47 Yeah, I think the big picture is that
00:23:50 the things that can kill you are a minority
00:23:52 of everything that’s out there.
00:23:54 And we’re talking about molecules.
00:23:57 So we have in us proteins that can kill us.
00:24:01 Preons that are just, it’s a protein in us.
00:24:04 And if it misfolds, it makes all of its other copies misfold
00:24:08 and then you die of a neurological disease.
00:24:11 That’s pretty rare.
00:24:13 So there are proteins, there are viruses.
00:24:16 And as I said, only certain ones can kill us.
00:24:20 But even if we get those from animals,
00:24:22 it’s not straightforward.
00:24:24 If you look at SARS CoV2, right?
00:24:26 This is probably a once in a hundred year pandemic,
00:24:29 I would say, equivalent to 1918 in its devastation.
00:24:34 And in between there have been smaller pandemics
00:24:36 of other viruses, but it doesn’t happen all that often.
00:24:39 So we have a lot of viruses.
00:24:40 We have a lot of bacteria of various sorts
00:24:43 that can cause infections in us.
00:24:46 And it’s a limited number, right?
00:24:49 You’re streptococci and staphylococci and clostridia.
00:24:52 We could go on and on, but we know how to handle those.
00:24:56 As long as we have antimicrobials,
00:24:58 it’s just that we abuse them and we get resistant.
00:25:00 So that can be a problem.
00:25:02 Then we have fungi, not mushrooms,
00:25:04 but much smaller fungi that multiply sub microscopic
00:25:09 or just at the microscopic level.
00:25:11 They can, in dry climates of the US,
00:25:13 you can inhale their spores and they can grow in your lung
00:25:16 if you’re immunosuppressed and so forth.
00:25:18 So those are the tiny guys.
00:25:21 And then we have parasites,
00:25:22 which we do this week in parasitism,
00:25:24 where single cells, even worms of various sorts
00:25:30 can invade you and cause all sorts of problems.
00:25:33 How, I was like kind of terrified to listen to that podcast.
00:25:37 What’s it like?
00:25:39 Well, I mean, what you learn is that you can,
00:25:45 you travel somewhere and you can get infected
00:25:47 and bring it back home.
00:25:48 Here in the US, we do have certain kinds of parasites,
00:25:52 but because of our lifestyle,
00:25:55 we more or less have avoided them.
00:25:56 For example, there’s a parasite called toxoplasma,
00:26:00 which is infected most of the world, actually,
00:26:03 because a lot of people like to eat raw meat
00:26:06 and you would get it from raw meat.
00:26:08 And we’re not as fond of that here in the US.
00:26:12 We like to cook our meat,
00:26:13 but that could be a consequence of eating raw meat.
00:26:16 Is that what leads to, what is it called, toxoplasmosis?
00:26:19 Yeah, so toxoplasmosis, it’s mainly,
00:26:25 a big issue is if you’re pregnant and you get toxo,
00:26:28 then your fetus is gonna be very badly malformed.
00:26:32 It’s gonna have brain defects and so forth.
00:26:36 And animals can get it as well.
00:26:39 So there are a lot of parasites of that nature,
00:26:41 which you often acquire by food,
00:26:43 eating food of different sorts.
00:26:45 And it usually happens elsewhere.
00:26:47 On This Week in Parasitism, we do a case.
00:26:50 So Daniel Griffin is our resident physician.
00:26:54 He’s a doctor, a real doctor, right?
00:26:56 And every month, he comes up with a case.
00:26:58 Okay, this is a person I saw.
00:27:00 And last month, this young lady had traveled somewhere
00:27:04 and she ate raw fish.
00:27:09 It was somewhere Southeast Asia or something.
00:27:11 And she ended up with red bumps all over her skin.
00:27:15 And it turned out it was a parasite from the fish
00:27:17 that moved around in her and very easy to cure.
00:27:21 We have, if the right doctors and the right drugs,
00:27:23 you can cure all these things.
00:27:24 What about diagnose, like connect the red spots
00:27:27 to the fact that it’s a parasite?
00:27:28 It’s very easy if you have the right diagnostics.
00:27:31 Now, Daniel often goes to parts of the world
00:27:33 where they don’t have diagnostics
00:27:34 and he has to use other mechanisms.
00:27:37 He may have to take a bit and look at it under a microscope.
00:27:40 And then he may not be able to get the drug
00:27:41 depending on where he is.
00:27:43 But often he sees patients who come back to the US
00:27:47 and they get diarrhea or they have a fever.
00:27:49 And he said, where have you been?
00:27:50 And he can put two and two together.
00:27:52 And so we let our listeners do that.
00:27:53 And they all send in guesses.
00:27:55 And it’s wonderful to hear them go through this.
00:27:57 So there are a lot of parasites that can get you.
00:28:00 You have to be careful about eating when you go overseas.
00:28:03 And water too?
00:28:04 Water as well.
00:28:05 And in parts of Africa, there are parasites in the lakes
00:28:09 that if you go swimming, they can invade you.
00:28:11 And in fact, they can go into your hair follicles
00:28:14 and burrow in and get into your bloodstream.
00:28:15 That’s exciting.
00:28:16 So Daniel is interesting because he’s very adventurous
00:28:20 and he’s not afraid of any of this.
00:28:22 So there’s a famous lake in Africa, Lake Malawi,
00:28:26 which harbors a lot of these parasites.
00:28:28 And he said, oh yeah, yeah, I just make sure
00:28:30 I towel off vigorously when I get out and get rid of them.
00:28:34 And that was the name of an episode.
00:28:37 But food is, sushi, you can get worms from sushi.
00:28:43 And the solution is to freeze it.
00:28:46 And many sushi restaurants now have liquid nitrogen.
00:28:49 They snap freeze their sushi and that kills all the parasites.
00:28:53 And a study was actually done in Japan
00:28:56 showing that freezing does not alter the taste of sushi
00:28:59 because it’s up, you see a big industry there.
00:29:01 Wow, that’s brilliant.
00:29:03 That’s brilliant.
00:29:04 Yeah, I was thinking about, I’m so boring and bland
00:29:10 that especially when I am now in Texas here
00:29:12 and I’ve been eating quite a bit of barbecue,
00:29:14 I realized I really haven’t explored the culinary world.
00:29:18 And I’ve been curious to travel and taste different foods.
00:29:22 Is there something you could say by way of advice,
00:29:26 channeling Daniel, I guess, if you were to travel
00:29:30 in the world, if eating is the thing
00:29:32 that gets you the parasites,
00:29:34 what’s a good advice for eating
00:29:37 in strange parts of the world, Mongolia, India, China?
00:29:41 Is there something you could say by way of advice?
00:29:43 I think Daniel would say,
00:29:45 make sure your food is cooked, right?
00:29:47 Cooked, but that’s so boring.
00:29:49 Yeah, it’s unfortunate.
00:29:50 And he would agree with you
00:29:52 because many vegetables are delicious.
00:29:55 Salads even are delicious, not cooked,
00:29:57 but they can have parasites in them.
00:29:59 Meats, fish, people like to have uncooked fish.
00:30:04 So if you wanna be really safe and boring,
00:30:06 just make sure everything is cooked.
00:30:07 And now we have a case this week on TWIP
00:30:11 of a young man who went, I forgot where he went,
00:30:14 but he stayed in a hotel.
00:30:15 I think, oh, Oaxaca, Mexico.
00:30:18 Stayed in a hotel.
00:30:20 And he came back with diarrhea and fever.
00:30:23 And he said, I don’t know where, I stayed in the hotel.
00:30:26 I just ate hotel food, lots of vegetables and fruits,
00:30:30 and probably they weren’t washed with clean water.
00:30:32 He got something from that.
00:30:34 The bottom line is most of these infections
00:30:38 with parasites can be diagnosed,
00:30:40 and you can be treated, and you’ll be fine.
00:30:42 So if you really wanna experience the cuisine,
00:30:47 I don’t think you should worry about it.
00:30:49 That’s what Daniel would say.
00:30:50 Let’s return to the basics.
00:30:51 We can then jump around all over the place.
00:30:54 What are the basic principles of virology?
00:30:58 Maybe a good place to start is what is a virus?
00:31:02 That’s great.
00:31:03 I mean, I talk in my first lecture for 20 minutes
00:31:05 before I get to that.
00:31:07 But, and I wonder if I should put it up front,
00:31:10 but it’s kind of a boring definition.
00:31:12 So if you do that first, people will turn off.
00:31:14 So first you tell them about all the millions and billions
00:31:17 of viruses around.
00:31:18 So a virus, we have a very specific definition
00:31:22 because it’s different from everything else on the planet.
00:31:26 Because first of all, it’s a parasite.
00:31:28 It takes, a parasite means you take something
00:31:32 from someone else.
00:31:33 We have human parasites who take money from others, right?
00:31:36 But in biological terms, a parasite takes something
00:31:40 from the host that the host would otherwise use energy
00:31:44 or some building block or something.
00:31:46 There’s never really a symbiotic relationship
00:31:48 between a virus and a host.
00:31:50 Well, there can be.
00:31:52 So that’s the dichotomy I think is that we define them
00:31:54 as parasites, yet I just told you 20 minutes ago
00:31:58 that many viruses are probably beneficial.
00:32:01 So I think what it means is we, at some point
00:32:04 we’re gonna have to change our definition, right?
00:32:06 Because after all, definitions we make are just constructs
00:32:12 that make it easy for us to study,
00:32:14 that don’t necessarily represent what’s right.
00:32:16 Yeah, like Pluto was a planet at first
00:32:20 and now it’s not a planet anymore
00:32:21 and a lot of people are very upset.
00:32:23 But it’s only according to us.
00:32:24 There may be another race living somewhere else
00:32:27 who thinks it’s a planet, right?
00:32:28 Well, maybe that’s why viruses are attacking humans.
00:32:30 They’re very angry.
00:32:31 They’re calling them parasites.
00:32:33 So right now our definition includes parasite
00:32:38 because a virus cannot do anything without a cell.
00:32:41 If this mug were full of viruses,
00:32:44 it would not do anything for years.
00:32:46 It would eventually probably lose its infectivity,
00:32:49 but it’s not gonna reproduce here, it needs cells.
00:32:52 And to the first people who discovered viruses,
00:32:54 that was astounding that they didn’t just reproduce,
00:32:57 divide on their own like bacteria.
00:32:59 So a virus needs to get inside of a cell,
00:33:02 inside the cell, it can’t just hang around on the surface.
00:33:05 It needs to get in in order to make more of itself.
00:33:09 And so we call it an obligate intracellular parasite
00:33:13 because it needs to get in a cell
00:33:15 and then it takes things from the cell
00:33:17 in the form of all kinds of molecules
00:33:19 and processes and energy and so forth to make new viruses.
00:33:23 Obligate means it’s obligated to be inside the cell.
00:33:26 Absolutely, it will not reproduce outside of the cell.
00:33:30 So this mug of viruses can in no way be living,
00:33:35 in my opinion.
00:33:36 However, once it gets inside of a cell,
00:33:39 now the cell is a virus infected cell, it’s alive.
00:33:42 So a virus, in my view, has two phases, right?
00:33:45 It’s this nonliving particulate phase
00:33:48 that everyone is used to.
00:33:50 I’ll send you, you need a virus for your table.
00:33:52 I’ll send you a nice model.
00:33:54 I think it would look good here.
00:33:55 Which, yes, definitely.
00:33:56 You don’t have to go with all this other stuff.
00:33:57 Yeah, well, these are all mechanical.
00:33:59 There’s no biology here.
00:34:01 So you wouldn’t want a virus here?
00:34:02 No, I’d want a virus, of course.
00:34:04 No, I’ll send you one and then you can look at it.
00:34:06 Because now that we have the three dimensional structures
00:34:09 solved by structural biologists,
00:34:12 we take the coordinates and we put it in a 3D printer
00:34:14 and you can make amazing models, right?
00:34:18 Of any virus.
00:34:18 And so there’s a huge variety of viruses?
00:34:21 Huge, that we know of,
00:34:23 which is only a fraction of what’s out there.
00:34:24 What’s the categories?
00:34:25 So there’s RNA, there’s DNA viruses.
00:34:27 What are those, what’s DNA and RNA?
00:34:30 Two broad categorizations.
00:34:33 RNA, these are genetic material.
00:34:37 Can be two different chemicals.
00:34:39 So RNA, everything else on the planet besides viruses
00:34:43 is all DNA based.
00:34:44 You and I are DNA based.
00:34:45 Everything on the planet today is DNA based,
00:34:47 except some viruses are RNA based.
00:34:50 And that’s because, as I mentioned earlier,
00:34:53 the first life that arose on the planet was RNA based.
00:34:57 Yeah, so these are like old school viruses.
00:34:59 These are old school.
00:35:00 We call relics, yeah.
00:35:02 Relics, and this has got a name,
00:35:04 it’s called the RNA world, which I think is great.
00:35:06 Is it big still, or are the relics dying out?
00:35:09 Oh no, the relics, in my opinion,
00:35:11 are the most successful viruses, the RNA viruses.
00:35:14 And SARS CoV2 is an RNA virus.
00:35:16 We can talk about why they’re so successful.
00:35:19 But you have, broadly speaking, viruses with RNA,
00:35:22 genetic information, which are relics.
00:35:24 Of course, they’re contemporary.
00:35:26 They have adapted to the modern world
00:35:28 and the modern organisms living in it.
00:35:31 And then we have DNA based viruses,
00:35:33 which are extremely conservative and slow.
00:35:36 They’re very successful.
00:35:37 Everyone has a herpes virus infection,
00:35:40 but they don’t get the news like the RNA viruses do.
00:35:44 The HIVs and the influenza viruses
00:35:46 and the SARS Coronaviruses, they get all the press
00:35:49 and they’re RNA based, because RNA lets you change
00:35:52 more so than DNA.
00:35:54 So they evolve much faster, the RNA viruses.
00:35:57 Much faster.
00:35:58 And in fact, I have an lecture on evolution.
00:36:01 I don’t know if you’ve listened to that one.
00:36:03 You should, it’s really, I think it’s really interesting.
00:36:07 RNA viruses exist at their error threshold,
00:36:13 which means they can’t make any more mutations
00:36:17 when they reproduce, otherwise they’re dead.
00:36:19 They would go extinct.
00:36:20 They’re evolving at their error threshold.
00:36:23 DNA viruses are hundreds of times lower
00:36:26 than their error thresholds.
00:36:28 And we know this, we can do an experiment to find that out.
00:36:31 Now, why that is, is a good question,
00:36:33 but that’s the reason why RNA viruses
00:36:38 are far more successful.
00:36:39 They infect many more hosts and they’re very,
00:36:42 I would say slippery.
00:36:44 They can change hosts really quickly,
00:36:46 because in any animal harboring an RNA virus,
00:36:50 like let’s say a bat in some cave somewhere,
00:36:52 it’s not just one genome.
00:36:55 It’s millions of different genomes of all kinds,
00:36:58 all within the framework of, say, coronavirus,
00:37:01 but they’re all different.
00:37:02 And one genome in there might just be right
00:37:04 for infecting a person if it ever encountered that person.
00:37:08 I mean, that’s the thing that.
00:37:09 Or there could be a large number.
00:37:11 This is a tiny fraction, but a large number of them.
00:37:15 And they’re all operating at the threshold of error.
00:37:18 That’s fascinating.
00:37:19 It’s like little, like it’s like startups,
00:37:21 little entrepreneurs, like a startup world.
00:37:23 Yes, and many of them fail.
00:37:25 Yeah, many of them fail.
00:37:26 Many of the changes fail.
00:37:26 And then there’s the DNA viruses that are like the IBM
00:37:29 and the Google. Exactly, exactly.
00:37:30 The big corporations.
00:37:31 That’s very good, I like that.
00:37:32 They become conservative with the bureaucracies
00:37:34 and all that kind of stuff, so they.
00:37:34 And a lot of baggage.
00:37:36 Yeah, yeah, it’s expensive for them to reproduce, yeah.
00:37:39 And they don’t move quickly.
00:37:40 Yes, the RNA viruses are the fast moving members.
00:37:43 So that’s what a virus is.
00:37:45 We call them ovulated intracellular parasites.
00:37:48 And then I told you there’s DNA and RNA,
00:37:50 but then let’s go further.
00:37:52 The nucleic acid is not naked.
00:37:56 Because naked nucleic acid in the world isn’t good.
00:37:59 I mean, it existed in the precellular world,
00:38:03 but there probably weren’t a lot of threats to it then.
00:38:07 Naked nucleic acid doesn’t last long in the environment.
00:38:09 So they’re covered, the nucleic acid is covered.
00:38:12 It can be covered with a protein shell,
00:38:13 a pure protein shell, or it can have a membrane around it,
00:38:18 which would be lipids from the host cell.
00:38:22 So lipids, so it’s a fatty membrane.
00:38:26 Fatty membrane, yeah, so our cells
00:38:27 are coated with fatty membranes, right?
00:38:30 Our cells, the outer plasma membrane, right?
00:38:32 That’s the same.
00:38:33 Viruses can be too.
00:38:34 So they’re kind of like cells,
00:38:35 but without the ability to do the mitochondria stuff.
00:38:38 Some are, they don’t have nuclei,
00:38:41 they don’t have mitochondria.
00:38:42 But they do have a nucleic acid, they have a membrane,
00:38:45 and then of course there’s spikes in the membrane
00:38:48 that allow them to attach to cells.
00:38:51 And so that completes our two different kinds.
00:38:53 So they have, they all have like attachment mechanisms,
00:38:55 like ways to, like keys into the cell.
00:38:59 They all have to get into cells.
00:39:01 There are a couple of exceptions though.
00:39:05 There are viruses of fungi and plants.
00:39:10 So let’s do the fungi.
00:39:11 Fungi would be like yeast.
00:39:13 The yeast cell wall is pretty hard to get through.
00:39:17 So viruses typically don’t attach to a yeast
00:39:21 and get inside.
00:39:22 Rather, they just live in the yeast forever.
00:39:24 And they multiply as mostly nucleic acids,
00:39:27 and as the yeast divide, they go into the daughter cells.
00:39:30 And that’s how they exist.
00:39:31 Plant viruses, also the plant cell wall
00:39:34 would be very hard to get across by binding a protein.
00:39:39 So plant viruses get into plants either by
00:39:43 pests that inject them in, they’re sucking sap out,
00:39:48 and they inject virus at the same time.
00:39:49 Or farmers, they have contaminated farm equipment
00:39:52 and they roll over the plants and introduces viruses.
00:39:55 So those fungi and plant viruses,
00:39:57 they don’t have this specific receptor binding
00:40:00 to get them into the cell.
00:40:01 But everything else, yeah, the virus binds
00:40:03 to something on the surface, very specific.
00:40:05 It’s taken into the cell because that’s what cells do.
00:40:09 When things bind their exterior, they take it in.
00:40:12 Because in most cases, it’s good.
00:40:14 It’s something they need.
00:40:15 And so the virus slips in.
00:40:17 I guess you’d call that a Trojan horse, right?
00:40:19 Trojan horse.
00:40:20 It’s so hard to not anthropomorphize this whole thing.
00:40:23 It is hard.
00:40:24 So obviously, they don’t know any of this.
00:40:26 It’s not an actual Trojan horse.
00:40:29 So they’re not getting actually tricked
00:40:32 in the way humans trick each other.
00:40:34 No, it’s all passive.
00:40:35 And it’s just through so many years of evolution,
00:40:38 you select something that works, and it continues.
00:40:42 And what survives then goes on
00:40:44 with perhaps a slightly different approach.
00:40:48 I love this idea of passive.
00:40:49 Of course, according to Sam Harris,
00:40:52 so for my sufficiently intelligent alien civilization
00:40:54 observing humans, our behavior might seem passive too
00:40:58 because they understand fully exactly what we’re doing.
00:41:00 And then there’s no free will,
00:41:02 and we’re all just operating in the same way.
00:41:04 Could be.
00:41:04 A cell does, but just a much higher level of complexity.
00:41:07 Yeah, so I love the distinction between active and passive.
00:41:11 I mean, the point is, I think anthropomorphizing
00:41:14 to a certain extent is fine
00:41:15 because it helps people understand.
00:41:17 But when you start to say,
00:41:19 I think the virus is doing that
00:41:21 because then you’re putting a human lens on it,
00:41:24 and you may be wrong.
00:41:26 Yeah.
00:41:27 Because you don’t know why things happen for a virus.
00:41:30 So right now, we have variants emerging,
00:41:33 and people say, well, I think it’s because the antibodies
00:41:35 are selecting for variants.
00:41:38 That’s a good idea,
00:41:39 but it may not be the only thing that’s going on.
00:41:41 You start imagining them coming to the table negotiating.
00:41:45 Yeah, you get into trouble with that.
00:41:47 That’s why I tell my students,
00:41:49 be careful about the anthropomorphizing
00:41:51 because you’re gonna apply your values to a virus,
00:41:55 and you have different values.
00:41:57 You’re a human, and you have,
00:41:58 what you think is the reason for this outcome
00:42:01 may not be right, that’s all.
00:42:02 Just be open minded about it.
00:42:04 In both directions.
00:42:05 I actually, one of the things that pushed back
00:42:07 on this in the space of robotics,
00:42:10 people, most people in robotics
00:42:12 try to not anthropomorphize.
00:42:14 For example, they don’t give a gender or a name to robots.
00:42:17 They really try to see it as a machine.
00:42:20 And to me, that makes sense in one way,
00:42:23 but it totally doesn’t make sense in another.
00:42:25 If that robot is to interact,
00:42:27 operate in the human world and interact with humans,
00:42:30 we have to anthropomorphize it
00:42:33 in order to understand, as an engineering problem,
00:42:38 how should it operate in a human world?
00:42:42 Now, the difference with viruses, the scale of operation,
00:42:46 it doesn’t make sense to treat them as humanlike
00:42:49 because the scale of operations is much smaller.
00:42:51 But with robots, you’re in the same time scale,
00:42:54 the same spatial scale.
00:42:55 Of course, in the movies,
00:42:56 they always give them names and personalities, right?
00:42:58 Yeah, well, yeah, that’s the,
00:43:00 but that’s my argument is we should do the same
00:43:02 when you’re trying to solve
00:43:03 the engineering problem of robotics too.
00:43:06 It’s not just for the movies.
00:43:07 Well, let me ask you this,
00:43:08 because you’ve said, controversially, not really,
00:43:12 that viruses are not living.
00:43:17 Defend yourself.
00:43:19 Are viruses alive or not?
00:43:20 So I’ve seen many people say, oh, they have to be,
00:43:22 they have nucleic acids, they evolve, they mutate.
00:43:27 That’s all true, but they don’t do it on their own.
00:43:29 The particles in my mug are just not doing any of that
00:43:32 unless they get into a cell.
00:43:33 So a virus infected cell is alive.
00:43:36 I totally agree with that,
00:43:37 because in fact, when a virus gets in a cell,
00:43:40 it converts it into a virus making factory, if you will.
00:43:45 It’s no longer a cell.
00:43:47 Some people call it a viro cell.
00:43:48 I don’t really like that, but it’s fine.
00:43:51 So that’s what I’m talking about.
00:43:53 The particle is not alive.
00:43:54 You can have your virus infected cell as alive,
00:43:57 but the particle, it just would not do anything forever
00:44:02 without getting inside of a cell.
00:44:03 But once it’s in a cell, it is alive then,
00:44:07 but it’s no longer a particle.
00:44:08 It’s taken apart and nucleic acid is moving
00:44:10 around the cell, it’s making proteins.
00:44:12 Eventually it makes new particles.
00:44:14 And then those particles released from the cell,
00:44:16 they’re not living anymore.
00:44:17 So it’s kind of, I think it’s kind of like a spore,
00:44:21 a spore of a, or a seed.
00:44:25 Although the seed just doesn’t work because the seeds,
00:44:28 the cells in the seed have the ability
00:44:29 to make their own energy and so forth.
00:44:31 But a bacterial spore, and it’s the same thing,
00:44:34 doesn’t do anything unless you add water and nutrients
00:44:36 and then it starts to divide.
00:44:37 But it doesn’t need to get into a cell.
00:44:39 It’s very different from a virus.
00:44:40 So that’s why the particle.
00:44:42 And when people think of virus,
00:44:45 they’re always thinking of the particle.
00:44:47 And that’s why I say it can’t be alive
00:44:49 because the particle can’t do anything on its own.
00:44:51 But if you think of a virus as an organism
00:44:53 with a particle phase in a cell,
00:44:55 then it makes sense to be alive.
00:44:58 And by the way, when you say particle,
00:44:59 you’re referring to that structure
00:45:01 that you’ve been mentioning,
00:45:02 some parts of the membrane and not,
00:45:03 that’s been called, what is that,
00:45:05 a virion particle or something?
00:45:06 Virion.
00:45:07 So it’s what you should have here.
00:45:09 I’ll send you one.
00:45:10 And then you can refer to it.
00:45:11 What’s the sexiest one to have?
00:45:13 Like what, in terms of particles to have on a table?
00:45:17 Well, unfortunately, the ones that you can 3D print.
00:45:21 Oh, they’re not going to be super.
00:45:23 They’re the ones that we know the structures of, right?
00:45:26 So someone sent me last year
00:45:29 a 3D model of SARS CoV2, and it’s beautiful.
00:45:32 It’s actually cracked open so you can see the RNA
00:45:34 and the spikes are sticking out.
00:45:36 And they even put some antibodies sticking onto the spikes.
00:45:39 And I mean, when I show this on a live stream,
00:45:42 people love this.
00:45:43 They go, oh my God, that’s beautiful.
00:45:45 It is, it’s absolutely gorgeous.
00:45:46 I have that.
00:45:47 I have my virus that I worked on
00:45:49 most of my career, poliovirus.
00:45:50 I have a 3D model of that, which I actually just had made.
00:45:54 It’s gorgeous.
00:45:55 And you can have it made in any color you want, right?
00:45:57 What would you say is the most fascinating,
00:46:01 terrifying, surprising, beautiful virus to you?
00:46:05 So of all the viruses you looked at,
00:46:08 sometimes when you just sit late at night
00:46:10 with a glass of wine looking over the sunset,
00:46:13 which virus do you think about?
00:46:16 So fulfilling all of those adjectives is hard, right?
00:46:21 Fascinating, exciting, terrifying.
00:46:24 Well, the terrifying is an optional one, I think,
00:46:27 because maybe that puts a lot of pressure.
00:46:30 See, terrifying, to me, I’m not terrified
00:46:34 because I think we can handle most viruses.
00:46:37 As you see with this brand new one that emerged a year ago,
00:46:40 we can handle it.
00:46:42 From a virology perspective.
00:46:44 Yeah, I mean, the human perspective
00:46:45 is a different story, right?
00:46:46 That’s always an issue.
00:46:47 But so I think there are a couple of different categories
00:46:55 of virus.
00:46:55 You could do the terrifying,
00:46:57 and I think rabies is a terrifying virus
00:47:00 because unless you’re vaccinated,
00:47:02 100% certainty you’re gonna die.
00:47:05 So you get bitten by a rabid raccoon or bat or dog, whatever,
00:47:11 and there’s still 70,000 deaths a year of rabies
00:47:15 throughout the world because there are a lot of feral dogs
00:47:17 running around that are infected.
00:47:19 Unless you’re vaccinated, you’re gonna die.
00:47:21 There’s nothing we can do.
00:47:23 But we do have a vaccine
00:47:24 which we can actually give you
00:47:26 even after you’ve been bitten,
00:47:27 which is the only vaccine that works that way.
00:47:31 It’s a therapeutic, right?
00:47:32 It will treat your illness
00:47:34 because the disease takes so long to develop.
00:47:38 Eventually, you get all kinds of neurological issues
00:47:41 and paralysis and so forth, but it takes time,
00:47:44 and you can be vaccinated.
00:47:45 It will prevent that in the meanwhile.
00:47:47 So people always say,
00:47:48 what’s the most lethal virus?
00:47:50 Is it Ebola?
00:47:51 I said, no, it’s actually rabies.
00:47:53 Unless you’re vaccinated, it will kill you.
00:47:56 Maybe it’s good to linger,
00:47:57 because we’ll talk about vaccines a few times today.
00:48:01 It’s good to linger on cases
00:48:04 where vaccines have clearly,
00:48:09 undoubtedly helped human civilization.
00:48:12 And it seems like rabies is a good example.
00:48:15 Oh, rabies is great because everyone knows what happens
00:48:19 when somebody gets rabies, right?
00:48:21 You have fear of water, hydrophobia.
00:48:26 Your body becomes spastic and stiff and jerks around,
00:48:31 and you lose consciousness.
00:48:33 You can’t, no more.
00:48:35 It’s not a fun ride to death.
00:48:36 It’s horrible.
00:48:37 It’s a horrible way to die.
00:48:39 So I think most people know that.
00:48:40 It’s been popularized enough in media, right?
00:48:44 So that nobody would probably object to getting,
00:48:47 oh, I was just bit by this raccoon and it ran off.
00:48:51 Okay, well, we should assume it’s rabid.
00:48:53 We should immunize you.
00:48:54 And most people are okay with that,
00:48:56 because they know the consequences.
00:48:57 And it’s also pretty rare, right?
00:48:59 It’s not like something that you’re trying to get
00:49:02 into the arms of 250, 300 million Americans.
00:49:06 That’s hard.
00:49:07 But the few thousand every year, it’s easy.
00:49:11 So the transmissibility is difficult, right?
00:49:13 It has to, oh, it’s not airborne.
00:49:16 It’s not airborne.
00:49:17 It’s just you have to be bitten.
00:49:19 Although some people claim you could walk into a cave
00:49:24 and the bats breathing out rabies virus could infect you,
00:49:28 but I don’t really think that’s well substantiated.
00:49:32 I think it’s a bite.
00:49:33 How would you do a study on that?
00:49:34 Yeah, it’s very hard to do.
00:49:36 You’d have to collect the vapors in the cave
00:49:38 and show that they’re infectious, which,
00:49:40 and by the way, someone emailed me the other day.
00:49:43 You’ll like this.
00:49:44 They say, why can’t we just immunize
00:49:45 all the bats in the world against these viruses?
00:49:49 And I said, well, how would you do that?
00:49:50 There are caves everywhere, right?
00:49:52 Yeah.
00:49:53 He said, well, maybe you could just go and aerosolize.
00:49:56 Yeah.
00:49:57 It’s pretty dangerous.
00:49:58 And then all the bats should have vaccine passports
00:50:01 to make sure that they’re all.
00:50:02 Yeah, and I said, you have to get their consent
00:50:03 before you do it.
00:50:05 But we do immunize wildlife against rabies.
00:50:12 We have rabies vaccines for wild animals.
00:50:15 There are a whole bunch of them that get rabies.
00:50:17 And we put it in bait
00:50:19 and drop it from helicopters in the woods
00:50:21 and it drops down the incidence of rabies in people.
00:50:25 People hiking, get bitten and so forth,
00:50:27 it drops the incidence.
00:50:28 So we can do that.
00:50:29 I didn’t know that.
00:50:30 I always wondered how much medical care
00:50:32 are we doing for animals in the wild
00:50:34 because I’ve recently become more and more aware
00:50:37 that animals are living in extreme poverty, right?
00:50:42 Like you don’t know, you think like natural, it’s great.
00:50:45 Like when animals are living on a farm, it’s terrible.
00:50:51 But then you also have to compare to like
00:50:53 what life is like in the, or like the zoo.
00:50:56 You have to compare what life is like in the wild.
00:50:58 Well, the life in the wild is very tough, I think.
00:51:01 Most animals have to, well, the carnivores anyway,
00:51:03 they have to catch their food every day, right?
00:51:06 And then there’s the viruses there.
00:51:08 Yeah, viruses as well.
00:51:09 So the rabies immunization is the only one I’m aware of
00:51:14 for wild animals.
00:51:17 We do immunize lots of other animals.
00:51:20 So we immunize chickens and pigs and cows,
00:51:24 even fish, farmed fish.
00:51:26 We pick each fish up and give it an injection,
00:51:30 you know, when it’s a small fish.
00:51:32 But that’s mostly so that the farmers get a good yield.
00:51:36 We don’t really care about the animals, right?
00:51:38 We want a good yield for market.
00:51:41 And then there’s some examples where we immunize animals
00:51:46 to prevent spillovers into people.
00:51:50 So there’s a disease called Hendra in Australia,
00:51:53 which was discovered in the 90s.
00:51:57 And it turns out that there are bats, fruit bats,
00:51:59 that have this virus, and the bats are fine,
00:52:02 but sometimes they fly into horse stalls
00:52:05 and the horses get infected.
00:52:06 In Australia, it was initially racehorses,
00:52:09 which are very expensive, right?
00:52:11 The horses got infected and they died,
00:52:12 and the humans who would take care of them would die also.
00:52:15 So now they immunize the horses to prevent the,
00:52:19 well, to save the horses.
00:52:20 Probably that’s the motivation,
00:52:21 because these horses are hundreds of thousands of dollars,
00:52:23 right?
00:52:24 And then the people don’t get sick
00:52:25 because the horses don’t get sick.
00:52:27 You don’t want to immunize all the people
00:52:29 because it’s too rare.
00:52:30 But that approach is called the one world health approach,
00:52:33 which means everything’s connected on the planet.
00:52:37 And we have to think of everything in the grander scheme,
00:52:39 not just us.
00:52:40 Yeah, so you can immunize some things
00:52:42 along the trajectory that a virus would take.
00:52:45 Exactly.
00:52:45 Some living beings.
00:52:48 In the Arabian Peninsula,
00:52:49 they have a MERS coronavirus issue every month.
00:52:52 There are a couple of cases where a camel
00:52:55 will infect a human, and the human can get very sick.
00:52:59 It’s a respiratory disease, very much like COVID.
00:53:03 And so camels are very common there.
00:53:05 They’re raced, they’re used as pets, they’re eaten.
00:53:10 So there’s a lot of human camel contact.
00:53:12 But the number of cases are rare, two a month.
00:53:15 So you don’t want to immunize all the humans.
00:53:16 So the idea would be to immunize the camels.
00:53:20 So.
00:53:21 I like it.
00:53:22 So, okay, so you put rabies.
00:53:23 But Ebola also is a famously deadly one.
00:53:30 What is it?
00:53:30 It kills like, I don’t know, 50%, 60% of its.
00:53:33 It could be 50 to 90, but that’s in Africa,
00:53:37 where the healthcare isn’t great.
00:53:38 You saw when the cases of Ebola came to the U.S.,
00:53:42 we could take care of it.
00:53:43 We knew how to take care of it.
00:53:45 We had fancy hospitals and so forth,
00:53:46 and now we have a vaccine, so we can.
00:53:49 And the vaccine is really good,
00:53:52 but there are many governments in Africa
00:53:54 that are suspicious of us,
00:53:56 and they don’t want to use our vaccine, so they.
00:53:58 So there’s a vaccine for Ebola.
00:54:00 There is, yeah.
00:54:01 And the effectiveness and safety of it,
00:54:04 to how much is understood.
00:54:06 So this is difficult,
00:54:08 because there’s not a lot of Ebola, right?
00:54:11 It’s not a continuous, ongoing thing.
00:54:14 There are sporadic outbreaks here and there.
00:54:16 Of a few thousand people.
00:54:17 At most, at most, usually a few hundred.
00:54:19 And the biggest ever, in fact,
00:54:23 this is why we didn’t for years have an Ebola vaccine.
00:54:25 The U.S. military, together with Canada,
00:54:27 developed an Ebola vaccine for service people, right?
00:54:30 They wanted to say, well, we’re sending people
00:54:32 into these Ebola areas, we want a vaccine for them.
00:54:34 So they had developed it through all the preclinical,
00:54:38 which means before it goes into people.
00:54:40 And that stopped, because there was no money
00:54:43 to do a phase one and a phase two and a phase three.
00:54:46 In fact, for phase two and three,
00:54:47 you need to have infections going on,
00:54:49 because you’re looking at how well
00:54:50 the vaccine prevents infections, right?
00:54:52 So then there was a West African outbreak in 2015.
00:54:57 2013, 2015.
00:54:58 The most cases ever, 25,000.
00:55:00 So they got to test the vaccine.
00:55:03 But they only put it in a few thousand people.
00:55:07 It’s not like it’s been in hundreds of thousands of people
00:55:10 like the COVID vaccines has been.
00:55:12 So it looks like it has high efficacy.
00:55:16 But we’d like to have more data.
00:55:18 Side effects maybe are not so great.
00:55:21 There are a couple of different available vaccines.
00:55:23 Some have been tested more than others.
00:55:25 I would say this would probably not be widely accepted
00:55:29 in the US.
00:55:31 But then neither would be something over 50%
00:55:36 deadliness of a virus.
00:55:38 No, I think if you were, in fact, many physicians
00:55:41 work in countries that have Ebola,
00:55:43 so they get vaccinated, because they understand the choice.
00:55:45 Yeah, right, it’s always about the choice.
00:55:48 So.
00:55:49 So then one more thing.
00:55:50 To answer the interesting,
00:55:53 what are some of the viruses you really are fascinated by?
00:55:57 There are a number of viruses that have clearly been shown
00:56:01 to alter host behavior, and that’s how they spread.
00:56:04 I think those are fascinating.
00:56:05 For example, there are some viruses of plants
00:56:11 that are spread by aphids.
00:56:14 And the aphid bites the plant,
00:56:16 the virus reproduces in the plant,
00:56:18 and it somehow engineers the plant
00:56:21 to give off volatile organics to attract more aphids,
00:56:26 which will spread the virus.
00:56:30 Isn’t that amazing?
00:56:31 Yeah.
00:56:32 So that’s altering the behavior.
00:56:35 Altering because somehow the virus infecting the plant cells
00:56:38 gives off these organics and attracts aphids.
00:56:40 And furthermore, somehow when the aphid bites,
00:56:44 it tastes horrible.
00:56:46 So they immediately leave with the virus
00:56:48 they’ve just picked up and go to another plant to spread it.
00:56:51 So they’re attracted and then repulsed at the same time.
00:56:53 And obviously you don’t want to anthropomorphize this
00:56:55 like a strategy they’re taking on.
00:56:57 Somehow this worked out.
00:56:58 It worked out this way.
00:56:59 It just evolved.
00:57:00 And you know, evolution is sometimes hard to trace, right?
00:57:04 Like Darwin famously said,
00:57:06 he could never figure out how an eye evolved
00:57:08 from a single cell, right?
00:57:09 But it did.
00:57:11 The more complicated, complex the holistic organism is
00:57:16 that the virus invades,
00:57:18 the less able it is to control that organism, right?
00:57:21 So I wonder if there’s viruses
00:57:22 that can control human behavior,
00:57:26 you know, to induce more spread of the virus.
00:57:32 Well, I don’t see why not.
00:57:34 There’s not enough humans
00:57:35 that’s supposed to like evolve through.
00:57:37 Well, we can’t do the experiment to test it, right?
00:57:39 We have to observe.
00:57:40 And that’s always hard when you’re observing
00:57:41 because there’s so many things that can confound
00:57:45 what you’re looking at.
00:57:45 Yeah, change human behavior, yeah.
00:57:47 I mean, there’s so many things that impinge on our behavior,
00:57:50 but yeah, I think it’s possible.
00:57:54 I think it’s highly possible.
00:57:56 If it does it in a plant,
00:57:58 why not change some other organism’s behavior?
00:58:00 I think it’s fine.
00:58:01 Anyway, those fascinate me.
00:58:02 There are lots of examples of those that are fascinating
00:58:06 and how they work, people are trying to figure out.
00:58:08 But there’s not a lot of money to work on, you know,
00:58:10 insect and plant viruses unless you’re going to the USDA.
00:58:13 So they don’t get a lot of work moving forward.
00:58:17 Well, is there, if you understand some of those viruses,
00:58:19 is that transferable to human viruses, that understanding?
00:58:23 I think some of it could be, sure.
00:58:25 I think the general principles, for example,
00:58:28 how does the virus cause volatile organics to be made?
00:58:32 It must be turning on some genes
00:58:34 and you could learn principles from that,
00:58:37 how the virus might do that.
00:58:38 Sure, I think everything is broadly applicable.
00:58:41 So to say it’s not useful to study viruses of insects
00:58:46 and plants is just wrong because in science,
00:58:49 we probably know this, maybe in your field it’s the same.
00:58:52 If you’re curious, you’re going to run into interesting
00:58:55 things that you never planned on, right?
00:58:57 That’s why people like, you can criticize,
00:58:59 why do we want to go on Mars?
00:59:01 Why do we want to colonize Mars?
00:59:03 Well, it’s like, why do you want to go to the moon?
00:59:06 The reality is when you do really difficult things,
00:59:10 engineering things, like all these inventions
00:59:13 along the way are created.
00:59:14 It’s kind of fascinating.
00:59:16 Basically just pick a thing that everyone can agree
00:59:21 is kind of cool and is really hard and do that.
00:59:24 And then you’ll have like thousands of inventions
00:59:26 that have nothing to do with the thing.
00:59:28 That’s right.
00:59:29 I think you should let curious scientists
00:59:32 just follow what they’re interested in
00:59:34 to a certain extent.
00:59:35 You can’t, in science we say we have translational research
00:59:38 where we say, okay, here’s some money,
00:59:40 go cure cancer or diabetes or heart disease, whatever.
00:59:43 And that’s fine.
00:59:44 But that often doesn’t work out very well.
00:59:46 What works better is to say, you have a good lab,
00:59:49 you have a good track record,
00:59:50 here’s some money, here’s something.
00:59:52 And that’s where PCR, CRISPR, recombinant DNA,
00:59:56 all that stuff which has made the field explode,
00:59:59 that’s all it came from.
01:00:00 Not from people saying, I want to cure genetic diseases
01:00:04 by gene editing, but by saying,
01:00:05 what are these repeated things in this bacterium doing?
01:00:09 Yep.
01:00:11 Can I ask you a big philosophical question?
01:00:14 So there’s these deadly viruses
01:00:17 that are not very transmissible, Ebola, rabies.
01:00:21 And then there’s these less deadly viruses
01:00:23 that are very transmissible, like COVID,
01:00:29 I guess kind of borderline.
01:00:31 But why isn’t there super transmissible,
01:00:35 super deadly viruses?
01:00:38 I think if you compare SARS one and two,
01:00:40 you get somewhat of an answer, right?
01:00:42 SARS one was more deadly.
01:00:45 In fact, over half of the time when people were infected,
01:00:50 they ended up in the hospital because they were that sick.
01:00:53 And then the peak of virus shedding from them
01:00:57 happened long after they went in the hospital.
01:00:59 So it’s easy to contain the infection
01:01:02 when you’re in a hospital, right?
01:01:04 There was not much pre symptomatic
01:01:07 or asymptomatic shedding with SARS one.
01:01:11 And shedding means you become infectious.
01:01:14 So in a respiratory virus,
01:01:16 you inhale the droplets with the virus
01:01:18 and they reproduce in your upper respiratory tract,
01:01:20 what we call the nasopharynx, right?
01:01:22 The nose and going back to that little cavity
01:01:24 just above your mouth.
01:01:27 So the virus reproduces really well.
01:01:28 And then as you talk and sneeze and cough,
01:01:30 you expel droplets and then those are inhaled
01:01:32 by other people and then they reproduce.
01:01:35 And for SARS two, we now know there’s a lot of reproduction
01:01:39 just before you feel anything, if at all.
01:01:42 So there’s a lot of shedding and transmission
01:01:45 before you get symptomatic.
01:01:47 And as many people don’t ever get symptomatic, right?
01:01:50 So they spread really easily.
01:01:52 So that explains why some viruses can transmit
01:01:55 a lot better than others.
01:01:57 And if one happens to knock you out,
01:02:00 then you’re never gonna transmit
01:02:01 because you’re in the hospital like SARS one.
01:02:03 But why can’t you have both?
01:02:05 Why can’t you just wait a while before it knocks you out
01:02:08 but when it knocks you out, it really kills you?
01:02:10 That is a philosophical question, right?
01:02:13 Because we could talk about why we haven’t observed it.
01:02:16 I mean, one issue is that if you’re killed too quickly
01:02:23 by a highly lethal virus,
01:02:25 you’re not gonna transmit it very well, right?
01:02:27 So Ebola can kill you quite rapidly.
01:02:31 And most of the transmission occurs when people
01:02:35 are being cared for at home or in hospitals.
01:02:38 The doctors and nurses get the virus,
01:02:40 but people walking around, you’re not walking around
01:02:42 when you have Ebola, you’re too sick.
01:02:45 You know, you have black, bloody diarrhea,
01:02:47 you’re vomiting, you’re bleeding from your skin
01:02:51 and mucous membranes, you’re not walking around,
01:02:54 you’re not going to parties.
01:02:55 So I think that’s part of it,
01:02:57 that if the infection is too lethal,
01:03:00 you’re simply not a good transmitter.
01:03:02 And I think transmission is probably one
01:03:05 of the most powerful selection forces for viruses
01:03:09 because a virus always has to find a new host.
01:03:12 If it doesn’t, it’s a startup that fails, right?
01:03:16 If it doesn’t find a new host, it’s gone.
01:03:18 And so anything that makes the virus transmit better
01:03:22 is gonna help it.
01:03:23 And if killing you, being less lethal is part of that,
01:03:27 that works too.
01:03:28 So there’s a strong selection pressure
01:03:30 against being lethal.
01:03:32 I think there’s a strong selection pressure
01:03:34 against being lethal and being more transmissible.
01:03:38 Those two seem to work in opposite ways.
01:03:41 And now we don’t have a lot of data to support this.
01:03:43 This is kind of a thought experiment,
01:03:46 but there is one experiment done in Australia
01:03:50 many years ago.
01:03:51 I don’t know if you know this, but in the 1800s,
01:03:54 the hunters in Australia imported a rabbit from Europe
01:03:57 so they could hunt it because the native rabbit
01:04:00 in Australia was too fast for them.
01:04:02 They couldn’t shoot them.
01:04:03 So they brought in this European rabbit
01:04:05 and they reproduced out of control.
01:04:07 Within a couple of years, they were everywhere,
01:04:10 millions of rabbits in all the watering holes.
01:04:13 And now they had a problem.
01:04:14 So they decided to use a virus
01:04:16 to get rid of these excess rabbits.
01:04:19 And they used a virus, a pox virus called myxoma virus,
01:04:22 which is a natural virus of a different kind of rabbit.
01:04:26 But for these European rabbits, it was quite lethal
01:04:28 and it’s spread by mosquitoes.
01:04:30 So they said, okay, let’s release this virus.
01:04:33 And the first year, 99.2% of the rabbits were killed,
01:04:40 but that 0.8% that were left had some form of resistance.
01:04:45 They were variants.
01:04:46 Every organism, not just viruses, makes mutants.
01:04:49 And there were some variants of the rabbits
01:04:51 that could survive infection.
01:04:52 And then in subsequent years, the virus became less lethal.
01:04:56 And then the mosquitoes had a better shot
01:04:59 of transmitting it from one rabbit to another
01:05:01 if the rabbit lived longer.
01:05:02 That’s the selection probably.
01:05:04 And so in the end, the rabbits lived on.
01:05:06 The virus was there.
01:05:07 It evolved to be more transmissible and less lethal.
01:05:11 So that’s the only.
01:05:12 Life is amazing.
01:05:13 That’s the only data. Life on Earth is amazing.
01:05:15 It is, it is.
01:05:15 If you take the time to look at it and see what’s happened,
01:05:19 it is amazing.
01:05:20 It’s also humbling that it just makes you realize
01:05:22 humans are just a small part of the picture.
01:05:25 Of course.
01:05:26 And we’re wrecking it, aren’t we?
01:05:28 Well, I mean, we’re not really.
01:05:32 I mean, viruses are wrecking it some ways.
01:05:35 We’re not really wrecking anything.
01:05:36 It’s all part of it.
01:05:38 But you know, when the ways that humans exist
01:05:41 encourages viruses to infect us, right?
01:05:43 When we were hunter gatherers,
01:05:45 living in bands of 100 people, very few viruses
01:05:49 because it was hard for the virus to go
01:05:51 from one band to another.
01:05:53 And perhaps a hunter would, one of these humans
01:05:55 would get an animal and bring a virus into camp
01:05:58 and some people would die,
01:05:59 but it would never spread to another.
01:06:02 And then when we started to congregate in cities,
01:06:04 we figured out agriculture and so forth
01:06:06 and how to harvest animals,
01:06:07 then we could get bigger and bigger populations
01:06:09 and the viruses went crazy.
01:06:10 And they went from animals to us.
01:06:12 So measles went from cows to humans
01:06:15 when humans learned to domesticate cows
01:06:17 and started gathering in big cities.
01:06:20 Yeah, but now that humans are able to communicate
01:06:24 and travel globally,
01:06:26 the viruses become more and more dangerous, transmissible.
01:06:31 Thereby, if you look at earth as an organism,
01:06:33 thereby pushing humans to be more innovative,
01:06:36 create alpha fold two and three and four and five,
01:06:39 create better systems and eventually there’s rockets
01:06:41 that keep flying from earth.
01:06:43 And eventually the virus is becoming super dangerous
01:06:47 and threatening all of human civilization,
01:06:49 will force it to become a multi planetary species
01:06:52 and its organism starts expanding.
01:06:54 So I think it’s a feature, not a bug, I don’t know.
01:06:57 Well, I think that we have our early,
01:07:00 probably the most of the,
01:07:03 we’re studying viruses since 1900, right?
01:07:06 Most of that time was because of diseases they caused.
01:07:09 The first viruses discovered, yellow fever,
01:07:12 virus, smallpox, polio virus, influenza virus,
01:07:17 those were all because people got sick and they said,
01:07:21 oh, look, this is a virus that’s associated with it.
01:07:24 And so we got good at learning how to take care
01:07:28 of these infections, making vaccines and so forth
01:07:31 over the years and it’s only in the last 20 years
01:07:33 that we recognize that there are more viruses out there
01:07:36 that are far more interesting, perhaps,
01:07:38 but we’ve learned how to deal with the bad ones for sure.
01:07:41 So we talked about what is a virus.
01:07:43 We talked about some of the most dangerous
01:07:45 and deadly viruses.
01:07:47 Can we zoom in and talk about COVID 19 virus?
01:07:51 Sure.
01:07:52 I don’t know what your preferred name is, but maybe for this.
01:07:54 Right, the virus is SARS CoV2, which is hard, it’s long,
01:07:58 and then COVID 19 is the disease.
01:08:00 So you could say the virus of COVID 19, that’s fine.
01:08:03 The virus of COVID 19.
01:08:04 But for the purpose of this conversation,
01:08:06 we’ll every once in a while just say COVID.
01:08:08 It’s fine, no problem.
01:08:10 What is this virus from,
01:08:14 I don’t know how many ways we can talk about it.
01:08:16 I think from a basic structural,
01:08:19 like the variant structure,
01:08:22 biological structure perspective, what is it?
01:08:25 What are its variants?
01:08:28 Can you describe the basics,
01:08:30 the important characteristics of the virus?
01:08:32 So viruses are classified by humans
01:08:35 just to make it easier to keep track of them, right?
01:08:38 So this is a coronavirus, which is because
01:08:42 when they were first discovered,
01:08:45 I think the first ones were animal coronaviruses.
01:08:48 They looked at them in the electron microscope
01:08:50 and it looked like the solar corona,
01:08:51 and that’s all there is to it.
01:08:53 And I have to say that early in the outbreak,
01:08:56 the place with the highest seropositivity in the US,
01:09:00 for a while, 68% was a working class neighborhood
01:09:03 in New York City called corona.
01:09:06 Can you beat that, right?
01:09:08 That’s crazy, yeah.
01:09:09 So coronaviruses, they have membranes, right?
01:09:12 We talked about membranes,
01:09:13 they have spike proteins in the membrane,
01:09:15 so they can attach to cells.
01:09:16 And inside, they have RNA.
01:09:19 And they are the viruses with the longest RNA
01:09:22 that we know of.
01:09:23 None other comes close.
01:09:25 For some reason, they’re able to maintain 30,000,
01:09:29 so SARS, COVID, two RNAs, 30,000 bases of RNA,
01:09:33 and some of the other coronas are even longer, 40,000.
01:09:37 This is a, coronas are family of viruses
01:09:40 that included the one you mentioned before, version one.
01:09:46 So SARS, COVID one, yeah.
01:09:47 COVID one, and I guess other ones as well.
01:09:49 So the first, we first learned of them in animals,
01:09:52 a lot of animals, pigs, and cows,
01:09:56 and horses have coronaviruses.
01:09:58 And then in the 60s, we discovered
01:10:01 a couple of human coronaviruses that just cause colds,
01:10:05 very mild colds that you wouldn’t even think twice about.
01:10:08 And then suddenly, in 2003, there’s this outbreak
01:10:14 of severe respiratory disease in China.
01:10:18 And it started in November,
01:10:21 and they didn’t tell the world until February.
01:10:24 And that was really bad, because it was already spreading
01:10:27 by the time they told people about it.
01:10:30 But this went to 29 different countries.
01:10:34 Only 8,000 people were infected, and then it stopped.
01:10:37 And that was the first time we saw an epidemic coronavirus.
01:10:43 And what they did afterwards is they said,
01:10:45 okay, it looks like it came from the meat markets.
01:10:48 They have live meat markets in Guangzhou,
01:10:50 in the south of China, where you can go
01:10:53 and pick out an animal and the guy will slaughter it for you
01:10:56 and give it to you, and then of course,
01:10:57 there’s blood everywhere, and that’s how they got infected.
01:11:00 And they figured out that there’s this animal
01:11:02 called a palm civet, that was the source of virus.
01:11:05 The palm civets are shipped in from the countryside,
01:11:08 and the palm civets somehow in the countryside
01:11:10 got it from a bat.
01:11:11 So they went looking in caves in the countryside,
01:11:13 and they found in one cave all the viruses
01:11:16 that could make up SARS 1.
01:11:19 And that was 2000, and I would say,
01:11:21 took about five, eight years after that outbreak.
01:11:24 So that was the first hint that bats have coronaviruses
01:11:30 that can infect people and cause problems, right?
01:11:32 And after that, we should have been ready.
01:11:35 So didn’t they already start developing
01:11:37 vaccines after then? Yes.
01:11:38 So some people started making vaccines.
01:11:41 They tested them in mice, but they never got into people.
01:11:46 And some people started working on antiviral drugs.
01:11:50 Nothing ever came of them because, you know,
01:11:54 industry, there’s no disease, it’s gone.
01:11:57 Why should we make vaccines and drugs?
01:11:59 And NIH in the US, you submit a grant,
01:12:02 and they say, ah, it’s too risky.
01:12:03 There’s none of this virus around.
01:12:05 So people were really shortsighted because I always say,
01:12:08 we could have had antivirals for this, absolutely, for sure.
01:12:13 No question.
01:12:14 In fact, the one antiviral that’s in phase three,
01:12:17 it’s called molnupiravir.
01:12:20 It’s the only one that you can take orally.
01:12:22 It’s a pill.
01:12:23 It looks really good.
01:12:24 That was developed five years ago,
01:12:26 but never taken into humans.
01:12:27 It could have been ready.
01:12:29 So we dropped the ball, and then the next decade, 2012,
01:12:33 MERS coronavirus comes up in the Arabian Peninsula.
01:12:38 This comes from camels and infects people,
01:12:41 but probably the camels got it from bats originally
01:12:44 some time ago.
01:12:46 But that never transmits from person to person, very rarely.
01:12:50 Every new little outbreak is a new infection from a camel.
01:12:55 So that was 2012, and now here we are, 2019,
01:12:59 the new outbreak of respiratory disease in China.
01:13:02 And this one really goes all over the world
01:13:06 where SARS1 could not.
01:13:07 It’s a coronavirus.
01:13:09 It’s different enough from SARS1
01:13:11 that it has very different properties.
01:13:12 Causes a lot.
01:13:13 But it still has a membrane.
01:13:14 It still has a very long RNA in the middle,
01:13:17 and then it still has the spike proteins.
01:13:19 That’s right.
01:13:20 What are the things that are,
01:13:22 what are the little unique things
01:13:24 that make it that much more effective?
01:13:27 That make it cause a pandemic of millions of people
01:13:30 as opposed to SARS1?
01:13:32 Well, the genome is 20% different from SARS1, say.
01:13:38 And in those bases, there’s some,
01:13:40 there are things that make it different from SARS1.
01:13:42 It binds the same receptor, ACE2, on the cell surface.
01:13:45 So that’s remarkable.
01:13:48 It has a lot of the same proteins.
01:13:50 They look similar.
01:13:50 Like if you look at the structure of the spikes,
01:13:53 they look similar,
01:13:54 but there’s enough amino acid differences
01:13:57 to make the bio.
01:13:58 And what it is, we don’t know,
01:14:00 because how do you figure that out?
01:14:03 You need to study animals,
01:14:04 because you can’t infect people.
01:14:06 And the animal models aren’t great.
01:14:10 So the way you figure that out
01:14:11 is you figure out how those differences,
01:14:14 what functional,
01:14:16 like how the difference in the amino acids
01:14:18 lead to functional difference of the virus.
01:14:20 That’s right.
01:14:21 Like how it attaches, how it breaks the cell wall.
01:14:23 Exactly.
01:14:24 And how the hell do you figure that out?
01:14:25 Like, I guess there’s models of interaction.
01:14:29 First, you need an animal of some kind to infect, right?
01:14:33 You can use mice.
01:14:34 People have used ferrets, guinea pigs,
01:14:38 nonhuman primates,
01:14:40 all of the above.
01:14:41 Nonhuman primates are very expensive,
01:14:43 so not many people do that.
01:14:45 And then you can put the virus in the respiratory tract.
01:14:48 But in fact, none of them get sick like people do.
01:14:52 Many people with COVID get a mild disease,
01:14:55 but 20% get a very severe, longer lasting disease.
01:14:59 They can die from it, right?
01:15:00 No animal does that yet.
01:15:03 So we have no insight into what’s controlling that.
01:15:05 But if you just wanna look at the very first part
01:15:07 of infection and the shedding and the transmission,
01:15:10 you can do it in any one of several animal models.
01:15:14 Ferrets are really good for transmission.
01:15:16 They tend to have nasal structures like humans
01:15:19 and you can put them in cages next to each other
01:15:22 and they’ll transmit the virus really nicely.
01:15:24 So you can study that.
01:15:26 But the other thing that’s important that we should mention
01:15:29 is how do you manipulate these viruses?
01:15:34 So these are RNA viruses.
01:15:36 You can’t manipulate RNA.
01:15:38 We don’t know how to do it.
01:15:40 But DNA, because of the recombinant DNA revolution
01:15:45 that occurred in the 70s,
01:15:47 we can change DNA any way we want.
01:15:51 We can change a single base, we can cut out bases,
01:15:53 we can put other things in really easily.
01:15:56 And if I may give it a personal aspect,
01:16:01 when I went to MIT as a postdoc in 1979,
01:16:05 David Baltimore said, here’s what I want you to do.
01:16:09 The moratorium on recombinant DNA experiments
01:16:12 on viruses has just been lifted.
01:16:14 I want you to make a DNA copy of polio
01:16:18 and see if you put that in a cell
01:16:19 whether it will start an infection.
01:16:21 It’s okay.
01:16:24 So I made a DNA copy of polio virus.
01:16:27 It’s only 7,500 bases.
01:16:29 It’s much smaller than corona.
01:16:31 And I took that DNA and I put it in a piece of DNA
01:16:35 from a bacteria called a plasmid.
01:16:37 And you can grow plasmids in many, many bacteria,
01:16:41 make lots of them and purify the DNA really easily.
01:16:44 And I took that DNA and I sequenced it
01:16:48 because we didn’t know the genome sequence
01:16:50 of polio at the time.
01:16:52 And that took me a year by the way,
01:16:54 because the techniques we had were really archaic
01:16:57 and nowadays you could do it in 15 minutes, right?
01:17:00 It’s amazing.
01:17:01 And I took the DNA, I put it into cells and out came polio.
01:17:06 So that’s the start.
01:17:07 Now, since then everybody has taken that technique
01:17:10 and used it for their virus.
01:17:11 You can now do it with SARS CoV2.
01:17:13 You make a DNA copy of any RNA virus,
01:17:16 you can modify it and you put it back into cells
01:17:19 and you’ll get your modified virus out.
01:17:21 So that’s an important part of understanding
01:17:23 the properties of the virus as, say, in an animal.
01:17:26 By changing the virus, you’re changing a DNA copy,
01:17:28 you’re making the virus then and putting it into the animal.
01:17:32 Can you clarify, so even in the RNA virus,
01:17:35 you can take and turn it into DNA?
01:17:38 Yes.
01:17:38 And then that allows you to modify it.
01:17:41 Yes.
01:17:41 What’s that mapping?
01:17:44 Well, no, no, no, what’s the process
01:17:46 of going from RNA to DNA?
01:17:48 Reverse transcription.
01:17:49 That’s reverse transcription.
01:17:50 Right.
01:17:51 Oh, so you actually go through the process
01:17:53 of reverse transcription to do this?
01:17:54 Yes.
01:17:55 Remember, David Baltimore and Howard had discovered
01:17:58 this enzyme in the 70s.
01:18:00 They got the Nobel Prize for that.
01:18:01 And when I went to David’s lab at MIT,
01:18:04 he had the enzyme in the freezer.
01:18:06 He said, here, take this and make a DNA copy of polio.
01:18:08 Yeah, I didn’t make the connection
01:18:10 that you can use that kind of thing for an RNA virus.
01:18:14 And so that’s.
01:18:14 And then modify it.
01:18:15 See, any DNA virus already exists as DNA.
01:18:18 So you can modify it.
01:18:19 But for RNA viruses, it was difficult.
01:18:22 And so then from that point on, for influenza,
01:18:25 every other RNA virus and coronaviruses,
01:18:28 people made DNA copies.
01:18:29 And that’s what they use to modify
01:18:31 and ask questions about what things are doing, right?
01:18:34 What’s this gene doing?
01:18:35 What if we take it out?
01:18:36 What happened?
01:18:37 Can you do the same thing with COVID?
01:18:39 Is take the RNA and then.
01:18:41 Of course.
01:18:42 And in fact, in January 2020,
01:18:44 as soon as the genome sequence was released from China,
01:18:47 the labs all over were synthesizing this 30,000 base DNA
01:18:52 and getting virus.
01:18:54 What can you figure out without infecting anything?
01:18:58 Just turning into, with the reverse transcription,
01:19:01 turning into DNA, modifying stuff,
01:19:03 and then putting it into a cell.
01:19:05 What can you figure out from that?
01:19:08 Oh, well, you could, let’s say you can cut out a gene.
01:19:11 You see some genes in the sequence.
01:19:13 I don’t know what these genes do.
01:19:14 Let’s cut them out.
01:19:16 And then you could cut them out of the DNA.
01:19:18 You put the DNA in cells and maybe you get virus out.
01:19:22 And you go, oh, clearly that gene’s not needed
01:19:25 for the virus to reproduce, at least in cells, right?
01:19:27 Or maybe you take the gene out
01:19:29 and you never get any virus, so it’s lethal.
01:19:31 Is there a nice systematic ways of doing this?
01:19:33 Do people kind of automate it?
01:19:35 Absolutely.
01:19:36 And we, I mean, the problem with SARS, the COVID virus,
01:19:41 is it’s 30,000 bases, a lot of stuff there.
01:19:44 And what makes it more difficult is that you have to,
01:19:48 it’s been classified as a BSL3 agent, biosafety level three.
01:19:55 And so not everyone has a lab that’s capable of doing that.
01:19:58 So it limits the number of people who can do experiments.
01:20:02 You know, we’re lucky to have a few in New York City,
01:20:05 but not every place has them.
01:20:07 So you cannot work with a virus just out on the bench
01:20:11 like we do with many other viruses.
01:20:13 You have to wear a suit and have to have special procedures
01:20:15 and containment and so forth.
01:20:16 So it makes it difficult to do basic experiments
01:20:19 on the virus.
01:20:20 But when it’s a pandemic, there’s a lot of money,
01:20:22 there’s a lot of incentive to work on it harder.
01:20:25 And also you don’t need to work on the virus.
01:20:27 You can take bits of it and work.
01:20:29 You could take, say, just the spike, right?
01:20:31 And say, can we make a vaccine with just the spike?
01:20:33 Because that doesn’t require BSL3, so yes.
01:20:36 So like building a vaccine requires you to figure out
01:20:40 how, or antiviral drugs, how to attack various structural
01:20:44 parts of the virus and the functional parts of the virus.
01:20:47 Right.
01:20:47 You have to decide on a target.
01:20:50 Yeah.
01:20:50 Like, I’m gonna make an antiviral,
01:20:52 what am I gonna target in the virus?
01:20:55 And there are a few things that make more sense than others.
01:21:00 Usually we like to target enzymes.
01:21:03 I don’t know if you remember your biochemistry,
01:21:05 but enzymes are catalytic.
01:21:07 You don’t need a lot of them to do a lot of things.
01:21:10 So they’re typically in low concentrations
01:21:12 in a virus infected cell.
01:21:14 So it’s easier to inhibit them with a drug.
01:21:17 And the coronas have a couple of enzymes that we can target.
01:21:20 So you have to figure that out ahead of time
01:21:23 and decide what to go after.
01:21:25 And then you can look for drugs that inhibit
01:21:27 what you’re interested in.
01:21:28 It’s not that hard to do.
01:21:31 There’s just something beautiful about biology,
01:21:34 about the mechanisms of biology.
01:21:36 And I kind of regret falling in love
01:21:40 with computer science so much
01:21:41 that I left that biology textbook on the show
01:21:46 and left it behind.
01:21:47 But hopefully we’ll return to it now
01:21:49 because I think one of the things you learn
01:21:51 even in computer science that studying biology
01:21:56 and certainly neurobiology,
01:22:00 you get inspired.
01:22:02 Here’s a mechanism of incredible complexity
01:22:05 that works really well, is very robust,
01:22:07 is very effective, efficient.
01:22:09 It inspires you to come up with techniques
01:22:11 that you can engineer in the machine.
01:22:13 That’s what drives a field forward
01:22:15 when people improvise and come up with new technologies
01:22:21 that really make a difference.
01:22:22 And we have a bunch of those now.
01:22:25 What’s the difference between the coronavirus family
01:22:28 and the other popular family, influenza virus family?
01:22:33 I mean, if I were, because you mentioned
01:22:37 we should have done a lot more
01:22:38 in terms of vaccine development,
01:22:39 that kind of thing for coronaviruses.
01:22:42 But if I were back then, from my understanding,
01:22:46 the thing we should all be afraid of is influenza,
01:22:49 like some strong variants coming out from that family.
01:22:53 That seems like the one that will destroy human civilization
01:22:57 or hurt us really badly.
01:23:00 I don’t know if you agree with this sense,
01:23:02 but maybe you can also just clarify
01:23:06 what to use as the difference between the families.
01:23:09 So it’s an interesting difference.
01:23:11 They both have membranes, right?
01:23:14 So then they have spike proteins embedded in them.
01:23:19 And they’re different spikes.
01:23:20 In fact, for influenza, there are two main ones.
01:23:24 They’re called the HA and the NA.
01:23:27 But what’s inside is RNA,
01:23:30 but it’s very different RNA.
01:23:33 And here we have to explain that.
01:23:35 So viruses with RNA can have three different kinds of RNA.
01:23:42 They can have what we call plus RNA.
01:23:45 They can have minus RNA,
01:23:48 or they could have plus minus,
01:23:49 actually two strands hybridized together.
01:23:54 The plus RNA simply means that
01:23:58 if you put that plus RNA in a cell,
01:24:01 you know, your cell has ribosomes in it
01:24:03 that make the proteins that you need.
01:24:05 The ribosomes will immediately latch onto the plus RNA
01:24:08 and begin to make proteins.
01:24:11 A minus RNA is not the right strand to make proteins.
01:24:15 So it has to be copied first.
01:24:17 And then the plus minus is both together.
01:24:19 So the SARS coronaviruses,
01:24:22 all the coronaviruses have plus RNA.
01:24:25 So as soon as that RNA gets in the cell,
01:24:26 boom, it starts an infectious cycle.
01:24:28 Same thing with poliovirus, by the way, which I worked on.
01:24:31 Influenza viruses are negative stranded.
01:24:34 So they cannot be translated when they get in the cell.
01:24:37 So that’s tough for the virus
01:24:40 because the cell actually cannot make plus RNA
01:24:45 from minus RNA.
01:24:47 It doesn’t have the enzyme to do it.
01:24:49 So the virus has to carry it in inside the virus particle.
01:24:53 And then when the minus RNA is in the cell,
01:24:55 the virus enzyme makes plus RNAs and those get translated.
01:24:59 So it’s a big difference.
01:25:00 And then in the influenza viruses,
01:25:03 not only is it minus RNA, but it’s in pieces.
01:25:07 It’s in eight pieces.
01:25:09 We call that segmented,
01:25:10 whereas the corona is in one long piece of RNA.
01:25:14 So they’re like floating separately?
01:25:17 Yeah, so the genes are on separate pieces.
01:25:19 They’re all packaged inside that virus particle
01:25:21 of influenza virus, but they’re in pieces.
01:25:23 And why that’s important
01:25:25 is because if two different influenza viruses
01:25:29 infect the same cell,
01:25:31 the pieces as they reproduce can mix
01:25:33 and out can come a virus with a new assortment of pieces.
01:25:38 And that allows influenza virus
01:25:40 to undergo extremely high frequency evolution.
01:25:43 That’s why we get pandemics.
01:25:45 When we have a new flu pandemics
01:25:47 is because somewhere in some animal,
01:25:49 two viruses have reassorted
01:25:51 and made a new virus that we hadn’t seen before.
01:25:54 So you’re talking about kind of biological characteristics,
01:26:00 but what am I incorrect in my intuition
01:26:03 that are from the things I’ve heard
01:26:05 that the influenza family viruses is more dangerous?
01:26:09 Like what makes it more dangerous to humans?
01:26:14 Well, it depends on the,
01:26:16 there are many flavors or vintages of influenza virus.
01:26:19 Some are dangerous and some are not, right?
01:26:21 It depends on which one.
01:26:22 Some like the 1918 apparently was very lethal,
01:26:26 killed a lot of people.
01:26:28 But more contemporary viruses,
01:26:30 we had a pandemic in 2009 of influenza.
01:26:35 That wasn’t such a lethal virus.
01:26:39 We don’t know exactly why,
01:26:40 but it didn’t kill that many people.
01:26:42 It transmitted pretty well.
01:26:43 Is that the bird flu one?
01:26:45 They’re all deriving.
01:26:47 That one was called swine influenza.
01:26:49 Swine, that’s right, swine, yeah.
01:26:50 It seemed to have started in a pig,
01:26:52 but it had bird, it had RNAs from bird influenza viruses.
01:26:57 These viruses are all reassortants of different viruses
01:27:00 from pigs and birds and humans.
01:27:04 But influenza can cause pneumonia
01:27:07 and can kill you as does SARS COVID too.
01:27:09 So it depends on the virus.
01:27:11 So there is another influenza virus
01:27:13 that’s currently circulating.
01:27:14 So right now we have the 2009 pandemic virus
01:27:18 that’s still around.
01:27:20 And then the 1968 pandemic virus,
01:27:23 which was the one before 2009,
01:27:25 that one is still around too.
01:27:27 And that’s more lethal.
01:27:29 And depending on the season,
01:27:30 some seasons the 2009 virus predominates,
01:27:33 some seasons the 1968.
01:27:36 And when the 68 is around, you get more lethality.
01:27:38 So we’re living with an influenza family.
01:27:41 We haven’t exterminated them.
01:27:43 Right, we never will, never exterminate them.
01:27:46 Why?
01:27:47 Because every shorebird in the world is infected with them.
01:27:51 Gulls and terns and ducks and all sorts of things.
01:27:54 Why can’t we develop strong vaccines that defend against?
01:27:59 Oh, we could do that, sure.
01:28:02 But that would not eliminate them from humans.
01:28:04 Even if you had the best vaccine,
01:28:06 you would never get rid of it in people
01:28:08 because there would always be someone who’s not vaccinated
01:28:12 or in which the vaccine didn’t work.
01:28:14 No vaccine is 100%.
01:28:16 So.
01:28:17 Well, you just contradicted yourself.
01:28:18 You said the perfect vaccine.
01:28:21 So.
01:28:21 Imperfect, imperfect.
01:28:23 But then you said, like, even if you had the perfect,
01:28:26 yeah, some people wouldn’t get vaccinated.
01:28:28 But I understand what you mean.
01:28:30 But I actually was asking how difficult is it
01:28:32 to make vaccines like that for,
01:28:35 it seems like it’s very difficult to do that
01:28:36 for the influenza virus.
01:28:38 So it’s really easy to make an old school vaccine.
01:28:42 So the way the first influenza vaccines were made
01:28:47 was actually Jonas Salk worked on them in the 40s.
01:28:51 You just grow lots of virus
01:28:53 and you grow it in eggs, by the way, chicken eggs.
01:28:55 Nice.
01:28:56 Literally?
01:28:57 Wait, wait.
01:28:58 Yeah, chicken, embryonated.
01:28:59 So they get fertilized and there’s a 10 or 12 day embryo
01:29:02 in it and you put virus in it, it grows up
01:29:04 and then you harvest it.
01:29:05 You get about 10 mls of fluid.
01:29:08 And then you take that,
01:29:09 you treat it with formaldehyde or formalin
01:29:12 and it inactivates the virus so it’s no longer infectious.
01:29:16 And you just inject that into people.
01:29:18 And that was the first flu vaccine.
01:29:19 It was made for the US Army actually.
01:29:22 And then it got moved over to people.
01:29:24 We still use that old school tech today.
01:29:27 So you’re taking, can you help me out here?
01:29:30 Okay, so this is a good time to talk about vaccines.
01:29:34 Okay, so you’re talking about,
01:29:36 you’re taking the actual virus,
01:29:39 you put it in an egg, you let it grow up.
01:29:42 It’s very funny that you put it in an egg.
01:29:44 It’s very poetic.
01:29:46 And then how do you make it not infection,
01:29:52 not effective or whatever?
01:29:53 Not infectious.
01:29:54 Not infectious, is that the right term here?
01:29:56 Yeah.
01:29:57 So how do you make it not infectious?
01:29:58 You can treat it with any number of chemicals
01:30:02 that’ll disrupt the particle so it no longer infects.
01:30:05 So that step of disrupting the particle
01:30:09 is that very specific to a particular variant particle?
01:30:12 No, the same collection of chemicals
01:30:14 you can use for all kinds of,
01:30:16 and which have been used for SARS CoV2 vaccines also.
01:30:19 Same technology.
01:30:20 Okay, so what are, there’s several things to ask.
01:30:23 So you called it old school in a way
01:30:25 that’s slightly dismissive,
01:30:27 like people talk about Windows 98 or something.
01:30:29 So is there risks involved with it?
01:30:34 Or is it just difficult to produce large amounts?
01:30:37 No, it’s only, it’s,
01:30:38 it’s very easy.
01:30:40 I mean, you could do it in cells and culture,
01:30:41 but eggs were convenient.
01:30:43 And in the 1940s, we didn’t have cells and culture.
01:30:46 We didn’t know how to do that.
01:30:47 So we had to use something else.
01:30:49 It’s easy to do,
01:30:52 but the process of inactivating the virus with a chemical
01:30:56 makes it not the best vaccine you can make.
01:30:59 The flu vaccines that we have today,
01:31:02 which are mostly based on this inactivation,
01:31:05 is called inactivated virus vaccines.
01:31:08 Oh, so like the kind of thing
01:31:12 it presents to the immune system to train on
01:31:14 is not close to the actual virus.
01:31:19 Yes, that’s what we think.
01:31:20 So that’s why probably the flu vaccines
01:31:22 are just not very good, you know?
01:31:24 60% efficiency at the best, right?
01:31:29 Which is not really good.
01:31:30 What does it mean?
01:31:31 What is the measure of efficiency for a vaccine?
01:31:33 Well, it’s how it does in the general population
01:31:37 at preventing influenza.
01:31:38 At preventing?
01:31:40 Illness, not infection.
01:31:41 We usually don’t measure infection
01:31:44 when we’re testing a vaccine.
01:31:46 We just measure sickness.
01:31:47 That’s really easy to score, right?
01:31:50 You do a trial and you say,
01:31:52 if you feel sick, give us a call.
01:31:53 We’ll tell you what to do.
01:31:55 So yeah, I mean, what’s sickness?
01:31:58 Sickness is the presence of symptoms?
01:32:01 So this is good time to say what a symptom is, okay?
01:32:04 A symptom is what you only can feel.
01:32:08 Only you can feel an upset stomach
01:32:11 or a sore throat or that sort of thing.
01:32:13 It’s the lived experience of a symptom.
01:32:15 Whereas a sign is something that someone could measure
01:32:19 and tell that you’re infected,
01:32:20 like virus in your nasopharynx or something else, right?
01:32:26 Signs and symptoms.
01:32:27 And so in a vaccine trial, they tell you,
01:32:30 well, if you have any of these symptoms,
01:32:31 they give you a paper with the exact symptoms listed
01:32:35 to make sure you’re picking them up, right?
01:32:36 So for flu, it would probably be fever, sore throat, cough.
01:32:41 You call them and then they will do a PCR,
01:32:44 make sure you’ve got flu and not some other virus
01:32:46 that makes similar symptoms.
01:32:49 And then they would say, are you a vaccine or non vaccine arm
01:32:53 and count up all the infections
01:32:55 and see how the vaccine did, basically.
01:32:57 That’s so fascinating because the reporting,
01:33:02 so symptom is what you feel.
01:33:03 Yes, for sure.
01:33:04 And certainly the mind has a ability to conjure up feelings.
01:33:10 Oh yes, absolutely.
01:33:11 And so like culturally, maybe there was a time
01:33:16 in our culture where it was looked down upon
01:33:20 to feel sick or something like that,
01:33:23 like toughen up kind of thing.
01:33:25 And so then you probably have very few symptoms
01:33:28 being reported.
01:33:29 Absolutely, absolutely.
01:33:30 And now is like much more, I don’t know,
01:33:36 perhaps you’re much more likely to report symptoms.
01:33:37 Now it’s fascinating because then it changes.
01:33:40 Oh, it is definitely a perception because for,
01:33:43 your symptom may be nothing to me or vice versa, right?
01:33:46 And so when you’re doing this,
01:33:47 it’s a little bit of a imprecise science because,
01:33:52 and even it’s a cultural thing in some countries,
01:33:56 something that would make us feel horrible,
01:33:57 they wouldn’t even bother reporting.
01:33:59 No, I didn’t have any symptoms.
01:34:00 So it’s a little bit imprecise and it clouds the results.
01:34:03 So if you can measure things, it’s always better,
01:34:05 but you start out with a symptom.
01:34:07 And if you say, if someone tells you this virus,
01:34:11 20% of the people are asymptomatic,
01:34:15 they don’t report symptoms,
01:34:19 that number is probably not a constant.
01:34:21 It depends where you did the study.
01:34:24 It could be different in China versus South America,
01:34:26 Europe, et cetera, yeah.
01:34:28 I mean, I was trying to figure,
01:34:29 so I took two shots of the Pfizer vaccine
01:34:32 and I had zero symptoms.
01:34:34 Wow.
01:34:35 So, and I was wondering, well, see,
01:34:37 but that’s my feelings, right?
01:34:38 This is not, because I felt fine, I was waiting.
01:34:42 Did you have pain at the injection site?
01:34:46 No, it was kind of pleasant.
01:34:48 You felt nothing the next day, no?
01:34:50 Nothing, no tiredness, no exhaustion, no.
01:34:54 But see, like I have an insane sleeping schedule.
01:34:56 I already put myself through crazy stuff.
01:34:59 That said, maybe I was expecting something really bad.
01:35:03 Like I was waiting and therefore didn’t feel it.
01:35:06 But I also got allergy shots
01:35:11 and those, I was out all next day,
01:35:14 like exhausted for some reason.
01:35:16 So that gave me like a sense like, okay,
01:35:20 at least sometimes I can feel shitty.
01:35:22 That’s good to know.
01:35:24 Sure, sure.
01:35:25 And then with the vaccine it didn’t,
01:35:27 but the question is like,
01:35:29 how much does my mind come into play there?
01:35:32 The expectations of symptoms,
01:35:35 the expectations of not feeling well,
01:35:39 how does that affect the sort of the self reporting
01:35:41 of the symptoms?
01:35:42 I think it’s definitely a variable there,
01:35:44 but there’s certainly many people that don’t feel anything
01:35:47 after the vaccines.
01:35:48 And there’s some that have a whole range of things
01:35:51 like soreness and fever, et cetera, yeah.
01:35:54 So okay, you were talking about the old school development
01:35:57 inside the egg.
01:35:58 Right.
01:35:59 What’s better than that?
01:36:02 So then the next generation of vaccines
01:36:04 which arose in the 50s were what we call
01:36:07 replication competent, where the virus you take
01:36:11 and it’s actually reproducing in you.
01:36:13 Yeah, that sounds safe.
01:36:16 And it can be somewhat problematic, yes,
01:36:19 as you might imagine,
01:36:20 because once you put that virus in you,
01:36:22 you have no more control, right?
01:36:24 It’s not like you have a kill switch in it,
01:36:25 which actually would be a great idea to put in.
01:36:29 Like nanobots, what can possibly go wrong?
01:36:32 No, you could just put something in there.
01:36:34 If you added a drug, you would shut it off, right?
01:36:37 And people are thinking about that
01:36:39 because now we’re engineering viruses to treat cancers
01:36:43 and other diseases and we may wanna put kill switches
01:36:46 in them just to make sure they don’t run away.
01:36:48 Oh, interesting, so you can deploy a drug
01:36:50 that binds to this virus that would shut it off
01:36:54 in the body, something like that.
01:36:56 Something like that, yeah, that would be the idea.
01:36:58 You’d have to engineer it in.
01:36:59 Anyway, these were, the first one was yellow fever vaccine
01:37:03 that was made because that was a big problem.
01:37:06 And this virus, and the way you do this,
01:37:09 back in the old day was empirical.
01:37:12 So Max Tyler, who did the yellow fever vaccine,
01:37:15 he took the virus, which is a human virus, right?
01:37:19 And he infected, I think he used chick embryos.
01:37:24 And he went from one embryo to another and just kept passing
01:37:27 and he did that hundreds of times.
01:37:29 And every 10 passages, he would take the virus
01:37:32 and put it in a mouse or a monkey, whatever his model was.
01:37:36 And then eventually he got a virus
01:37:38 that didn’t cause any disease after 200 and some passages.
01:37:41 And then that was tested in people
01:37:43 and it became the yellow fever vaccine that we use today.
01:37:46 He selected for mutations that made the virus
01:37:50 not cause disease, but still make an immune response.
01:37:55 So those are called replication competent.
01:37:57 We now have the polio vaccine,
01:37:59 which was developed in the 50s after the yellow fever.
01:38:03 Then we had measles, mumps, rubella.
01:38:05 Those are all replication competent vaccines.
01:38:09 And you mentioned is that’s a good idea.
01:38:12 They are all safe vaccines.
01:38:15 The only one that has had an issue
01:38:18 is the polio replication competent vaccine.
01:38:21 It was called Sabin vaccine or oral polio virus vaccine
01:38:25 because you take it orally, it’s wonderful
01:38:29 because you don’t have to inject it.
01:38:31 This is the perfect delivery.
01:38:34 Either intranasal for a respiratory virus
01:38:37 or orally for polio goes into your intestines.
01:38:39 It reproduces and it gives you wonderful protection
01:38:42 against polio.
01:38:45 However, you do shed virus out
01:38:49 and that virus is no longer a vaccine.
01:38:52 It’s reverted genetically in your intestine.
01:38:55 So you can infect others with polio.
01:38:57 Take that virus and put it into an animal and give it polio.
01:39:00 And in fact, the parents of some kids in the 60s and 70s
01:39:05 who were immunized got polio from the vaccine.
01:39:08 The rate was about one and one and a half million
01:39:12 cases of polio.
01:39:13 So it’s called vaccine associated polio.
01:39:15 And I always argue that
01:39:18 we may not have picked the right vaccine.
01:39:21 There was a big fight in the US and other countries
01:39:25 between the inactivated polio
01:39:27 and the infectious polio vaccines,
01:39:29 which ones we should be using
01:39:31 because we found out that the infectious vaccine
01:39:33 actually caused polio.
01:39:35 And eight to 10 kids a year in the US alone
01:39:38 got polio from the vaccine,
01:39:39 which looking back is really not acceptable in my view,
01:39:43 although the public health community said it was
01:39:46 to get rid of polio.
01:39:47 So now we’re close to eradicating polio globally,
01:39:53 but this vaccine derived polio is a problem.
01:39:55 So now we have to go back to the inactivated vaccine,
01:39:59 which is tough because it’s injected.
01:40:01 So, okay, so the basic high level,
01:40:05 how vaccines work principle is
01:40:09 you want to deploy something in the body
01:40:11 that’s as close to the actual virus as possible,
01:40:13 but doesn’t do nearly as much harm.
01:40:15 And there’s like a million, not a million,
01:40:17 but there’s a bunch of ways you could possibly do that.
01:40:19 So those are two ways.
01:40:20 And now of course we have modern ways
01:40:22 we can make mRNA vaccines, right?
01:40:25 What are the modern ways?
01:40:26 I did, you wanna look, mRNA vaccine.
01:40:29 So that’s one of the, that’s the most modern,
01:40:31 but even before mRNA vaccines,
01:40:33 we learned that we could use viruses
01:40:36 to deliver proteins from a virus that you wanna prevent.
01:40:41 And so the Ebola vaccine,
01:40:43 we took the spike gene of Ebola virus
01:40:46 and put it in a different virus
01:40:47 and we deliver that to people
01:40:49 and that’s called a vector vaccine.
01:40:52 And some of the COVID vaccines are vectors
01:40:54 of different kinds of most famous are adenovirus vectors
01:40:57 carrying the spike gene into the cell.
01:41:00 Can you explain how the vector vaccine works again?
01:41:03 So we have, we take a virus that will infect humans
01:41:09 but will not make you sick.
01:41:11 In the case of adenovirus,
01:41:13 the years and years of people studying it
01:41:16 has told us what genes you could cut out
01:41:18 and allow the virus to infect the cell
01:41:20 but not cause any disease.
01:41:22 So instead of doing selection on it,
01:41:24 you actually genetically modify it.
01:41:27 Yes, you modify the vector, yeah.
01:41:29 So you’re much more precise about it.
01:41:30 You’re very precise
01:41:31 and then you splice in the gene for the spike
01:41:34 and then you use that to deliver the gene
01:41:37 and it becomes produced as protein
01:41:39 and then you make an immune response.
01:41:40 And vector is the term for this modified.
01:41:43 Right, so we’re now using viruses at our bidding.
01:41:47 We’re using them as vectors, not just for vaccines.
01:41:50 We can cure monogenic diseases.
01:41:52 That is if you have, if you’re born with a genetic disease,
01:41:55 you have a deletion or a mutation in a gene,
01:41:57 single gene, we can give you the regular gene back
01:42:01 using a virus vector.
01:42:03 So cancers too, we can cure cancers with vectors.
01:42:07 Wow, really?
01:42:09 Interesting. Yeah.
01:42:10 I think in 10 to 15 years,
01:42:12 most cancers will be treatable with viruses, yeah.
01:42:15 Wow.
01:42:16 And not only can we put things in the vector
01:42:19 to kill the tumor,
01:42:21 we can target the vector to the tumor specifically
01:42:25 in a number of ways.
01:42:26 And that makes it less toxic, right?
01:42:28 It doesn’t infect all your other cells.
01:42:31 But it takes time to develop a vector for a particular thing
01:42:34 because it requires a deep understanding.
01:42:37 Yeah, in fact, we have about a dozen different virus vectors
01:42:40 that have been studied for 20 years.
01:42:42 And those are the set of vaccine vectors that we’re using.
01:42:46 So it includes adenovirus, vesicular stomatitis virus,
01:42:50 which is a cousin of rabies, but doesn’t make people sick.
01:42:54 Influenza virus is being used as a vector
01:42:57 and even measles virus.
01:43:00 So we’re familiar with how to modify those to be vectors
01:43:04 and those are being used for COVID vaccines.
01:43:07 And then of course we have the newest,
01:43:10 which is the nucleic acid vaccines.
01:43:12 So years ago, people said,
01:43:15 why can’t we just inject DNA into people?
01:43:18 Take the spike and put it in a DNA and inject it.
01:43:22 So people tried many, many different vaccines.
01:43:25 And in fact, there are no human licensed vaccines
01:43:28 that are DNA vaccines.
01:43:29 Although there is a West Nile vaccine for horses
01:43:33 that’s a DNA based vaccine.
01:43:35 So if you have a horse, you can give it this vaccine,
01:43:38 but no human.
01:43:38 Can you clarify, does a DNA vaccine
01:43:42 only work for DNA viruses?
01:43:44 No, it can work for DNA or RNA.
01:43:46 Because remember, for an RNA virus,
01:43:48 we can make a DNA copy of it.
01:43:50 And it will still, when you put that DNA in a cell,
01:43:53 it goes into the nucleus.
01:43:55 Okay, right.
01:43:56 So it’s, you’re just skipping a step.
01:43:58 You get proteins.
01:43:59 For RNA vaccines, you’re giving, okay, I got it.
01:44:02 So those didn’t work for human vaccines.
01:44:04 And there were many HIV AIDS vaccine trials
01:44:07 that used DNA vaccines, didn’t work.
01:44:10 And then a number of years ago,
01:44:13 people started thinking, how about RNA, RNA vaccines?
01:44:17 And I first heard this, I thought, what?
01:44:20 I’ve worked with RNA my whole career.
01:44:22 It’s so fragile.
01:44:24 If you look at it the wrong way, it breaks.
01:44:27 I mean, that’s being facetious, right?
01:44:29 But you have to be very careful
01:44:31 because your hands are full of enzymes
01:44:34 that will degrade RNA.
01:44:37 So I thought, how could this possibly work,
01:44:38 injecting it into someone’s?
01:44:40 It’s an example of I was skeptical and I was wrong.
01:44:43 It turns out that if you modify the RNA properly
01:44:47 and protect it in a lipid capsule,
01:44:50 it actually works as a vaccine.
01:44:52 And people were working on this years
01:44:54 before COVID came around.
01:44:57 They were doing experimental mRNA vaccines
01:45:00 and there were a couple of companies
01:45:01 that were working on it.
01:45:02 And so at the beginning of 2020, they said, let’s try it.
01:45:07 And I was skeptical, frankly,
01:45:09 because I just thought RNA would be too labile,
01:45:12 but I was wrong.
01:45:13 So this is, as we’re saying offline, one of the great things
01:45:17 about you is you’re able to say when you’re wrong
01:45:20 about intuitions you’ve had in the past,
01:45:22 which is a beautiful thing for a scientist.
01:45:25 But I still think it’s very surprising
01:45:28 that something like that works, right?
01:45:30 Yeah, I am surprised.
01:45:31 So you’re just launching RNA in a protective membrane.
01:45:36 And then now one thing is surprising
01:45:39 that the RNA sort of lasts long enough in its structure.
01:45:45 But then the other thing is why does it work
01:45:50 that that’s a good training ground for the immune system?
01:45:56 Is that obvious that that should work?
01:45:59 I don’t think it’s obvious to most people
01:46:01 and it’s worth going into it
01:46:03 because it’s really interesting.
01:46:04 I mean, first of all, they wrap the RNA in fats,
01:46:09 in lipid membranes, right?
01:46:10 And the particular formulation they test for years
01:46:14 to make sure it’s stable,
01:46:16 it lasts a long time after it’s injected.
01:46:17 And the two companies that make the current COVID vaccines,
01:46:22 right, Moderna and Pfizer,
01:46:23 they have different lipid formulations to get to the same.
01:46:26 So that’s a real part of it.
01:46:29 And it’s not simple.
01:46:30 There are quite a few different lipids
01:46:31 that they put into this coding.
01:46:34 And they test to see how long they protect the RNA
01:46:37 after it’s injected, say, into a mouse,
01:46:39 how long does it last?
01:46:40 And the way it works is these,
01:46:43 apparently these lipid nanoparticles,
01:46:46 they get injected into your muscle,
01:46:48 they bump into cells and they get taken up.
01:46:52 So lipid fat is sticky.
01:46:56 It’s greasy, we like to say.
01:46:59 And so your cells are covered with a greasy membrane also.
01:47:03 So when these lipid nanoparticles bump into them,
01:47:06 they stick and they eventually get taken up.
01:47:08 And they figured this out right at the beginning.
01:47:11 If we put RNA in a lipid nanoparticle,
01:47:13 will it get taken up into a cell?
01:47:15 And the answer was yes, it was just let’s try it.
01:47:17 And it worked.
01:47:18 So it’s basically experiment.
01:47:20 It’s not like some deep understanding of biology.
01:47:22 It’s experimentally speaking, it just seems to work.
01:47:25 Yeah, well, they had some idea
01:47:26 that lipids would target this to a cell membrane.
01:47:30 And remember, there’s no receptor involved.
01:47:33 Like the virus has a specific protein
01:47:36 that attaches to a receptor.
01:47:39 It’s not efficient enough to just bump around
01:47:41 and get into a cell.
01:47:43 That’s what these things are doing.
01:47:44 And they probably optimize the lipids
01:47:47 to get more efficient uptake.
01:47:49 But it’s not as efficient as a virus would be
01:47:51 to get into a cell.
01:47:52 Right, so you have no specific,
01:47:54 I mean, which is why it’s surprising
01:47:57 that you can crack into the safe with a hammer.
01:48:02 Or with some fat.
01:48:06 I mean, that’s kind of surprising.
01:48:08 It’s kind of amazing that it works.
01:48:11 But so maybe let’s try to talk about this.
01:48:17 So one of the hesitancies around vaccines
01:48:22 or basically around any new technology
01:48:24 is the fact that mRNA is a new idea.
01:48:28 And it’s an idea that was shrouded in some skepticism,
01:48:32 as you said, by the scientific community.
01:48:35 Because it’s a cool new technology.
01:48:40 Surprising that it works.
01:48:42 What’s your intuition?
01:48:44 I think one nice way to approach this
01:48:46 is try to play devil’s advocate and say both sides.
01:48:53 One side is why your intuition says
01:48:56 that it’s safe for humans.
01:48:59 And what arguments can you see if you could steal man
01:49:03 and argument why it’s unsafe for humans.
01:49:06 Or not unsafe for humans,
01:49:09 but the hesitancy to take an mRNA vaccine is justified.
01:49:15 So many people are afraid because it’s new technology
01:49:19 and they feel it hasn’t been tested.
01:49:22 I mean, in theory, what could go wrong?
01:49:25 This is the nice thing about mRNA
01:49:29 is that it doesn’t last forever.
01:49:32 As opposed to DNA, which doesn’t last forever,
01:49:35 but it can last a lot longer.
01:49:38 And it could even go into your DNA, right?
01:49:41 So mRNA has a shorter lifetime,
01:49:44 maybe days after it’s injected into your arm,
01:49:47 then it’s gone.
01:49:48 So that’s a good thing
01:49:49 because it’s not gonna be around forever.
01:49:53 So that would say, okay, so it’s sticking around
01:49:56 for your lifetime is not happening.
01:49:58 But what else could happen?
01:50:00 Well, let’s see the protein that’s made,
01:50:03 could that be an issue?
01:50:05 And again, proteins don’t last forever.
01:50:08 They have a finite longevity in the body.
01:50:12 And this one also lasts perhaps at the best a few weeks.
01:50:17 Now this is a protein that’s made
01:50:18 after the RNA gets into the cell.
01:50:22 Yeah, so the lipid nanoparticles taken up into a cell
01:50:25 and the mRNA is translated and you get protein made.
01:50:27 And there’s also a question, I’m sorry to interrupt,
01:50:30 where in the body, so because it’s not well targeted,
01:50:35 or I don’t know if it’s supposed to be targeted,
01:50:38 but it can go throughout the body,
01:50:39 that’s one of the concerns.
01:50:40 Right, so it’s injected deep into your deltoid muscle,
01:50:43 right here, shoulder.
01:50:46 And the idea is not to put it in a blood vessel,
01:50:49 otherwise it would then for sure circulate everywhere.
01:50:52 So they go deep in a blood vessel and it’s locally injected.
01:50:57 And they did, before this even went into people,
01:51:00 they did experiments in mice
01:51:01 where they gave them a thousand times higher concentrations
01:51:05 than they would ever give to people.
01:51:06 And then when you do that, it can go everywhere basically.
01:51:09 You can find these nanoparticles
01:51:11 in every tissue of the mouse.
01:51:14 But that’s at a thousand fold higher concentration, right?
01:51:17 So I think at the levels that we’re using in people,
01:51:21 most of it’s staying in the muscle,
01:51:22 but sure, small amounts go elsewhere.
01:51:25 Could there be a lot of harm caused if it goes elsewhere?
01:51:30 Like let’s say ridiculously high quantities.
01:51:33 I’m trying to understand what is the damage
01:51:35 that could be done from an RNA just floating about.
01:51:39 So the RNA itself is not gonna be a problem,
01:51:41 it’s the protein that is encoded in it, right?
01:51:43 This is a viral RNA which has no sequence in us,
01:51:48 so there’s nothing that it could do.
01:51:50 It’s the protein that I would say you could ask,
01:51:54 what is that gonna do?
01:51:56 And the one property we know about the spike
01:52:01 is that it can cause fusion of cells, right?
01:52:06 That’s how the virus gets in in the beginning.
01:52:09 The spike attaches to the cell by this H2 receptor
01:52:14 and it causes the virus and the cell to fuse.
01:52:19 And that’s how the RNA gets out of the particle.
01:52:21 But so wait, I’m a bit confused.
01:52:24 So with this mRNA vaccine with the lipids and the RNA,
01:52:28 there’s no spike, right?
01:52:30 The mRNA codes for the spike.
01:52:33 Oh, the mRNA codes, so it creates the spike.
01:52:35 Creates a spike.
01:52:36 And so that spike could cause fusion of cells.
01:52:39 Yes, except they modified the spike so it wouldn’t.
01:52:44 Got it.
01:52:45 They made two amino acid changes in the spike
01:52:46 so it would not fuse.
01:52:47 So they understand enough which amino acids
01:52:49 are responsible for the fusion.
01:52:51 That’s right.
01:52:51 Interesting.
01:52:52 This is so cool.
01:52:53 So they could modify it.
01:52:54 So now it’s not gonna cause fusion, so that’s not an issue.
01:52:57 It’s called the prefusion stabilized spike.
01:53:00 Cool.
01:53:01 So the spike, when it binds ACE2,
01:53:04 that top falls off and the part of the spike
01:53:07 that causes fusion is now exposed.
01:53:09 And that doesn’t happen in this mRNA vaccine.
01:53:11 So those are the things that could have happened,
01:53:14 but I think they’re ruled out by what we’ve just said.
01:53:18 But there’s no better test
01:53:19 than putting it into people, right?
01:53:22 And doing phase one, phase two, and phase three,
01:53:25 and increasing numbers of people and asking,
01:53:27 what do we see?
01:53:28 Do we have any concerns?
01:53:30 And so now it’s been in many millions of people
01:53:35 and we don’t see most of the effects you see in a vaccine,
01:53:40 you see in the first couple of months.
01:53:43 Things like the myocarditis with some of the vaccines,
01:53:46 the clotting issues with the AstraZeneca vaccine,
01:53:49 Guillain Barre, you see those relatively quickly.
01:53:54 And we’ve seen small numbers of those occur,
01:53:58 but other things we haven’t seen,
01:54:01 and you never say never, right?
01:54:04 Right, so I mean, this is fascinating, right?
01:54:07 It’s like I drink, I put Splenda in my coffee
01:54:12 and it has supposedly no calories,
01:54:20 but it tastes really good.
01:54:22 And despite what like rumors and blogs and so on,
01:54:26 I have not seen good medical evidence
01:54:28 that is harmful to you, but it’s like, it tastes too good.
01:54:33 So I’m thinking like,
01:54:35 there’s gotta be longterm consequences,
01:54:37 but it’s very difficult to understand
01:54:40 what the longterm consequences are.
01:54:43 And there’s this kind of like distant fear
01:54:47 or anxiety about it.
01:54:49 Like this thing tastes too good, it’s too good to be true.
01:54:53 There’s gotta be, there’s no free lunch in this world.
01:54:55 This is the kind of feeling that people have
01:54:57 about the longterm effects of the vaccine,
01:55:01 that you mentioned that there’s some intuition
01:55:04 about near term effects that you want to remove,
01:55:09 like the diffusion of cells and all those kinds of things,
01:55:11 but they think, okay,
01:55:12 this travels to other cells in the body,
01:55:14 this travels to neurons or that kind of stuff.
01:55:18 And then what kind of effect does that have longterm
01:55:20 that’s yet to be discovered?
01:55:22 What do you make me for this vaccine,
01:55:25 but in general in science about making statements
01:55:28 about longterm negative effects?
01:55:32 Is that something that weighs heavy on you?
01:55:34 Is that something we can kind of escape
01:55:36 through just large scale experimentation
01:55:39 with animals and humans?
01:55:41 Well, if you’re really, if you’re concerned about longterm,
01:55:44 then you have to do a longterm experiment, right?
01:55:46 And maybe you don’t see something for 50, 60 years.
01:55:50 So if someone says to you,
01:55:53 there are no longterm effects of the COVID vaccines,
01:55:56 they can’t say that
01:55:57 because they haven’t done the long experiment, right?
01:56:00 There’s always the possibility, but you have to weigh it.
01:56:02 It’s always, there’s no free lunch, right?
01:56:06 There’s always a risk benefit calculation you have to make.
01:56:10 You can have the study, it goes 50 years and then decide,
01:56:14 but I guess what you’re doing is just like we said,
01:56:19 I forget which one, with polio, with rabies, I forget,
01:56:22 but you’re weighing the side effects.
01:56:25 Yeah, polio, right.
01:56:26 The vaccine versus the effects of the virus.
01:56:31 And like both of them, you don’t know longterm effects,
01:56:34 but you’re building up intuition as you study,
01:56:38 which what are the longterm effects?
01:56:41 Like there’s a huge number of people,
01:56:46 like that have like, I don’t want to say experts
01:56:51 because I don’t like the word,
01:56:52 but people have studied it long enough
01:56:54 to where they build up intuition.
01:56:56 They don’t know for sure.
01:56:57 There’s basic science being done, there’s basic studies.
01:57:00 But you start to build up an intuition of what might be
01:57:05 a problem down the line and what is not,
01:57:08 biologically speaking.
01:57:09 And so given that map, then considering the virus,
01:57:14 there seems to be a lot of evidence for COVID
01:57:16 having negative effects on all aspects of the body,
01:57:21 not just even respiratory, which is kind of interesting.
01:57:24 So the cognitive stuff is terrifying.
01:57:27 All kinds of systems evolve, yes.
01:57:28 And then you look at the same thing with the vaccine
01:57:32 and there seems to be less of that.
01:57:34 But of course you don’t know
01:57:36 if it’s some kind of dormant thing that’s just going to.
01:57:39 You won’t know.
01:57:40 You have to make a judgment.
01:57:42 And for a lot of people they can’t, right?
01:57:44 Because they don’t have the tools to make the judgment.
01:57:47 I totally understand that.
01:57:49 And we have let people down a few times in medicine, right?
01:57:54 And I know two very specific examples.
01:57:57 The first polio vaccine ever made,
01:58:00 the Salk vaccine was released in 1955.
01:58:04 Immediately within months,
01:58:06 a few hundred cases of paralysis in kids who got it
01:58:09 because it was not properly inactivated.
01:58:14 Now you have to understand,
01:58:15 parents were dying for a polio vaccine
01:58:17 because kids were getting paralyzed every summer,
01:58:20 30,000 kids a year.
01:58:22 And so they went and took it.
01:58:24 They took the word of the medical establishment
01:58:27 that it was safe and it wasn’t.
01:58:29 Big letdown, never going to forget something.
01:58:31 Although I think a lot of people today aren’t aware of that.
01:58:36 I think that was a big problem that’s everlasting.
01:58:38 Then the attenuated vaccine that we talked about,
01:58:42 the infectious causing polio.
01:58:45 Yet parents continued to bring their kids to be vaccinated
01:58:49 because they were said,
01:58:50 this is the right thing to do.
01:58:52 And I have to say,
01:58:53 I was involved in several lawsuits
01:58:55 where parents of a kid who got paralyzed
01:58:58 from the polio vaccine decided to sue the manufacturer
01:59:01 and get some money for their kid.
01:59:04 And so they got mad.
01:59:07 And I think you could not…
01:59:11 The first issue could have been prevented,
01:59:15 could have been prevented by inactivating it properly.
01:59:18 I think the company just did the wrong thing.
01:59:21 The second we had evidence for,
01:59:23 and we should probably have not used that vaccine any longer,
01:59:25 but I think that destroys public confidence.
01:59:28 But those aren’t…
01:59:29 They’re not long term.
01:59:30 That’s a minority of cases.
01:59:30 This is a minority.
01:59:31 This is a very rare event, yeah.
01:59:32 But nevertheless,
01:59:33 science as an institution didn’t make corrections
01:59:38 in that case.
01:59:39 No, they didn’t.
01:59:40 And so what do you make of that?
01:59:44 I mean, it’s very unfortunate
01:59:45 that those few things can destroy trust.
01:59:49 But I don’t think that lasts till today.
01:59:51 I think today is a different era, right?
01:59:53 And most people don’t know about those stories.
01:59:55 I tell them to you because that’s what could happen.
01:59:58 I think it could happen today.
02:00:01 If you look at the history of the polio vaccine,
02:00:06 the US Public Health Service wanted kids to be vaccinated.
02:00:10 So they did things that probably weren’t correct
02:00:13 to get the vaccine back online.
02:00:15 Right?
02:00:16 But they did it and they pushed it through.
02:00:20 So the question is, what do we do today?
02:00:23 So I can look at, as we just said,
02:00:27 I can look at what might happen
02:00:29 and I can make reasonable decisions
02:00:33 about the likelihood of them happening.
02:00:35 And I can also say, I don’t wanna get COVID of any kind
02:00:38 because I’ve seen how nasty it can be.
02:00:41 And I decide I’m taking the risk,
02:00:44 whatever small of a long term effect,
02:00:46 I’m gonna take the risk.
02:00:47 My family took the risk and many other people did.
02:00:49 Of a vaccine.
02:00:50 Of getting vaccinated.
02:00:52 Because I think it’s very small.
02:00:53 But I understand where people can’t make that decision.
02:00:56 And that begs the question,
02:00:58 what would they need to make a decision?
02:01:01 So if you’re concerned about an effect in 40 years,
02:01:06 we’re not gonna know for 40 years.
02:01:09 Yeah, so I think if I were to speak,
02:01:11 because I talked to, like I mentioned offline to Joe Rogan
02:01:14 and his podcast yesterday,
02:01:15 I talked to him all the time about this.
02:01:18 I think the concern is less about the long term effects
02:01:27 like on paper.
02:01:28 It’s more about the, like people like Anthony Fauci
02:01:34 and people at the top are simply misrepresenting the data
02:01:39 or like are not accurately being transparent.
02:01:42 Not collecting the data properly.
02:01:45 Not reporting on the data properly.
02:01:46 Not being transparent.
02:01:48 Not representing the uncertainties.
02:01:50 Not openly saying they were wrong two months ago.
02:01:55 Like in a way that’s not like dramatic,
02:01:58 but revealing the basic process of science
02:02:00 when you have to do your best under uncertainty.
02:02:03 Just also just being inauthentic.
02:02:06 There’s a sense, especially with like a younger generation
02:02:09 now, there’s a certain way on the internet.
02:02:11 Like the internet can smell bullshit
02:02:14 much better than previous generations could.
02:02:16 And so they see there’s a kind of inauthenticity
02:02:21 that comes with being like representing authority.
02:02:26 Like I am a scientist.
02:02:27 I’m an expert.
02:02:29 I have a PhD.
02:02:30 I have four decades of work.
02:02:31 Therefore everyone should listen to me.
02:02:34 And somehow that maps to this feeling of,
02:02:38 well, what are they hiding?
02:02:40 If they’re speaking from authority like this,
02:02:43 if everyone is in agreement like this,
02:02:45 that means they all have emails between each other.
02:02:48 They said, we’re gonna tell this.
02:02:49 This is the message we’re gonna tell the public.
02:02:51 Then what is the truth, the actual truth?
02:02:54 Maybe there’s a much bigger uncertainty.
02:02:57 Maybe there’s dead people in the basement
02:02:59 that they’re hiding from bad mRNA vaccine experiments.
02:03:03 Maybe they’re, and then the conspiracy theory
02:03:06 starts to grow naturally
02:03:09 when there’s this kind of mistrust of that.
02:03:11 So it’s less about kind of like a deep concern
02:03:17 about longterm effects.
02:03:18 It’s a concern about longterm effects
02:03:24 if we find out that there’s some secret stuff
02:03:27 that we’re not being told.
02:03:28 It all lands on that.
02:03:30 So what the heck, I mean, so I put the blame
02:03:32 not on the data, but basically on the leaders
02:03:35 and the communicators of the science at the top.
02:03:39 Well, to that I would say all the data,
02:03:43 as far as I know, are made public.
02:03:47 So you can dive into it.
02:03:48 And I know a lot of people ask me questions
02:03:51 and I just say, it’s right here in the data.
02:03:54 And I know a lot of people can’t do that.
02:03:55 They can’t dive into it.
02:03:57 But that’s one solution for people who are able.
02:04:00 Now you could argue, well,
02:04:01 maybe they’ve left data out.
02:04:03 Well, then not even I can help
02:04:05 because then they’re hiding it from me too.
02:04:07 And I think that’s highly unlikely.
02:04:08 I think for the most part,
02:04:09 the FDA requires the release
02:04:11 of all the clinical trial data, right?
02:04:14 So, okay, so this clinical trial data, that’s one thing.
02:04:17 So that’s the data that we should be focusing on, right?
02:04:20 So there’s a lot of different data sets here.
02:04:24 So there’s preclinical data,
02:04:25 which is everything that was done in the lab
02:04:28 before this vaccine ever went into a human arm.
02:04:30 It’s all the cell culture work
02:04:32 that we talked about a little, experiments in animals.
02:04:35 All of that is publicly accessible.
02:04:38 Most of it gets published.
02:04:39 And then there’s the initial drug filing,
02:04:42 which is huge, the books of,
02:04:45 you can get that and look at it, right?
02:04:46 This is me sort of asking sort of difficult questions here.
02:04:49 It’s okay.
02:04:51 So there’s a lot of money to be made by makers of the vaccine.
02:04:56 So for these companies, and obviously there’s a distrust
02:05:00 of those folks too.
02:05:02 They’ve done a lot of really good things in this world,
02:05:04 but the incentives are such
02:05:07 that you wanna sweep stuff under the rug
02:05:09 if you’re not 100% pure in your ethics.
02:05:15 And how hard is it for that data to be fabricated,
02:05:21 manipulated, like what’s your intuition
02:05:24 for the pre trial stuff?
02:05:26 I think when you start fabricating,
02:05:29 then you get inconsistencies,
02:05:31 which are pretty easy to pick up.
02:05:34 When you’re talking about some large scale things
02:05:36 of this nature.
02:05:38 Because then you can look through the data very,
02:05:40 you’re gonna, I mean, we require looking very carefully,
02:05:43 but you will see inconsistencies from one trial to another.
02:05:46 And that might ring a bell that something’s been done.
02:05:50 Yeah, it’s like the moon landing thing.
02:05:55 Sometimes like going to the moon is easier than faking it.
02:05:58 Right.
02:06:00 In the sense it might be easier to do a large scale trial
02:06:03 and get an effective vaccine versus faking it.
02:06:05 But when you brought up the for profit issue,
02:06:08 I think that is always been an issue.
02:06:11 I’ve always felt that having your health depend
02:06:15 on for profit industry may not be the best solution.
02:06:20 And I don’t know how else to do it.
02:06:23 People tell me I’m a dreamer that thinking that,
02:06:26 all medicines could be nonprofit.
02:06:28 But I also think that the world should have one health
02:06:30 system that takes care of everyone, right?
02:06:32 Because there’s some countries that can’t
02:06:34 and other countries have an excess like us.
02:06:37 So I wish we could do that.
02:06:40 Well, the argument is the speed of which the vaccines
02:06:44 for COVID were produced would never happen
02:06:47 in a nonprofit system,
02:06:49 would never happen in a non capitalist system.
02:06:51 Oh, I could set up a vaccine production institute
02:06:56 in the US that would get the vaccines done
02:06:58 because you just need to put money into it.
02:07:00 That’s what made these vaccines get done money.
02:07:03 They poured billions of dollars and they got it done quickly.
02:07:06 But if I set up a nonprofit institutes of vaccines
02:07:09 throughout the US staffed with really talented people,
02:07:12 pay them well, keep them motivated,
02:07:15 you’ll get your vaccine.
02:07:15 No, but that’s the thing with capitalism is that
02:07:19 the selection of who to hire a good,
02:07:22 when you say good people,
02:07:24 capitalism has a machine that fires people
02:07:28 who are not good and selects people that are good.
02:07:30 Coming from the Soviet Union,
02:07:32 the dream of communism is similar
02:07:35 to what you’re saying broadly defined.
02:07:37 It certainly doesn’t work in the broads.
02:07:40 The question of whether it works in the healthcare space,
02:07:45 there is some aspect to the machine of capitalism
02:07:49 being the most effective way to select for good people
02:07:53 and to effectively produce the thing.
02:07:56 But then of course, a lot of people would argue
02:07:58 the current, even the current healthcare is not
02:08:01 with like regulations, there’s some weird mix
02:08:03 where there’s a lot of opportunities for inefficiencies.
02:08:07 There’s a lot of opportunities for bureaucracy.
02:08:09 So you have like the worst of all worlds.
02:08:11 Can’t there be some intermediate that works
02:08:13 because I mean, the other issue that we haven’t mentioned
02:08:17 is that politics gets thrown into this
02:08:19 and that really messes up
02:08:21 and it should never be mixed with healthcare,
02:08:22 but it is because a lot of funding comes from the government
02:08:26 so that’s another confounding factor.
02:08:29 But I really think I could make a vaccine institute
02:08:33 that if someone didn’t do well, I’d fire them.
02:08:36 No, you’re not gonna stay if you can’t do your job
02:08:39 and do it well, you don’t give them incentives,
02:08:41 but it doesn’t have to be the two extremes I think.
02:08:44 There has to be a solution that people don’t have
02:08:47 this mistrust for a company making huge profits
02:08:51 off of a drug.
02:08:52 But you know what, it’s funny,
02:08:55 it seems that vaccines and antivirals bear the brunt
02:08:58 of this criticism yet there are many other pharmaceuticals
02:09:01 that people rely on of all sorts.
02:09:04 They don’t seem to question and have issues
02:09:06 with those and they have far more side effects than vaccines.
02:09:09 It’s a very strange how we’re picking that way,
02:09:11 but I should also say that if you have one big
02:09:17 vaccine institute, one of the other sets
02:09:22 of vaccine conspiracies, I mean, I would say they’re
02:09:28 a little farther out into the wild side of ideas,
02:09:32 but there’s one way to control the populace
02:09:37 is by injecting substances into them, right?
02:09:41 People, I mean, part of that, funny enough,
02:09:44 it probably has to do with needles
02:09:46 versus something you put in your mouth,
02:09:48 but there’s something about the government,
02:09:50 especially when it’s government mandated injection
02:09:53 of a substance into you.
02:09:54 I don’t care what the science says,
02:09:57 if it’s 100% effective, 100% safe,
02:10:00 there’s a natural distrust of what,
02:10:03 like even if this is effective and safe,
02:10:08 giving the government power to do this,
02:10:11 aren’t they gonna start getting ideas down the line for,
02:10:15 you know.
02:10:17 I think that they can barely govern.
02:10:20 I don’t think they’re gonna do that,
02:10:22 but you don’t have to take, unless you’re a federal employee,
02:10:25 you don’t have to take a COVID vaccine.
02:10:27 Yeah, but that largely has to do, not largely,
02:10:32 but there is an individualistic spirit
02:10:39 to the American people.
02:10:41 There’s this, like, you’re not gonna take my gun away
02:10:44 from me, you’re not going, and I think that,
02:10:52 that’s something that makes America what it is.
02:10:56 Just coming from the Soviet Union,
02:10:57 there’s a power to sort of resisting
02:10:59 the overreach of government.
02:11:01 That’s quite interesting, because I’m a believer,
02:11:04 I hope that it’s possible to have,
02:11:08 to strive towards a government that works extremely well.
02:11:11 I think at its best, a government represents the people
02:11:14 and functions in the similar way that you’re mentioning,
02:11:17 but that, like, pushback,
02:11:20 even if it turns into conspiracy theory sometimes,
02:11:22 I think is actually healthy in the long arc of history.
02:11:25 It can be frustrating sometimes,
02:11:28 but that mechanism of pushing back against power,
02:11:30 against authority, can be healthy.
02:11:32 I agree, I think it’s fine to question the vaccines.
02:11:36 What I have issue with is that many people
02:11:40 put out incorrect information,
02:11:43 and I’m not sure what their motivations are,
02:11:45 and it’s very hard to fight that,
02:11:47 because then it’s my word versus theirs,
02:11:50 and I’m happy to talk with people
02:11:52 about any of their concerns,
02:11:54 but if you start getting into the stuff
02:11:56 that just isn’t true, then we have a problem.
02:11:59 The thing I struggle with is conspiracy theories,
02:12:03 whatever language you want to use,
02:12:04 but sort of ideas that challenge
02:12:09 the mainstream quote unquote narrative,
02:12:13 given our current social media and internet,
02:12:16 like the way it operates,
02:12:17 they can become viral much easier.
02:12:20 There’s something much more compelling about them.
02:12:22 Like I have a secret about the way things really work.
02:12:27 That becomes viral, and that’s very frustrating,
02:12:30 because then you’re not having
02:12:31 a conversation on level ground.
02:12:36 When you’re trying to present scientific ideas,
02:12:38 and then there’s conspiracy theories,
02:12:39 the conspiracy theories become viral much faster,
02:12:42 and then you’re not just having a discussion
02:12:44 on level ground.
02:12:47 That’s the frustrating part,
02:12:49 that it’s not an even discussion.
02:12:51 Can I just say one more thing?
02:12:53 I mean, the internet is here to stay,
02:12:54 so we’re gonna have to figure out
02:12:56 how to deal with it, right?
02:12:57 But from my perspective,
02:12:59 I was skeptical that any COVID vaccine
02:13:03 would be ready within a year.
02:13:05 That’s amazing.
02:13:07 Plus, the way I look at the mRNA vaccine as a scientist,
02:13:12 it’s gee whiz to me.
02:13:13 It’s amazing that it worked,
02:13:15 and I think the data are great, so I want it.
02:13:19 As a scientist, I want it.
02:13:21 One of the really sad things, again,
02:13:23 with me, too, as a scientist or as an admirer of science,
02:13:29 I don’t know if it’s politics,
02:13:31 but one of the sad things to me about the previous year
02:13:34 is that I wasn’t free to celebrate
02:13:38 the incredible accomplishment of science with the vaccines.
02:13:42 I was very skeptical that it’s possible
02:13:44 to develop a vaccine so quickly.
02:13:47 So it’s unfortunate that we can’t celebrate
02:13:50 how amazing humans are to come up with this vaccine.
02:13:54 Now, this vaccine might have long term effects.
02:13:57 That doesn’t mean this is not incredible.
02:14:00 Why couldn’t you celebrate?
02:14:06 Because I would love to inspire the world
02:14:08 with the amazing things science can do.
02:14:11 And when you say something about the vaccines,
02:14:14 they’re not listening to the science.
02:14:15 A lot of people are not listening to the science.
02:14:17 What they hear is, oh, you’re a Republican
02:14:22 or you’re a Democrat, and you’re social signaling,
02:14:25 doing some kind of signaling.
02:14:26 No, I think that the vaccine,
02:14:27 you’re talking about injecting something into you,
02:14:30 and maybe you’re right that the rhetoric is like,
02:14:33 you better take this or you’re dumb.
02:14:37 It’s not the right approach.
02:14:38 I’ve seen, actually, it’s kind of interesting.
02:14:40 I’ve seen both sides kind of imply that.
02:14:42 So the people who are against the vaccine
02:14:48 are dumb for not trusting science,
02:14:52 and the people who are for the vaccine
02:14:55 are called dumb for trusting science,
02:14:59 the scientific institution.
02:15:00 And nobody wins, yeah.
02:15:01 And they both kind of have a point.
02:15:03 Like, because you can always,
02:15:07 it’s like, is the glass half full or half empty?
02:15:10 Because you can always look at, like, science
02:15:15 from a perspective of certain individuals
02:15:18 that don’t represent, perhaps, the not greatest leaders,
02:15:23 almost like political leaders.
02:15:25 There’s a lot of, you know,
02:15:27 yesterday I went on a whole rant against,
02:15:31 I said a lot of positive things about Anthony Fauci
02:15:34 before I went on a rant against him.
02:15:36 Because ultimately, you know,
02:15:40 I think he failed as a leader,
02:15:41 and I know it’s very difficult to be a leader,
02:15:44 but I still wanted to hold him accountable for that
02:15:47 as a great communicator of science and as a great leader.
02:15:50 What do you think he didn’t do right?
02:15:52 I’m curious.
02:15:55 So the core of the problem is the several characteristics
02:16:00 of the way he was communicating to the public.
02:16:06 So one is the general inauthenticity.
02:16:10 Two is a thing that, it’s very hard to put into words,
02:16:14 but there’s certain ways of speaking to people
02:16:18 that sounds like you’re hiding something from them.
02:16:21 That sounds like you’re full of shit.
02:16:23 That’s the authenticity piece.
02:16:25 Like, it sounds like you’re not really speaking
02:16:30 to the full truth of what you know
02:16:34 and that you did some shady shit in your past
02:16:38 that you’re trying to hide.
02:16:40 So that’s a way of communicating
02:16:42 that I think the internet and people in general
02:16:45 are becoming much better at detecting.
02:16:46 Yeah, it’s like you said, they’re good BS detectors.
02:16:48 Yeah, good BS detectors.
02:16:51 But contributing to that is speaking from authority,
02:16:55 speaking with authority and confidence
02:17:01 where neither is deserved.
02:17:04 So first of all, nobody’s an authority on this new virus.
02:17:10 We’re facing a deadly pandemic,
02:17:12 and especially in the early stages,
02:17:15 it was unclear how deadly it would be.
02:17:17 It was unclear, probably still unclear,
02:17:19 fully how it’s transmitted.
02:17:22 The full dynamics of the virus,
02:17:24 the full understanding of which solutions work and not,
02:17:28 how well masks of different kinds work,
02:17:31 how easy or difficult it is to create tests,
02:17:34 how many months or years it’s gonna take
02:17:36 to create a vaccine,
02:17:38 how well in history or currently do quarantine methods
02:17:43 or lockdown methods work,
02:17:45 what are the different data mechanisms
02:17:48 that are data collection mechanisms
02:17:50 that are being implemented,
02:17:52 what are the clear plans that need to happen,
02:17:55 what the epidemiology that’s happening,
02:17:58 what is the uncertainty around that?
02:18:02 Then there’s the geopolitical stuff with China.
02:18:09 I personally believe there should have been
02:18:11 much more openness about the origins of the virus,
02:18:15 whether they’re leaked from a lab or not.
02:18:17 I think communicating that you’re open to these ideas
02:18:21 is actually the way to get people to trust you,
02:18:25 that you are legitimately open to ideas
02:18:28 that are very unpleasant, that go against the mainstream.
02:18:32 Showing that openness is going to get people to trust you
02:18:35 when you finally decrease the variance in your uncertainty,
02:18:40 like decrease uncertainty and have,
02:18:42 we still have a lot of uncertainty,
02:18:44 but this is the best course of action.
02:18:46 Vaccines still have a lot of uncertainty around them.
02:18:49 mRNA is a new technology,
02:18:51 but we have increasing amounts of data,
02:18:53 and here’s the data sources,
02:18:54 and laying them out in a very clear way
02:18:58 of this is the best course of action that we have now.
02:19:01 We don’t know if it’s the perfect course of action,
02:19:04 but it’s by far the best course of action.
02:19:06 And that would come from a leader
02:19:09 that has earned the capital of trust from people.
02:19:13 I mean, I think in recent history,
02:19:15 the worst pandemic is 1918 flu, right?
02:19:19 But that’s mainly because we didn’t know what to do.
02:19:22 We didn’t have many tools at our disposal.
02:19:24 And that was tied up with World War I.
02:19:26 That’s right, that’s right.
02:19:27 So the leadership there, I mean.
02:19:30 But I don’t know what is a lot of deaths, right?
02:19:32 And any one person is someone’s family,
02:19:35 so to them it’s a lot, right?
02:19:37 But that logic, we don’t apply that logic generally,
02:19:41 because there’s a lot of people suffering
02:19:43 and dying throughout the world,
02:19:44 and we turn the other way all the time.
02:19:47 And that’s the story of history.
02:19:49 So saying you all of a sudden.
02:19:51 What bothers me though, I mean, personally,
02:19:53 I don’t like anyone dying anywhere,
02:19:56 but, and especially considering what technology
02:20:00 we’re able to muster, yet we still kill each other.
02:20:02 It’s just a dichotomy to me.
02:20:04 Yeah, but I mean, this is the, what is it, Paul Farmer?
02:20:08 There’s these great stories.
02:20:10 I mean, that’s the,
02:20:11 that’s the burden of being in healthcare,
02:20:17 being a doctor, is you have to help.
02:20:23 You can’t help but help a person in front of you
02:20:25 who’s hurting, but you also are burdened
02:20:28 by the knowledge that you helping them,
02:20:31 you spending money and effort and time on them,
02:20:34 means you’re not going to help others,
02:20:36 and you cannot possibly allocate
02:20:38 that amount of time to everybody.
02:20:40 So you’re choosing which person lives and which person dies.
02:20:44 And you’re doing so,
02:20:45 the reason you’re helping the person in front of you
02:20:47 is because they’re in front of you.
02:20:49 And so the reason right now we care a lot about COVID
02:20:53 is because the eye of the world has turned to COVID,
02:20:56 but we’re not seeing all the other atrocities
02:20:59 going on in the world.
02:21:00 They’re not necessarily related to deaths,
02:21:02 they’re related to suffering, human suffering,
02:21:05 which you could argue is worse than death,
02:21:07 prolonged suffering.
02:21:08 So there’s all of these questions.
02:21:11 And the fundamental question here is,
02:21:15 are we overreacting to COVID in our policies?
02:21:19 So this is the, when we turn our eye
02:21:23 and care about this particular thing and not other things,
02:21:26 are we dismissing the pain that business owners
02:21:29 who’ve lost their businesses are going to feel?
02:21:31 And then the long, talking about long COVID,
02:21:35 the long term effects, economic effects on the millions
02:21:39 of people that will suffer, that suffer financially,
02:21:42 but also suffer from their dreams
02:21:44 being completely collapsed.
02:21:46 So a lot of people seek gain meaning from work.
02:21:50 And if you take away that work,
02:21:52 there’s anger that can be born, there’s pain.
02:21:55 And so what does that lead to?
02:21:57 That can lead to the rising up of charismatic leaders
02:22:01 that channel that anger towards destructive things.
02:22:05 That’s been done throughout history.
02:22:06 So you have to balance that with the policies
02:22:10 that you have in COVID.
02:22:12 And then, I mean, very much my main opposition
02:22:16 to Fauci is not on the details, but the final result,
02:22:20 which is I just observe that there’s a significant decrease
02:22:25 in trust in science as a, not the institution,
02:22:30 but the very sort of mechanisms of science.
02:22:32 I think science is both beautiful and powerful.
02:22:35 And the reason why we have so many amazing things
02:22:38 and such a high quality of life.
02:22:40 And distrust in that, that the thing we need now
02:22:44 to get out of all the troubles we’re in,
02:22:46 continue getting out of the troubles we’re in is science,
02:22:49 the scientific process, broadly defined like innovation,
02:22:53 technological innovation, scientific innovation,
02:22:55 all of that, distrust in that is totally
02:23:00 the wrong thing we need.
02:23:02 And so anybody who gets in,
02:23:04 who causes a distrust in science to me,
02:23:12 carries the responsibility of that
02:23:14 and should be in, because the response,
02:23:16 I mean, should be fired, should be,
02:23:20 or at least openly have to carry the burden of that,
02:23:24 of having caused of that kind of level of mistrust.
02:23:27 Now, it’s maybe unfair to place it on any one individual,
02:23:30 but you have to, I think in your pocket said,
02:23:34 the buck stops at the top, like the leaders have to.
02:23:37 No, no, there’s a clear leader here, yes, absolutely.
02:23:40 So even if it’s not directly his fault,
02:23:44 he has to carry the price of that.
02:23:48 Do you think we should at this point say,
02:23:50 okay, we have vaccines,
02:23:53 you can decide whether you take them or not,
02:23:55 let’s move forward?
02:23:57 Maybe you can help me understand this,
02:23:59 because it seems like, why is that not the right solution?
02:24:04 Completely open society, the vaccines,
02:24:07 at least in the United States,
02:24:09 as I understand are widely available.
02:24:14 So this is the American way, you have the decision to make.
02:24:18 If you have conditions that make you worried to get COVID
02:24:23 and go to the hospital, then you should get vaccinated
02:24:26 because here’s the data that shows
02:24:27 that it’s much less likely for you to die
02:24:31 if you get vaccinated,
02:24:34 if you don’t want to get vaccinated
02:24:35 because you’re worried about longterm effects of vaccine
02:24:39 that you don’t have to,
02:24:40 but then you suffer the consequences of that,
02:24:43 and that’s it.
02:24:44 So here’s what I think is driving,
02:24:47 I think it’s all about kids,
02:24:50 because they’re gonna go back to school in the fall
02:24:51 and many of them can’t be vaccinated.
02:24:53 So if they get infected, they do have less frequency
02:24:59 of disease, but it’s not zero.
02:25:01 They do get sick and they can have longterm consequences.
02:25:04 And at that age, it would be a shame, right?
02:25:09 And not even their choice,
02:25:10 they can’t decide to get vaccinated or not
02:25:13 because they can’t have access to it.
02:25:15 So I think that’s what would drive my efforts
02:25:19 to try and get more people, at least in schools, vaccinated,
02:25:22 but I might be wrong, it may not be that.
02:25:24 So can you kind of dig into that a little bit?
02:25:26 So there’s,
02:25:30 so you’re saying that there should be an effort
02:25:33 for increased vaccinations of kids going to school,
02:25:37 just not for societal benefit,
02:25:39 but for the benefit of each individual kid, right?
02:25:42 So right now, kids under 12, right,
02:25:46 are not yet vaccinated, is that correct?
02:25:48 Yeah, I think so.
02:25:49 And it’s not gonna be in time for school opening
02:25:53 that they get vaccinated.
02:25:56 And then, I suppose the teachers
02:25:59 are all gonna be vaccinated,
02:26:01 makes sense for them to do that,
02:26:02 but I’m just worried the kids
02:26:04 are gonna be transmitting it amongst them
02:26:05 and many states don’t allow mask mandate in school.
02:26:08 So I think that’s what’s driving the larger narrative
02:26:14 in the US to protect kids.
02:26:16 It’s kind of what I hear from Daniel Griffin,
02:26:18 because increasing numbers of kids
02:26:21 are being admitted to hospitals now,
02:26:23 because they’re becoming the major unvaccinated population.
02:26:28 They’re hanging out over the summer
02:26:29 and that’s just gonna get worse in the fall.
02:26:32 And so you could have a lot of kids with long COVID
02:26:35 and disabled their entire lives, right, so.
02:26:38 And of course, hearing from people who are vaccine hesitant,
02:26:42 I hear exactly the kids statement,
02:26:44 but they’re saying they don’t want
02:26:47 the long term effects of the vaccine to affect the kids.
02:26:53 That’s of this new vaccine.
02:26:56 Which I would say is, as I said before,
02:26:58 you can’t say never,
02:27:00 but we do know that long COVID exists.
02:27:05 We don’t know for how long,
02:27:06 because we’ve only looked out six or eight months.
02:27:09 We know that exists and the frequency is increasing.
02:27:12 It certainly exists in young kids
02:27:14 and we have no idea about long vaccine effects.
02:27:16 So I think they have to make their decision based on that.
02:27:22 But yeah.
02:27:24 But your question is why don’t we just open up society,
02:27:28 say here we have these vaccines
02:27:29 if you wanna protect yourself.
02:27:30 I think it’s mainly the school
02:27:32 that’s driving the whole narrative, that’s my opinion.
02:27:35 In which direction, not to open up or?
02:27:37 No, to open up, but to try and get their efforts
02:27:41 at the federal level to get people vaccinated, right?
02:27:43 But see, how high are the risks for kids?
02:27:45 I mean, my understanding was it’s,
02:27:48 I mean, yes, it’s nonzero, but it’s very low.
02:27:52 But what is the numbers?
02:27:53 Now, 70,000 hospitalizations so far
02:27:57 in kids as of last week.
02:27:59 So yes, it’s low, but polio was low.
02:28:05 Polio was 20, 30,000 kids a year paralyzed.
02:28:08 And well, many people have actually argued
02:28:11 that that vaccine wasn’t necessary.
02:28:13 Now, that wasn’t a substantial enough health problem.
02:28:17 But paralyzed is different than hospital.
02:28:18 So what does hospitalized mean?
02:28:20 Long COVID.
02:28:21 But this is the long COVID question.
02:28:23 I mean, this is the open question.
02:28:24 It was long COVID in kids.
02:28:26 What is that?
02:28:27 Well, a lot of the same issues,
02:28:30 cognitive issues, motor issues,
02:28:34 respiratory, GI dysfunction.
02:28:37 How long?
02:28:39 We don’t know.
02:28:41 I mean, it could end in a year.
02:28:43 As you know, there are other post acute infectious sequelae
02:28:47 that we know about.
02:28:48 Chronic fatigue, ME, CFS is thought
02:28:51 to be a post infectious sequelae,
02:28:53 which has gone for many decades now
02:28:55 in many millions of people.
02:28:56 This could be another one of those.
02:28:58 So I’m just saying it might be worth erring
02:29:02 on the side of not letting the kids get infected.
02:29:05 Yeah, well, I’m trying to keep an open mind here
02:29:09 and I appreciate you doing the same.
02:29:12 Of course, I lean on definitely not requiring people
02:29:18 to get vaccinated,
02:29:19 but I do think getting vaccinated
02:29:21 is just the wiser choice,
02:29:24 looking at all the different trajectories before us.
02:29:28 Getting vaccinated seems like from the data,
02:29:33 it seems like the obvious choice, frankly.
02:29:35 But I’m also trying to keep an open mind
02:29:38 because some things in the past that seemed obvious
02:29:40 would turn out to be completely wrong.
02:29:42 So I’m trying to keep an open mind here.
02:29:44 So for example, one of the things,
02:29:48 I’d love to get your thoughts on this is antiviral ideas.
02:29:52 So ideas outside of the vaccine.
02:29:56 So ivermectin, something that Brett Weinstein
02:30:00 and a few others have been talking about.
02:30:02 There’s been a few studies.
02:30:03 Some of them have been shown not to be very good studies,
02:30:07 but nevertheless, there seems to be some promise.
02:30:11 And I wanted to talk to Brett
02:30:14 about this particular topic for two reasons.
02:30:17 One, I was really bothered by censorship of this.
02:30:19 That’s a whole nother topic.
02:30:22 I just, I’m bothered by censorship.
02:30:25 There’s a gray area, of course,
02:30:28 but it just feels like that should not have been censored
02:30:32 from YouTube, like discussions of ivermectin.
02:30:34 We can set that aside.
02:30:36 The other thing I was bothered by
02:30:39 the lack of open mindedness
02:30:42 on exploring things like ivermectin in the early days,
02:30:46 especially when at least I thought
02:30:49 the vaccine would take a long time.
02:30:51 I mean, it’s not just ivermectin.
02:30:53 It’s really seriously at a large scale,
02:30:57 rigorously exploring the effectiveness of masks.
02:31:01 And the big one for me is testing.
02:31:03 Like the fact that that wasn’t explored aggressively
02:31:07 to lead to mass manufacturing like May, 2020 is absurd.
02:31:11 Anyway, so I was bothered by these solutions
02:31:14 not being explored and not by now
02:31:16 having really good ivermectin studies.
02:31:19 Can I talk about ivermectin?
02:31:20 Yeah, I would love that, yeah.
02:31:21 Sure, so full disclosure,
02:31:23 my wife worked on ivermectin at Merck for 20 years.
02:31:26 Okay, so they just want people to know,
02:31:30 but I don’t talk to her all the time about it.
02:31:34 And anyway, she hasn’t been at Merck for a long time.
02:31:37 As you know, ivermectin is a very safe drug
02:31:39 used to treat certain parasitic infections, right?
02:31:43 And it is approved, it’s amazing.
02:31:47 You can take one dose a year
02:31:48 and be protected against river blindness in Africa
02:31:51 and certain parts of Africa.
02:31:52 It’s remarkably effective.
02:31:54 And so it’s quite a safe drug
02:31:57 at the doses that are approved.
02:32:01 Now, early last year, a study was done,
02:32:04 I believe in Australia, which showed in cells in the lab,
02:32:07 if you infect with SARS CoV2 and then put ivermectin in,
02:32:11 it would inhibit the virus production substantially.
02:32:13 It was quite clear, right?
02:32:16 But the concentrations they were using were rather high
02:32:19 and could not be achieved by the approved dosing.
02:32:24 So you would need to do a dosing study
02:32:27 to make sure it’s safe.
02:32:28 And the reason is that ivermectin binds to receptors
02:32:32 in your brain and it can have high doses.
02:32:34 So some people take high doses inappropriately
02:32:37 and they have neurological consequences.
02:32:39 So if you needed 10 times more ivermectin,
02:32:42 you’d have to make sure it would be safe in people.
02:32:44 So this is a question of safety too.
02:32:46 Right, so I think it has always been the case
02:32:51 that it should have been properly studied, but it wasn’t.
02:32:54 There were lots of trials here and there,
02:32:56 lots of improperly controlled trials
02:32:58 where someone would just treat some patients
02:33:00 and say, hey, they all did fine, but have no control arm.
02:33:03 And there were some controlled trials,
02:33:05 but they were very small.
02:33:06 So right now, a 4,000 person trial is enrolling
02:33:12 to test in a randomly controlled trial setting,
02:33:16 whether it works or not.
02:33:17 There’s still plenty of cases that you can do that.
02:33:20 So you can ask whether there are any side effects.
02:33:23 I think that’s completely fine.
02:33:25 And if it says it works, then we should use it.
02:33:28 In the meantime, I always tell people,
02:33:31 if you wanna use ivermectin, you can do it off label.
02:33:33 It’s FDA approved.
02:33:35 And if your physician says,
02:33:36 I’m gonna give you this off label,
02:33:38 I don’t have any objection,
02:33:41 but I don’t know if it’s gonna work.
02:33:43 Now, a friend of ours last week in New Jersey got COVID.
02:33:49 He went to his local hospital
02:33:50 and their regimen was remdesivir, dexamethasone, ivermectin.
02:33:56 It’s written, that’s what they do for every COVID patient.
02:33:59 They just give it to them automatically.
02:34:01 And so he recovered.
02:34:04 So who’s to say it was or was not ivermectin, right?
02:34:08 So I don’t have any strong ideological opposition.
02:34:12 I just think it should be tested
02:34:14 for what you wanna use it for.
02:34:16 And that’s being done, and I think that’s fine.
02:34:19 Is it strange to you that ivermectin
02:34:23 or other things like it
02:34:24 weren’t tested aggressively in the beginning?
02:34:27 From a broad scientific community aspect,
02:34:33 I can be a little bit conspiratorial,
02:34:35 and this is what people talk about with ivermectin,
02:34:39 is with the vaccines,
02:34:40 there’s quite a lot of money to be made.
02:34:42 With ivermectin, there’s not as much money to be made.
02:34:45 Is that too conspiratorial?
02:34:48 Like why didn’t we try more solutions in the beginning?
02:34:51 Well, all the money was put into vaccines, right?
02:34:55 Very little was put into antivirals,
02:34:57 because the decision was made at a very high level,
02:34:59 probably involving Dr. Fauci.
02:35:01 We’re gonna put 24 billion into vaccines, right?
02:35:06 And I think part of the reasoning is
02:35:08 they give you years worth of protection,
02:35:10 whereas an antiviral works
02:35:11 and you have to keep dosing and so forth.
02:35:13 But ivermectin is not trivial in this.
02:35:16 I agree, it should have been tested early on,
02:35:18 but we had a really bad experience with hydroxychloroquine,
02:35:21 which we can talk about too.
02:35:25 Ivermectin is very hard to synthesize.
02:35:28 Most drugs, you synthesize chemically.
02:35:31 You devise a formulation and a synthesis,
02:35:34 and they do it, they scale it up, and it’s fine.
02:35:36 Ivermectin is really hard.
02:35:38 And so what they do instead is they take the culture
02:35:41 of the bacterium that makes it,
02:35:43 and they grow it up, and they ferment it,
02:35:45 and then they purify it.
02:35:47 And Merck owns the bacteria.
02:35:51 A number of years ago, two employees of Merck stole it
02:35:55 and left the company and tried to market it,
02:35:58 and they were arrested and they got put in jail.
02:35:59 So they protect it very carefully.
02:36:02 So you can’t just make it.
02:36:05 If you do, it’s incredibly expensive.
02:36:07 And now India, it’s very cheap apparently.
02:36:10 They use it quite liberally there,
02:36:12 and I don’t know how they’re making it.
02:36:14 Maybe they’ve licensed it from Merck and so forth.
02:36:16 But that’s why it hasn’t been tested more widely, I think.
02:36:21 There’s complexities in terms of getting a lot of it
02:36:24 and manufacturing a lot of it.
02:36:25 Yes. Okay.
02:36:26 So what was the hydroxychloroquine?
02:36:28 So hydroxychloroquine was also shown early on
02:36:32 to inhibit virus in cell culture.
02:36:36 And that’s not surprising.
02:36:37 Hydroxychloroquine, of course, is used for malaria.
02:36:41 And what it does, when your cell takes up things
02:36:46 from the plasma membrane, including viruses,
02:36:49 it goes through a pathway called the endocytic pathway,
02:36:52 which involves a vesicle moving through the cell.
02:36:54 And as it moves through the cell, its pH drops.
02:36:57 And that lets a lot of viruses out actually.
02:37:00 And hydroxychloroquine blocks that.
02:37:01 So it blocks infection with a lot of viruses.
02:37:06 So the problem with those early studies that were published
02:37:10 is that they were done in kidney cells and culture,
02:37:14 where the only way the virus can get in
02:37:16 is through the endosome.
02:37:18 And hydroxychloroquine inhibits that,
02:37:20 and that’s why it inhibits in kidney cells and culture.
02:37:24 But lung cells and respiratory cells of humans
02:37:28 where the virus reproduces can get in two different ways.
02:37:31 It can get in from this endocytic pathway,
02:37:34 which is inhibited by hydroxychloroquine,
02:37:37 or it can get in at the cell surface,
02:37:40 which is not inhibited by hydroxychloroquine.
02:37:43 So when you treat patients, it has no effect in the lung
02:37:46 because the virus can just bypass it.
02:37:50 And all the usage initially were based on
02:37:54 the studies done in kidney cells and culture.
02:37:57 So that was just wrong, scientifically incorrect,
02:38:00 yet it drove a lot of, and today many people
02:38:02 still think they should be taking it, but.
02:38:04 So that not panning out kind of resulted
02:38:09 in a loss of optimism about other similar things panning out.
02:38:14 Well, that and many other repurposed drugs were tried,
02:38:17 and a lot of HIV antivirals were tried.
02:38:20 I think the problem with hydroxychloroquine
02:38:23 influenced the ivermectin narrative.
02:38:26 People thought that the data was being hidden
02:38:29 about hydroxychloroquine, so they said,
02:38:30 well, they must be doing the same thing with ivermectin,
02:38:33 but with hydroxychloroquine, it just scientifically
02:38:36 could not work as an antiviral.
02:38:39 The other problem that is more broad
02:38:42 that is important to point out is that
02:38:45 when you have COVID and you need an antiviral,
02:38:49 it’s usually because you can’t breathe
02:38:50 and you go in a hospital.
02:38:52 Because if you’re mildly ill,
02:38:53 you’re never gonna go to your doctor
02:38:55 and ask for an antiviral.
02:38:56 And the problem is when you can’t breathe,
02:38:58 it’s no longer a viral issue.
02:39:00 It is now an inflammatory issue,
02:39:02 and no antiviral in the world is gonna help you.
02:39:05 So that’s why remdesivir doesn’t work very well,
02:39:08 because it’s mainly given intravenously
02:39:10 to people who go in a hospital.
02:39:13 If you get ivermectin in the hospital,
02:39:16 it’s not gonna do anything for reducing virus,
02:39:18 because by that time, you have very little virus
02:39:20 to begin with.
02:39:21 You have an inflammatory problem
02:39:23 that you need to treat in other ways.
02:39:24 So this is why a lot of the antivirals failed,
02:39:28 because they’re used too late.
02:39:30 What you need is a pill you take
02:39:32 on that first positive test,
02:39:34 when you have a scratchy throat.
02:39:36 You get a PCR in 15 minutes, I’m positive,
02:39:39 take a pill, boom, that’s gonna inhibit it.
02:39:42 If you wait till you can’t breathe,
02:39:44 and that’s why the monoclonals even don’t work
02:39:47 if you’re in hospital that well,
02:39:49 because it’s too late.
02:39:50 And the approach now is if you’re in a high risk group,
02:39:54 if you’re over 65, if you are obese or have diabetes
02:39:58 or any other comorbidities,
02:40:00 your first sign of a scratchy throat positive,
02:40:03 you get monoclonals, then they might help you.
02:40:07 But if you wait till you go in a hospital, it’s too late,
02:40:09 because the viral curve drops.
02:40:12 After that first symptom, within three days,
02:40:15 you’re no longer shedding enough virus to transmit.
02:40:19 Drops really quickly.
02:40:20 So that’s the reason a lot of these antivirals failed,
02:40:23 because they were tested in hospitalized patients.
02:40:25 And we have nothing but remdesivir now, unfortunately.
02:40:29 So it was the wrong approach.
02:40:30 We should have been giving it to people
02:40:33 who just tested positive from the start.
02:40:35 Or just even for preventative and see.
02:40:38 You could do that too.
02:40:39 But I have to say, the other issue is,
02:40:42 this molnupiravir is a drug in phase three now,
02:40:45 it’s an oral antiviral, it looks good.
02:40:48 If we go ahead with just one,
02:40:51 we’re gonna get resistance within a few months,
02:40:53 and it will be useless.
02:40:54 We need to have at least two or three drugs
02:40:56 that we can give in combinations.
02:40:58 And we know that, because that’s what took care of HIV,
02:41:01 that’s what took care of HCV, hepatitis C virus.
02:41:05 It really reduces the emergence of resistance.
02:41:08 Joe Rogan got quite a bit of heat recently
02:41:11 about mentioning a paper and a broader idea,
02:41:16 which I don’t think is that controversial,
02:41:19 but maybe we can expand on it.
02:41:22 And the idea is that vaccines
02:41:26 create selective pressure for a virus to mutate
02:41:32 and for variants to form.
02:41:37 First of all, from a biological perspective,
02:41:40 can you explain this process?
02:41:42 And from a societal perspective,
02:41:45 what are we supposed to do about that?
02:41:47 So let’s get the terminology right.
02:41:49 So as we talked about earlier,
02:41:51 viruses are always mutating.
02:41:54 So no vaccine or no drug makes a virus mutate.
02:41:57 Right, that’s the wrong perspective
02:41:59 in which to look at it, got it.
02:42:01 What the immune response is putting pressure,
02:42:04 selection pressure on the virus.
02:42:07 And if there’s one particle with the right mutation
02:42:11 that can escape the antibody, that will emerge, right?
02:42:15 So that’s what happens with influenza virus, right?
02:42:17 We vaccinate every year,
02:42:20 and there are not a lot of people that get infected,
02:42:22 so they get natural immunity.
02:42:24 And then the virus is incredibly varied.
02:42:28 It mutates like crazy.
02:42:30 And in some person somewhere,
02:42:32 there’s one variant that escapes the antibody,
02:42:34 which has been induced either by infection or vaccination.
02:42:37 It can be both.
02:42:38 And that drives the emergence of the new variants,
02:42:41 so the next year we need to change the vaccine.
02:42:43 So I would say both natural infection and vaccination,
02:42:48 sure, select for variants.
02:42:51 Absolutely, there’s no question,
02:42:53 because they’re inducing immunity.
02:42:55 Now, what happened last year was at the beginning of 2020,
02:43:00 very few people in the world were immune
02:43:02 as the virus first started spreading.
02:43:05 But you can see in the sequences of those isolates
02:43:09 from the beginning of 2020,
02:43:11 you can see all of the changes that are now present
02:43:14 in the variants of concern at very, very low frequencies.
02:43:17 They were already there,
02:43:18 but there was no selection for them to emerge.
02:43:21 Until November, when we now had many millions of people
02:43:25 who had mostly been infected, but also some vaccinated,
02:43:29 then we saw the alpha variant emerge in England,
02:43:33 probably because of immune selection.
02:43:35 Now, the virus that had the change
02:43:38 that evaded the antibody had an advantage,
02:43:41 and that virus drove through the population.
02:43:44 So that’s what we’re seeing.
02:43:45 All these variants are simply antigenic selection.
02:43:47 So the variants, the mutations
02:43:50 that are at the core of these, quote unquote, variants,
02:43:55 they were always there all along the vaccine,
02:43:58 or the infections did not create them.
02:44:00 No, the infections don’t create them, they’re selected.
02:44:02 It’s like the vaccine wipe out a lot of the variants,
02:44:09 and then by making your body immune to them,
02:44:13 but some of them survive.
02:44:15 Yeah, exactly.
02:44:16 And then there’s another tree that’s built,
02:44:19 and it’s unclear what that tree leads to.
02:44:23 I mean, it could make things much worse or much better,
02:44:26 and we don’t know.
02:44:28 Well, with flu, we see year after year the virus changes,
02:44:31 we change the vaccine, we deal with it,
02:44:33 we change it again, there’s an unending series.
02:44:35 But see, that’s a very different story.
02:44:37 If, do you think COVID will be with some likelihood,
02:44:42 like the flu, where it’s basically variants,
02:44:47 we’ll never be able to eradicate it?
02:44:52 It will never eradicate it in any case, ever.
02:44:57 Well, come up with a vaccine
02:44:59 that makes you immune to enough variants
02:45:03 where there’s not enough evolutionary room.
02:45:07 Well, if you cut down the number of infections,
02:45:09 then you reduce the diversity, sure, right?
02:45:12 The problem is if, let’s say you’re a cynic
02:45:15 and you say, well, vaccination is just selecting
02:45:18 for variants, so let’s stop it.
02:45:20 But then you’re gonna have infection,
02:45:21 and that’s gonna select for variants.
02:45:23 And there, you’re more likely to get very sick
02:45:26 because we know the vaccines are really good
02:45:28 at preventing you from dying.
02:45:30 So that’s why it still makes sense to use vaccines
02:45:34 because they prevent you from dying.
02:45:36 That’s the bottom line.
02:45:38 But can we ever make a vaccine that deals with all variants?
02:45:44 Absolutely.
02:45:45 And the reason I say that is because people
02:45:49 who get naturally infected with SARS COVID,
02:45:53 they develop COVID, they recover.
02:45:56 If you give them one vaccine dose,
02:45:59 they make an immune response
02:46:01 that handles all the variants that are around right now.
02:46:05 All of them.
02:46:06 Much better than people who’ve gotten two doses of vaccine.
02:46:10 For some reason, their immune response is suddenly broadened
02:46:14 after the infection vaccination,
02:46:16 and they can handle all the variants that we know of so far.
02:46:19 So that tells me we can devise a strategy
02:46:22 to do the same thing with a vaccine
02:46:24 that makes a really broad vaccine
02:46:26 that’ll handle all the variants.
02:46:27 Well, you actually, on the virology blog,
02:46:30 I don’t know if you’re the author of that, but.
02:46:32 I am, I am, yes.
02:46:33 Oh, the blog, yes, but there’s a particular post
02:46:36 that’s talking about reporting on a paper
02:46:39 that a mix and match strategy.
02:46:40 Oh, yes, that’s one of my co writers, Trudy Ray, yeah.
02:46:44 Yeah, it’s an interesting idea
02:46:46 that there’s some early evidence now
02:46:49 that mixing and matching vaccines,
02:46:52 like one shot of Pfizer and one of like Moderna or something,
02:46:56 that creates a much better immunity
02:47:00 than does two shots of Pfizer.
02:47:02 I think that’s worth exploring, absolutely.
02:47:05 And this is relevant, what we’re doing with influenza,
02:47:09 you know, instead of having to vaccinate people every year,
02:47:11 why can’t we devise a vaccine
02:47:12 which you’d get once in your lifetime
02:47:14 or maybe once every 10 years, okay?
02:47:17 So the spike of influenza, it’s a long protein,
02:47:22 kind of like the spike of SARS CoV2,
02:47:24 it’s stuck in the virus membrane,
02:47:26 and the very tip, that’s the part that changes every year.
02:47:31 This is where the antibodies bind.
02:47:33 But the stem doesn’t change.
02:47:37 And if you make antibodies to the stem,
02:47:39 they can also prevent infection.
02:47:41 It’s just that when people are infected
02:47:44 or with the current vaccines,
02:47:45 they don’t make many antibodies to that stem part,
02:47:48 but we’re trying to figure out how to make those
02:47:51 and we think they would be broadly protective
02:47:53 and you’d never be able to,
02:47:55 or more rarely be able to have a variant emerge
02:47:59 that escaped it.
02:48:00 And I think we can do the same thing
02:48:02 with coronavirus too, for sure.
02:48:06 Can I ask you about testing?
02:48:08 Sure, sure.
02:48:10 You mentioned PCR, what kind of tests are there?
02:48:13 The antigen test, what are your thoughts on each?
02:48:18 Maybe this is a good place to also mention like viral load
02:48:22 and the history of the virus as it passes through your body
02:48:27 in terms of what’s being tested for
02:48:31 and all those kinds of things.
02:48:33 So the first tests that were developed were PCR,
02:48:39 polymerase chain reaction.
02:48:40 They’re basically nucleic acid amplification tests.
02:48:43 And they were very first ones.
02:48:44 They stuck the swab all the way up into your brain almost.
02:48:49 I had that done a couple of weeks ago.
02:48:50 Oh my gosh, it’s really nasty.
02:48:53 But now they do an anterior Nares swab.
02:48:56 They get a little, they get a bunch of cells
02:48:58 and some mucus which has virus and parts of virus,
02:49:02 stick it in a test tube and then they run a reaction
02:49:05 which by the way involves reverse transcriptase
02:49:09 because it converts the viral RNA to DNA
02:49:11 and then you amplify it.
02:49:14 And you can specify what part of the viral RNA
02:49:18 you wanna amplify and then a machine will detect it
02:49:22 and it can be done in 15 minutes.
02:49:25 But you’re detecting pieces of RNA, not infectious virus.
02:49:29 So we’re measuring viral RNA loads, right?
02:49:32 And a common mistake that many people
02:49:36 who should know better, physicians and scientists
02:49:38 of all kinds, they think that indicates
02:49:41 how much virus you have.
02:49:43 It doesn’t.
02:49:45 It’s a diagnostic of whether you have bits of RNA in you
02:49:48 and it probably means you’re infected.
02:49:51 But you can’t use it to shed light on what’s going on
02:49:55 and I’ll tell you why in a bit.
02:49:56 But first we have to explain some other things.
02:50:01 So until you get to about a million copies of RNA,
02:50:06 so you can measure the copy number in this test,
02:50:08 this PCR test.
02:50:10 It’s a number called CT or cycle threshold.
02:50:13 The test, the way the machine works, it goes through cycles
02:50:16 and every cycle it amplifies what you put in
02:50:19 and the more cycles you need to see something,
02:50:23 that means there’s not a lot of RNA there.
02:50:26 So if you do a test and you have a cycle threshold of 35,
02:50:31 you have very little RNA in you.
02:50:33 Contrary, if you have a cycle threshold of 10,
02:50:36 you have a ton of RNA and it only took 10 cycles
02:50:38 to detect it.
02:50:40 And you can extrapolate from that number,
02:50:42 the number of copies you have per sample, say per swab.
02:50:46 And if you don’t have a million, you’re not infectious.
02:50:49 You’re not gonna infect anyone.
02:50:50 So in the early days, no matter what CT,
02:50:53 what PCR result you had, they would quarantine you.
02:50:56 And that was wrong because you’re not shedding.
02:50:58 You don’t need to be quarantined,
02:51:00 but wasn’t thought through properly, right?
02:51:02 And that’s where you had like 14 days
02:51:04 or something like that.
02:51:05 14 days, which is now we know is too long
02:51:07 because you don’t shed for that long in a normal infection.
02:51:11 Now it’s 10 days should be fine.
02:51:14 So what happens is you get infected,
02:51:16 you don’t know it of course.
02:51:17 The virus starts to grow very quickly.
02:51:19 And within four or five days,
02:51:21 you reach a peak of shedding.
02:51:24 You’re making a lot of RNA and you may be asymptomatic.
02:51:28 You’re shedding, you can infect others.
02:51:30 And then you may or may not have your symptom onset.
02:51:33 So you shed for a couple of days before symptom onset.
02:51:36 And then within three days, four days,
02:51:38 the viral RNA crashes and you’re no longer shedding,
02:51:41 you’re no longer transmitting.
02:51:42 So that’s the one kind of test we have.
02:51:44 It can tell you if you’re infected at the moment,
02:51:47 but it won’t tell you
02:51:49 if you’re gonna be infected tomorrow, right?
02:51:51 Cause if you’re negative today,
02:51:52 you could be positive tomorrow.
02:51:54 You just might be in a different part
02:51:56 of the incubation period, right?
02:51:58 So that’s one test been used the most.
02:52:01 You can now get 15 minute versions of them
02:52:05 in a walk in or whatever fine.
02:52:06 Then there are antigen tests,
02:52:08 which look for the proteins that the virus is making.
02:52:11 So as it’s reproducing in your nose,
02:52:13 it’s not only making genomes, it’s making proteins.
02:52:16 And so these you can buy in the drug store.
02:52:18 And these would have been great if they had,
02:52:22 Michael Minna last year had the idea
02:52:24 that if we could make a little stick,
02:52:26 a little piece of paper that you would suck on
02:52:28 and it would tell you if you’re infected or not,
02:52:30 if this could cost less than a buck,
02:52:32 everybody could test themselves.
02:52:33 Which they can cost less than a buck, by the way.
02:52:37 Yeah, but they were never made, right?
02:52:38 Right, they’re never mass manufactured.
02:52:42 So his idea is to do like daily tests.
02:52:44 Yeah, daily and then the kid’s going to school,
02:52:47 he’s positive or she’s positive.
02:52:49 Well, if it’s cheap enough, you just take another test
02:52:51 because they have a certain error frequency.
02:52:53 If it’s positive twice, you stay home
02:52:55 and the next day you try again.
02:52:57 And I think this would have revolutionized
02:52:59 because the PCR tests are more expensive at the time
02:53:02 and they take longer to do and so forth.
02:53:05 But that never happened.
02:53:07 But now we do have $20 Binax now
02:53:09 and others that you can buy and people buy them.
02:53:12 But that can still happen, right?
02:53:13 And this is the very frustrating thing to me
02:53:16 because I’m worried about variants,
02:53:18 but I’m also worried about future,
02:53:20 much more deadly pandemics.
02:53:23 Like I know we kind of said, yes, COVID, lots of deaths,
02:53:28 but like it could be a lot worse too.
02:53:31 And so I’m thinking what is going to be the right response
02:53:35 for the future pandemic of its kind?
02:53:38 And what’s the right response
02:53:39 for continued number of variants
02:53:41 and some of the variants might be deadlier
02:53:44 or more transmissible?
02:53:45 Well, we can, the antigen tests
02:53:49 will pick up the variants.
02:53:51 That’s not a question.
02:53:52 The PCR may be influenced by changes,
02:53:55 but you can quickly adapt the primers that you use.
02:53:58 So that’s what I mean.
02:53:59 Like to me, all of these discussions
02:54:00 about vaccines and so on.
02:54:03 Vaccines, we got very lucky that they took so little time.
02:54:08 And you have to be aware no matter what
02:54:10 that there’s hesitancy with the vaccines
02:54:12 in this country before.
02:54:13 I mean, yeah, that’s a reality.
02:54:15 You can’t just be like magically saying
02:54:17 that you’re going to overcome that.
02:54:20 And I don’t think there’s any hesitancy
02:54:22 and cheap tests at home.
02:54:24 I agree.
02:54:24 I think if someone, so the question is
02:54:27 if someone tested positive, would they stay home?
02:54:29 That’s the question.
02:54:30 What if their job depends on them going in?
02:54:32 I mean, that’s.
02:54:33 Well, you have to look at sort of aggregate,
02:54:36 how many people would decide.
02:54:38 And I think, again, a lot of that is in leadership,
02:54:43 but I think a lot of them,
02:54:45 I would say most people would stay home.
02:54:47 I think that Mina had the idea
02:54:49 and it would have changed the whole situation for sure.
02:54:53 If it could have been made when we talked to him last spring,
02:54:56 I think, or summer, we would have gotten around
02:54:59 a lot of the issues that we’re in today
02:55:01 because I think people would have stayed home
02:55:03 and not transmitted.
02:55:04 And I think it’s still valuable to this day.
02:55:06 In the fall, if we don’t have vaccine uptake,
02:55:09 we could just test kids every day
02:55:12 and keep them home when they’re infected.
02:55:14 It cuts, and we don’t have it.
02:55:17 But I think, and I’m not privy to what was going on,
02:55:20 but I don’t think a lot of emphasis
02:55:22 was put on testing early on.
02:55:25 The CDC developed the first one, it was flawed.
02:55:27 They had to recall the kits.
02:55:29 I mean, that’s a fiasco.
02:55:30 They should have had 100 companies
02:55:32 making the tests initially, right?
02:55:34 So for the future, I think what we have learned
02:55:37 is we need to have a rapid antigen test right off the bat.
02:55:42 It’s doable.
02:55:43 You can’t do it in a day like you can for PCR
02:55:46 because you need to make antibodies
02:55:49 to the protein that you’re looking for
02:55:51 and you need to do those in animals.
02:55:52 But you can do it in weeks and we should be ready for that.
02:55:57 Yeah, because I mean, to me, that’s obvious.
02:56:00 That’s obviously the best solution.
02:56:02 Second to that, if we understood how well masks work.
02:56:08 Like, maybe let me ask you this question.
02:56:11 Let’s put masks aside.
02:56:14 How well do we understand how COVID is transmitted?
02:56:18 There’s droplets of different sizes,
02:56:22 aerosols, tiny, tiny droplets.
02:56:26 It seems like that’s a very difficult thing
02:56:28 to understand thoroughly.
02:56:29 So it seems like it’s transmitted both ways.
02:56:33 It’s unclear how exactly.
02:56:35 So how much do we understand
02:56:38 and why is it so difficult to understand fully?
02:56:40 Well, I think it’s clear that it’s transmitted
02:56:43 through the air mostly.
02:56:44 It’s not touching.
02:56:46 We thought initially it would be a lot of touch,
02:56:47 but very little of that.
02:56:50 It’s through the air and when you talk,
02:56:53 mainly when you talk, you expel a lot of droplets, right?
02:56:56 Even the plosives that your foam thing here
02:56:59 are meant to pee, right?
02:57:01 That you send out little sprays
02:57:03 and those have viruses in them.
02:57:05 And the big drops fall to the ground
02:57:08 and the little ones can go 100 feet or more, right?
02:57:11 But the little ones also have less virus in them.
02:57:15 So I’m not sure, well, we certainly do not know
02:57:18 how much virus you need to be infected.
02:57:21 But it’s probably at least several thousand particles,
02:57:24 if not more.
02:57:26 And it could be that for most people,
02:57:30 the tiny droplets don’t have enough virus
02:57:32 to infect someone else.
02:57:34 But there’s one observation about this virus
02:57:37 that’s really interesting.
02:57:38 And that is that 80% of transmissions
02:57:42 are done by 20% of the people, of the infected people.
02:57:46 Not every infected person transmits.
02:57:49 That’s been borne out in multiple studies.
02:57:51 And in fact, there’s a study at University of Colorado
02:57:55 where they quantified the viral RNA loads
02:57:58 in all the swabs that had been done of students
02:58:01 for like a six month period.
02:58:03 And most of the infectious virus,
02:58:07 most of the RNA copies were found
02:58:10 in 15 to 20% of the people.
02:58:14 The rest had really low
02:58:15 and that’s probably why they don’t transmit.
02:58:18 So those are the ones that might get enough virus
02:58:22 in the tiny droplets to be able to infect
02:58:24 someone at a distance.
02:58:26 And I think that’s entirely possible.
02:58:28 Why is it hard to study?
02:58:31 You can’t do it in real life
02:58:32 because you don’t know who’s infected.
02:58:35 And if you do, there’s not a controlled environment
02:58:37 to measure droplets and so forth.
02:58:39 You’d have to do it in a laboratory situation.
02:58:42 If you use an animal, you just don’t know
02:58:44 what the relevance of that is to people.
02:58:46 You’d have to use human and do challenge experiments.
02:58:50 And we don’t do that at this point,
02:58:51 at least not for this virus.
02:58:53 So that’s why it’s hard to know what’s going on.
02:58:55 So we have to make inferences
02:58:58 from epidemiological associations
02:59:01 where you’re studying, say transmission in a household
02:59:03 where people are stuck in the same rooms together
02:59:06 and you can get an idea of what kind of droplets
02:59:09 were involved.
02:59:10 So that makes it much harder too.
02:59:11 If you’re leaning on epidemiological stuff
02:59:14 as opposed to like biophysics
02:59:15 or something like the mechanic.
02:59:17 Very hard.
02:59:18 So that makes it really hard to then develop solutions
02:59:23 like masks, to ask the question, how well do masks work?
02:59:26 Because then to answer that question,
02:59:28 you can lean on epidemiological stuff again,
02:59:32 like looking at populations that wear masks
02:59:34 versus don’t wear masks.
02:59:36 As opposed to actually saying,
02:59:40 like from an engineering perspective,
02:59:41 like what kind of material and what kind of tightness
02:59:46 by which amount decreases the viral load
02:59:50 that’s received on the other end.
02:59:52 But some experiments have been done with masks
02:59:55 and just droplets with no virus in them, right?
02:59:58 And you can measure the efficiency
03:00:01 of different mask materials at keeping those in.
03:00:04 So if I say that this mask stops 70%
03:00:09 of this or larger size droplet,
03:00:13 that leads to this percent decreased transmission.
03:00:18 And also on both the generation
03:00:23 and the receiving end and the giving end.
03:00:27 Sure.
03:00:28 So how well do masks protect you from others?
03:00:30 How well do you do mask protect others from you?
03:00:34 Like all of those things seem like
03:00:36 they could be more rigorously studied.
03:00:40 There’s no doubt about it.
03:00:41 And now is the time because once this is over,
03:00:46 nobody’s gonna do it.
03:00:47 Nobody’s gonna care.
03:00:48 No. Right.
03:00:49 But it seems like to me, so tests is one thing,
03:00:52 but masks, like the good mask,
03:00:57 whatever the good means, whatever that means,
03:00:59 like some level of quality of material on your face,
03:01:04 if it’s shown to actually like thoroughly shown to work well,
03:01:08 that seems like an obvious solution
03:01:12 to reopen society with.
03:01:14 If you have a good understanding of how well they work.
03:01:17 Because if you don’t have a good understanding,
03:01:20 if there’s a lot of uncertainty,
03:01:21 that’s when you get,
03:01:23 and you have people speaking from authority,
03:01:24 that’s when you start getting the politicization
03:01:27 of the solution.
03:01:28 Of course, of course.
03:01:29 No, the data, there are some data,
03:01:33 most, they’re mostly epidemiological
03:01:36 and they show some effect in some countries, right?
03:01:39 But they could be way better.
03:01:40 Yeah.
03:01:41 And, but the fact that they’re not perfect,
03:01:44 then people take advantage of and say,
03:01:46 well, look, they don’t work that well,
03:01:48 so I’m not gonna wear it.
03:01:49 I think, as you said, people can use it as an excuse.
03:01:53 But even if it works, so Daniel always says,
03:01:56 a mask will cut down transmission by 50 to 60%,
03:02:00 and then distance will do another 30%.
03:02:03 Yeah, those numbers are made up though.
03:02:05 I mean, they’re not made up, but they’re estimates.
03:02:08 Absolutely.
03:02:09 And many of them are made based on models, right?
03:02:12 Yeah.
03:02:13 We make this model,
03:02:14 and let’s say the mask cuts down this much,
03:02:16 what will be the effect on it?
03:02:17 I mean, yeah, they’re models,
03:02:19 and it’s for the same reason.
03:02:20 I don’t believe the transmission of the variants
03:02:25 because it’s all based on statistical models as well,
03:02:27 not biological experiments done in a lab.
03:02:29 So in that sense, vaccine data is much better
03:02:32 than mask data.
03:02:33 For sure, for sure.
03:02:34 So my problem with the mask data,
03:02:37 which I always thought was fascinating,
03:02:38 I stopped talking about it.
03:02:39 I was in a paper about masks.
03:02:41 I stopped talking about it
03:02:42 because what started happening
03:02:45 is masks created assholes on both sides.
03:02:48 The people that were like in Silicon Valley,
03:02:50 the friends of mine that were wearing masks,
03:02:52 the way they look at others who don’t is like…
03:02:56 Well, that’s a whole nother issue, right?
03:02:58 Yeah, I understand.
03:02:59 That happens when you don’t have solid science.
03:03:02 Understood.
03:03:03 They now start judging you like you’re a lesser human being.
03:03:07 You’re not only dumb, but you’re almost like evil.
03:03:11 You’re doing bad for society by not wearing a mask.
03:03:14 And then the people looking in the other way
03:03:17 are seeing you for the asshole that you’re being
03:03:19 for judging them unrightly.
03:03:22 So they almost wanna say F you by not wearing the mask.
03:03:24 And there’s this division that’s created
03:03:26 that was heartbreaking to me because masks like testing
03:03:30 is a solution that was available early on.
03:03:33 And if understood well, it could be deployed
03:03:35 in a mass scale, and it seems like there’s
03:03:37 some historical evidence for other viruses
03:03:40 where it does very well.
03:03:41 That’s correct.
03:03:42 And so like the fact that this was politicized,
03:03:47 yeah, it was a little bit heartbreaking.
03:03:48 You can find in the literature studies,
03:03:51 mostly of healthcare workers and influenza,
03:03:54 where you can actually,
03:03:56 because you see the people every day that can sample them,
03:03:58 you can actually see what masking does.
03:04:00 And some of them show an effect and others do not,
03:04:04 then that’s the problem.
03:04:05 Like any trial, sometimes if it’s not big enough
03:04:08 and then people latch onto that, see,
03:04:10 it doesn’t really work.
03:04:11 But I think the main issue is that in January,
03:04:15 both CDC and WHO said masks don’t work, don’t use them.
03:04:20 That was the kiss of death for masks
03:04:22 because when they then changed their mind,
03:04:25 they didn’t say we screwed up.
03:04:28 They just said wear masks.
03:04:29 If they had said we made a mistake, we were wrong,
03:04:33 I think more people would have worn masks.
03:04:35 But they didn’t.
03:04:36 And like you said, admitting you’re wrong
03:04:39 is like a real big part of it.
03:04:41 And I also think almost the better way
03:04:43 is not just saying you’re wrong,
03:04:46 but in January saying,
03:04:49 like revealing the uncertainty under which we operate.
03:04:52 Like actually, like reveal what was done
03:04:56 with the Spanish flu at the beginning
03:04:58 of the previous century,
03:05:01 because there’s a lot of mass controversy then too.
03:05:03 It went back and forth.
03:05:04 And that was actually the source of a lot of distrust
03:05:05 there too.
03:05:06 So, and then look at influenza,
03:05:09 like how is it effective with that?
03:05:11 And just reveal this, we don’t know,
03:05:13 but like with some probability,
03:05:17 this is the best option we got currently.
03:05:20 And then in a month or two, adjust it,
03:05:23 saying that, you know what,
03:05:25 our like uncertainty decreased a little bit.
03:05:27 We have a better idea.
03:05:29 Like that was an incorrect estimate,
03:05:32 but reveal that you’re struggling.
03:05:34 It’s not like this weird binary clock
03:05:36 that goes one direction or the other.
03:05:38 You’re struggling with uncertainty.
03:05:41 And like trusting,
03:05:43 people maybe criticize me sometimes for this,
03:05:45 but I think most people are actually intelligent.
03:05:48 Like trusting the public to be intelligent
03:05:51 with if you give them, if you have transparent
03:05:54 and give them information in a real authentic way,
03:05:57 like don’t look like you’re hiding something.
03:05:59 I think they’re intelligent enough to use that data
03:06:01 to make decisions.
03:06:03 It’s the same thing as with the testing,
03:06:05 is if you put that power in the people’s hands
03:06:07 to know if they’re sick or not,
03:06:08 they’re gonna make unmasked the right decision, I think.
03:06:14 The masks and the testing has been a bit heartbreaking.
03:06:18 I think that’s a good point though,
03:06:19 that most people don’t seem to have an objection
03:06:21 to testing.
03:06:23 It’s a good point.
03:06:23 Yes. Yeah.
03:06:24 And then obviously Macamina makes that point brilliantly.
03:06:27 And still there’s very little excitement around that.
03:06:33 But he said he was going to do it.
03:06:35 I don’t understand.
03:06:35 I mean, I haven’t spoken to him since then.
03:06:37 So I don’t know why.
03:06:38 He’s pushing it.
03:06:39 Well, I mean, but he can’t do it alone.
03:06:41 He has to get, so one of the resistances,
03:06:44 FDA doesn’t like cheap things.
03:06:48 Yeah.
03:06:49 They don’t wanna approve it.
03:06:50 So they makes the mass manufacture
03:06:52 like with the emergency exceptions,
03:06:55 all those kinds of things very difficult.
03:06:57 And then there’s not much money to be made on it
03:06:59 without that.
03:07:00 I don’t know.
03:07:01 I think there’s just economic pressures against it.
03:07:04 And because so much investment was placed on the vaccines
03:07:10 and obviously there’s an incentive mechanism there
03:07:13 where the companies, lobbyists and all those,
03:07:17 there’s this machine that says arguing for tests
03:07:21 is difficult because the thing that’s worked
03:07:23 for most severe viruses in the past is vaccines.
03:07:27 Now we have vaccines.
03:07:28 Why the hell would you need tests?
03:07:30 At that time, like why the hell do you need tests
03:07:34 when we can be working on vaccines?
03:07:36 It seems like the obvious thing to be working
03:07:37 is the vaccines from their perspective,
03:07:40 but it’s not obvious at all to me.
03:07:43 I think you should have both.
03:07:44 I think have vaccines and good testing
03:07:46 and that covers you really well
03:07:48 because you’re always gonna have people
03:07:50 who don’t get vaccinated.
03:07:52 I don’t know if you’ve been paying attention to this.
03:07:54 There’s a guy named Brett Weinstein.
03:07:55 There’s a guy named Sam Harris.
03:07:57 They have good representation.
03:08:00 I would say of two sides of a perspective on the vaccine.
03:08:06 So from Sam Harris’s perspective,
03:08:09 it’s obvious that everybody should get vaccinated
03:08:13 and it’s irresponsible to not get vaccinated.
03:08:18 I think he represents a lot of people’s belief in that.
03:08:22 And then Brett talks a lot about ivermectin,
03:08:28 but also talks about hesitancy towards the vaccine
03:08:32 for people who are healthy,
03:08:35 for people who are younger, that kind of thing,
03:08:38 and saying we should consider longterm effects
03:08:40 of the vaccine in making this calculation.
03:08:45 What do you make about this conversation?
03:08:47 Some of it happens on Twitter.
03:08:49 Some of it happens in the space of podcasts.
03:08:54 Do you pay attention to this kind of thing?
03:08:56 What’s your role in this?
03:08:58 What do you hope is the way to resolve this conversation?
03:09:02 Do you think it’s healthy?
03:09:04 Well, a conversation is always healthy,
03:09:05 but to make definitive statements is not
03:09:09 because it suggests you have information that you don’t have.
03:09:12 So we talked about longterm effects.
03:09:16 I think you need to balance those versus longterm effects
03:09:20 of the disease and you can make your decision.
03:09:22 I don’t think you need to tell everybody to get vaccinated.
03:09:26 I think you need to present the case.
03:09:28 You say, here, we made good vaccines.
03:09:30 Here are the safety profile.
03:09:32 Here’s the risk benefit balance.
03:09:34 And you should decide.
03:09:35 You’re a smart person.
03:09:36 You should decide.
03:09:37 Now, companies are gonna do differently, right?
03:09:41 Companies may say you have to be vaccinated to work here.
03:09:43 My employer, Columbia, said we have to be vaccinated
03:09:46 to work in the fall.
03:09:47 And if you wanna be a student, you have to be vaccinated.
03:09:49 So you decide whether you wanna go or not.
03:09:52 But the idea that you should make a decision
03:09:58 based on longterm effects, there is no evidence, right?
03:10:02 So how can you make a decision
03:10:03 when we don’t have evidence,
03:10:05 whereas we do have evidence
03:10:06 that there are longterm effects of getting COVID?
03:10:08 So I don’t think that’s a fair argument
03:10:10 and it just makes people scared to say that.
03:10:13 But on the other hand, for someone to say
03:10:15 it’s a no brainer and to denigrate people
03:10:18 for not being vaccinated, that’s not the approach either
03:10:20 because they’re gonna dig in and say,
03:10:23 I’m not doing this because you tell me to, right?
03:10:25 I think the middle ground is to say,
03:10:28 take a bit of both and say, here are the potential issues
03:10:33 and here are the benefits and this is what I would do.
03:10:37 And you have to just decide on your own.
03:10:38 I’d leave it to them.
03:10:39 I say, you decide.
03:10:40 And if you don’t want to, it’s up to you.
03:10:42 You don’t have to get vaccinated.
03:10:44 And you’ll probably get infected at some point
03:10:46 and maybe you’ll be okay.
03:10:50 But here’s the best available data
03:10:51 and it looks like the vaccines are pretty damn smart solution.
03:10:56 They seem to work.
03:10:57 I think you tell people what you did
03:11:00 and present both sides calmly.
03:11:01 And I think digging in, like in a debate,
03:11:04 I don’t think that’s terribly useful.
03:11:06 So that’s my view.
03:11:08 I mean, people come to me all the time and ask me,
03:11:11 I’m worried, what should I do?
03:11:14 And I say, what are you worried about?
03:11:16 Let’s talk about it and go through it calmly.
03:11:18 And if they want to still take ivermectin,
03:11:20 I say, it’s fine, it’s your choice.
03:11:22 And I have a problem with that.
03:11:23 I love that.
03:11:24 I love that’s the way you think.
03:11:26 People should definitely listen to This Week in Virology
03:11:32 and follow your work, it’s brilliant.
03:11:33 I’ve been really enjoying it lately.
03:11:35 It’s like, it’s my favorite way to stay in touch
03:11:38 with the happenings of COVID.
03:11:42 Obviously you put in a lot of other stuff in there, but.
03:11:45 We used to do other viruses before COVID.
03:11:47 It was quite interesting.
03:11:50 And I’m trying to slip other viruses in
03:11:52 because I think they’re informative in many ways.
03:11:56 And we’re gonna do more and more of that.
03:11:57 But I have to say I canceled,
03:11:58 usually I record on Tuesday and Friday
03:12:00 and I canceled today so I could be with you.
03:12:02 It’s a huge honor, I appreciate that.
03:12:05 No, no, it’s fine.
03:12:06 I think a couple of other people were gonna be away anyway.
03:12:10 So I do a lot of different pods.
03:12:12 They’re all on YouTube, but I also do a live stream
03:12:15 on Wednesday nights on YouTube, which you can find.
03:12:18 And that’s where people can come and ask questions.
03:12:21 We don’t have an agenda.
03:12:22 We just start and by 30 minutes in,
03:12:25 there’s 700 people with questions
03:12:27 that I can’t even get through
03:12:28 because there’s so many of them.
03:12:29 And I’m actually astounded
03:12:31 that so many people have really good questions.
03:12:35 Most of them are reasonable and they come back every week.
03:12:38 So it’s turning into a great forum
03:12:41 to have a nice discussion.
03:12:44 And the YouTube channel is called what?
03:12:46 So you could search for my name,
03:12:48 which is Vincent Racaniello, it’ll turn up.
03:12:51 Or my handle on YouTube is ProfVRR, P R O F V R R.
03:13:00 Have you read The Plague by Camus by any chance?
03:13:03 Years ago, years ago.
03:13:05 I have to read it again.
03:13:07 That’s really relevant.
03:13:08 Let me sort of ask you a question about it.
03:13:10 It describes a town that’s overtaken by a plague
03:13:14 and it’s blocked off from the rest of the world.
03:13:16 And it kind of reveals the best, the worst of human nature.
03:13:19 That’s like how people respond to that.
03:13:21 Sort of the encroaching, their own mortality,
03:13:25 their own death on the horizon.
03:13:27 I think one of the messages in the book
03:13:28 that ultimately like love for others.
03:13:34 So like a lot of people want to become isolated
03:13:36 and they hide from each other,
03:13:38 but ultimately the thing that saves you is love,
03:13:42 which is one of the things of just watching this pandemic,
03:13:46 with the distance, with the masks, that’s all fine.
03:13:50 But there’s a distancing from people of that tension,
03:13:55 the breaking of the common humanity between people.
03:13:59 That’s one of the reasons when I came to Austin
03:14:02 earlier this year just to visit,
03:14:05 I fell in love with the city
03:14:06 because even with the masks and the distance,
03:14:09 there was still a camaraderie, like, I don’t know,
03:14:14 just a love for each other,
03:14:15 just a kindness towards each other.
03:14:18 And that’s why I took away from The Plague.
03:14:20 Mostly it’s told to the story of the doctor
03:14:23 who basically gives in
03:14:27 and just gives himself as a service to others.
03:14:30 And that love is the thing that liberates him
03:14:33 from his own conception of mortality,
03:14:34 the fact that he’s here, he’s going to die.
03:14:37 What do you think about the effect of the virus?
03:14:41 We talked a lot about biology,
03:14:43 but the effect of the virus
03:14:45 on the fabric of the common humanity that connects us.
03:14:50 Well, that’s what a pandemic does.
03:14:54 It really cuts that, right?
03:14:56 Because small outbreaks, they’re local,
03:14:58 they don’t have global effects.
03:15:00 But when you have something this big
03:15:03 where pretty much nobody escapes,
03:15:07 and not just making people sick,
03:15:10 it changes your life, right?
03:15:12 People lose jobs, they change jobs,
03:15:14 they move somewhere else.
03:15:17 They have all kinds of disruptions.
03:15:20 You know, kids can’t go to school.
03:15:22 It really shows you.
03:15:23 I mean, I always like to say,
03:15:25 a tiny virus can bring Earth to its knees.
03:15:30 A tiny virus that you can’t even see them,
03:15:31 that most people don’t even think about most of the time.
03:15:35 And the real effect is not just sickness,
03:15:37 it’s what it does to people.
03:15:39 Because in the end, we are animals,
03:15:42 and most animals like each other, and they interact,
03:15:46 they have great social structures,
03:15:47 and that makes them do well.
03:15:49 And I guess the exception is people in AI, right?
03:15:53 They could be on their own.
03:15:56 Well, that’s why you build robots,
03:15:57 that you fall in love with.
03:15:58 That’s right.
03:15:59 And so I think when a,
03:16:02 the real story is what it does to society, for sure.
03:16:06 Which has ramifications way beyond
03:16:08 the number of people dying,
03:16:10 and the vaccines, and the tests, and all of that.
03:16:12 And this one has really made a big rupture.
03:16:15 And you could tell, not now so much,
03:16:17 I think being out and about now,
03:16:18 things look pretty normal,
03:16:21 except for some people wearing masks.
03:16:23 You would never know.
03:16:25 I mean, the airport this morning was completely jammed.
03:16:28 People going, and they’re all on vacation,
03:16:29 they’re all wearing shorts, right?
03:16:31 So they’re back to normal.
03:16:32 It’s August.
03:16:34 But last year is really different.
03:16:36 In New York, where you’re used
03:16:38 to lots of people on the street, it was eerie.
03:16:41 It was just quiet.
03:16:43 But under it all, people are still,
03:16:46 most people help each other when they have to, right?
03:16:50 Most people are willing to,
03:16:52 if something happens to someone,
03:16:53 to reach out and help them.
03:16:56 There are always exceptions where people are mean,
03:16:58 and that’s just the way animals are.
03:17:01 We’re not the only ones that can be mean to our own species.
03:17:05 But I think most of the motivation
03:17:08 for everything that was done is to help other people.
03:17:12 I mean, I do think that the vaccine manufacturers,
03:17:15 maybe not the leaders, but the people working in the labs
03:17:18 really wanted to get this out quickly
03:17:20 and help people, right?
03:17:22 I think at every level, people who are contributing
03:17:26 really wanted to help other people
03:17:27 and feel proud that they’re able to do that.
03:17:30 So I view it as we’re never gonna be 100% good
03:17:35 because animals are not.
03:17:37 Evolution made us, I mean, we’re lucky.
03:17:40 We somehow rose above by having incredible brain
03:17:43 and so forth, but a lot of our base instincts
03:17:45 are animals, and they chase each other
03:17:47 and have alpha males and all that stuff,
03:17:51 and we always have a little bit of that in us.
03:17:53 But we do have some humanity
03:17:56 that this really ripped up, it really did.
03:18:00 And I think for me, someone who studied viruses
03:18:05 for over 40 years, it’s just amazing
03:18:07 that an invisible thing can do that, right?
03:18:11 It goes back to the thing you found fascinating,
03:18:13 which is a virus affecting human behavior.
03:18:15 Yes.
03:18:16 Or behavior of the organism.
03:18:18 Yes, so humans can make weapons and do harm
03:18:22 and you can see that, but this you can’t even see.
03:18:25 Yeah.
03:18:26 You can’t, and look what it has done.
03:18:27 And it’ll do it again, there’ll be more.
03:18:29 I just, I wish we would be more prepared
03:18:32 because we know what to do.
03:18:34 We know we should be making antivirals vaccines,
03:18:38 masks, testing masks, making test modalities
03:18:42 that we can really quickly redesign.
03:18:46 But after SARS one, all that went out the door.
03:18:49 People didn’t do anything,
03:18:50 and that’s why we’re in this situation.
03:18:51 So people ask me this all the time,
03:18:54 are we gonna be ready for the next one?
03:18:57 And I always say, we should be.
03:18:59 We have all the information we need to know what to do.
03:19:03 But somehow I think people forget.
03:19:05 That said, sometimes we really step up
03:19:12 when the tragedies run in front of us.
03:19:14 We do.
03:19:15 When the catastrophe.
03:19:16 So I don’t know, somehow humans have still survived.
03:19:18 The fact that we had nuclear weapons for so many decades
03:19:21 and we still have not blown each other up,
03:19:23 whether by terrorists or by nation is quite surprising.
03:19:27 That’s always, after reading the Pentagon Papers,
03:19:30 it’s even more amazing, right?
03:19:32 So I don’t know how we do it.
03:19:34 I tend to believe there’s that at the surface,
03:19:40 you notice the greed, the corruption, the evil,
03:19:43 but the core of human nature, the human spirit
03:19:46 is one in the scientific realm is curiosity,
03:19:50 and more deeply is kindness, compassion,
03:19:54 and wanting to do good for the world.
03:19:56 I believe that desire to do good outpowers
03:20:00 all the other stuff by a large amount.
03:20:03 And that’s why we have not yet destroyed ourselves.
03:20:06 There’s a lot of bickering.
03:20:08 There’s a lot of wars on the surface,
03:20:10 but underneath it all,
03:20:11 there’s this ocean of love for each other.
03:20:16 I mean, I think there’s an evolutionary advantage to that.
03:20:21 And it would be a good explanation
03:20:23 why we still haven’t destroyed ourselves.
03:20:25 God, we had so many opportunities.
03:20:27 If you look at all the wars in history, so many.
03:20:29 I was just, my son was telling me
03:20:33 about the Ottoman Empire, right?
03:20:35 I mean, it’s just war after war,
03:20:39 and then other countries splitting up countries
03:20:42 with no regard to who’s living where, right?
03:20:46 It’s just, how can these people do this?
03:20:49 Yeah, it’s fascinating.
03:20:50 Human history is fascinating,
03:20:52 and we’re still young as a species.
03:20:54 We have a lot more time to go,
03:20:57 and a lot more ways to destroy ourselves.
03:21:00 Do you have advice?
03:21:01 Like you said, you have many decades of research
03:21:03 and an incredible career and life.
03:21:06 Do you have advice for young people about career,
03:21:09 about life, people in high school, people in college,
03:21:13 of how to live a life they can be proud of?
03:21:17 So what I like to do is tell people,
03:21:20 don’t plan it, because I didn’t plan anything.
03:21:22 Everything I did was one step at a time.
03:21:25 You don’t have to plan.
03:21:26 I just found things that were interesting to me.
03:21:30 And so my father was a doctor,
03:21:33 and he wanted me to be a doctor,
03:21:35 but I was not interested in taking care of people.
03:21:39 I learned that, but I couldn’t say no to him.
03:21:43 So I was a biology major in college,
03:21:46 and I graduated, and I didn’t have anything to do.
03:21:51 So I liked science, so I got a job in a lab.
03:21:54 And it was very exciting,
03:21:57 and that led to everything else
03:22:00 that I’ve done one step at a time.
03:22:02 And I think the most important thing you can do,
03:22:05 well, there are two important things.
03:22:06 You can be really curious all the time.
03:22:08 You mentioned curiosity.
03:22:10 I think curiosity is essential.
03:22:12 You have to be curious about everything.
03:22:15 And if you are, you’re never gonna be bored.
03:22:19 And so people who say they’re bored,
03:22:20 I say, you are not curious.
03:22:22 You should just think about things
03:22:24 and say, look at something and say, how does that work?
03:22:27 Or what is it doing, and how do they get there?
03:22:29 And you’ll never be bored.
03:22:30 And the other thing is when you find something,
03:22:32 which may take time, it’s fine.
03:22:36 You have to be passionate about it.
03:22:38 You have to put everything into it.
03:22:40 And that’s what I did with viruses.
03:22:42 So I think they’re amazing.
03:22:46 And I tell my classes, I love viruses.
03:22:51 They’re amazing, and people think I’m morbid
03:22:53 because obviously they kill people,
03:22:55 and I shouldn’t love something.
03:22:56 But that’s not the point.
03:22:57 That’s not what I mean.
03:22:58 I love them in the way they have emerged
03:23:00 and how they work and so forth
03:23:03 and all that we don’t know about them.
03:23:04 So you need to be curious and passionate,
03:23:06 and don’t plan too much.
03:23:07 And just find something that you don’t call a job.
03:23:12 As someone said on the livestream last week,
03:23:14 I wish I had a job I liked as much as you.
03:23:17 I said, it’s not a job.
03:23:18 I never looked at it as a job.
03:23:20 It’s my vocation, it’s my passion.
03:23:23 If it’s a job, then you’re not gonna like it.
03:23:25 Yeah, something that doesn’t feel like a job.
03:23:28 So you said viruses are kind of passive,
03:23:33 nonliving, you could say, or even cells are passive.
03:23:38 And humans are kind of active.
03:23:39 We seem to be making our own decisions.
03:23:42 So let me ask you the why question.
03:23:44 What do you think is the meaning of this life of ours?
03:23:47 Oh, there’s no meaning.
03:23:49 It just happened.
03:23:51 It’s an accident.
03:23:53 I think there’s no life elsewhere
03:23:55 because this is just a rare accident
03:23:56 that happened in the right conditions.
03:23:58 I mean, people all think I’m wrong
03:24:00 because there are billions and billions
03:24:01 of stars out there, right?
03:24:02 So there’s a lot of opportunity.
03:24:05 There’s no meaning.
03:24:06 It’s just, what do they call it?
03:24:10 A perfect storm of events
03:24:12 that led to molecules being formed.
03:24:14 And eventually, I mean, it took a long time
03:24:17 for life to evolve, right?
03:24:19 But it’s just driven by conditions.
03:24:23 If something emerged that worked,
03:24:25 it would then go on to the next step.
03:24:26 There’s no meaning other than that.
03:24:29 The only difference is that we,
03:24:32 and I think many other animals can probably,
03:24:34 we have the ability, we’re sentient, right?
03:24:36 We can influence what happens to us.
03:24:39 We can take medicines, right?
03:24:41 We can alter what would normally happen to us.
03:24:44 So we can remove some of the selection pressure.
03:24:48 But I think everything else on the planet
03:24:50 just goes, looks for food and give a lot of offspring
03:24:55 so you can perpetuate.
03:24:56 It’s just a natural biological function.
03:24:58 Yeah, they’re much more directly concerned with survival.
03:25:01 I think humans are able to contemplate their mortality.
03:25:04 We can see that even if we’re okay today,
03:25:08 we’re eventually going to die
03:25:10 and we really don’t like that.
03:25:13 So we try to come up with ways to push that deadline
03:25:16 farther and farther away.
03:25:17 Well, we have really, I mean,
03:25:18 we used to die in our 30s, right?
03:25:20 Now it’s 70s, 80s.
03:25:22 Well, most of us used to die in the first few weeks.
03:25:26 That’s true.
03:25:27 Yeah, infant death.
03:25:29 I always tell people the only thing that’s 100% is death.
03:25:34 It’s the only thing in the world that’s 100%.
03:25:36 Do you think about your own mortality?
03:25:37 No, I never think about it.
03:25:39 I’m just enjoying day to day and I don’t think about it.
03:25:42 Really?
03:25:43 You work on viruses.
03:25:44 You don’t contemplate your own mortality
03:25:47 given the deadliness of the viruses around us?
03:25:51 I never thought COVID would kill me.
03:25:53 No, I never was afraid of that.
03:25:55 Not at all.
03:25:56 I mostly feared for other people getting sick,
03:26:00 especially people who could die of it.
03:26:02 I didn’t want that to happen to them.
03:26:03 But I always thought that it’s obviously
03:26:06 not a realistic viewpoint not to be worried
03:26:10 because many people are.
03:26:13 But I’ve been relatively healthy.
03:26:17 They should sequence my genome because it works really well
03:26:19 and I have a good immune system.
03:26:21 Maybe you’d be the first immortal person.
03:26:24 There’s gotta be a first.
03:26:25 I don’t think so.
03:26:27 I think that biologically you just can’t,
03:26:31 the ends of our chromosomes keep getting
03:26:32 shorter and shorter and that’s eventually what kills us.
03:26:37 So you just can’t keep going on.
03:26:39 But that’s fine, I don’t need to.
03:26:42 I understand from the vampires
03:26:43 that it’s not good to live forever.
03:26:47 I guess make the most of the time you got.
03:26:50 That’s the, bacteria live a much shorter time
03:26:53 so we got that on bacteria.
03:26:55 Bacteria are just little bags of chemicals that split.
03:27:00 So they have no stake in the matter at all.
03:27:05 It doesn’t bother.
03:27:06 I think that you have to go a long ways
03:27:08 before you get into some kind of consciousness.
03:27:12 Yeah, it’s weird that this bag of chemicals
03:27:15 has a stake in the matter.
03:27:17 Like our human body, consciousness is a weird thing.
03:27:21 Not just in us, but they make half of the oxygen
03:27:23 on the planet.
03:27:24 20% of the oxygen comes from bacteria.
03:27:27 And they made, in the beginning of Earth,
03:27:29 they made enough oxygen to start oxygenation going,
03:27:34 life going.
03:27:34 I mean, they have an incredible role.
03:27:36 It’s all an accident, just happened.
03:27:40 Well, Vincent, like I told you, I’m a huge fan.
03:27:44 It’s a big honor that you would talk to me today.
03:27:47 Thank you so much for coming down.
03:27:48 Thank you for spending so much time with me.
03:27:51 And thank you for everything you do
03:27:53 in terms of educating about viruses,
03:27:54 about biology, microbiology, and everything else.
03:27:57 I can’t wait.
03:27:58 Everybody should check out Vincent’s YouTube,
03:28:00 watch his lectures, listen to the podcast.
03:28:03 It’s truly incredible.
03:28:05 Thank you so much for talking to me, Vincent.
03:28:06 My pleasure.
03:28:08 Thanks for listening to this conversation
03:28:10 with Vincent Racaniello.
03:28:12 To support this podcast,
03:28:13 please check out our sponsors in the description.
03:28:16 And now, let me leave you with some words
03:28:18 from Isaac Asimov.
03:28:20 The saddest aspect of life right now
03:28:23 is that science gathers knowledge
03:28:25 faster than society gathers wisdom.
03:28:27 Thank you for listening and hope to see you next time.