Vincent Racaniello: Viruses and Vaccines
生物与进化音乐与艺术技术与编程AI 与机器学习心理与人性
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🎙️ 完整对话（4735 条）
Lex Fridman (00:00.000)
The following is a conversation with Vincent Recaniello,
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professor of microbiology and immunology at Columbia.
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Vincent is one of the best educators in biology
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and in general that I've ever had
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the pleasure of speaking with.
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I highly recommend you check out
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his This Week in Virology podcast
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and watch his introductory lectures on YouTube.
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In particular, the playlist I recommend
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is called Virology Lectures 2021.
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To support this podcast,
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please check out the sponsors in the description.
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As a side note, please allow me to say
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a few words about the COVID vaccines.
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Some people are scared of a virus hurting
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or killing somebody they love.
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Some are scared of their government betraying them,
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their leaders blinded by power and greed.
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I have both of these fears.
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And two, I'm afraid, as FDR said, of fear itself.
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Fear manifests as anger and anger leads to division
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in the hands of charismatic leaders
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who then manufacture truth in quotes
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that maximize controversy and a sense of imminent crisis
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that only they can save us from.
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And though I'm sometimes mocked for this,
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I still believe that love, compassion, empathy
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is the way out from this vicious downward spiral of division.
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I personally took the vaccine
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based on my understanding of the data,
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deciding that for me, the risk of negative effects
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from COVID, short term and long term,
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are far worse than the negative effects
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from the mRNA vaccine.
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I read, I thought, I decided, for me.
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But I never have and never will talk down to people
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who don't take the vaccine.
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I'm humble enough to know just how little I know,
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how wrong I have been and will be
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on many of my beliefs and ideas.
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I think dogmatic certainty and division
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is more destructive in the long term than any virus.
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The solution for me personally, like I said,
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is to choose empathy and compassion
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towards all fellow human beings,
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no matter who they voted for.
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I hope you do the same.
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Read, think, and try to imagine
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that what you currently think is the truth
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may be totally wrong.
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This mindset is one that opens you to discovery,
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innovation, and wisdom.
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I hope my conversation with Vincent Racanello
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is a useful resource for just this kind of exploration.
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He doesn't talk down to people
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and he's the most knowledgeable virologist
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I've ever spoken to.
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He has no political agenda,
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no desire to mock those who disagree with him.
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He just loves biology
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and explaining the fundamental mechanisms
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of how biological systems work.
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That's a great person to listen to
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and learn from with an open mind.
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I hope you join me in doing so,
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and no matter what,
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try to put more love out there in the world.
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This is the Lex Friedman Podcast
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and here is my conversation with Vincent Racanello.
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You mentioned in one of your lectures on virology
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that there are more viruses
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in a leader of coastal seawater
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than people on earth.
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In the Nature article titled Microbiology by Numbers,
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it says there are 10 to the 31 viruses on earth.
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Also it says that the rate of viral infection
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in the ocean stands at 10 to the 23 infections per second.
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And these infections remove 20 to 40%
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of all bacterial cells each day.
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There's a war going on.
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Do you, what do you make of these numbers?
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Or why are there so many viruses?
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So the numbers you're quoting,
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they're in my first virology lecture, right?
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Because people don't know these numbers
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and they get, whoa, they get wild by them.
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So I love to give them.
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So the way, sorry to interrupt.
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As I was saying offline,
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you have one of the best introductory lectures on virology
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that I've ever seen, introductory lectures, period.
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So I highly recommend people
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find you on YouTube and watch it
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if you're curious at all about viruses.
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It, yeah, there's a lot of times throughout watching it,
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I felt like, whoa.
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Yeah, that's my goal is to work.
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And that's what my students tell me.
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One student once said, every day after every lecture,
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I could go home and tell my roommate something
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she didn't know and blew her away.
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So the number of viruses is really an amazing number.
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So that number 10 to the 31 is actually
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just the bacterial viruses in the ocean.
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So there are viruses that infect everything
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on the planet, including bacteria.
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There are a lot of bacteria in the ocean.
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And so 10 to the 31 is from basically particle counts
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of seawater all over the world.
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So there are more viruses than 10 to the 31,
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but just in the ocean.
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And that number is so big.
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First of all, the mass exceeds that of elephants
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on the planet by a thousand fold.
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And if you lined up those viruses end to end,
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they would go 200 million light years into space.
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It's so big a number.
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It's amazing.
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And then yes, 10 to the 20 some infections per second
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of these viruses killing bacteria
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and releasing all this organic matter.
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And that's part of this, what we call
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the biogeochemical pump, cycling of material in the ocean.
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The bacteria die, they start to sink
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and then they get metabolized
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and converted to compounds that are needed.
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A lot of it gets released as carbon dioxide and so forth.
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So these are actually really important cycles
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that are catalyzed by the virus.
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Well, it's so wild that nature has developed
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a mechanism for mass murder of bacteria.
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That's one way to look at it,
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but it's just what happened, right?
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It's interesting.
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I mean, I wonder what the evolutionary advantage
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of like such fast cycling of life is.
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Is it just an accident of evolution
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that viruses are so numerous
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or is it a feature and not a bug?
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So the fast is, it's not all fast.
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Not all viruses are fast.
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Some are 20 minutes per cycle.
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Some take weeks per cycle, but that's just per second.
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There's so many viruses in the ocean
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that that's what you get per second,
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no matter how fast the cycle is.
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But I look at it this way.
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Viruses were probably the first organic entities
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to evolve on the planet.
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Long ago, billion years ago,
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just as the earth cooled
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and organic molecules began to form,
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I think these self, we call them self replicators.
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They're just short things that today,
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would look like RNA, which is the basis of many viruses.
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They evolved and they were able to replicate.
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Of course, they were just naked molecules.
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They had no protection and it was just RNA based.
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And that's tough because RNA is pretty fragile in the world.
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And it probably didn't get very big as a consequence.
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But then proteins evolved and I'm skipping like hundreds
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of millions of years of evolution.
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Proteins evolved, maybe without a cell, maybe with a cell.
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But then to make a cell,
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there probably were some RNA based cells early on,
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but they were pretty simple.
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But the cells that we know of today,
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even bacteria and single celled eukaryotes,
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they have very long DNA genomes.
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And you need a lot of DNA to make a complicated cell.
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And so we think at some point, the RNA became DNA.
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And probably one of the earliest enzymes that arose
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is the enzyme that could copy that RNA into DNA,
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which we now know today as reverse transcriptase,
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which my former boss, David Baltimore
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and Howard Temin co discovered.
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And that enzyme arose and copied RNA to DNA.
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And then you could build big cells with DNA
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because DNA can be millions and millions of bases
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in length and RNA, the longest RNA we know of
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is 40,000 bases, not much bigger than the SARS CoV2.
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What would you say is the magic moment along that line?
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I saw it was one or two billion,
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maybe three billion years it took
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to go from bacteria to complex organism.
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It seems like Earth had a very long time,
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not a very long time without life,
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and then a very long time with very primitive life.
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Maybe I'm discriminating, calling bacteria primitive life.
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People would object to you doing that for sure.
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But it seems like complex organism
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when it starts becoming something like,
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I don't know what's a good, not animal like,
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but more complexity than just like a single cell.
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What do you think is the magic there?
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What's the hardest thing?
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If you were trying to engineer Earth and build life
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and build the simulations,
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obviously we're living in a video game, what this is.
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So if you were trying to build this video game,
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what's the hardest part along this evolution?
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Bacteria are mostly single cells.
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They do make colonies.
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They get together in biofilms, which are really important.
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But they're all single bacteria in that.
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And the key is making an organism
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where cells do different things.
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We have skin cells and eye cells and brain cells.
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Bacteria never do that.
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And the reason is probably energy.
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Bacteria can't make enough energy to do that.
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And so there was another cell
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existing at the time, the archaea.
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And the idea is that a bacteria went into an archaea
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and became the modern day mitochondria,
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the energy factory of the cell.
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And that now led that cell
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develop into more and more complicated organisms
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like we have today.
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It was all about energy.
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So the mitochondria, the energy,
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the mitochondria is the magic thing.
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I think so.
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It's just actually not my idea.
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It's Nick Jones.
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Have you heard of Nick Jones?
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He's an evolutionary biologist in the UK.
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And he's done experimental work on this.
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And it's his idea that the defining point
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was the ability to make a lot of energy,
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which a mitochondria can do.
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It's basically a whole bacteria inside of a bigger cell.
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And that becomes what we now call eukaryotes
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and that they can get more and more complicated.
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So let me bring you back to the viruses.
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I wanna finish that story.
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Yeah, which points of viruses come along?
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So remember, we have these precellular,
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they're called precellular replicons, right?
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And so we have a precellular stage
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where we have these self replicating molecules
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and then cells arise.
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And then the self replicating molecules invade the cells.
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Why?
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Because it's a hospitable environment.
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I mean, they didn't know that.
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They just went in and it turned out
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it was beneficial for them, so it stuck.
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And they replicate inside the cell now
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where they have pools of everything they need.
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They get more and more complicated.
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And then they steal proteins from the cell
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to build a protective shell.
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And then they can be released as virus particles.
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They're now protected.
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They can move from host to host.
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And because they're at the earliest stages
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of cellular evolution, they can diversify
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to infect anything that arises.
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And that is why I think there's so many of them
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and everything on the planet is infected
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because the ancestor of everything
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was infected many years ago.
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So it's easier to steal than to build from scratch.
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So it's easier to sort of break into somebody else's thing
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and steal their proteins.
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Yes.
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My colleague, Dixon de Palmier, calls viruses safe crackers.
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Safe crackers.
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So it's just, from an evolutionary perspective,
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it's easier to steal because you can select.
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But then you have to figure out mechanisms for stealing,
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for breaking into, for cracking the state.
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Well, you don't have to figure out.
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It just happens, right?
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Because molecules are so diverse
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that a molecule gets into a cell
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and if there's a protein that sticks to it,
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it's gonna stick and that gives an advantage.
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There's no planning.
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There's no thinking about it, right?
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It just happens.
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Oh, we'll return to that.
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Ha ha ha ha ha.
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What, but these numbers are crazy.
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So what, as these more complex organisms evolved,
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let's take us humans as an example,
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should we be afraid of these high numbers?
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Should we be worried
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that there's so many viruses in the world?
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Well, to a certain extent.
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I mean, they have, it's twofold.
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They're good and bad, right?
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Viruses are no, there was no question they can be bad.
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We know that because they've infected
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and caused disease throughout history,
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but we're also, you and I are full of viruses
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that don't hurt us at all and probably help us
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and every organism is the same.
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So they are clearly beneficial as a consequence.
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So I think, so every living thing on the planet
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has multiple viruses infecting everything you can see.
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And most of them I think we don't worry about
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because they can't infect us.
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They're unable.
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In fact, now you can actually take your feces
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and send them to a company
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and they will sequence your viruses in your feces for you,
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your fecal virome, right?
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And the most common virus in human feces
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is a plant virus that infects peppers.
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It's called pepper model mosaic virus.
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And that's because people eat a lot of peppers
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and it just passes right through you.
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Cabbage is full of viruses from the insects
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that walk on the cabbage in the fields.
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We eat them, they just pass us.
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So I think most of the viruses we don't need to worry about
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except when we're talking about species
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that are closest to us, mammals, of course.
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And I think the most numerous ones
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are the most concerning, they're viruses like bats.
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Bats are 20% of mammals and rodents are 40% of mammals.
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And we humans live nearby, right?
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And we know throughout history,
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many viruses have come from bats and from rodents to people,
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no question about it.
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So there's a proximity in terms of just living together
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and a proximity genetically too.
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So it's more likely that a virus will jump
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from a bat and a rodent.
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And birds too.
Lex Fridman (14:50.880)
Birds can give us their viruses that's happened.
Vincent Racaniello (14:53.880)
Influenza viruses come from birds mainly.
Lex Fridman (14:57.080)
So I think those are the three species,
Vincent Racaniello (15:00.640)
not species, it's higher than species obviously,
Lex Fridman (15:02.680)
but those are the three I would worry about
Vincent Racaniello (15:04.240)
in terms of getting their viruses.
Lex Fridman (15:05.960)
And we don't really know what's out there, right?
Vincent Racaniello (15:09.520)
We have very little clue about what viruses,
Lex Fridman (15:12.480)
and I've for years wanted to capture wild mice
Vincent Racaniello (15:16.480)
in my backyard and see what viruses they have
Lex Fridman (15:18.640)
because no one knows.
Lex Fridman (15:20.960)
And it's an easy.
Lex Fridman (15:21.800)
We can't ask them, so you mean map,
Lex Fridman (15:23.760)
like is there a way?
Lex Fridman (15:24.600)
I can't ask them, yeah.
Vincent Racaniello (15:25.440)
No, I would have to sacrifice them and take tissue
Lex Fridman (15:27.640)
and then bring it in the lab and do genome sequencing.
Lex Fridman (15:30.120)
So you can do a thorough sequencing
Lex Fridman (15:32.160)
to determine which viruses.
Vincent Racaniello (15:33.800)
Is there a sufficiently good categorization of viruses
Lex Fridman (15:37.400)
where you'd be?
Vincent Racaniello (15:38.240)
That's a very good question.
Lex Fridman (15:40.080)
So whenever you do sequence, right?
Vincent Racaniello (15:42.640)
You get some environmental sample
Lex Fridman (15:44.160)
and you extract nucleic acid and you sequence it.
Lex Fridman (15:47.120)
What you do is you run it past the database.
Lex Fridman (15:49.680)
The gold standard is the GenBank database
Vincent Racaniello (15:52.120)
which is maintained here in the US.
Lex Fridman (15:54.360)
And you see if you get any hits.
Lex Fridman (15:56.600)
And then you can say, ah, look,
Lex Fridman (15:58.560)
this sequence is similar to this virus.
Lex Fridman (16:01.080)
And you can classify all the viruses you see.
Lex Fridman (16:03.560)
The problem is 90% of your sequence is dark matter.
Vincent Racaniello (16:09.200)
It doesn't hit with anything.
Lex Fridman (16:11.120)
It's probably a lot of it is unknown viruses.
Lex Fridman (16:14.480)
And that's gonna be hard to figure out
Lex Fridman (16:16.080)
because someone's gonna have to go after it
Lex Fridman (16:17.640)
and sort it through.
Lex Fridman (16:18.960)
So yes, you can find a lot of viruses
Lex Fridman (16:21.600)
and the numbers you get are astounding.
Lex Fridman (16:22.960)
You can find thousands of new viruses
Vincent Racaniello (16:25.200)
just by looking in various life forms.
Lex Fridman (16:28.160)
But there are many more that we don't pick up
Vincent Racaniello (16:30.400)
because they're not in the database.
Lex Fridman (16:32.200)
Maybe this is a good time to take a quick tangent.
Lex Fridman (16:36.120)
What do you think about Alpha Fold 2?
Lex Fridman (16:38.000)
I don't know if you've been paying attention to that.
Vincent Racaniello (16:40.280)
With them DeepMind solving the protein folding problem
Lex Fridman (16:44.200)
and then also releasing, first of all,
Vincent Racaniello (16:47.800)
open sourcing the code, which is for me
Lex Fridman (16:49.960)
as a software person, I love.
Lex Fridman (16:52.240)
And then second of all, also making like 300,000 predictions
Lex Fridman (16:57.000)
or something like that for different protein structures
Lex Fridman (17:00.040)
and releasing that data.
Lex Fridman (17:01.760)
Yeah.
Vincent Racaniello (17:03.520)
On the side of,
Lex Fridman (17:04.360)
because you're saying there's dark matter.
Vincent Racaniello (17:06.840)
Right.
Lex Fridman (17:07.680)
Is there something, first, what are your general thoughts,
Lex Fridman (17:12.920)
level of excitement about their work?
Lex Fridman (17:15.920)
And second, how can that be applied to viruses?
Lex Fridman (17:19.400)
Do you think we'll be able to explore
Lex Fridman (17:20.800)
the dark matter of virology using machine learning?
Vincent Racaniello (17:24.520)
Absolutely.
Lex Fridman (17:25.360)
Because in all this dark sequence,
Vincent Racaniello (17:26.800)
you can translate it and make a protein.
Lex Fridman (17:29.880)
You can see what a protein looks like.
Lex Fridman (17:31.480)
It has what we call an open reading frame, right?
Lex Fridman (17:34.000)
A start and a stop.
Lex Fridman (17:35.280)
And right now it's just a bunch of amino acids,
Lex Fridman (17:37.520)
but if we could fold it,
Vincent Racaniello (17:39.800)
maybe the fold would be like something we already know,
Lex Fridman (17:43.200)
some protein fold, which gives you a lot of clues, right?
Vincent Racaniello (17:46.480)
Because there are only so many protein folds in biology
Lex Fridman (17:49.640)
and that dark matter is probably one of them.
Lex Fridman (17:52.600)
So I think that's very exciting because for years,
Lex Fridman (17:55.200)
I've followed structural biologists for years
Lex Fridman (17:59.560)
and in the beginning,
Lex Fridman (18:01.960)
we couldn't even solve structures of viruses, they're too big.
Vincent Racaniello (18:04.480)
We could do small molecules like myoglobin,
Lex Fridman (18:06.760)
that was the first one done, took years to do that.
Vincent Racaniello (18:09.400)
Then as computational power increased,
Lex Fridman (18:13.040)
then they could start to do viruses,
Lex Fridman (18:14.720)
but it took a long time.
Lex Fridman (18:16.760)
X ray crystallography,
Lex Fridman (18:18.400)
depending on getting crystals of the virus, right?
Lex Fridman (18:21.520)
And now we can do cryo electron microscopy,
Vincent Racaniello (18:24.440)
which is much faster.
Lex Fridman (18:26.360)
You could solve,
Vincent Racaniello (18:27.240)
the spike of SARS COVID 2 was solved in two months
Lex Fridman (18:29.680)
by Jason McClelland here in Austin actually
Vincent Racaniello (18:32.520)
at the beginning of the pandemic,
Lex Fridman (18:34.840)
but you're limited, you can't do huge proteins.
Vincent Racaniello (18:38.720)
You can only do moderately sized ones.
Lex Fridman (18:41.960)
So, or actually you can do viruses,
Lex Fridman (18:45.440)
but you can't do small proteins.
Lex Fridman (18:47.000)
So that's speeded it up, but it's still too fast to solve.
Vincent Racaniello (18:50.720)
You get a new protein, you wanna solve its structure.
Lex Fridman (18:52.720)
So if we could predict it,
Lex Fridman (18:53.840)
and I know from talking to structural biologists,
Lex Fridman (18:55.960)
this has been their holy grail from day one.
Vincent Racaniello (18:58.280)
They wanna be able to take a sequence of a protein,
Lex Fridman (19:00.880)
put it in a computer and have the structure put out
Vincent Racaniello (19:03.320)
without having to do all the experiment.
Lex Fridman (19:05.200)
So that's why this is very exciting
Vincent Racaniello (19:06.840)
that you can predict it.
Lex Fridman (19:08.560)
That mean it's not finished obviously,
Lex Fridman (19:10.800)
and there's more to do,
Lex Fridman (19:11.840)
but I think it will be a day
Vincent Racaniello (19:12.960)
where you could take any amino acid sequence
Lex Fridman (19:15.540)
and predict what it's gonna look like.
Vincent Racaniello (19:17.360)
See, but like aren't structural biologists
Lex Fridman (19:19.520)
gonna get greedy?
Lex Fridman (19:20.400)
So once you have that,
Lex Fridman (19:21.720)
don't you wanna go more complicated then?
Vincent Racaniello (19:24.040)
Don't you wanna go,
Lex Fridman (19:25.440)
because that's just the first step, right?
Vincent Racaniello (19:27.680)
You go from amino acid to the structure,
Lex Fridman (19:29.480)
then there's like multiple protein interactions.
Lex Fridman (19:32.120)
Like how do you get to the virus?
Lex Fridman (19:34.400)
Well, so that's what the ultimate goal
Vincent Racaniello (19:37.020)
of getting a structure is that then you can do experiments
Lex Fridman (19:39.700)
and figure out what the structure means, right?
Lex Fridman (19:42.400)
So many, in the old days,
Lex Fridman (19:44.880)
structural biology was a career in itself.
Vincent Racaniello (19:48.160)
You worked with people who had a system
Lex Fridman (19:50.000)
and just solve proteins for them,
Lex Fridman (19:51.360)
and then you moved on to another one.
Lex Fridman (19:52.520)
You didn't really do any experiments.
Vincent Racaniello (19:54.200)
The other people got to do all the interesting experiments.
Lex Fridman (19:57.000)
Now, young structural biologists are multifaceted.
Vincent Racaniello (1:00:00.760)
Not from people saying, I want to cure genetic diseases
Lex Fridman (1:00:04.280)
by gene editing, but by saying,
Lex Fridman (1:00:05.840)
what are these repeated things in this bacterium doing?
Lex Fridman (1:00:09.800)
Yep.
Lex Fridman (1:00:11.120)
Can I ask you a big philosophical question?
Lex Fridman (1:00:14.640)
So there's these deadly viruses
Vincent Racaniello (1:00:17.200)
that are not very transmissible, Ebola, rabies.
Lex Fridman (1:00:21.520)
And then there's these less deadly viruses
Vincent Racaniello (1:00:23.800)
that are very transmissible, like COVID,
Lex Fridman (1:00:29.200)
I guess kind of borderline.
Lex Fridman (1:00:31.000)
But why isn't there super transmissible,
Lex Fridman (1:00:35.560)
super deadly viruses?
Vincent Racaniello (1:00:38.360)
I think if you compare SARS one and two,
Lex Fridman (1:00:40.360)
you get somewhat of an answer, right?
Vincent Racaniello (1:00:42.600)
SARS one was more deadly.
Lex Fridman (1:00:45.560)
In fact, over half of the time when people were infected,
Vincent Racaniello (1:00:50.400)
they ended up in the hospital because they were that sick.
Lex Fridman (1:00:53.440)
And then the peak of virus shedding from them
Vincent Racaniello (1:00:57.400)
happened long after they went in the hospital.
Lex Fridman (1:00:59.640)
So it's easy to contain the infection
Lex Fridman (1:01:02.760)
when you're in a hospital, right?
Lex Fridman (1:01:04.640)
There was not much pre symptomatic
Vincent Racaniello (1:01:07.480)
or asymptomatic shedding with SARS one.
Lex Fridman (1:01:11.360)
And shedding means you become infectious.
Lex Fridman (1:01:14.000)
So in a respiratory virus,
Lex Fridman (1:01:16.040)
you inhale the droplets with the virus
Lex Fridman (1:01:18.160)
and they reproduce in your upper respiratory tract,
Lex Fridman (1:01:20.840)
what we call the nasopharynx, right?
Vincent Racaniello (1:01:22.920)
The nose and going back to that little cavity
Lex Fridman (1:01:24.880)
just above your mouth.
Lex Fridman (1:01:27.000)
So the virus reproduces really well.
Lex Fridman (1:01:28.440)
And then as you talk and sneeze and cough,
Vincent Racaniello (1:01:30.120)
you expel droplets and then those are inhaled
Lex Fridman (1:01:32.560)
by other people and then they reproduce.
Lex Fridman (1:01:35.160)
And for SARS two, we now know there's a lot of reproduction
Lex Fridman (1:01:39.640)
just before you feel anything, if at all.
Lex Fridman (1:01:42.320)
So there's a lot of shedding and transmission
Lex Fridman (1:01:45.560)
before you get symptomatic.
Lex Fridman (1:01:47.680)
And as many people don't ever get symptomatic, right?
Lex Fridman (1:01:50.200)
So they spread really easily.
Lex Fridman (1:01:52.840)
So that explains why some viruses can transmit
Lex Fridman (1:01:55.960)
a lot better than others.
Lex Fridman (1:01:57.360)
And if one happens to knock you out,
Lex Fridman (1:02:00.040)
then you're never gonna transmit
Vincent Racaniello (1:02:01.400)
because you're in the hospital like SARS one.
Lex Fridman (1:02:03.400)
But why can't you have both?
Lex Fridman (1:02:05.840)
Why can't you just wait a while before it knocks you out
Lex Fridman (1:02:08.680)
but when it knocks you out, it really kills you?
Lex Fridman (1:02:10.800)
That is a philosophical question, right?
Lex Fridman (1:02:13.200)
Because we could talk about why we haven't observed it.
Vincent Racaniello (1:02:16.640)
I mean, one issue is that if you're killed too quickly
Lex Fridman (1:02:23.480)
by a highly lethal virus,
Lex Fridman (1:02:25.840)
you're not gonna transmit it very well, right?
Lex Fridman (1:02:27.920)
So Ebola can kill you quite rapidly.
Lex Fridman (1:02:31.040)
And most of the transmission occurs when people
Lex Fridman (1:02:35.840)
are being cared for at home or in hospitals.
Vincent Racaniello (1:02:38.640)
The doctors and nurses get the virus,
Lex Fridman (1:02:40.440)
but people walking around, you're not walking around
Vincent Racaniello (1:02:42.880)
when you have Ebola, you're too sick.
Lex Fridman (1:02:45.160)
You know, you have black, bloody diarrhea,
Vincent Racaniello (1:02:47.360)
you're vomiting, you're bleeding from your skin
Lex Fridman (1:02:51.680)
and mucous membranes, you're not walking around,
Vincent Racaniello (1:02:54.360)
you're not going to parties.
Lex Fridman (1:02:55.440)
So I think that's part of it,
Vincent Racaniello (1:02:57.920)
that if the infection is too lethal,
Lex Fridman (1:03:00.400)
you're simply not a good transmitter.
Lex Fridman (1:03:02.520)
And I think transmission is probably one
Lex Fridman (1:03:05.880)
of the most powerful selection forces for viruses
Vincent Racaniello (1:03:09.720)
because a virus always has to find a new host.
Lex Fridman (1:03:12.720)
If it doesn't, it's a startup that fails, right?
Vincent Racaniello (1:03:16.400)
If it doesn't find a new host, it's gone.
Lex Fridman (1:03:18.560)
And so anything that makes the virus transmit better
Vincent Racaniello (1:03:22.520)
is gonna help it.
Lex Fridman (1:03:23.600)
And if killing you, being less lethal is part of that,
Vincent Racaniello (1:03:27.480)
that works too.
Lex Fridman (1:03:28.360)
So there's a strong selection pressure
Vincent Racaniello (1:03:30.720)
against being lethal.
Lex Fridman (1:03:32.360)
I think there's a strong selection pressure
Vincent Racaniello (1:03:34.880)
against being lethal and being more transmissible.
Lex Fridman (1:03:38.680)
Those two seem to work in opposite ways.
Lex Fridman (1:03:41.600)
And now we don't have a lot of data to support this.
Lex Fridman (1:03:43.440)
This is kind of a thought experiment,
Lex Fridman (1:03:46.520)
but there is one experiment done in Australia
Lex Fridman (1:03:50.560)
many years ago.
Vincent Racaniello (1:03:51.840)
I don't know if you know this, but in the 1800s,
Lex Fridman (1:03:54.720)
the hunters in Australia imported a rabbit from Europe
Lex Fridman (1:03:57.400)
so they could hunt it because the native rabbit
Lex Fridman (1:04:00.560)
in Australia was too fast for them.
Vincent Racaniello (1:04:02.000)
They couldn't shoot them.
Lex Fridman (1:04:03.440)
So they brought in this European rabbit
Lex Fridman (1:04:05.560)
and they reproduced out of control.
Lex Fridman (1:04:07.800)
Within a couple of years, they were everywhere,
Vincent Racaniello (1:04:10.320)
millions of rabbits in all the watering holes.
Lex Fridman (1:04:13.440)
And now they had a problem.
Lex Fridman (1:04:14.960)
So they decided to use a virus
Lex Fridman (1:04:16.520)
to get rid of these excess rabbits.
Lex Fridman (1:04:19.120)
And they used a virus, a pox virus called myxoma virus,
Lex Fridman (1:04:22.880)
which is a natural virus of a different kind of rabbit.
Lex Fridman (1:04:26.240)
But for these European rabbits, it was quite lethal
Lex Fridman (1:04:28.640)
and it's spread by mosquitoes.
Lex Fridman (1:04:30.080)
So they said, okay, let's release this virus.
Lex Fridman (1:04:33.840)
And the first year, 99.2% of the rabbits were killed,
Lex Fridman (1:04:40.320)
but that 0.8% that were left had some form of resistance.
Lex Fridman (1:04:45.120)
They were variants.
Vincent Racaniello (1:04:46.360)
Every organism, not just viruses, makes mutants.
Lex Fridman (1:04:49.040)
And there were some variants of the rabbits
Vincent Racaniello (1:04:51.000)
that could survive infection.
Lex Fridman (1:04:52.760)
And then in subsequent years, the virus became less lethal.
Lex Fridman (1:04:56.560)
And then the mosquitoes had a better shot
Lex Fridman (1:04:59.120)
of transmitting it from one rabbit to another
Vincent Racaniello (1:05:01.120)
if the rabbit lived longer.
Lex Fridman (1:05:02.320)
That's the selection probably.
Lex Fridman (1:05:04.200)
And so in the end, the rabbits lived on.
Lex Fridman (1:05:06.520)
The virus was there.
Vincent Racaniello (1:05:07.480)
It evolved to be more transmissible and less lethal.
Lex Fridman (1:05:11.440)
So that's the only.
Vincent Racaniello (1:05:12.280)
Life is amazing.
Lex Fridman (1:05:13.160)
That's the only data. Life on Earth is amazing.
Vincent Racaniello (1:05:15.080)
It is, it is.
Lex Fridman (1:05:15.920)
If you take the time to look at it and see what's happened,
Vincent Racaniello (1:05:19.440)
it is amazing.
Lex Fridman (1:05:20.760)
It's also humbling that it just makes you realize
Vincent Racaniello (1:05:22.720)
humans are just a small part of the picture.
Lex Fridman (1:05:25.280)
Of course.
Lex Fridman (1:05:26.360)
And we're wrecking it, aren't we?
Lex Fridman (1:05:28.320)
Well, I mean, we're not really.
Vincent Racaniello (1:05:32.520)
I mean, viruses are wrecking it some ways.
Lex Fridman (1:05:35.400)
We're not really wrecking anything.
Vincent Racaniello (1:05:36.880)
It's all part of it.
Lex Fridman (1:05:38.240)
But you know, when the ways that humans exist
Lex Fridman (1:05:41.480)
encourages viruses to infect us, right?
Lex Fridman (1:05:43.960)
When we were hunter gatherers,
Vincent Racaniello (1:05:45.840)
living in bands of 100 people, very few viruses
Lex Fridman (1:05:49.640)
because it was hard for the virus to go
Vincent Racaniello (1:05:51.760)
from one band to another.
Lex Fridman (1:05:53.200)
And perhaps a hunter would, one of these humans
Vincent Racaniello (1:05:55.840)
would get an animal and bring a virus into camp
Lex Fridman (1:05:58.600)
and some people would die,
Lex Fridman (1:05:59.560)
but it would never spread to another.
Lex Fridman (1:06:02.160)
And then when we started to congregate in cities,
Vincent Racaniello (1:06:04.480)
we figured out agriculture and so forth
Lex Fridman (1:06:06.640)
and how to harvest animals,
Vincent Racaniello (1:06:07.760)
then we could get bigger and bigger populations
Lex Fridman (1:06:09.480)
and the viruses went crazy.
Lex Fridman (1:06:10.960)
And they went from animals to us.
Lex Fridman (1:06:12.560)
So measles went from cows to humans
Vincent Racaniello (1:06:15.120)
when humans learned to domesticate cows
Lex Fridman (1:06:17.480)
and started gathering in big cities.
Vincent Racaniello (1:06:20.680)
Yeah, but now that humans are able to communicate
Lex Fridman (1:06:24.880)
and travel globally,
Vincent Racaniello (1:06:26.960)
the viruses become more and more dangerous, transmissible.
Lex Fridman (1:06:31.760)
Thereby, if you look at earth as an organism,
Vincent Racaniello (1:06:33.960)
thereby pushing humans to be more innovative,
Lex Fridman (1:06:36.800)
create alpha fold two and three and four and five,
Vincent Racaniello (1:06:39.600)
create better systems and eventually there's rockets
Lex Fridman (1:06:41.800)
that keep flying from earth.
Lex Fridman (1:06:43.960)
And eventually the virus is becoming super dangerous
Lex Fridman (1:06:47.480)
and threatening all of human civilization,
Vincent Racaniello (1:06:49.680)
will force it to become a multi planetary species
Lex Fridman (1:06:52.520)
and its organism starts expanding.
Lex Fridman (1:06:54.520)
So I think it's a feature, not a bug, I don't know.
Lex Fridman (1:06:57.520)
Well, I think that we have our early,
Vincent Racaniello (1:07:00.720)
probably the most of the,
Lex Fridman (1:07:03.120)
we're studying viruses since 1900, right?
Vincent Racaniello (1:07:06.120)
Most of that time was because of diseases they caused.
Lex Fridman (1:07:09.680)
The first viruses discovered, yellow fever,
Vincent Racaniello (1:07:12.920)
virus, smallpox, polio virus, influenza virus,
Lex Fridman (1:07:17.920)
those were all because people got sick and they said,
Vincent Racaniello (1:07:21.520)
oh, look, this is a virus that's associated with it.
Lex Fridman (1:07:24.560)
And so we got good at learning how to take care
Vincent Racaniello (1:07:28.840)
of these infections, making vaccines and so forth
Lex Fridman (1:07:31.040)
over the years and it's only in the last 20 years
Vincent Racaniello (1:07:33.240)
that we recognize that there are more viruses out there
Lex Fridman (1:07:36.120)
that are far more interesting, perhaps,
Lex Fridman (1:07:38.240)
but we've learned how to deal with the bad ones for sure.
Lex Fridman (1:07:41.120)
So we talked about what is a virus.
Vincent Racaniello (1:07:43.480)
We talked about some of the most dangerous
Lex Fridman (1:07:45.560)
and deadly viruses.
Lex Fridman (1:07:47.080)
Can we zoom in and talk about COVID 19 virus?
Lex Fridman (1:07:51.320)
Sure.
Vincent Racaniello (1:07:52.160)
I don't know what your preferred name is, but maybe for this.
Lex Fridman (1:07:54.400)
Right, the virus is SARS CoV2, which is hard, it's long,
Lex Fridman (1:07:58.360)
and then COVID 19 is the disease.
Lex Fridman (1:08:00.440)
So you could say the virus of COVID 19, that's fine.
Vincent Racaniello (1:08:03.280)
The virus of COVID 19.
Lex Fridman (1:08:04.680)
But for the purpose of this conversation,
Vincent Racaniello (1:08:06.240)
we'll every once in a while just say COVID.
Lex Fridman (1:08:08.320)
It's fine, no problem.
Lex Fridman (1:08:10.480)
What is this virus from,
Lex Fridman (1:08:14.280)
I don't know how many ways we can talk about it.
Vincent Racaniello (1:08:16.640)
I think from a basic structural,
Lex Fridman (1:08:19.680)
like the variant structure,
Lex Fridman (1:08:22.960)
biological structure perspective, what is it?
Lex Fridman (1:08:25.920)
What are its variants?
Lex Fridman (1:08:28.080)
Can you describe the basics,
Lex Fridman (1:08:30.080)
the important characteristics of the virus?
Lex Fridman (1:08:32.040)
So viruses are classified by humans
Lex Fridman (1:08:35.020)
just to make it easier to keep track of them, right?
Lex Fridman (1:08:38.280)
So this is a coronavirus, which is because
Lex Fridman (1:08:42.340)
when they were first discovered,
Vincent Racaniello (1:08:45.160)
I think the first ones were animal coronaviruses.
Lex Fridman (1:08:48.280)
They looked at them in the electron microscope
Lex Fridman (1:08:50.440)
and it looked like the solar corona,
Lex Fridman (1:08:51.960)
and that's all there is to it.
Lex Fridman (1:08:53.480)
And I have to say that early in the outbreak,
Lex Fridman (1:08:56.320)
the place with the highest seropositivity in the US,
Vincent Racaniello (1:09:00.240)
for a while, 68% was a working class neighborhood
Lex Fridman (1:09:03.800)
in New York City called corona.
Lex Fridman (1:09:06.520)
Can you beat that, right?
Lex Fridman (1:09:08.120)
That's crazy, yeah.
Lex Fridman (1:09:09.600)
So coronaviruses, they have membranes, right?
Lex Fridman (1:09:12.220)
We talked about membranes,
Vincent Racaniello (1:09:13.160)
they have spike proteins in the membrane,
Lex Fridman (1:09:15.000)
so they can attach to cells.
Lex Fridman (1:09:16.320)
And inside, they have RNA.
Lex Fridman (1:09:19.040)
And they are the viruses with the longest RNA
Vincent Racaniello (1:09:22.000)
that we know of.
Lex Fridman (1:09:23.400)
None other comes close.
Vincent Racaniello (1:09:25.120)
For some reason, they're able to maintain 30,000,
Lex Fridman (1:09:29.640)
so SARS, COVID, two RNAs, 30,000 bases of RNA,
Lex Fridman (1:09:33.860)
and some of the other coronas are even longer, 40,000.
Lex Fridman (1:09:37.240)
This is a, coronas are family of viruses
Vincent Racaniello (1:09:40.920)
that included the one you mentioned before, version one.
Lex Fridman (1:09:46.320)
So SARS, COVID one, yeah.
Vincent Racaniello (1:09:47.800)
COVID one, and I guess other ones as well.
Lex Fridman (1:09:49.640)
So the first, we first learned of them in animals,
Vincent Racaniello (1:09:52.520)
a lot of animals, pigs, and cows,
Lex Fridman (1:09:56.360)
and horses have coronaviruses.
Lex Fridman (1:09:58.240)
And then in the 60s, we discovered
Lex Fridman (1:10:01.440)
a couple of human coronaviruses that just cause colds,
Vincent Racaniello (1:10:05.220)
very mild colds that you wouldn't even think twice about.
Lex Fridman (1:10:08.920)
And then suddenly, in 2003, there's this outbreak
Vincent Racaniello (1:10:14.160)
of severe respiratory disease in China.
Lex Fridman (1:10:18.600)
And it started in November,
Lex Fridman (1:10:21.560)
and they didn't tell the world until February.
Lex Fridman (1:10:24.000)
And that was really bad, because it was already spreading
Vincent Racaniello (1:10:27.220)
by the time they told people about it.
Lex Fridman (1:10:30.080)
But this went to 29 different countries.
Vincent Racaniello (1:10:34.600)
Only 8,000 people were infected, and then it stopped.
Lex Fridman (1:10:37.480)
And that was the first time we saw an epidemic coronavirus.
Lex Fridman (1:10:43.060)
And what they did afterwards is they said,
Lex Fridman (1:10:45.780)
okay, it looks like it came from the meat markets.
Vincent Racaniello (1:10:48.380)
They have live meat markets in Guangzhou,
Lex Fridman (1:10:50.620)
in the south of China, where you can go
Lex Fridman (1:10:53.220)
and pick out an animal and the guy will slaughter it for you
Lex Fridman (1:10:56.440)
and give it to you, and then of course,
Vincent Racaniello (1:10:57.780)
there's blood everywhere, and that's how they got infected.
Lex Fridman (1:11:00.580)
And they figured out that there's this animal
Vincent Racaniello (1:11:02.760)
called a palm civet, that was the source of virus.
Lex Fridman (1:11:05.780)
The palm civets are shipped in from the countryside,
Lex Fridman (1:11:08.460)
and the palm civets somehow in the countryside
Lex Fridman (1:11:10.660)
got it from a bat.
Lex Fridman (1:11:11.700)
So they went looking in caves in the countryside,
Lex Fridman (1:11:13.900)
and they found in one cave all the viruses
Vincent Racaniello (1:11:16.860)
that could make up SARS 1.
Lex Fridman (1:11:19.140)
And that was 2000, and I would say,
Vincent Racaniello (1:11:21.620)
took about five, eight years after that outbreak.
Lex Fridman (1:11:24.340)
So that was the first hint that bats have coronaviruses
Lex Fridman (1:11:30.040)
that can infect people and cause problems, right?
Lex Fridman (1:11:32.940)
And after that, we should have been ready.
Lex Fridman (1:11:35.620)
So didn't they already start developing
Lex Fridman (1:11:37.580)
vaccines after then? Yes.
Lex Fridman (1:11:38.860)
So some people started making vaccines.
Lex Fridman (1:11:41.300)
They tested them in mice, but they never got into people.
Lex Fridman (1:11:46.780)
And some people started working on antiviral drugs.
Lex Fridman (1:11:50.860)
Nothing ever came of them because, you know,
Vincent Racaniello (1:11:54.140)
industry, there's no disease, it's gone.
Lex Fridman (1:11:57.460)
Why should we make vaccines and drugs?
Lex Fridman (1:11:59.420)
And NIH in the US, you submit a grant,
Lex Fridman (1:12:02.540)
and they say, ah, it's too risky.
Vincent Racaniello (1:12:03.960)
There's none of this virus around.
Lex Fridman (1:12:05.520)
So people were really shortsighted because I always say,
Vincent Racaniello (1:12:08.180)
we could have had antivirals for this, absolutely, for sure.
Lex Fridman (1:12:13.060)
No question.
Vincent Racaniello (1:12:14.260)
In fact, the one antiviral that's in phase three,
Lex Fridman (1:12:17.180)
it's called molnupiravir.
Vincent Racaniello (1:12:20.220)
It's the only one that you can take orally.
Lex Fridman (1:12:22.260)
It's a pill.
Vincent Racaniello (1:12:23.100)
It looks really good.
Lex Fridman (1:12:24.220)
That was developed five years ago,
Lex Fridman (1:12:26.340)
but never taken into humans.
Lex Fridman (1:12:27.980)
It could have been ready.
Lex Fridman (1:12:29.340)
So we dropped the ball, and then the next decade, 2012,
Lex Fridman (1:12:33.940)
MERS coronavirus comes up in the Arabian Peninsula.
Vincent Racaniello (1:12:38.900)
This comes from camels and infects people,
Lex Fridman (1:12:41.580)
but probably the camels got it from bats originally
Vincent Racaniello (1:12:44.820)
some time ago.
Lex Fridman (1:12:46.260)
But that never transmits from person to person, very rarely.
Vincent Racaniello (1:12:50.580)
Every new little outbreak is a new infection from a camel.
Lex Fridman (1:12:55.460)
So that was 2012, and now here we are, 2019,
Vincent Racaniello (1:12:59.260)
the new outbreak of respiratory disease in China.
Lex Fridman (1:13:02.680)
And this one really goes all over the world
Vincent Racaniello (1:13:06.420)
where SARS1 could not.
Lex Fridman (1:13:07.780)
It's a coronavirus.
Vincent Racaniello (1:13:09.380)
It's different enough from SARS1
Lex Fridman (1:13:11.100)
that it has very different properties.
Vincent Racaniello (1:13:12.940)
Causes a lot.
Lex Fridman (1:13:13.780)
But it still has a membrane.
Vincent Racaniello (1:13:14.620)
It still has a very long RNA in the middle,
Lex Fridman (1:13:17.820)
and then it still has the spike proteins.
Vincent Racaniello (1:13:19.900)
That's right.
Lex Fridman (1:13:20.740)
What are the things that are,
Lex Fridman (1:13:22.460)
what are the little unique things
Lex Fridman (1:13:24.780)
that make it that much more effective?
Vincent Racaniello (1:13:27.740)
That make it cause a pandemic of millions of people
Lex Fridman (1:13:30.940)
as opposed to SARS1?
Vincent Racaniello (1:13:32.500)
Well, the genome is 20% different from SARS1, say.
Lex Fridman (1:13:38.540)
And in those bases, there's some,
Vincent Racaniello (1:13:40.300)
there are things that make it different from SARS1.
Lex Fridman (1:13:42.900)
It binds the same receptor, ACE2, on the cell surface.
Lex Fridman (1:13:45.580)
So that's remarkable.
Lex Fridman (1:13:48.020)
It has a lot of the same proteins.
Vincent Racaniello (1:13:50.100)
They look similar.
Lex Fridman (1:13:50.980)
Like if you look at the structure of the spikes,
Vincent Racaniello (1:13:53.100)
they look similar,
Lex Fridman (1:13:54.660)
but there's enough amino acid differences
Vincent Racaniello (1:13:57.020)
to make the bio.
Lex Fridman (1:13:58.500)
And what it is, we don't know,
Lex Fridman (1:14:00.060)
because how do you figure that out?
Lex Fridman (1:14:03.200)
You need to study animals,
Vincent Racaniello (1:14:04.900)
because you can't infect people.
Lex Fridman (1:14:06.700)
And the animal models aren't great.
Lex Fridman (1:14:10.220)
So the way you figure that out
Lex Fridman (1:14:11.600)
is you figure out how those differences,
Lex Fridman (1:14:14.980)
what functional,
Lex Fridman (1:14:16.780)
like how the difference in the amino acids
Vincent Racaniello (1:14:18.540)
lead to functional difference of the virus.
Lex Fridman (1:14:20.860)
That's right.
Vincent Racaniello (1:14:21.700)
Like how it attaches, how it breaks the cell wall.
Lex Fridman (1:14:23.180)
Exactly.
Lex Fridman (1:14:24.020)
And how the hell do you figure that out?
Lex Fridman (1:14:25.700)
Like, I guess there's models of interaction.
Lex Fridman (1:14:29.980)
First, you need an animal of some kind to infect, right?
Lex Fridman (1:14:33.180)
You can use mice.
Vincent Racaniello (1:14:34.920)
People have used ferrets, guinea pigs,
Lex Fridman (1:14:38.660)
nonhuman primates,
Vincent Racaniello (1:14:40.820)
all of the above.
Lex Fridman (1:14:41.780)
Nonhuman primates are very expensive,
Lex Fridman (1:14:43.260)
so not many people do that.
Lex Fridman (1:14:45.740)
And then you can put the virus in the respiratory tract.
Lex Fridman (1:14:48.500)
But in fact, none of them get sick like people do.
Lex Fridman (1:14:52.720)
Many people with COVID get a mild disease,
Lex Fridman (1:14:55.580)
but 20% get a very severe, longer lasting disease.
Lex Fridman (1:14:59.620)
They can die from it, right?
Vincent Racaniello (1:15:00.780)
No animal does that yet.
Lex Fridman (1:15:03.020)
So we have no insight into what's controlling that.
Lex Fridman (1:15:05.460)
But if you just wanna look at the very first part
Lex Fridman (1:15:07.500)
of infection and the shedding and the transmission,
Vincent Racaniello (1:15:10.880)
you can do it in any one of several animal models.
Lex Fridman (1:15:14.620)
Ferrets are really good for transmission.
Vincent Racaniello (1:15:16.660)
They tend to have nasal structures like humans
Lex Fridman (1:15:19.620)
and you can put them in cages next to each other
Lex Fridman (1:15:22.780)
and they'll transmit the virus really nicely.
Lex Fridman (1:15:24.900)
So you can study that.
Lex Fridman (1:15:26.620)
But the other thing that's important that we should mention
Lex Fridman (1:15:29.740)
is how do you manipulate these viruses?
Lex Fridman (1:15:34.100)
So these are RNA viruses.
Lex Fridman (1:15:36.680)
You can't manipulate RNA.
Vincent Racaniello (1:15:38.740)
We don't know how to do it.
Lex Fridman (1:15:40.820)
But DNA, because of the recombinant DNA revolution
Vincent Racaniello (1:15:45.740)
that occurred in the 70s,
Lex Fridman (1:15:47.980)
we can change DNA any way we want.
Vincent Racaniello (1:15:51.460)
We can change a single base, we can cut out bases,
Lex Fridman (1:15:53.680)
we can put other things in really easily.
Lex Fridman (1:15:56.960)
And if I may give it a personal aspect,
Lex Fridman (1:16:01.680)
when I went to MIT as a postdoc in 1979,
Vincent Racaniello (1:16:05.820)
David Baltimore said, here's what I want you to do.
Lex Fridman (1:16:09.020)
The moratorium on recombinant DNA experiments
Vincent Racaniello (1:16:12.580)
on viruses has just been lifted.
Lex Fridman (1:16:14.740)
I want you to make a DNA copy of polio
Lex Fridman (1:16:18.180)
and see if you put that in a cell
Lex Fridman (1:16:19.820)
whether it will start an infection.
Vincent Racaniello (1:16:21.600)
It's okay.
Lex Fridman (1:16:24.440)
So I made a DNA copy of polio virus.
Vincent Racaniello (1:16:27.280)
It's only 7,500 bases.
Lex Fridman (1:16:29.360)
It's much smaller than corona.
Lex Fridman (1:16:31.760)
And I took that DNA and I put it in a piece of DNA
Lex Fridman (1:16:35.560)
from a bacteria called a plasmid.
Lex Fridman (1:16:37.960)
And you can grow plasmids in many, many bacteria,
Lex Fridman (1:16:41.440)
make lots of them and purify the DNA really easily.
Lex Fridman (1:16:44.600)
And I took that DNA and I sequenced it
Lex Fridman (1:16:48.680)
because we didn't know the genome sequence
Vincent Racaniello (1:16:50.880)
of polio at the time.
Lex Fridman (1:16:52.680)
And that took me a year by the way,
Vincent Racaniello (1:16:54.640)
because the techniques we had were really archaic
Lex Fridman (1:16:57.280)
and nowadays you could do it in 15 minutes, right?
Vincent Racaniello (1:17:00.000)
It's amazing.
Lex Fridman (1:17:01.520)
And I took the DNA, I put it into cells and out came polio.
Lex Fridman (1:17:06.800)
So that's the start.
Lex Fridman (1:17:07.980)
Now, since then everybody has taken that technique
Lex Fridman (1:17:10.720)
and used it for their virus.
Lex Fridman (1:17:11.720)
You can now do it with SARS CoV2.
Vincent Racaniello (1:17:13.180)
You make a DNA copy of any RNA virus,
Lex Fridman (1:17:16.000)
you can modify it and you put it back into cells
Lex Fridman (1:17:19.040)
and you'll get your modified virus out.
Lex Fridman (1:17:21.440)
So that's an important part of understanding
Vincent Racaniello (1:17:23.780)
the properties of the virus as, say, in an animal.
Lex Fridman (1:17:26.620)
By changing the virus, you're changing a DNA copy,
Vincent Racaniello (1:17:28.840)
you're making the virus then and putting it into the animal.
Lex Fridman (1:17:32.500)
Can you clarify, so even in the RNA virus,
Lex Fridman (1:17:35.360)
you can take and turn it into DNA?
Lex Fridman (1:17:38.040)
Yes.
Lex Fridman (1:17:38.880)
And then that allows you to modify it.
Lex Fridman (1:17:41.000)
Yes.
Lex Fridman (1:17:41.840)
What's that mapping?
Lex Fridman (1:17:44.240)
Well, no, no, no, what's the process
Lex Fridman (1:17:46.000)
of going from RNA to DNA?
Lex Fridman (1:17:48.320)
Reverse transcription.
Vincent Racaniello (1:17:49.680)
That's reverse transcription.
Lex Fridman (1:17:50.680)
Right.
Vincent Racaniello (1:17:51.520)
Oh, so you actually go through the process
Lex Fridman (1:17:53.120)
of reverse transcription to do this?
Vincent Racaniello (1:17:54.720)
Yes.
Lex Fridman (1:17:55.540)
Remember, David Baltimore and Howard had discovered
Vincent Racaniello (1:17:58.400)
this enzyme in the 70s.
Lex Fridman (1:18:00.080)
They got the Nobel Prize for that.
Lex Fridman (1:18:01.720)
And when I went to David's lab at MIT,
Lex Fridman (1:18:04.560)
he had the enzyme in the freezer.
Vincent Racaniello (1:18:06.360)
He said, here, take this and make a DNA copy of polio.
Lex Fridman (1:18:08.760)
Yeah, I didn't make the connection
Vincent Racaniello (1:18:10.160)
that you can use that kind of thing for an RNA virus.
Lex Fridman (1:18:14.000)
And so that's.
Lex Fridman (1:18:14.840)
And then modify it.
Lex Fridman (1:18:15.880)
See, any DNA virus already exists as DNA.
Lex Fridman (1:18:18.200)
So you can modify it.
Lex Fridman (1:18:19.760)
But for RNA viruses, it was difficult.
Lex Fridman (1:18:22.280)
And so then from that point on, for influenza,
Lex Fridman (1:18:25.640)
every other RNA virus and coronaviruses,
Vincent Racaniello (1:18:28.000)
people made DNA copies.
Lex Fridman (1:18:29.840)
And that's what they use to modify
Lex Fridman (1:18:31.520)
and ask questions about what things are doing, right?
Lex Fridman (1:18:34.600)
What's this gene doing?
Lex Fridman (1:18:35.560)
What if we take it out?
Lex Fridman (1:18:36.400)
What happened?
Lex Fridman (1:18:37.220)
Can you do the same thing with COVID?
Lex Fridman (1:18:39.560)
Is take the RNA and then.
Vincent Racaniello (1:18:41.160)
Of course.
Lex Fridman (1:18:42.000)
And in fact, in January 2020,
Vincent Racaniello (1:18:44.160)
as soon as the genome sequence was released from China,
Lex Fridman (1:18:47.600)
the labs all over were synthesizing this 30,000 base DNA
Lex Fridman (1:18:52.760)
and getting virus.
Lex Fridman (1:18:54.320)
What can you figure out without infecting anything?
Vincent Racaniello (1:18:58.280)
Just turning into, with the reverse transcription,
Lex Fridman (1:19:01.720)
turning into DNA, modifying stuff,
Lex Fridman (1:19:03.560)
and then putting it into a cell.
Lex Fridman (1:19:05.520)
What can you figure out from that?
Vincent Racaniello (1:19:08.360)
Oh, well, you could, let's say you can cut out a gene.
Lex Fridman (1:19:11.640)
You see some genes in the sequence.
Vincent Racaniello (1:19:13.280)
I don't know what these genes do.
Lex Fridman (1:19:14.720)
Let's cut them out.
Lex Fridman (1:19:16.040)
And then you could cut them out of the DNA.
Lex Fridman (1:19:18.840)
You put the DNA in cells and maybe you get virus out.
Lex Fridman (1:19:22.080)
And you go, oh, clearly that gene's not needed
Lex Fridman (1:19:25.440)
for the virus to reproduce, at least in cells, right?
Vincent Racaniello (1:19:27.820)
Or maybe you take the gene out
Lex Fridman (1:19:29.200)
and you never get any virus, so it's lethal.
Lex Fridman (1:19:31.600)
Is there a nice systematic ways of doing this?
Lex Fridman (1:19:33.520)
Do people kind of automate it?
Vincent Racaniello (1:19:35.480)
Absolutely.
Lex Fridman (1:19:36.320)
And we, I mean, the problem with SARS, the COVID virus,
Vincent Racaniello (1:19:41.080)
is it's 30,000 bases, a lot of stuff there.
Lex Fridman (1:19:44.460)
And what makes it more difficult is that you have to,
Vincent Racaniello (1:19:48.480)
it's been classified as a BSL3 agent, biosafety level three.
Lex Fridman (1:19:55.600)
And so not everyone has a lab that's capable of doing that.
Lex Fridman (1:19:58.960)
So it limits the number of people who can do experiments.
Lex Fridman (1:20:02.760)
You know, we're lucky to have a few in New York City,
Lex Fridman (1:20:05.720)
but not every place has them.
Lex Fridman (1:20:07.520)
So you cannot work with a virus just out on the bench
Vincent Racaniello (1:20:11.520)
like we do with many other viruses.
Lex Fridman (1:20:13.040)
You have to wear a suit and have to have special procedures
Lex Fridman (1:20:15.800)
and containment and so forth.
Lex Fridman (1:20:16.920)
So it makes it difficult to do basic experiments
Vincent Racaniello (1:20:19.240)
on the virus.
Lex Fridman (1:20:20.080)
But when it's a pandemic, there's a lot of money,
Vincent Racaniello (1:20:22.800)
there's a lot of incentive to work on it harder.
Lex Fridman (1:20:25.600)
And also you don't need to work on the virus.
Vincent Racaniello (1:20:27.360)
You can take bits of it and work.
Lex Fridman (1:20:29.280)
You could take, say, just the spike, right?
Lex Fridman (1:20:31.200)
And say, can we make a vaccine with just the spike?
Lex Fridman (1:20:33.880)
Because that doesn't require BSL3, so yes.
Lex Fridman (1:20:36.800)
So like building a vaccine requires you to figure out
Lex Fridman (1:20:40.480)
how, or antiviral drugs, how to attack various structural
Vincent Racaniello (1:20:44.680)
parts of the virus and the functional parts of the virus.
Lex Fridman (1:20:47.040)
Right.
Vincent Racaniello (1:20:47.880)
You have to decide on a target.
Lex Fridman (1:20:50.040)
Yeah.
Vincent Racaniello (1:20:50.880)
Like, I'm gonna make an antiviral,
Lex Fridman (1:20:52.360)
what am I gonna target in the virus?
Lex Fridman (1:20:55.480)
And there are a few things that make more sense than others.
Lex Fridman (1:21:00.440)
Usually we like to target enzymes.
Vincent Racaniello (1:21:03.400)
I don't know if you remember your biochemistry,
Lex Fridman (1:21:05.560)
but enzymes are catalytic.
Vincent Racaniello (1:21:07.840)
You don't need a lot of them to do a lot of things.
Lex Fridman (1:21:10.480)
So they're typically in low concentrations
Vincent Racaniello (1:21:12.880)
in a virus infected cell.
Lex Fridman (1:21:14.360)
So it's easier to inhibit them with a drug.
Lex Fridman (1:21:17.120)
And the coronas have a couple of enzymes that we can target.
Lex Fridman (1:21:20.920)
So you have to figure that out ahead of time
Lex Fridman (1:21:23.640)
and decide what to go after.
Lex Fridman (1:21:25.080)
And then you can look for drugs that inhibit
Lex Fridman (1:21:27.320)
what you're interested in.
Lex Fridman (1:21:28.400)
It's not that hard to do.
Vincent Racaniello (1:21:31.200)
There's just something beautiful about biology,
Lex Fridman (1:21:34.040)
about the mechanisms of biology.
Lex Fridman (1:21:36.080)
And I kind of regret falling in love
Lex Fridman (1:21:40.040)
with computer science so much
Vincent Racaniello (1:21:41.840)
that I left that biology textbook on the show
Lex Fridman (1:21:46.280)
and left it behind.
Lex Fridman (1:21:47.360)
But hopefully we'll return to it now
Lex Fridman (1:21:49.480)
because I think one of the things you learn
Vincent Racaniello (1:21:51.920)
even in computer science that studying biology
Lex Fridman (1:21:56.040)
and certainly neurobiology,
Vincent Racaniello (1:22:00.080)
you get inspired.
Lex Fridman (1:22:02.760)
Here's a mechanism of incredible complexity
Vincent Racaniello (1:22:05.160)
that works really well, is very robust,
Lex Fridman (1:22:07.520)
is very effective, efficient.
Vincent Racaniello (1:22:09.520)
It inspires you to come up with techniques
Lex Fridman (1:22:11.800)
that you can engineer in the machine.
Vincent Racaniello (1:22:13.760)
That's what drives a field forward
Lex Fridman (1:22:15.760)
when people improvise and come up with new technologies
Vincent Racaniello (1:22:21.280)
that really make a difference.
Lex Fridman (1:22:22.720)
And we have a bunch of those now.
Vincent Racaniello (1:22:25.240)
What's the difference between the coronavirus family
Lex Fridman (1:22:28.440)
and the other popular family, influenza virus family?
Vincent Racaniello (1:22:33.200)
I mean, if I were, because you mentioned
Lex Fridman (1:22:37.320)
we should have done a lot more
Vincent Racaniello (1:22:38.480)
in terms of vaccine development,
Lex Fridman (1:22:39.920)
that kind of thing for coronaviruses.
Lex Fridman (1:22:42.320)
But if I were back then, from my understanding,
Lex Fridman (1:22:46.440)
the thing we should all be afraid of is influenza,
Vincent Racaniello (1:22:49.840)
like some strong variants coming out from that family.
Lex Fridman (1:22:53.840)
That seems like the one that will destroy human civilization
Vincent Racaniello (1:22:57.880)
or hurt us really badly.
Lex Fridman (1:23:00.240)
I don't know if you agree with this sense,
Lex Fridman (1:23:02.520)
but maybe you can also just clarify
Lex Fridman (1:23:06.520)
what to use as the difference between the families.
Lex Fridman (1:23:09.560)
So it's an interesting difference.
Lex Fridman (1:23:11.000)
They both have membranes, right?
Lex Fridman (1:23:14.440)
So then they have spike proteins embedded in them.
Lex Fridman (1:23:19.000)
And they're different spikes.
Vincent Racaniello (1:23:20.720)
In fact, for influenza, there are two main ones.
Lex Fridman (1:23:24.240)
They're called the HA and the NA.
Lex Fridman (1:23:27.200)
But what's inside is RNA,
Lex Fridman (1:23:30.840)
but it's very different RNA.
Lex Fridman (1:23:33.560)
And here we have to explain that.
Lex Fridman (1:23:35.640)
So viruses with RNA can have three different kinds of RNA.
Vincent Racaniello (1:23:42.080)
They can have what we call plus RNA.
Lex Fridman (1:23:45.480)
They can have minus RNA,
Vincent Racaniello (1:23:48.160)
or they could have plus minus,
Lex Fridman (1:23:49.800)
actually two strands hybridized together.
Vincent Racaniello (1:23:54.480)
The plus RNA simply means that
Lex Fridman (1:23:58.440)
if you put that plus RNA in a cell,
Vincent Racaniello (1:24:01.800)
you know, your cell has ribosomes in it
Lex Fridman (1:24:03.640)
that make the proteins that you need.
Vincent Racaniello (1:24:05.720)
The ribosomes will immediately latch onto the plus RNA
Lex Fridman (1:24:08.560)
and begin to make proteins.
Vincent Racaniello (1:24:11.280)
A minus RNA is not the right strand to make proteins.
Lex Fridman (1:24:15.280)
So it has to be copied first.
Lex Fridman (1:24:17.160)
And then the plus minus is both together.
Lex Fridman (1:24:19.560)
So the SARS coronaviruses,
Vincent Racaniello (1:24:22.520)
all the coronaviruses have plus RNA.
Lex Fridman (1:24:25.240)
So as soon as that RNA gets in the cell,
Vincent Racaniello (1:24:26.800)
boom, it starts an infectious cycle.
Lex Fridman (1:24:28.440)
Same thing with poliovirus, by the way, which I worked on.
Vincent Racaniello (1:24:31.280)
Influenza viruses are negative stranded.
Lex Fridman (1:24:34.920)
So they cannot be translated when they get in the cell.
Lex Fridman (1:24:37.800)
So that's tough for the virus
Lex Fridman (1:24:40.040)
because the cell actually cannot make plus RNA
Vincent Racaniello (1:24:45.720)
from minus RNA.
Lex Fridman (1:24:47.000)
It doesn't have the enzyme to do it.
Lex Fridman (1:24:49.160)
So the virus has to carry it in inside the virus particle.
Lex Fridman (1:24:53.600)
And then when the minus RNA is in the cell,
Vincent Racaniello (1:24:55.600)
the virus enzyme makes plus RNAs and those get translated.
Lex Fridman (1:24:59.440)
So it's a big difference.
Lex Fridman (1:25:00.320)
And then in the influenza viruses,
Lex Fridman (1:25:03.400)
not only is it minus RNA, but it's in pieces.
Vincent Racaniello (1:25:07.040)
It's in eight pieces.
Lex Fridman (1:25:09.460)
We call that segmented,
Vincent Racaniello (1:25:10.880)
whereas the corona is in one long piece of RNA.
Lex Fridman (1:25:14.880)
So they're like floating separately?
Vincent Racaniello (1:25:17.880)
Yeah, so the genes are on separate pieces.
Lex Fridman (1:25:19.580)
They're all packaged inside that virus particle
Vincent Racaniello (1:25:21.800)
of influenza virus, but they're in pieces.
Lex Fridman (1:25:23.760)
And why that's important
Vincent Racaniello (1:25:25.480)
is because if two different influenza viruses
Lex Fridman (1:25:29.320)
infect the same cell,
Vincent Racaniello (1:25:31.520)
the pieces as they reproduce can mix
Lex Fridman (1:25:33.760)
and out can come a virus with a new assortment of pieces.
Lex Fridman (1:25:38.200)
And that allows influenza virus
Lex Fridman (1:25:40.240)
to undergo extremely high frequency evolution.
Vincent Racaniello (1:25:43.840)
That's why we get pandemics.
Lex Fridman (1:25:45.640)
When we have a new flu pandemics
Vincent Racaniello (1:25:47.040)
is because somewhere in some animal,
Lex Fridman (1:25:49.960)
two viruses have reassorted
Lex Fridman (1:25:51.880)
and made a new virus that we hadn't seen before.
Lex Fridman (1:25:54.400)
So you're talking about kind of biological characteristics,
Lex Fridman (1:26:00.720)
but what am I incorrect in my intuition
Lex Fridman (1:26:03.640)
that are from the things I've heard
Lex Fridman (1:26:05.680)
that the influenza family viruses is more dangerous?
Lex Fridman (1:26:09.880)
Like what makes it more dangerous to humans?
Vincent Racaniello (1:26:14.880)
Well, it depends on the,
Lex Fridman (1:26:16.080)
there are many flavors or vintages of influenza virus.
Lex Fridman (1:26:19.400)
Some are dangerous and some are not, right?
Lex Fridman (1:26:21.200)
It depends on which one.
Vincent Racaniello (1:26:22.560)
Some like the 1918 apparently was very lethal,
Lex Fridman (1:26:26.360)
killed a lot of people.
Lex Fridman (1:26:28.280)
But more contemporary viruses,
Lex Fridman (1:26:30.080)
we had a pandemic in 2009 of influenza.
Vincent Racaniello (1:26:35.800)
That wasn't such a lethal virus.
Lex Fridman (1:26:39.280)
We don't know exactly why,
Lex Fridman (1:26:40.640)
but it didn't kill that many people.
Lex Fridman (1:26:42.280)
It transmitted pretty well.
Lex Fridman (1:26:43.760)
Is that the bird flu one?
Lex Fridman (1:26:45.200)
They're all deriving.
Vincent Racaniello (1:26:47.600)
That one was called swine influenza.
Lex Fridman (1:26:49.720)
Swine, that's right, swine, yeah.
Vincent Racaniello (1:26:50.560)
It seemed to have started in a pig,
Lex Fridman (1:26:52.280)
but it had bird, it had RNAs from bird influenza viruses.
Vincent Racaniello (1:26:57.040)
These viruses are all reassortants of different viruses
Lex Fridman (1:27:00.600)
from pigs and birds and humans.
Lex Fridman (1:27:04.920)
But influenza can cause pneumonia
Lex Fridman (1:27:07.120)
and can kill you as does SARS COVID too.
Lex Fridman (1:27:09.960)
So it depends on the virus.
Lex Fridman (1:27:11.520)
So there is another influenza virus
Vincent Racaniello (1:27:13.640)
that's currently circulating.
Lex Fridman (1:27:14.960)
So right now we have the 2009 pandemic virus
Vincent Racaniello (1:27:18.600)
that's still around.
Lex Fridman (1:27:20.040)
And then the 1968 pandemic virus,
Vincent Racaniello (1:27:23.840)
which was the one before 2009,
Lex Fridman (1:27:25.760)
that one is still around too.
Lex Fridman (1:27:27.400)
And that's more lethal.
Lex Fridman (1:27:29.080)
And depending on the season,
Vincent Racaniello (1:27:30.360)
some seasons the 2009 virus predominates,
Lex Fridman (1:27:33.800)
some seasons the 1968.
Lex Fridman (1:27:36.200)
And when the 68 is around, you get more lethality.
Lex Fridman (1:27:38.800)
So we're living with an influenza family.
Vincent Racaniello (1:27:41.680)
We haven't exterminated them.
Lex Fridman (1:27:43.960)
Right, we never will, never exterminate them.
Lex Fridman (1:27:46.280)
Why?
Lex Fridman (1:27:47.120)
Because every shorebird in the world is infected with them.
Vincent Racaniello (1:27:51.080)
Gulls and terns and ducks and all sorts of things.
Lex Fridman (1:27:54.760)
Why can't we develop strong vaccines that defend against?
Vincent Racaniello (1:27:59.440)
Oh, we could do that, sure.
Lex Fridman (1:28:02.160)
But that would not eliminate them from humans.
Vincent Racaniello (1:28:04.880)
Even if you had the best vaccine,
Lex Fridman (1:28:06.760)
you would never get rid of it in people
Vincent Racaniello (1:28:08.840)
because there would always be someone who's not vaccinated
Lex Fridman (1:28:12.080)
or in which the vaccine didn't work.
Vincent Racaniello (1:28:14.400)
No vaccine is 100%.
Lex Fridman (1:28:16.600)
So.
Vincent Racaniello (1:28:17.440)
Well, you just contradicted yourself.
Lex Fridman (1:28:18.680)
You said the perfect vaccine.
Vincent Racaniello (1:28:21.080)
So.
Lex Fridman (1:28:21.920)
Imperfect, imperfect.
Lex Fridman (1:28:23.160)
But then you said, like, even if you had the perfect,
Lex Fridman (1:28:26.640)
yeah, some people wouldn't get vaccinated.
Lex Fridman (1:28:28.960)
But I understand what you mean.
Lex Fridman (1:28:30.440)
But I actually was asking how difficult is it
Vincent Racaniello (1:28:32.640)
to make vaccines like that for,
Lex Fridman (1:28:35.200)
it seems like it's very difficult to do that
Vincent Racaniello (1:28:36.920)
for the influenza virus.
Lex Fridman (1:28:38.840)
So it's really easy to make an old school vaccine.
Lex Fridman (1:28:42.960)
So the way the first influenza vaccines were made
Lex Fridman (1:28:47.480)
was actually Jonas Salk worked on them in the 40s.
Vincent Racaniello (1:28:51.040)
You just grow lots of virus
Lex Fridman (1:28:53.240)
and you grow it in eggs, by the way, chicken eggs.
Vincent Racaniello (1:28:55.920)
Nice.
Lex Fridman (1:28:56.920)
Literally?
Vincent Racaniello (1:28:57.880)
Wait, wait.
Lex Fridman (1:28:58.720)
Yeah, chicken, embryonated.
Lex Fridman (1:28:59.760)
So they get fertilized and there's a 10 or 12 day embryo
Lex Fridman (1:29:02.760)
in it and you put virus in it, it grows up
Lex Fridman (1:29:04.880)
and then you harvest it.
Lex Fridman (1:29:05.720)
You get about 10 mls of fluid.
Lex Fridman (1:29:08.440)
And then you take that,
Lex Fridman (1:29:09.560)
you treat it with formaldehyde or formalin
Lex Fridman (1:29:12.400)
and it inactivates the virus so it's no longer infectious.
Lex Fridman (1:29:16.560)
And you just inject that into people.
Lex Fridman (1:29:18.440)
And that was the first flu vaccine.
Lex Fridman (1:29:19.840)
It was made for the US Army actually.
Lex Fridman (1:29:22.160)
And then it got moved over to people.
Lex Fridman (1:29:24.200)
We still use that old school tech today.
Lex Fridman (1:29:27.360)
So you're taking, can you help me out here?
Lex Fridman (1:29:30.640)
Okay, so this is a good time to talk about vaccines.
Vincent Racaniello (1:29:34.440)
Okay, so you're talking about,
Lex Fridman (1:29:36.960)
you're taking the actual virus,
Vincent Racaniello (1:29:39.160)
you put it in an egg, you let it grow up.
Lex Fridman (1:29:42.520)
It's very funny that you put it in an egg.
Vincent Racaniello (1:29:44.120)
It's very poetic.
Lex Fridman (1:29:46.720)
And then how do you make it not infection,
Lex Fridman (1:29:52.680)
not effective or whatever?
Lex Fridman (1:29:53.920)
Not infectious.
Lex Fridman (1:29:54.760)
Not infectious, is that the right term here?
Lex Fridman (1:29:56.640)
Yeah.
Lex Fridman (1:29:57.480)
So how do you make it not infectious?
Lex Fridman (1:29:58.920)
You can treat it with any number of chemicals
Vincent Racaniello (1:30:02.000)
that'll disrupt the particle so it no longer infects.
Lex Fridman (1:30:05.400)
So that step of disrupting the particle
Lex Fridman (1:30:09.040)
is that very specific to a particular variant particle?
Lex Fridman (1:30:12.880)
No, the same collection of chemicals
Vincent Racaniello (1:30:14.840)
you can use for all kinds of,
Lex Fridman (1:30:16.240)
and which have been used for SARS CoV2 vaccines also.
Vincent Racaniello (1:30:19.600)
Same technology.
Lex Fridman (1:30:20.440)
Okay, so what are, there's several things to ask.
Lex Fridman (1:30:23.600)
So you called it old school in a way
Lex Fridman (1:30:25.280)
that's slightly dismissive,
Vincent Racaniello (1:30:27.560)
like people talk about Windows 98 or something.
Lex Fridman (1:30:29.960)
So is there risks involved with it?
Lex Fridman (1:30:34.760)
Or is it just difficult to produce large amounts?
Lex Fridman (1:30:37.320)
No, it's only, it's,
Vincent Racaniello (1:30:38.800)
it's very easy.
Lex Fridman (1:30:40.080)
I mean, you could do it in cells and culture,
Lex Fridman (1:30:41.600)
but eggs were convenient.
Lex Fridman (1:30:43.000)
And in the 1940s, we didn't have cells and culture.
Vincent Racaniello (1:30:46.240)
We didn't know how to do that.
Lex Fridman (1:30:47.240)
So we had to use something else.
Vincent Racaniello (1:30:49.680)
It's easy to do,
Lex Fridman (1:30:52.280)
but the process of inactivating the virus with a chemical
Vincent Racaniello (1:30:56.920)
makes it not the best vaccine you can make.
Lex Fridman (1:30:59.920)
The flu vaccines that we have today,
Vincent Racaniello (1:31:02.440)
which are mostly based on this inactivation,
Lex Fridman (1:31:05.680)
is called inactivated virus vaccines.
Vincent Racaniello (1:31:08.480)
Oh, so like the kind of thing
Lex Fridman (1:31:12.280)
it presents to the immune system to train on
Vincent Racaniello (1:31:14.920)
is not close to the actual virus.
Lex Fridman (1:31:19.520)
Yes, that's what we think.
Lex Fridman (1:31:20.480)
So that's why probably the flu vaccines
Lex Fridman (1:31:22.360)
are just not very good, you know?
Lex Fridman (1:31:24.880)
60% efficiency at the best, right?
Lex Fridman (1:31:29.000)
Which is not really good.
Lex Fridman (1:31:30.040)
What does it mean?
Lex Fridman (1:31:31.160)
What is the measure of efficiency for a vaccine?
Vincent Racaniello (1:31:33.920)
Well, it's how it does in the general population
Lex Fridman (1:31:37.440)
at preventing influenza.
Lex Fridman (1:31:38.800)
At preventing?
Lex Fridman (1:31:40.760)
Illness, not infection.
Vincent Racaniello (1:31:41.880)
We usually don't measure infection
Lex Fridman (1:31:44.800)
when we're testing a vaccine.
Vincent Racaniello (1:31:46.040)
We just measure sickness.
Lex Fridman (1:31:47.640)
That's really easy to score, right?
Vincent Racaniello (1:31:50.200)
You do a trial and you say,
Lex Fridman (1:31:52.040)
if you feel sick, give us a call.
Vincent Racaniello (1:31:53.840)
We'll tell you what to do.
Lex Fridman (1:31:55.280)
So yeah, I mean, what's sickness?
Lex Fridman (1:31:58.040)
Sickness is the presence of symptoms?
Lex Fridman (1:32:01.520)
So this is good time to say what a symptom is, okay?
Vincent Racaniello (1:32:04.920)
A symptom is what you only can feel.
Lex Fridman (1:32:08.880)
Only you can feel an upset stomach
Vincent Racaniello (1:32:11.560)
or a sore throat or that sort of thing.
Lex Fridman (1:32:13.320)
It's the lived experience of a symptom.
Vincent Racaniello (1:32:15.160)
Whereas a sign is something that someone could measure
Lex Fridman (1:32:19.040)
and tell that you're infected,
Lex Fridman (1:32:20.480)
like virus in your nasopharynx or something else, right?
Lex Fridman (1:32:26.040)
Signs and symptoms.
Lex Fridman (1:32:27.080)
And so in a vaccine trial, they tell you,
Lex Fridman (1:32:30.040)
well, if you have any of these symptoms,
Vincent Racaniello (1:32:31.800)
they give you a paper with the exact symptoms listed
Lex Fridman (1:32:35.040)
to make sure you're picking them up, right?
Lex Fridman (1:32:36.840)
So for flu, it would probably be fever, sore throat, cough.
Lex Fridman (1:32:41.480)
You call them and then they will do a PCR,
Vincent Racaniello (1:32:44.160)
make sure you've got flu and not some other virus
Lex Fridman (1:32:46.560)
that makes similar symptoms.
Lex Fridman (1:32:49.000)
And then they would say, are you a vaccine or non vaccine arm
Lex Fridman (1:32:53.760)
and count up all the infections
Lex Fridman (1:32:55.760)
and see how the vaccine did, basically.
Lex Fridman (1:32:57.680)
That's so fascinating because the reporting,
Lex Fridman (1:33:02.080)
so symptom is what you feel.
Lex Fridman (1:33:03.760)
Yes, for sure.
Lex Fridman (1:33:04.600)
And certainly the mind has a ability to conjure up feelings.
Lex Fridman (1:33:10.120)
Oh yes, absolutely.
Lex Fridman (1:33:11.800)
And so like culturally, maybe there was a time
Lex Fridman (1:33:16.080)
in our culture where it was looked down upon
Vincent Racaniello (1:33:20.440)
to feel sick or something like that,
Lex Fridman (1:33:23.480)
like toughen up kind of thing.
Lex Fridman (1:33:25.080)
And so then you probably have very few symptoms
Lex Fridman (1:33:28.560)
being reported.
Vincent Racaniello (1:33:29.480)
Absolutely, absolutely.
Lex Fridman (1:33:30.960)
And now is like much more, I don't know,
Vincent Racaniello (1:33:36.000)
perhaps you're much more likely to report symptoms.
Lex Fridman (1:33:37.880)
Now it's fascinating because then it changes.
Vincent Racaniello (1:33:40.800)
Oh, it is definitely a perception because for,
Lex Fridman (1:33:43.280)
your symptom may be nothing to me or vice versa, right?
Lex Fridman (1:33:46.080)
And so when you're doing this,
Lex Fridman (1:33:47.480)
it's a little bit of a imprecise science because,
Lex Fridman (1:33:52.080)
and even it's a cultural thing in some countries,
Lex Fridman (1:33:56.160)
something that would make us feel horrible,
Vincent Racaniello (1:33:57.800)
they wouldn't even bother reporting.
Lex Fridman (1:33:59.200)
No, I didn't have any symptoms.
Lex Fridman (1:34:00.440)
So it's a little bit imprecise and it clouds the results.
Lex Fridman (1:34:03.400)
So if you can measure things, it's always better,
Lex Fridman (1:34:05.800)
but you start out with a symptom.
Lex Fridman (1:34:07.720)
And if you say, if someone tells you this virus,
Vincent Racaniello (1:34:11.120)
20% of the people are asymptomatic,
Lex Fridman (1:34:15.720)
they don't report symptoms,
Vincent Racaniello (1:34:19.400)
that number is probably not a constant.
Lex Fridman (1:34:21.960)
It depends where you did the study.
Vincent Racaniello (1:34:24.200)
It could be different in China versus South America,
Lex Fridman (1:34:26.880)
Europe, et cetera, yeah.
Vincent Racaniello (1:34:28.400)
I mean, I was trying to figure,
Lex Fridman (1:34:29.560)
so I took two shots of the Pfizer vaccine
Lex Fridman (1:34:32.400)
and I had zero symptoms.
Lex Fridman (1:34:34.560)
Wow.
Vincent Racaniello (1:34:35.400)
So, and I was wondering, well, see,
Lex Fridman (1:34:37.160)
but that's my feelings, right?
Vincent Racaniello (1:34:38.760)
This is not, because I felt fine, I was waiting.
Lex Fridman (1:34:42.040)
Did you have pain at the injection site?
Vincent Racaniello (1:34:46.160)
No, it was kind of pleasant.
Lex Fridman (1:34:48.360)
You felt nothing the next day, no?
Vincent Racaniello (1:34:50.280)
Nothing, no tiredness, no exhaustion, no.
Lex Fridman (1:34:54.520)
But see, like I have an insane sleeping schedule.
Vincent Racaniello (1:34:56.720)
I already put myself through crazy stuff.
Lex Fridman (1:34:59.280)
That said, maybe I was expecting something really bad.
Vincent Racaniello (1:35:03.280)
Like I was waiting and therefore didn't feel it.
Lex Fridman (1:35:06.760)
But I also got allergy shots
Lex Fridman (1:35:11.120)
and those, I was out all next day,
Lex Fridman (1:35:14.600)
like exhausted for some reason.
Lex Fridman (1:35:16.400)
So that gave me like a sense like, okay,
Lex Fridman (1:35:20.600)
at least sometimes I can feel shitty.
Vincent Racaniello (1:35:22.640)
That's good to know.
Lex Fridman (1:35:24.440)
Sure, sure.
Lex Fridman (1:35:25.280)
And then with the vaccine it didn't,
Lex Fridman (1:35:27.160)
but the question is like,
Lex Fridman (1:35:29.000)
how much does my mind come into play there?
Lex Fridman (1:35:32.560)
The expectations of symptoms,
Vincent Racaniello (1:35:35.920)
the expectations of not feeling well,
Lex Fridman (1:35:39.280)
how does that affect the sort of the self reporting
Lex Fridman (1:35:41.280)
of the symptoms?
Lex Fridman (1:35:42.120)
I think it's definitely a variable there,
Lex Fridman (1:35:44.560)
but there's certainly many people that don't feel anything
Lex Fridman (1:35:47.560)
after the vaccines.
Lex Fridman (1:35:48.440)
And there's some that have a whole range of things
Lex Fridman (1:35:51.980)
like soreness and fever, et cetera, yeah.
Lex Fridman (1:35:54.920)
So okay, you were talking about the old school development
Lex Fridman (1:35:57.040)
inside the egg.
Vincent Racaniello (1:35:58.560)
Right.
Lex Fridman (1:35:59.400)
What's better than that?
Lex Fridman (1:36:02.000)
So then the next generation of vaccines
Lex Fridman (1:36:04.420)
which arose in the 50s were what we call
Vincent Racaniello (1:36:07.840)
replication competent, where the virus you take
Lex Fridman (1:36:11.440)
and it's actually reproducing in you.
Vincent Racaniello (1:36:13.920)
Yeah, that sounds safe.
Lex Fridman (1:36:16.040)
And it can be somewhat problematic, yes,
Vincent Racaniello (1:36:19.040)
as you might imagine,
Lex Fridman (1:36:20.080)
because once you put that virus in you,
Lex Fridman (1:36:22.320)
you have no more control, right?
Lex Fridman (1:36:24.120)
It's not like you have a kill switch in it,
Vincent Racaniello (1:36:25.720)
which actually would be a great idea to put in.
Lex Fridman (1:36:29.960)
Like nanobots, what can possibly go wrong?
Vincent Racaniello (1:36:32.200)
No, you could just put something in there.
Lex Fridman (1:36:34.200)
If you added a drug, you would shut it off, right?
Lex Fridman (1:36:37.880)
And people are thinking about that
Lex Fridman (1:36:39.880)
because now we're engineering viruses to treat cancers
Lex Fridman (1:36:43.560)
and other diseases and we may wanna put kill switches
Lex Fridman (1:36:46.680)
in them just to make sure they don't run away.
Vincent Racaniello (1:36:48.560)
Oh, interesting, so you can deploy a drug
Lex Fridman (1:36:50.360)
that binds to this virus that would shut it off
Vincent Racaniello (1:36:54.960)
in the body, something like that.
Lex Fridman (1:36:56.480)
Something like that, yeah, that would be the idea.
Vincent Racaniello (1:36:58.620)
You'd have to engineer it in.
Lex Fridman (1:36:59.880)
Anyway, these were, the first one was yellow fever vaccine
Vincent Racaniello (1:37:03.580)
that was made because that was a big problem.
Lex Fridman (1:37:06.220)
And this virus, and the way you do this,
Vincent Racaniello (1:37:09.640)
back in the old day was empirical.
Lex Fridman (1:37:12.640)
So Max Tyler, who did the yellow fever vaccine,
Lex Fridman (1:37:15.280)
he took the virus, which is a human virus, right?
Lex Fridman (1:37:19.640)
And he infected, I think he used chick embryos.
Lex Fridman (1:37:24.980)
And he went from one embryo to another and just kept passing
Lex Fridman (1:37:27.340)
and he did that hundreds of times.
Lex Fridman (1:37:29.320)
And every 10 passages, he would take the virus
Lex Fridman (1:37:32.680)
and put it in a mouse or a monkey, whatever his model was.
Lex Fridman (1:37:36.560)
And then eventually he got a virus
Lex Fridman (1:37:38.040)
that didn't cause any disease after 200 and some passages.
Lex Fridman (1:37:41.880)
And then that was tested in people
Lex Fridman (1:37:43.840)
and it became the yellow fever vaccine that we use today.
Vincent Racaniello (1:37:46.800)
He selected for mutations that made the virus
Lex Fridman (1:37:50.420)
not cause disease, but still make an immune response.
Lex Fridman (1:37:55.420)
So those are called replication competent.
Lex Fridman (1:37:57.620)
We now have the polio vaccine,
Vincent Racaniello (1:37:59.480)
which was developed in the 50s after the yellow fever.
Lex Fridman (1:38:03.160)
Then we had measles, mumps, rubella.
Vincent Racaniello (1:38:05.440)
Those are all replication competent vaccines.
Lex Fridman (1:38:09.160)
And you mentioned is that's a good idea.
Vincent Racaniello (1:38:12.400)
They are all safe vaccines.
Lex Fridman (1:38:15.460)
The only one that has had an issue
Vincent Racaniello (1:38:18.440)
is the polio replication competent vaccine.
Lex Fridman (1:38:21.360)
It was called Sabin vaccine or oral polio virus vaccine
Vincent Racaniello (1:38:25.960)
because you take it orally, it's wonderful
Lex Fridman (1:38:29.720)
because you don't have to inject it.
Vincent Racaniello (1:38:31.420)
This is the perfect delivery.
Lex Fridman (1:38:34.280)
Either intranasal for a respiratory virus
Vincent Racaniello (1:38:37.000)
or orally for polio goes into your intestines.
Lex Fridman (1:38:39.040)
It reproduces and it gives you wonderful protection
Vincent Racaniello (1:38:42.920)
against polio.
Lex Fridman (1:38:45.280)
However, you do shed virus out
Lex Fridman (1:38:49.000)
and that virus is no longer a vaccine.
Lex Fridman (1:38:52.760)
It's reverted genetically in your intestine.
Lex Fridman (1:38:55.600)
So you can infect others with polio.
Lex Fridman (1:38:57.440)
Take that virus and put it into an animal and give it polio.
Lex Fridman (1:39:00.500)
And in fact, the parents of some kids in the 60s and 70s
Lex Fridman (1:39:05.720)
who were immunized got polio from the vaccine.
Vincent Racaniello (1:39:08.340)
The rate was about one and one and a half million
Lex Fridman (1:39:12.400)
cases of polio.
Lex Fridman (1:39:13.760)
So it's called vaccine associated polio.
Lex Fridman (1:39:15.360)
And I always argue that
Vincent Racaniello (1:39:18.040)
we may not have picked the right vaccine.
Lex Fridman (1:39:21.180)
There was a big fight in the US and other countries
Vincent Racaniello (1:39:25.440)
between the inactivated polio
Lex Fridman (1:39:27.560)
and the infectious polio vaccines,
Vincent Racaniello (1:39:29.800)
which ones we should be using
Lex Fridman (1:39:31.560)
because we found out that the infectious vaccine
Vincent Racaniello (1:39:33.980)
actually caused polio.
Lex Fridman (1:39:35.280)
And eight to 10 kids a year in the US alone
Vincent Racaniello (1:39:38.040)
got polio from the vaccine,
Lex Fridman (1:39:39.800)
which looking back is really not acceptable in my view,
Vincent Racaniello (1:39:43.520)
although the public health community said it was
Lex Fridman (1:39:46.060)
to get rid of polio.
Lex Fridman (1:39:47.560)
So now we're close to eradicating polio globally,
Lex Fridman (1:39:53.120)
but this vaccine derived polio is a problem.
Lex Fridman (1:39:55.960)
So now we have to go back to the inactivated vaccine,
Lex Fridman (1:39:59.200)
which is tough because it's injected.
Vincent Racaniello (1:40:01.440)
So, okay, so the basic high level,
Lex Fridman (1:40:05.000)
how vaccines work principle is
Vincent Racaniello (1:40:09.360)
you want to deploy something in the body
Lex Fridman (1:40:11.200)
that's as close to the actual virus as possible,
Lex Fridman (1:40:13.880)
but doesn't do nearly as much harm.
Lex Fridman (1:40:15.880)
And there's like a million, not a million,
Lex Fridman (1:40:17.840)
but there's a bunch of ways you could possibly do that.
Lex Fridman (1:40:19.640)
So those are two ways.
Lex Fridman (1:40:20.600)
And now of course we have modern ways
Lex Fridman (1:40:22.020)
we can make mRNA vaccines, right?
Lex Fridman (1:40:25.680)
What are the modern ways?
Lex Fridman (1:40:26.800)
I did, you wanna look, mRNA vaccine.
Lex Fridman (1:40:29.160)
So that's one of the, that's the most modern,
Lex Fridman (1:40:31.140)
but even before mRNA vaccines,
Vincent Racaniello (1:40:33.160)
we learned that we could use viruses
Lex Fridman (1:40:36.080)
to deliver proteins from a virus that you wanna prevent.
Lex Fridman (1:40:41.640)
And so the Ebola vaccine,
Lex Fridman (1:40:43.960)
we took the spike gene of Ebola virus
Lex Fridman (1:40:46.560)
and put it in a different virus
Lex Fridman (1:40:47.980)
and we deliver that to people
Lex Fridman (1:40:49.560)
and that's called a vector vaccine.
Lex Fridman (1:40:52.000)
And some of the COVID vaccines are vectors
Vincent Racaniello (1:40:54.560)
of different kinds of most famous are adenovirus vectors
Lex Fridman (1:40:57.680)
carrying the spike gene into the cell.
Lex Fridman (1:41:00.440)
Can you explain how the vector vaccine works again?
Lex Fridman (1:41:03.320)
So we have, we take a virus that will infect humans
Lex Fridman (1:41:09.160)
but will not make you sick.
Lex Fridman (1:41:11.480)
In the case of adenovirus,
Vincent Racaniello (1:41:13.480)
the years and years of people studying it
Lex Fridman (1:41:16.000)
has told us what genes you could cut out
Lex Fridman (1:41:18.720)
and allow the virus to infect the cell
Lex Fridman (1:41:20.960)
but not cause any disease.
Lex Fridman (1:41:22.120)
So instead of doing selection on it,
Lex Fridman (1:41:24.480)
you actually genetically modify it.
Vincent Racaniello (1:41:27.400)
Yes, you modify the vector, yeah.
Lex Fridman (1:41:29.160)
So you're much more precise about it.
Vincent Racaniello (1:41:30.640)
You're very precise
Lex Fridman (1:41:31.480)
and then you splice in the gene for the spike
Lex Fridman (1:41:34.880)
and then you use that to deliver the gene
Lex Fridman (1:41:37.640)
and it becomes produced as protein
Lex Fridman (1:41:39.680)
and then you make an immune response.
Lex Fridman (1:41:40.920)
And vector is the term for this modified.
Vincent Racaniello (1:41:43.200)
Right, so we're now using viruses at our bidding.
Lex Fridman (1:41:47.880)
We're using them as vectors, not just for vaccines.
Vincent Racaniello (1:41:50.180)
We can cure monogenic diseases.
Lex Fridman (1:41:52.380)
That is if you have, if you're born with a genetic disease,
Vincent Racaniello (1:41:55.560)
you have a deletion or a mutation in a gene,
Lex Fridman (1:41:57.840)
single gene, we can give you the regular gene back
Vincent Racaniello (1:42:01.960)
using a virus vector.
Lex Fridman (1:42:03.720)
So cancers too, we can cure cancers with vectors.
Lex Fridman (1:42:07.180)
Wow, really?
Lex Fridman (1:42:09.920)
Interesting. Yeah.
Vincent Racaniello (1:42:10.880)
I think in 10 to 15 years,
Lex Fridman (1:42:12.540)
most cancers will be treatable with viruses, yeah.
Vincent Racaniello (1:42:15.920)
Wow.
Lex Fridman (1:42:16.760)
And not only can we put things in the vector
Vincent Racaniello (1:42:19.640)
to kill the tumor,
Lex Fridman (1:42:21.080)
we can target the vector to the tumor specifically
Vincent Racaniello (1:42:25.360)
in a number of ways.
Lex Fridman (1:42:26.840)
And that makes it less toxic, right?
Vincent Racaniello (1:42:28.200)
It doesn't infect all your other cells.
Lex Fridman (1:42:31.100)
But it takes time to develop a vector for a particular thing
Vincent Racaniello (1:42:34.800)
because it requires a deep understanding.
Lex Fridman (1:42:37.560)
Yeah, in fact, we have about a dozen different virus vectors
Vincent Racaniello (1:42:40.880)
that have been studied for 20 years.
Lex Fridman (1:42:42.900)
And those are the set of vaccine vectors that we're using.
Lex Fridman (1:42:46.320)
So it includes adenovirus, vesicular stomatitis virus,
Lex Fridman (1:42:50.760)
which is a cousin of rabies, but doesn't make people sick.
Vincent Racaniello (1:42:54.200)
Influenza virus is being used as a vector
Lex Fridman (1:42:57.600)
and even measles virus.
Lex Fridman (1:43:00.200)
So we're familiar with how to modify those to be vectors
Lex Fridman (1:43:04.080)
and those are being used for COVID vaccines.
Lex Fridman (1:43:07.400)
And then of course we have the newest,
Lex Fridman (1:43:10.560)
which is the nucleic acid vaccines.
Lex Fridman (1:43:12.540)
So years ago, people said,
Lex Fridman (1:43:15.220)
why can't we just inject DNA into people?
Vincent Racaniello (1:43:18.960)
Take the spike and put it in a DNA and inject it.
Lex Fridman (1:43:22.320)
So people tried many, many different vaccines.
Lex Fridman (1:43:25.240)
And in fact, there are no human licensed vaccines
Lex Fridman (1:43:28.240)
that are DNA vaccines.
Vincent Racaniello (1:43:29.440)
Although there is a West Nile vaccine for horses
Lex Fridman (1:43:33.040)
that's a DNA based vaccine.
Lex Fridman (1:43:35.880)
So if you have a horse, you can give it this vaccine,
Lex Fridman (1:43:38.120)
but no human.
Lex Fridman (1:43:38.960)
Can you clarify, does a DNA vaccine
Lex Fridman (1:43:42.560)
only work for DNA viruses?
Vincent Racaniello (1:43:44.860)
No, it can work for DNA or RNA.
Lex Fridman (1:43:46.800)
Because remember, for an RNA virus,
Vincent Racaniello (1:43:48.360)
we can make a DNA copy of it.
Lex Fridman (1:43:50.700)
And it will still, when you put that DNA in a cell,
Vincent Racaniello (1:43:53.760)
it goes into the nucleus.
Lex Fridman (1:43:55.440)
Okay, right.
Lex Fridman (1:43:56.680)
So it's, you're just skipping a step.
Lex Fridman (1:43:58.440)
You get proteins.
Vincent Racaniello (1:43:59.280)
For RNA vaccines, you're giving, okay, I got it.
Lex Fridman (1:44:02.080)
So those didn't work for human vaccines.
Lex Fridman (1:44:04.260)
And there were many HIV AIDS vaccine trials
Lex Fridman (1:44:07.280)
that used DNA vaccines, didn't work.
Lex Fridman (1:44:10.820)
And then a number of years ago,
Lex Fridman (1:44:13.320)
people started thinking, how about RNA, RNA vaccines?
Lex Fridman (1:44:17.800)
And I first heard this, I thought, what?
Lex Fridman (1:44:20.280)
I've worked with RNA my whole career.
Vincent Racaniello (1:44:22.320)
It's so fragile.
Lex Fridman (1:44:24.280)
If you look at it the wrong way, it breaks.
Lex Fridman (1:44:27.600)
I mean, that's being facetious, right?
Lex Fridman (1:44:29.780)
But you have to be very careful
Vincent Racaniello (1:44:31.600)
because your hands are full of enzymes
Lex Fridman (1:44:34.540)
that will degrade RNA.
Lex Fridman (1:44:37.360)
So I thought, how could this possibly work,
Lex Fridman (1:44:38.860)
injecting it into someone's?
Vincent Racaniello (1:44:40.160)
It's an example of I was skeptical and I was wrong.
Lex Fridman (1:44:43.920)
It turns out that if you modify the RNA properly
Lex Fridman (1:44:47.160)
and protect it in a lipid capsule,
Lex Fridman (1:44:50.400)
it actually works as a vaccine.
Lex Fridman (1:44:52.920)
And people were working on this years
Lex Fridman (1:44:54.920)
before COVID came around.
Vincent Racaniello (1:44:57.060)
They were doing experimental mRNA vaccines
Lex Fridman (1:45:00.280)
and there were a couple of companies
Vincent Racaniello (1:45:01.480)
that were working on it.
Lex Fridman (1:45:02.500)
And so at the beginning of 2020, they said, let's try it.
Lex Fridman (1:45:07.440)
And I was skeptical, frankly,
Lex Fridman (1:45:09.680)
because I just thought RNA would be too labile,
Lex Fridman (1:45:12.120)
but I was wrong.
Lex Fridman (1:45:13.600)
So this is, as we're saying offline, one of the great things
Vincent Racaniello (1:45:17.600)
about you is you're able to say when you're wrong
Lex Fridman (1:45:20.600)
about intuitions you've had in the past,
Vincent Racaniello (1:45:22.320)
which is a beautiful thing for a scientist.
Lex Fridman (1:45:25.140)
But I still think it's very surprising
Lex Fridman (1:45:28.120)
that something like that works, right?
Lex Fridman (1:45:30.120)
Yeah, I am surprised.
Lex Fridman (1:45:31.400)
So you're just launching RNA in a protective membrane.
Lex Fridman (1:45:36.200)
And then now one thing is surprising
Vincent Racaniello (1:45:39.800)
that the RNA sort of lasts long enough in its structure.
Lex Fridman (1:45:45.720)
But then the other thing is why does it work
Lex Fridman (1:45:50.440)
that that's a good training ground for the immune system?
Lex Fridman (1:45:56.760)
Is that obvious that that should work?
Vincent Racaniello (1:45:59.800)
I don't think it's obvious to most people
Lex Fridman (1:46:01.260)
and it's worth going into it
Vincent Racaniello (1:46:03.040)
because it's really interesting.
Lex Fridman (1:46:04.560)
I mean, first of all, they wrap the RNA in fats,
Lex Fridman (1:46:09.040)
in lipid membranes, right?
Lex Fridman (1:46:10.560)
And the particular formulation they test for years
Vincent Racaniello (1:46:14.160)
to make sure it's stable,
Lex Fridman (1:46:16.040)
it lasts a long time after it's injected.
Lex Fridman (1:46:17.960)
And the two companies that make the current COVID vaccines,
Lex Fridman (1:46:22.120)
right, Moderna and Pfizer,
Vincent Racaniello (1:46:23.240)
they have different lipid formulations to get to the same.
Lex Fridman (1:46:26.660)
So that's a real part of it.
Lex Fridman (1:46:29.040)
And it's not simple.
Lex Fridman (1:46:30.220)
There are quite a few different lipids
Vincent Racaniello (1:46:31.880)
that they put into this coding.
Lex Fridman (1:46:34.080)
And they test to see how long they protect the RNA
Vincent Racaniello (1:46:37.040)
after it's injected, say, into a mouse,
Lex Fridman (1:46:39.160)
how long does it last?
Lex Fridman (1:46:40.620)
And the way it works is these,
Lex Fridman (1:46:43.320)
apparently these lipid nanoparticles,
Vincent Racaniello (1:46:46.160)
they get injected into your muscle,
Lex Fridman (1:46:48.800)
they bump into cells and they get taken up.
Lex Fridman (1:46:52.120)
So lipid fat is sticky.
Lex Fridman (1:46:56.960)
It's greasy, we like to say.
Lex Fridman (1:46:59.880)
And so your cells are covered with a greasy membrane also.
Lex Fridman (1:47:03.680)
So when these lipid nanoparticles bump into them,
Vincent Racaniello (1:47:06.560)
they stick and they eventually get taken up.
Lex Fridman (1:47:08.360)
And they figured this out right at the beginning.
Vincent Racaniello (1:47:11.240)
If we put RNA in a lipid nanoparticle,
Lex Fridman (1:47:13.720)
will it get taken up into a cell?
Lex Fridman (1:47:15.240)
And the answer was yes, it was just let's try it.
Lex Fridman (1:47:17.960)
And it worked.
Lex Fridman (1:47:18.800)
So it's basically experiment.
Lex Fridman (1:47:20.340)
It's not like some deep understanding of biology.
Vincent Racaniello (1:47:22.640)
It's experimentally speaking, it just seems to work.
Lex Fridman (1:47:25.480)
Yeah, well, they had some idea
Vincent Racaniello (1:47:26.800)
that lipids would target this to a cell membrane.
Lex Fridman (1:47:30.440)
And remember, there's no receptor involved.
Vincent Racaniello (1:47:33.880)
Like the virus has a specific protein
Lex Fridman (1:47:36.900)
that attaches to a receptor.
Vincent Racaniello (1:47:39.240)
It's not efficient enough to just bump around
Lex Fridman (1:47:41.640)
and get into a cell.
Vincent Racaniello (1:47:43.240)
That's what these things are doing.
Lex Fridman (1:47:44.920)
And they probably optimize the lipids
Vincent Racaniello (1:47:47.240)
to get more efficient uptake.
Lex Fridman (1:47:49.780)
But it's not as efficient as a virus would be
Vincent Racaniello (1:47:51.920)
to get into a cell.
Lex Fridman (1:47:52.760)
Right, so you have no specific,
Vincent Racaniello (1:47:54.480)
I mean, which is why it's surprising
Lex Fridman (1:47:57.600)
that you can crack into the safe with a hammer.
Vincent Racaniello (1:48:02.600)
Or with some fat.
Lex Fridman (1:48:06.080)
I mean, that's kind of surprising.
Vincent Racaniello (1:48:08.840)
It's kind of amazing that it works.
Lex Fridman (1:48:11.920)
But so maybe let's try to talk about this.
Lex Fridman (1:48:17.360)
So one of the hesitancies around vaccines
Lex Fridman (1:48:22.560)
or basically around any new technology
Vincent Racaniello (1:48:24.680)
is the fact that mRNA is a new idea.
Lex Fridman (1:48:28.600)
And it's an idea that was shrouded in some skepticism,
Vincent Racaniello (1:48:32.200)
as you said, by the scientific community.
Lex Fridman (1:48:35.320)
Because it's a cool new technology.
Vincent Racaniello (1:48:40.240)
Surprising that it works.
Lex Fridman (1:48:42.560)
What's your intuition?
Vincent Racaniello (1:48:44.400)
I think one nice way to approach this
Lex Fridman (1:48:46.400)
is try to play devil's advocate and say both sides.
Vincent Racaniello (1:48:53.040)
One side is why your intuition says
Lex Fridman (1:48:56.160)
that it's safe for humans.
Lex Fridman (1:48:59.080)
And what arguments can you see if you could steal man
Lex Fridman (1:49:03.520)
and argument why it's unsafe for humans.
Vincent Racaniello (1:49:06.680)
Or not unsafe for humans,
Lex Fridman (1:49:09.340)
but the hesitancy to take an mRNA vaccine is justified.
Lex Fridman (1:49:15.160)
So many people are afraid because it's new technology
Lex Fridman (1:49:19.520)
and they feel it hasn't been tested.
Lex Fridman (1:49:22.280)
I mean, in theory, what could go wrong?
Lex Fridman (1:49:25.160)
This is the nice thing about mRNA
Vincent Racaniello (1:49:29.040)
is that it doesn't last forever.
Lex Fridman (1:49:32.300)
As opposed to DNA, which doesn't last forever,
Lex Fridman (1:49:35.020)
but it can last a lot longer.
Lex Fridman (1:49:38.180)
And it could even go into your DNA, right?
Lex Fridman (1:49:41.680)
So mRNA has a shorter lifetime,
Lex Fridman (1:49:44.340)
maybe days after it's injected into your arm,
Vincent Racaniello (1:49:47.300)
then it's gone.
Lex Fridman (1:49:48.720)
So that's a good thing
Vincent Racaniello (1:49:49.740)
because it's not gonna be around forever.
Lex Fridman (1:49:53.000)
So that would say, okay, so it's sticking around
Vincent Racaniello (1:49:56.640)
for your lifetime is not happening.
Lex Fridman (1:49:58.300)
But what else could happen?
Vincent Racaniello (1:50:00.000)
Well, let's see the protein that's made,
Lex Fridman (1:50:03.100)
could that be an issue?
Lex Fridman (1:50:05.240)
And again, proteins don't last forever.
Lex Fridman (1:50:08.980)
They have a finite longevity in the body.
Lex Fridman (1:50:12.500)
And this one also lasts perhaps at the best a few weeks.
Lex Fridman (1:50:17.440)
Now this is a protein that's made
Vincent Racaniello (1:50:18.880)
after the RNA gets into the cell.
Lex Fridman (1:50:22.060)
Yeah, so the lipid nanoparticles taken up into a cell
Lex Fridman (1:50:25.060)
and the mRNA is translated and you get protein made.
Lex Fridman (1:50:27.860)
And there's also a question, I'm sorry to interrupt,
Vincent Racaniello (1:50:30.280)
where in the body, so because it's not well targeted,
Lex Fridman (1:50:35.100)
or I don't know if it's supposed to be targeted,
Lex Fridman (1:50:38.320)
but it can go throughout the body,
Lex Fridman (1:50:39.920)
that's one of the concerns.
Vincent Racaniello (1:50:40.760)
Right, so it's injected deep into your deltoid muscle,
Lex Fridman (1:50:43.660)
right here, shoulder.
Lex Fridman (1:50:46.100)
And the idea is not to put it in a blood vessel,
Lex Fridman (1:50:49.780)
otherwise it would then for sure circulate everywhere.
Lex Fridman (1:50:52.400)
So they go deep in a blood vessel and it's locally injected.
Lex Fridman (1:50:57.200)
And they did, before this even went into people,
Vincent Racaniello (1:51:00.380)
they did experiments in mice
Lex Fridman (1:51:01.820)
where they gave them a thousand times higher concentrations
Vincent Racaniello (1:51:05.060)
than they would ever give to people.
Lex Fridman (1:51:06.860)
And then when you do that, it can go everywhere basically.
Vincent Racaniello (1:51:09.340)
You can find these nanoparticles
Lex Fridman (1:51:11.320)
in every tissue of the mouse.
Lex Fridman (1:51:14.080)
But that's at a thousand fold higher concentration, right?
Lex Fridman (1:51:17.200)
So I think at the levels that we're using in people,
Vincent Racaniello (1:51:21.180)
most of it's staying in the muscle,
Lex Fridman (1:51:22.520)
but sure, small amounts go elsewhere.
Lex Fridman (1:51:25.620)
Could there be a lot of harm caused if it goes elsewhere?
Lex Fridman (1:51:30.460)
Like let's say ridiculously high quantities.
Vincent Racaniello (1:51:33.140)
I'm trying to understand what is the damage
Lex Fridman (1:51:35.500)
that could be done from an RNA just floating about.
Lex Fridman (1:51:39.420)
So the RNA itself is not gonna be a problem,
Lex Fridman (1:51:41.260)
it's the protein that is encoded in it, right?
Vincent Racaniello (1:51:43.940)
This is a viral RNA which has no sequence in us,
Lex Fridman (1:51:48.820)
so there's nothing that it could do.
Vincent Racaniello (1:51:50.540)
It's the protein that I would say you could ask,
Lex Fridman (1:51:54.040)
what is that gonna do?
Lex Fridman (1:51:56.160)
And the one property we know about the spike
Lex Fridman (1:52:01.740)
is that it can cause fusion of cells, right?
Vincent Racaniello (1:52:06.740)
That's how the virus gets in in the beginning.
Lex Fridman (1:52:09.280)
The spike attaches to the cell by this H2 receptor
Lex Fridman (1:52:14.520)
and it causes the virus and the cell to fuse.
Lex Fridman (1:52:19.180)
And that's how the RNA gets out of the particle.
Lex Fridman (1:52:21.060)
But so wait, I'm a bit confused.
Lex Fridman (1:52:24.100)
So with this mRNA vaccine with the lipids and the RNA,
Lex Fridman (1:52:28.580)
there's no spike, right?
Lex Fridman (1:52:30.700)
The mRNA codes for the spike.
Vincent Racaniello (1:52:33.100)
Oh, the mRNA codes, so it creates the spike.
Lex Fridman (1:52:35.860)
Creates a spike.
Lex Fridman (1:52:36.700)
And so that spike could cause fusion of cells.
Lex Fridman (1:52:39.260)
Yes, except they modified the spike so it wouldn't.
Vincent Racaniello (1:52:44.240)
Got it.
Lex Fridman (1:52:45.080)
They made two amino acid changes in the spike
Lex Fridman (1:52:46.420)
so it would not fuse.
Lex Fridman (1:52:47.260)
So they understand enough which amino acids
Vincent Racaniello (1:52:49.540)
are responsible for the fusion.
Lex Fridman (1:52:51.100)
That's right.
Vincent Racaniello (1:52:51.940)
Interesting.
Lex Fridman (1:52:52.760)
This is so cool.
Lex Fridman (1:52:53.600)
So they could modify it.
Lex Fridman (1:52:54.440)
So now it's not gonna cause fusion, so that's not an issue.
Vincent Racaniello (1:52:57.140)
It's called the prefusion stabilized spike.
Lex Fridman (1:53:00.980)
Cool.
Lex Fridman (1:53:01.820)
So the spike, when it binds ACE2,
Lex Fridman (1:53:04.160)
that top falls off and the part of the spike
Vincent Racaniello (1:53:07.720)
that causes fusion is now exposed.
Lex Fridman (1:53:09.300)
And that doesn't happen in this mRNA vaccine.
Lex Fridman (1:53:11.980)
So those are the things that could have happened,
Lex Fridman (1:53:14.900)
but I think they're ruled out by what we've just said.
Lex Fridman (1:53:18.340)
But there's no better test
Lex Fridman (1:53:19.700)
than putting it into people, right?
Lex Fridman (1:53:22.300)
And doing phase one, phase two, and phase three,
Lex Fridman (1:53:25.060)
and increasing numbers of people and asking,
Lex Fridman (1:53:27.620)
what do we see?
Lex Fridman (1:53:28.860)
Do we have any concerns?
Lex Fridman (1:53:30.860)
And so now it's been in many millions of people
Lex Fridman (1:53:35.260)
and we don't see most of the effects you see in a vaccine,
Vincent Racaniello (1:53:40.820)
you see in the first couple of months.
Lex Fridman (1:53:43.180)
Things like the myocarditis with some of the vaccines,
Vincent Racaniello (1:53:46.060)
the clotting issues with the AstraZeneca vaccine,
Lex Fridman (1:53:49.300)
Guillain Barre, you see those relatively quickly.
Lex Fridman (1:53:54.860)
And we've seen small numbers of those occur,
Lex Fridman (1:53:58.300)
but other things we haven't seen,
Lex Fridman (1:54:01.460)
and you never say never, right?
Lex Fridman (1:54:04.820)
Right, so I mean, this is fascinating, right?
Vincent Racaniello (1:54:07.780)
It's like I drink, I put Splenda in my coffee
Lex Fridman (1:54:12.780)
and it has supposedly no calories,
Lex Fridman (1:54:20.460)
but it tastes really good.
Lex Fridman (1:54:22.340)
And despite what like rumors and blogs and so on,
Vincent Racaniello (1:54:26.140)
I have not seen good medical evidence
Lex Fridman (1:54:28.900)
that is harmful to you, but it's like, it tastes too good.
Lex Fridman (1:54:33.560)
So I'm thinking like,
Lex Fridman (1:54:35.420)
there's gotta be longterm consequences,
Lex Fridman (1:54:37.740)
but it's very difficult to understand
Lex Fridman (1:54:40.020)
what the longterm consequences are.
Lex Fridman (1:54:43.100)
And there's this kind of like distant fear
Lex Fridman (1:54:47.660)
or anxiety about it.
Vincent Racaniello (1:54:49.540)
Like this thing tastes too good, it's too good to be true.
Lex Fridman (1:54:53.020)
There's gotta be, there's no free lunch in this world.
Vincent Racaniello (1:54:55.700)
This is the kind of feeling that people have
Lex Fridman (1:54:57.820)
about the longterm effects of the vaccine,
Vincent Racaniello (1:55:01.660)
that you mentioned that there's some intuition
Lex Fridman (1:55:04.420)
about near term effects that you want to remove,
Vincent Racaniello (1:55:09.000)
like the diffusion of cells and all those kinds of things,
Lex Fridman (1:55:11.500)
but they think, okay,
Vincent Racaniello (1:55:12.860)
this travels to other cells in the body,
Lex Fridman (1:55:14.860)
this travels to neurons or that kind of stuff.
Lex Fridman (1:55:18.660)
And then what kind of effect does that have longterm
Lex Fridman (1:55:20.700)
that's yet to be discovered?
Lex Fridman (1:55:22.680)
What do you make me for this vaccine,
Lex Fridman (1:55:25.140)
but in general in science about making statements
Lex Fridman (1:55:28.240)
about longterm negative effects?
Lex Fridman (1:55:32.260)
Is that something that weighs heavy on you?
Vincent Racaniello (1:55:34.500)
Is that something we can kind of escape
Lex Fridman (1:55:36.440)
through just large scale experimentation
Lex Fridman (1:55:39.020)
with animals and humans?
Lex Fridman (1:55:41.300)
Well, if you're really, if you're concerned about longterm,
Lex Fridman (1:55:44.220)
then you have to do a longterm experiment, right?
Lex Fridman (1:55:46.700)
And maybe you don't see something for 50, 60 years.
Lex Fridman (1:55:50.580)
So if someone says to you,
Lex Fridman (1:55:53.060)
there are no longterm effects of the COVID vaccines,
Vincent Racaniello (1:55:56.620)
they can't say that
Lex Fridman (1:55:57.460)
because they haven't done the long experiment, right?
Vincent Racaniello (1:56:00.280)
There's always the possibility, but you have to weigh it.
Lex Fridman (1:56:02.820)
It's always, there's no free lunch, right?
Vincent Racaniello (1:56:06.120)
There's always a risk benefit calculation you have to make.
Lex Fridman (1:56:10.300)
You can have the study, it goes 50 years and then decide,
Lex Fridman (1:56:14.060)
but I guess what you're doing is just like we said,
Lex Fridman (1:56:19.080)
I forget which one, with polio, with rabies, I forget,
Lex Fridman (1:56:22.200)
but you're weighing the side effects.
Lex Fridman (1:56:25.460)
Yeah, polio, right.
Vincent Racaniello (1:56:26.460)
The vaccine versus the effects of the virus.
Lex Fridman (1:56:31.100)
And like both of them, you don't know longterm effects,
Lex Fridman (1:56:34.540)
but you're building up intuition as you study,
Lex Fridman (1:56:38.620)
which what are the longterm effects?
Vincent Racaniello (1:56:41.140)
Like there's a huge number of people,
Lex Fridman (1:56:46.140)
like that have like, I don't want to say experts
Vincent Racaniello (1:56:51.460)
because I don't like the word,
Lex Fridman (1:56:52.420)
but people have studied it long enough
Vincent Racaniello (1:56:54.460)
to where they build up intuition.
Lex Fridman (1:56:56.260)
They don't know for sure.
Vincent Racaniello (1:56:57.780)
There's basic science being done, there's basic studies.
Lex Fridman (1:57:00.580)
But you start to build up an intuition of what might be
Vincent Racaniello (1:57:05.880)
a problem down the line and what is not,
Lex Fridman (1:57:08.580)
biologically speaking.
Lex Fridman (1:57:09.980)
And so given that map, then considering the virus,
Lex Fridman (1:57:14.260)
there seems to be a lot of evidence for COVID
Vincent Racaniello (1:57:16.800)
having negative effects on all aspects of the body,
Lex Fridman (1:57:21.820)
not just even respiratory, which is kind of interesting.
Lex Fridman (1:57:24.860)
So the cognitive stuff is terrifying.
Lex Fridman (1:57:27.060)
All kinds of systems evolve, yes.
Lex Fridman (1:57:28.940)
And then you look at the same thing with the vaccine
Lex Fridman (1:57:32.380)
and there seems to be less of that.
Lex Fridman (1:57:34.700)
But of course you don't know
Lex Fridman (1:57:36.340)
if it's some kind of dormant thing that's just going to.
Vincent Racaniello (1:57:39.260)
You won't know.
Lex Fridman (1:57:40.380)
You have to make a judgment.
Lex Fridman (1:57:42.580)
And for a lot of people they can't, right?
Lex Fridman (1:57:44.900)
Because they don't have the tools to make the judgment.
Vincent Racaniello (1:57:47.580)
I totally understand that.
Lex Fridman (1:57:49.340)
And we have let people down a few times in medicine, right?
Lex Fridman (1:57:54.340)
And I know two very specific examples.
Lex Fridman (1:57:57.820)
The first polio vaccine ever made,
Vincent Racaniello (1:58:00.580)
the Salk vaccine was released in 1955.
Lex Fridman (1:58:04.460)
Immediately within months,
Vincent Racaniello (1:58:06.420)
a few hundred cases of paralysis in kids who got it
Lex Fridman (1:58:09.460)
because it was not properly inactivated.
Vincent Racaniello (1:58:14.180)
Now you have to understand,
Lex Fridman (1:58:15.340)
parents were dying for a polio vaccine
Vincent Racaniello (1:58:17.820)
because kids were getting paralyzed every summer,
Lex Fridman (1:58:20.020)
30,000 kids a year.
Lex Fridman (1:58:22.340)
And so they went and took it.
Lex Fridman (1:58:24.860)
They took the word of the medical establishment
Vincent Racaniello (1:58:27.060)
that it was safe and it wasn't.
Lex Fridman (1:58:29.580)
Big letdown, never going to forget something.
Vincent Racaniello (1:58:31.980)
Although I think a lot of people today aren't aware of that.
Lex Fridman (1:58:36.020)
I think that was a big problem that's everlasting.
Vincent Racaniello (1:58:38.220)
Then the attenuated vaccine that we talked about,
Lex Fridman (1:58:42.060)
the infectious causing polio.
Vincent Racaniello (1:58:45.900)
Yet parents continued to bring their kids to be vaccinated
Lex Fridman (1:58:49.940)
because they were said,
Vincent Racaniello (1:58:50.780)
this is the right thing to do.
Lex Fridman (1:58:52.380)
And I have to say,
Vincent Racaniello (1:58:53.220)
I was involved in several lawsuits
Lex Fridman (1:58:55.020)
where parents of a kid who got paralyzed
Vincent Racaniello (1:58:58.420)
from the polio vaccine decided to sue the manufacturer
Lex Fridman (1:59:01.860)
and get some money for their kid.
Lex Fridman (1:59:04.620)
And so they got mad.
Lex Fridman (1:59:07.020)
And I think you could not...
Vincent Racaniello (1:59:11.620)
The first issue could have been prevented,
Lex Fridman (1:59:15.780)
could have been prevented by inactivating it properly.
Vincent Racaniello (1:59:18.540)
I think the company just did the wrong thing.
Lex Fridman (1:59:21.180)
The second we had evidence for,
Lex Fridman (1:59:23.220)
and we should probably have not used that vaccine any longer,
Lex Fridman (1:59:25.900)
but I think that destroys public confidence.
Lex Fridman (1:59:28.180)
But those aren't...
Lex Fridman (1:59:29.220)
They're not long term.
Vincent Racaniello (1:59:30.060)
That's a minority of cases.
Lex Fridman (1:59:30.900)
This is a minority.
Vincent Racaniello (1:59:31.740)
This is a very rare event, yeah.
Lex Fridman (1:59:32.580)
But nevertheless,
Vincent Racaniello (1:59:33.420)
science as an institution didn't make corrections
Lex Fridman (1:59:38.700)
in that case.
Vincent Racaniello (1:59:39.540)
No, they didn't.
Lex Fridman (1:59:40.380)
And so what do you make of that?
Vincent Racaniello (1:59:44.580)
I mean, it's very unfortunate
Lex Fridman (1:59:45.980)
that those few things can destroy trust.
Lex Fridman (1:59:49.460)
But I don't think that lasts till today.
Lex Fridman (1:59:51.140)
I think today is a different era, right?
Lex Fridman (1:59:53.660)
And most people don't know about those stories.
Lex Fridman (1:59:55.340)
I tell them to you because that's what could happen.
Vincent Racaniello (1:59:58.900)
I think it could happen today.
Lex Fridman (20:02.300)
They solve the structure,
Lex Fridman (20:03.640)
and then they say,
Lex Fridman (20:04.480)
what happens if we change this amino acid?
Vincent Racaniello (20:06.520)
Oh, look, it blocks binding to the receptor.
Lex Fridman (20:09.000)
This must be the receptor binding interface.
Lex Fridman (20:11.240)
So that's the exciting stuff, absolutely,
Lex Fridman (20:13.400)
is doing the experiment.
Vincent Racaniello (20:14.480)
Well, I wonder if you can do some kinds of like simulations
Lex Fridman (20:18.780)
of like, you know, different proteins
Vincent Racaniello (20:22.240)
or multi protein systems going to war against each other,
Lex Fridman (20:27.640)
like to try to figure out, you know,
Vincent Racaniello (20:31.400)
reinforcement learning is used in alpha zero, for example,
Lex Fridman (20:35.360)
to learn chess and go,
Lex Fridman (20:37.120)
and that's using the self play mechanism
Lex Fridman (20:39.200)
where the thing plays against itself
Lex Fridman (20:41.360)
and learns better and better.
Lex Fridman (20:42.760)
Whether you can, I wonder if you can simulate
Vincent Racaniello (20:45.080)
almost evolution in that way
Lex Fridman (20:46.680)
for primitive biological systems,
Vincent Racaniello (20:49.560)
have them in simulation, fight each other,
Lex Fridman (20:52.600)
and then see what comes out,
Vincent Racaniello (20:53.640)
like a super dangerous virus comes out
Lex Fridman (20:55.680)
or super like Chuck Norris type of thing
Vincent Racaniello (20:58.480)
that defends against the super dangerous virus,
Lex Fridman (21:00.640)
and it's all in simulation.
Lex Fridman (21:01.840)
So an example would be,
Lex Fridman (21:03.680)
we have all these variants of SARS COVID 2 arising, right?
Vincent Racaniello (21:07.840)
Which look to be selected by immune responses,
Lex Fridman (21:13.080)
but we know what amino acids are changing in the spike
Lex Fridman (21:17.280)
and how they block antibody binding.
Lex Fridman (21:19.080)
You could simulate that.
Lex Fridman (21:20.360)
You could say, what is the antibody looking at?
Lex Fridman (21:24.960)
Where antibodies bind on proteins are called epitopes, right?
Vincent Racaniello (21:28.040)
You could map them all and change them in a simulation
Lex Fridman (21:30.400)
one by one and go back and forth
Vincent Racaniello (21:32.120)
between the antibody and the virus.
Lex Fridman (21:33.800)
So all these, evolution is what we call an arms race, right?
Vincent Racaniello (21:38.400)
The virus changes and then it evades the host
Lex Fridman (21:41.600)
and then the host can change.
Vincent Racaniello (21:43.240)
The host takes longer to change though, unfortunately.
Lex Fridman (21:45.240)
It takes geological time, but it can.
Lex Fridman (21:47.960)
And then the virus can change
Lex Fridman (21:49.640)
and it can go back and forth.
Lex Fridman (21:50.600)
And we can see evidence of this in genome sequences
Lex Fridman (21:54.360)
of both viruses and their hosts.
Lex Fridman (21:56.240)
And so you can take a protein in a host
Lex Fridman (22:00.040)
that is a receptor for multiple viruses
Lex Fridman (22:02.720)
and you can see all the impacts of virus pressure on it.
Lex Fridman (22:05.720)
And you could simulate that for sure.
Lex Fridman (22:07.280)
And that's just one thing that you could do.
Lex Fridman (22:09.000)
You could simulate changes in say an enzyme
Vincent Racaniello (22:13.680)
that makes it resistant to a drug
Lex Fridman (22:15.120)
and predict all the drug resistance.
Lex Fridman (22:18.240)
But the problem is people like me,
Lex Fridman (22:21.280)
the experimental virologists
Vincent Racaniello (22:22.800)
don't know how to do any of that.
Lex Fridman (22:24.040)
So we need to collaborate with people, I guess.
Vincent Racaniello (22:27.720)
Oh, with other humans.
Lex Fridman (22:29.680)
We do that, we do that.
Lex Fridman (22:31.480)
But with people from a field that we're not used to,
Lex Fridman (22:35.720)
I suppose people who, would it be AI, I suppose?
Vincent Racaniello (22:39.160)
Yeah, machine learning people.
Lex Fridman (22:40.000)
Machine learning people.
Lex Fridman (22:41.320)
And you would say, look, this is the biological problem.
Lex Fridman (22:44.400)
Is there a way we can use your tools to attack it?
Vincent Racaniello (22:46.960)
The problem is those people are antisocial introverts
Lex Fridman (22:51.680)
that have a place like this
Lex Fridman (22:55.160)
and try to hide from other people in the world.
Lex Fridman (22:57.200)
Very difficult to find in the wild.
Vincent Racaniello (23:00.120)
Okay, so outside of doing amazing brilliant lectures online,
Lex Fridman (23:04.960)
you host and produce five, I would say, related podcasts,
Vincent Racaniello (23:09.960)
including my favorite, This Week in Virology,
Lex Fridman (23:13.600)
also This Week in Parasitism,
Vincent Racaniello (23:16.280)
This Week in Microbiology, and so on.
Lex Fridman (23:18.640)
So you're a good person to ask,
Lex Fridman (23:21.080)
what are the categories of small things,
Lex Fridman (23:23.960)
small biological things in this world that can kill you,
Lex Fridman (23:27.320)
kill us humans?
Lex Fridman (23:30.120)
Let's look, you said like most viruses are friendly
Vincent Racaniello (23:33.360)
or at least not unfriendly.
Lex Fridman (23:35.840)
But let's look at the unfriendly ones.
Lex Fridman (23:38.960)
And viruses and bacteria and those kinds of things.
Lex Fridman (23:42.160)
When you look at the full spectrum of things
Lex Fridman (23:43.960)
that can kill you, can you kind of paint a brief picture?
Lex Fridman (23:47.240)
Yeah, I think the big picture is that
Vincent Racaniello (23:50.720)
the things that can kill you are a minority
Lex Fridman (23:52.720)
of everything that's out there.
Lex Fridman (23:54.320)
And we're talking about molecules.
Lex Fridman (23:57.240)
So we have in us proteins that can kill us.
Vincent Racaniello (24:01.320)
Preons that are just, it's a protein in us.
Lex Fridman (24:04.560)
And if it misfolds, it makes all of its other copies misfold
Lex Fridman (24:08.680)
and then you die of a neurological disease.
Lex Fridman (24:11.680)
That's pretty rare.
Lex Fridman (24:13.840)
So there are proteins, there are viruses.
Lex Fridman (24:16.480)
And as I said, only certain ones can kill us.
Lex Fridman (24:20.200)
But even if we get those from animals,
Lex Fridman (24:22.960)
it's not straightforward.
Lex Fridman (24:24.440)
If you look at SARS CoV2, right?
Lex Fridman (24:26.760)
This is probably a once in a hundred year pandemic,
Vincent Racaniello (24:29.880)
I would say, equivalent to 1918 in its devastation.
Lex Fridman (24:34.760)
And in between there have been smaller pandemics
Vincent Racaniello (24:36.560)
of other viruses, but it doesn't happen all that often.
Lex Fridman (24:39.600)
So we have a lot of viruses.
Vincent Racaniello (24:40.560)
We have a lot of bacteria of various sorts
Lex Fridman (24:43.600)
that can cause infections in us.
Lex Fridman (24:46.240)
And it's a limited number, right?
Lex Fridman (24:49.240)
You're streptococci and staphylococci and clostridia.
Vincent Racaniello (24:52.680)
We could go on and on, but we know how to handle those.
Lex Fridman (24:56.360)
As long as we have antimicrobials,
Vincent Racaniello (24:58.280)
it's just that we abuse them and we get resistant.
Lex Fridman (25:00.360)
So that can be a problem.
Vincent Racaniello (25:02.120)
Then we have fungi, not mushrooms,
Lex Fridman (25:04.840)
but much smaller fungi that multiply sub microscopic
Vincent Racaniello (25:09.440)
or just at the microscopic level.
Lex Fridman (25:11.400)
They can, in dry climates of the US,
Vincent Racaniello (25:13.920)
you can inhale their spores and they can grow in your lung
Lex Fridman (25:16.280)
if you're immunosuppressed and so forth.
Lex Fridman (25:18.800)
So those are the tiny guys.
Lex Fridman (25:21.080)
And then we have parasites,
Vincent Racaniello (25:22.320)
which we do this week in parasitism,
Lex Fridman (25:24.960)
where single cells, even worms of various sorts
Vincent Racaniello (25:30.040)
can invade you and cause all sorts of problems.
Lex Fridman (25:33.640)
How, I was like kind of terrified to listen to that podcast.
Lex Fridman (25:37.200)
What's it like?
Lex Fridman (25:39.720)
Well, I mean, what you learn is that you can,
Vincent Racaniello (25:45.200)
you travel somewhere and you can get infected
Lex Fridman (25:47.200)
and bring it back home.
Vincent Racaniello (25:48.720)
Here in the US, we do have certain kinds of parasites,
Lex Fridman (25:52.640)
but because of our lifestyle,
Vincent Racaniello (25:55.000)
we more or less have avoided them.
Lex Fridman (25:56.560)
For example, there's a parasite called toxoplasma,
Vincent Racaniello (26:00.440)
which is infected most of the world, actually,
Lex Fridman (26:03.960)
because a lot of people like to eat raw meat
Lex Fridman (26:06.160)
and you would get it from raw meat.
Lex Fridman (26:08.400)
And we're not as fond of that here in the US.
Vincent Racaniello (26:12.320)
We like to cook our meat,
Lex Fridman (26:13.320)
but that could be a consequence of eating raw meat.
Lex Fridman (26:16.440)
Is that what leads to, what is it called, toxoplasmosis?
Lex Fridman (26:19.840)
Yeah, so toxoplasmosis, it's mainly,
Vincent Racaniello (26:25.560)
a big issue is if you're pregnant and you get toxo,
Lex Fridman (26:28.400)
then your fetus is gonna be very badly malformed.
Vincent Racaniello (26:32.520)
It's gonna have brain defects and so forth.
Lex Fridman (26:36.240)
And animals can get it as well.
Lex Fridman (26:39.480)
So there are a lot of parasites of that nature,
Lex Fridman (26:41.280)
which you often acquire by food,
Vincent Racaniello (26:43.280)
eating food of different sorts.
Lex Fridman (26:45.000)
And it usually happens elsewhere.
Vincent Racaniello (26:47.560)
On This Week in Parasitism, we do a case.
Lex Fridman (26:50.840)
So Daniel Griffin is our resident physician.
Lex Fridman (26:54.320)
He's a doctor, a real doctor, right?
Lex Fridman (26:56.480)
And every month, he comes up with a case.
Vincent Racaniello (26:58.640)
Okay, this is a person I saw.
Lex Fridman (27:00.880)
And last month, this young lady had traveled somewhere
Lex Fridman (27:04.960)
and she ate raw fish.
Lex Fridman (27:09.600)
It was somewhere Southeast Asia or something.
Lex Fridman (27:11.920)
And she ended up with red bumps all over her skin.
Lex Fridman (27:15.880)
And it turned out it was a parasite from the fish
Vincent Racaniello (27:17.720)
that moved around in her and very easy to cure.
Lex Fridman (27:21.720)
We have, if the right doctors and the right drugs,
Vincent Racaniello (27:23.720)
you can cure all these things.
Lex Fridman (27:24.640)
What about diagnose, like connect the red spots
Lex Fridman (27:27.600)
to the fact that it's a parasite?
Lex Fridman (27:28.760)
It's very easy if you have the right diagnostics.
Vincent Racaniello (27:31.240)
Now, Daniel often goes to parts of the world
Lex Fridman (27:33.080)
where they don't have diagnostics
Lex Fridman (27:34.560)
and he has to use other mechanisms.
Lex Fridman (27:37.240)
He may have to take a bit and look at it under a microscope.
Lex Fridman (27:40.320)
And then he may not be able to get the drug
Lex Fridman (27:41.960)
depending on where he is.
Lex Fridman (27:43.840)
But often he sees patients who come back to the US
Lex Fridman (27:47.160)
and they get diarrhea or they have a fever.
Lex Fridman (27:49.640)
And he said, where have you been?
Lex Fridman (27:50.720)
And he can put two and two together.
Lex Fridman (27:52.200)
And so we let our listeners do that.
Lex Fridman (27:53.800)
And they all send in guesses.
Lex Fridman (27:55.240)
And it's wonderful to hear them go through this.
Lex Fridman (27:57.840)
So there are a lot of parasites that can get you.
Vincent Racaniello (28:00.760)
You have to be careful about eating when you go overseas.
Lex Fridman (28:03.360)
And water too?
Vincent Racaniello (28:04.640)
Water as well.
Lex Fridman (28:05.520)
And in parts of Africa, there are parasites in the lakes
Vincent Racaniello (28:09.200)
that if you go swimming, they can invade you.
Lex Fridman (28:11.840)
And in fact, they can go into your hair follicles
Lex Fridman (28:14.080)
and burrow in and get into your bloodstream.
Lex Fridman (28:15.960)
That's exciting.
Lex Fridman (28:16.960)
So Daniel is interesting because he's very adventurous
Lex Fridman (28:20.320)
and he's not afraid of any of this.
Lex Fridman (28:22.800)
So there's a famous lake in Africa, Lake Malawi,
Lex Fridman (28:26.040)
which harbors a lot of these parasites.
Lex Fridman (28:28.480)
And he said, oh yeah, yeah, I just make sure
Lex Fridman (28:30.280)
I towel off vigorously when I get out and get rid of them.
Lex Fridman (28:34.840)
And that was the name of an episode.
Lex Fridman (28:37.160)
But food is, sushi, you can get worms from sushi.
Lex Fridman (28:43.400)
And the solution is to freeze it.
Lex Fridman (28:46.800)
And many sushi restaurants now have liquid nitrogen.
Vincent Racaniello (28:49.880)
They snap freeze their sushi and that kills all the parasites.
Lex Fridman (28:53.000)
And a study was actually done in Japan
Vincent Racaniello (28:56.400)
showing that freezing does not alter the taste of sushi
Lex Fridman (28:59.240)
because it's up, you see a big industry there.
Vincent Racaniello (29:01.680)
Wow, that's brilliant.
Lex Fridman (29:03.240)
That's brilliant.
Vincent Racaniello (29:04.440)
Yeah, I was thinking about, I'm so boring and bland
Lex Fridman (29:10.560)
that especially when I am now in Texas here
Lex Fridman (29:12.640)
and I've been eating quite a bit of barbecue,
Lex Fridman (29:14.280)
I realized I really haven't explored the culinary world.
Lex Fridman (29:18.960)
And I've been curious to travel and taste different foods.
Lex Fridman (29:22.280)
Is there something you could say by way of advice,
Vincent Racaniello (29:26.680)
channeling Daniel, I guess, if you were to travel
Lex Fridman (29:30.160)
in the world, if eating is the thing
Vincent Racaniello (29:32.600)
that gets you the parasites,
Lex Fridman (29:34.560)
what's a good advice for eating
Lex Fridman (29:37.040)
in strange parts of the world, Mongolia, India, China?
Lex Fridman (29:41.760)
Is there something you could say by way of advice?
Vincent Racaniello (29:43.840)
I think Daniel would say,
Lex Fridman (29:45.200)
make sure your food is cooked, right?
Vincent Racaniello (29:47.520)
Cooked, but that's so boring.
Lex Fridman (29:49.040)
Yeah, it's unfortunate.
Lex Fridman (29:50.440)
And he would agree with you
Lex Fridman (29:52.200)
because many vegetables are delicious.
Vincent Racaniello (29:55.520)
Salads even are delicious, not cooked,
Lex Fridman (29:57.840)
but they can have parasites in them.
Vincent Racaniello (29:59.520)
Meats, fish, people like to have uncooked fish.
Lex Fridman (2:00:01.340)
If you look at the history of the polio vaccine,
Vincent Racaniello (2:00:06.620)
the US Public Health Service wanted kids to be vaccinated.
Lex Fridman (2:00:10.820)
So they did things that probably weren't correct
Vincent Racaniello (2:00:13.500)
to get the vaccine back online.
Lex Fridman (2:00:15.740)
Right?
Lex Fridman (2:00:16.580)
But they did it and they pushed it through.
Lex Fridman (2:00:20.300)
So the question is, what do we do today?
Lex Fridman (2:00:23.660)
So I can look at, as we just said,
Lex Fridman (2:00:27.300)
I can look at what might happen
Lex Fridman (2:00:29.100)
and I can make reasonable decisions
Lex Fridman (2:00:33.300)
about the likelihood of them happening.
Lex Fridman (2:00:35.060)
And I can also say, I don't wanna get COVID of any kind
Lex Fridman (2:00:38.940)
because I've seen how nasty it can be.
Lex Fridman (2:00:41.700)
And I decide I'm taking the risk,
Lex Fridman (2:00:44.020)
whatever small of a long term effect,
Vincent Racaniello (2:00:46.060)
I'm gonna take the risk.
Lex Fridman (2:00:47.020)
My family took the risk and many other people did.
Vincent Racaniello (2:00:49.980)
Of a vaccine.
Lex Fridman (2:00:50.900)
Of getting vaccinated.
Vincent Racaniello (2:00:52.460)
Because I think it's very small.
Lex Fridman (2:00:53.980)
But I understand where people can't make that decision.
Lex Fridman (2:00:56.900)
And that begs the question,
Lex Fridman (2:00:58.380)
what would they need to make a decision?
Lex Fridman (2:01:01.260)
So if you're concerned about an effect in 40 years,
Lex Fridman (2:01:06.820)
we're not gonna know for 40 years.
Vincent Racaniello (2:01:09.180)
Yeah, so I think if I were to speak,
Lex Fridman (2:01:11.020)
because I talked to, like I mentioned offline to Joe Rogan
Lex Fridman (2:01:14.820)
and his podcast yesterday,
Lex Fridman (2:01:15.980)
I talked to him all the time about this.
Vincent Racaniello (2:01:18.780)
I think the concern is less about the long term effects
Lex Fridman (2:01:27.260)
like on paper.
Vincent Racaniello (2:01:28.460)
It's more about the, like people like Anthony Fauci
Lex Fridman (2:01:34.540)
and people at the top are simply misrepresenting the data
Vincent Racaniello (2:01:39.140)
or like are not accurately being transparent.
Lex Fridman (2:01:42.980)
Not collecting the data properly.
Vincent Racaniello (2:01:45.020)
Not reporting on the data properly.
Lex Fridman (2:01:46.820)
Not being transparent.
Vincent Racaniello (2:01:48.300)
Not representing the uncertainties.
Lex Fridman (2:01:50.380)
Not openly saying they were wrong two months ago.
Vincent Racaniello (2:01:55.780)
Like in a way that's not like dramatic,
Lex Fridman (2:01:58.100)
but revealing the basic process of science
Vincent Racaniello (2:02:00.980)
when you have to do your best under uncertainty.
Lex Fridman (2:02:03.740)
Just also just being inauthentic.
Vincent Racaniello (2:02:06.060)
There's a sense, especially with like a younger generation
Lex Fridman (2:02:09.500)
now, there's a certain way on the internet.
Vincent Racaniello (2:02:11.700)
Like the internet can smell bullshit
Lex Fridman (2:02:14.260)
much better than previous generations could.
Lex Fridman (2:02:16.900)
And so they see there's a kind of inauthenticity
Lex Fridman (2:02:21.740)
that comes with being like representing authority.
Vincent Racaniello (2:02:26.420)
Like I am a scientist.
Lex Fridman (2:02:27.980)
I'm an expert.
Vincent Racaniello (2:02:29.020)
I have a PhD.
Lex Fridman (2:02:30.460)
I have four decades of work.
Vincent Racaniello (2:02:31.900)
Therefore everyone should listen to me.
Lex Fridman (2:02:34.020)
And somehow that maps to this feeling of,
Lex Fridman (2:02:38.940)
well, what are they hiding?
Lex Fridman (2:02:40.740)
If they're speaking from authority like this,
Vincent Racaniello (2:02:43.100)
if everyone is in agreement like this,
Lex Fridman (2:02:45.740)
that means they all have emails between each other.
Vincent Racaniello (2:02:48.180)
They said, we're gonna tell this.
Lex Fridman (2:02:49.500)
This is the message we're gonna tell the public.
Lex Fridman (2:02:51.860)
Then what is the truth, the actual truth?
Lex Fridman (2:02:54.860)
Maybe there's a much bigger uncertainty.
Vincent Racaniello (2:02:57.220)
Maybe there's dead people in the basement
Lex Fridman (2:02:59.980)
that they're hiding from bad mRNA vaccine experiments.
Vincent Racaniello (2:03:03.860)
Maybe they're, and then the conspiracy theory
Lex Fridman (2:03:06.660)
starts to grow naturally
Vincent Racaniello (2:03:09.140)
when there's this kind of mistrust of that.
Lex Fridman (2:03:11.860)
So it's less about kind of like a deep concern
Vincent Racaniello (2:03:17.180)
about longterm effects.
Lex Fridman (2:03:18.980)
It's a concern about longterm effects
Vincent Racaniello (2:03:24.660)
if we find out that there's some secret stuff
Lex Fridman (2:03:27.100)
that we're not being told.
Vincent Racaniello (2:03:28.420)
It all lands on that.
Lex Fridman (2:03:30.060)
So what the heck, I mean, so I put the blame
Vincent Racaniello (2:03:32.380)
not on the data, but basically on the leaders
Lex Fridman (2:03:35.580)
and the communicators of the science at the top.
Vincent Racaniello (2:03:39.260)
Well, to that I would say all the data,
Lex Fridman (2:03:43.780)
as far as I know, are made public.
Lex Fridman (2:03:47.060)
So you can dive into it.
Lex Fridman (2:03:48.780)
And I know a lot of people ask me questions
Lex Fridman (2:03:51.540)
and I just say, it's right here in the data.
Lex Fridman (2:03:54.180)
And I know a lot of people can't do that.
Vincent Racaniello (2:03:55.820)
They can't dive into it.
Lex Fridman (2:03:57.460)
But that's one solution for people who are able.
Vincent Racaniello (2:04:00.340)
Now you could argue, well,
Lex Fridman (2:04:01.860)
maybe they've left data out.
Vincent Racaniello (2:04:03.460)
Well, then not even I can help
Lex Fridman (2:04:05.460)
because then they're hiding it from me too.
Lex Fridman (2:04:07.180)
And I think that's highly unlikely.
Lex Fridman (2:04:08.580)
I think for the most part,
Vincent Racaniello (2:04:09.940)
the FDA requires the release
Lex Fridman (2:04:11.860)
of all the clinical trial data, right?
Vincent Racaniello (2:04:14.260)
So, okay, so this clinical trial data, that's one thing.
Lex Fridman (2:04:17.600)
So that's the data that we should be focusing on, right?
Lex Fridman (2:04:20.180)
So there's a lot of different data sets here.
Lex Fridman (2:04:24.180)
So there's preclinical data,
Vincent Racaniello (2:04:25.700)
which is everything that was done in the lab
Lex Fridman (2:04:28.260)
before this vaccine ever went into a human arm.
Vincent Racaniello (2:04:30.900)
It's all the cell culture work
Lex Fridman (2:04:32.260)
that we talked about a little, experiments in animals.
Vincent Racaniello (2:04:35.900)
All of that is publicly accessible.
Lex Fridman (2:04:38.380)
Most of it gets published.
Lex Fridman (2:04:39.980)
And then there's the initial drug filing,
Lex Fridman (2:04:42.580)
which is huge, the books of,
Lex Fridman (2:04:45.060)
you can get that and look at it, right?
Lex Fridman (2:04:46.980)
This is me sort of asking sort of difficult questions here.
Vincent Racaniello (2:04:49.820)
It's okay.
Lex Fridman (2:04:51.980)
So there's a lot of money to be made by makers of the vaccine.
Lex Fridman (2:04:56.060)
So for these companies, and obviously there's a distrust
Lex Fridman (2:05:00.940)
of those folks too.
Vincent Racaniello (2:05:02.460)
They've done a lot of really good things in this world,
Lex Fridman (2:05:04.540)
but the incentives are such
Vincent Racaniello (2:05:07.380)
that you wanna sweep stuff under the rug
Lex Fridman (2:05:09.940)
if you're not 100% pure in your ethics.
Lex Fridman (2:05:15.420)
And how hard is it for that data to be fabricated,
Lex Fridman (2:05:21.140)
manipulated, like what's your intuition
Lex Fridman (2:05:24.540)
for the pre trial stuff?
Lex Fridman (2:05:26.100)
I think when you start fabricating,
Vincent Racaniello (2:05:29.020)
then you get inconsistencies,
Lex Fridman (2:05:31.380)
which are pretty easy to pick up.
Vincent Racaniello (2:05:34.380)
When you're talking about some large scale things
Lex Fridman (2:05:36.700)
of this nature.
Vincent Racaniello (2:05:38.020)
Because then you can look through the data very,
Lex Fridman (2:05:40.940)
you're gonna, I mean, we require looking very carefully,
Lex Fridman (2:05:43.660)
but you will see inconsistencies from one trial to another.
Lex Fridman (2:05:46.860)
And that might ring a bell that something's been done.
Vincent Racaniello (2:05:50.740)
Yeah, it's like the moon landing thing.
Lex Fridman (2:05:55.180)
Sometimes like going to the moon is easier than faking it.
Vincent Racaniello (2:05:58.380)
Right.
Lex Fridman (2:06:00.100)
In the sense it might be easier to do a large scale trial
Lex Fridman (2:06:03.380)
and get an effective vaccine versus faking it.
Lex Fridman (2:06:05.940)
But when you brought up the for profit issue,
Vincent Racaniello (2:06:08.340)
I think that is always been an issue.
Lex Fridman (2:06:11.460)
I've always felt that having your health depend
Vincent Racaniello (2:06:15.780)
on for profit industry may not be the best solution.
Lex Fridman (2:06:20.820)
And I don't know how else to do it.
Vincent Racaniello (2:06:23.180)
People tell me I'm a dreamer that thinking that,
Lex Fridman (2:06:26.540)
all medicines could be nonprofit.
Lex Fridman (2:06:28.300)
But I also think that the world should have one health
Lex Fridman (2:06:30.980)
system that takes care of everyone, right?
Vincent Racaniello (2:06:32.780)
Because there's some countries that can't
Lex Fridman (2:06:34.700)
and other countries have an excess like us.
Lex Fridman (2:06:37.580)
So I wish we could do that.
Lex Fridman (2:06:40.220)
Well, the argument is the speed of which the vaccines
Vincent Racaniello (2:06:44.140)
for COVID were produced would never happen
Lex Fridman (2:06:47.420)
in a nonprofit system,
Vincent Racaniello (2:06:49.180)
would never happen in a non capitalist system.
Lex Fridman (2:06:51.700)
Oh, I could set up a vaccine production institute
Vincent Racaniello (2:06:56.060)
in the US that would get the vaccines done
Lex Fridman (2:06:58.860)
because you just need to put money into it.
Vincent Racaniello (2:07:00.860)
That's what made these vaccines get done money.
Lex Fridman (2:07:03.540)
They poured billions of dollars and they got it done quickly.
Lex Fridman (2:07:06.900)
But if I set up a nonprofit institutes of vaccines
Lex Fridman (2:07:09.700)
throughout the US staffed with really talented people,
Vincent Racaniello (2:07:12.500)
pay them well, keep them motivated,
Lex Fridman (2:07:15.020)
you'll get your vaccine.
Vincent Racaniello (2:07:15.860)
No, but that's the thing with capitalism is that
Lex Fridman (2:07:19.940)
the selection of who to hire a good,
Vincent Racaniello (2:07:22.820)
when you say good people,
Lex Fridman (2:07:24.940)
capitalism has a machine that fires people
Vincent Racaniello (2:07:28.140)
who are not good and selects people that are good.
Lex Fridman (2:07:30.900)
Coming from the Soviet Union,
Vincent Racaniello (2:07:32.660)
the dream of communism is similar
Lex Fridman (2:07:35.020)
to what you're saying broadly defined.
Vincent Racaniello (2:07:37.340)
It certainly doesn't work in the broads.
Lex Fridman (2:07:40.020)
The question of whether it works in the healthcare space,
Vincent Racaniello (2:07:45.820)
there is some aspect to the machine of capitalism
Lex Fridman (2:07:49.500)
being the most effective way to select for good people
Lex Fridman (2:07:53.020)
and to effectively produce the thing.
Lex Fridman (2:07:56.100)
But then of course, a lot of people would argue
Vincent Racaniello (2:07:58.500)
the current, even the current healthcare is not
Lex Fridman (2:08:01.140)
with like regulations, there's some weird mix
Vincent Racaniello (2:08:03.620)
where there's a lot of opportunities for inefficiencies.
Lex Fridman (2:08:07.060)
There's a lot of opportunities for bureaucracy.
Lex Fridman (2:08:09.020)
So you have like the worst of all worlds.
Lex Fridman (2:08:11.820)
Can't there be some intermediate that works
Vincent Racaniello (2:08:13.980)
because I mean, the other issue that we haven't mentioned
Lex Fridman (2:08:17.260)
is that politics gets thrown into this
Lex Fridman (2:08:19.220)
and that really messes up
Lex Fridman (2:08:21.380)
and it should never be mixed with healthcare,
Lex Fridman (2:08:22.980)
but it is because a lot of funding comes from the government
Lex Fridman (2:08:26.820)
so that's another confounding factor.
Lex Fridman (2:08:29.300)
But I really think I could make a vaccine institute
Lex Fridman (2:08:33.660)
that if someone didn't do well, I'd fire them.
Vincent Racaniello (2:08:36.620)
No, you're not gonna stay if you can't do your job
Lex Fridman (2:08:39.100)
and do it well, you don't give them incentives,
Lex Fridman (2:08:41.380)
but it doesn't have to be the two extremes I think.
Lex Fridman (2:08:44.700)
There has to be a solution that people don't have
Vincent Racaniello (2:08:47.740)
this mistrust for a company making huge profits
Lex Fridman (2:08:51.580)
off of a drug.
Lex Fridman (2:08:52.460)
But you know what, it's funny,
Lex Fridman (2:08:55.340)
it seems that vaccines and antivirals bear the brunt
Vincent Racaniello (2:08:58.300)
of this criticism yet there are many other pharmaceuticals
Lex Fridman (2:09:01.380)
that people rely on of all sorts.
Vincent Racaniello (2:09:04.380)
They don't seem to question and have issues
Lex Fridman (2:09:06.400)
with those and they have far more side effects than vaccines.
Vincent Racaniello (2:09:09.180)
It's a very strange how we're picking that way,
Lex Fridman (2:09:11.900)
but I should also say that if you have one big
Vincent Racaniello (2:09:17.420)
vaccine institute, one of the other sets
Lex Fridman (2:09:22.220)
of vaccine conspiracies, I mean, I would say they're
Vincent Racaniello (2:09:28.420)
a little farther out into the wild side of ideas,
Lex Fridman (2:09:32.460)
but there's one way to control the populace
Lex Fridman (2:09:37.220)
is by injecting substances into them, right?
Lex Fridman (2:09:41.140)
People, I mean, part of that, funny enough,
Vincent Racaniello (2:09:44.860)
it probably has to do with needles
Lex Fridman (2:09:46.180)
versus something you put in your mouth,
Lex Fridman (2:09:48.940)
but there's something about the government,
Lex Fridman (2:09:50.820)
especially when it's government mandated injection
Vincent Racaniello (2:09:53.580)
of a substance into you.
Lex Fridman (2:09:54.960)
I don't care what the science says,
Vincent Racaniello (2:09:57.780)
if it's 100% effective, 100% safe,
Lex Fridman (2:10:00.940)
there's a natural distrust of what,
Vincent Racaniello (2:10:03.980)
like even if this is effective and safe,
Lex Fridman (2:10:08.660)
giving the government power to do this,
Vincent Racaniello (2:10:11.980)
aren't they gonna start getting ideas down the line for,
Lex Fridman (2:10:15.080)
you know.
Vincent Racaniello (2:10:17.920)
I think that they can barely govern.
Lex Fridman (2:10:20.760)
I don't think they're gonna do that,
Lex Fridman (2:10:22.220)
but you don't have to take, unless you're a federal employee,
Lex Fridman (2:10:25.980)
you don't have to take a COVID vaccine.
Vincent Racaniello (2:10:27.900)
Yeah, but that largely has to do, not largely,
Lex Fridman (2:10:32.980)
but there is an individualistic spirit
Vincent Racaniello (2:10:39.740)
to the American people.
Lex Fridman (2:10:41.420)
There's this, like, you're not gonna take my gun away
Vincent Racaniello (2:10:44.400)
from me, you're not going, and I think that,
Lex Fridman (2:10:52.420)
that's something that makes America what it is.
Vincent Racaniello (2:10:56.060)
Just coming from the Soviet Union,
Lex Fridman (2:10:57.500)
there's a power to sort of resisting
Vincent Racaniello (2:10:59.940)
the overreach of government.
Lex Fridman (2:11:01.720)
That's quite interesting, because I'm a believer,
Vincent Racaniello (2:11:04.440)
I hope that it's possible to have,
Lex Fridman (2:11:08.020)
to strive towards a government that works extremely well.
Vincent Racaniello (2:11:11.600)
I think at its best, a government represents the people
Lex Fridman (2:11:14.860)
and functions in the similar way that you're mentioning,
Lex Fridman (2:11:17.880)
but that, like, pushback,
Lex Fridman (2:11:20.140)
even if it turns into conspiracy theory sometimes,
Vincent Racaniello (2:11:22.580)
I think is actually healthy in the long arc of history.
Lex Fridman (2:11:25.980)
It can be frustrating sometimes,
Lex Fridman (2:11:28.100)
but that mechanism of pushing back against power,
Lex Fridman (2:11:30.900)
against authority, can be healthy.
Vincent Racaniello (2:11:32.980)
I agree, I think it's fine to question the vaccines.
Lex Fridman (2:11:36.500)
What I have issue with is that many people
Vincent Racaniello (2:11:40.140)
put out incorrect information,
Lex Fridman (2:11:43.180)
and I'm not sure what their motivations are,
Lex Fridman (2:11:45.380)
and it's very hard to fight that,
Lex Fridman (2:11:47.020)
because then it's my word versus theirs,
Lex Fridman (2:11:50.100)
and I'm happy to talk with people
Lex Fridman (2:11:52.340)
about any of their concerns,
Lex Fridman (2:11:54.300)
but if you start getting into the stuff
Lex Fridman (2:11:56.700)
that just isn't true, then we have a problem.
Vincent Racaniello (2:11:59.260)
The thing I struggle with is conspiracy theories,
Lex Fridman (2:12:03.340)
whatever language you want to use,
Lex Fridman (2:12:04.660)
but sort of ideas that challenge
Lex Fridman (2:12:09.360)
the mainstream quote unquote narrative,
Vincent Racaniello (2:12:13.600)
given our current social media and internet,
Lex Fridman (2:12:16.180)
like the way it operates,
Vincent Racaniello (2:12:17.820)
they can become viral much easier.
Lex Fridman (2:12:20.340)
There's something much more compelling about them.
Vincent Racaniello (2:12:22.700)
Like I have a secret about the way things really work.
Lex Fridman (2:12:27.760)
That becomes viral, and that's very frustrating,
Vincent Racaniello (2:12:30.200)
because then you're not having
Lex Fridman (2:12:31.740)
a conversation on level ground.
Vincent Racaniello (2:12:36.140)
When you're trying to present scientific ideas,
Lex Fridman (2:12:38.280)
and then there's conspiracy theories,
Vincent Racaniello (2:12:39.820)
the conspiracy theories become viral much faster,
Lex Fridman (2:12:42.780)
and then you're not just having a discussion
Vincent Racaniello (2:12:44.820)
on level ground.
Lex Fridman (2:12:47.980)
That's the frustrating part,
Vincent Racaniello (2:12:49.180)
that it's not an even discussion.
Lex Fridman (2:12:51.880)
Can I just say one more thing?
Vincent Racaniello (2:12:53.580)
I mean, the internet is here to stay,
Lex Fridman (2:12:54.860)
so we're gonna have to figure out
Lex Fridman (2:12:56.140)
how to deal with it, right?
Lex Fridman (2:12:57.300)
But from my perspective,
Vincent Racaniello (2:12:59.340)
I was skeptical that any COVID vaccine
Lex Fridman (2:13:03.020)
would be ready within a year.
Vincent Racaniello (2:13:05.860)
That's amazing.
Lex Fridman (2:13:07.020)
Plus, the way I look at the mRNA vaccine as a scientist,
Vincent Racaniello (2:13:12.340)
it's gee whiz to me.
Lex Fridman (2:13:13.900)
It's amazing that it worked,
Lex Fridman (2:13:15.560)
and I think the data are great, so I want it.
Lex Fridman (2:13:19.980)
As a scientist, I want it.
Vincent Racaniello (2:13:21.260)
One of the really sad things, again,
Lex Fridman (2:13:23.140)
with me, too, as a scientist or as an admirer of science,
Vincent Racaniello (2:13:29.780)
I don't know if it's politics,
Lex Fridman (2:13:31.260)
but one of the sad things to me about the previous year
Vincent Racaniello (2:13:34.940)
is that I wasn't free to celebrate
Lex Fridman (2:13:38.440)
the incredible accomplishment of science with the vaccines.
Vincent Racaniello (2:13:42.380)
I was very skeptical that it's possible
Lex Fridman (2:13:44.140)
to develop a vaccine so quickly.
Lex Fridman (2:13:47.660)
So it's unfortunate that we can't celebrate
Lex Fridman (2:13:50.740)
how amazing humans are to come up with this vaccine.
Vincent Racaniello (2:13:54.100)
Now, this vaccine might have long term effects.
Lex Fridman (2:13:57.300)
That doesn't mean this is not incredible.
Lex Fridman (2:14:00.180)
Why couldn't you celebrate?
Lex Fridman (2:14:06.580)
Because I would love to inspire the world
Vincent Racaniello (2:14:08.620)
with the amazing things science can do.
Lex Fridman (2:14:11.340)
And when you say something about the vaccines,
Vincent Racaniello (2:14:14.000)
they're not listening to the science.
Lex Fridman (2:14:15.660)
A lot of people are not listening to the science.
Lex Fridman (2:14:17.440)
What they hear is, oh, you're a Republican
Lex Fridman (2:14:22.440)
or you're a Democrat, and you're social signaling,
Vincent Racaniello (2:14:25.220)
doing some kind of signaling.
Lex Fridman (2:14:26.700)
No, I think that the vaccine,
Vincent Racaniello (2:14:27.820)
you're talking about injecting something into you,
Lex Fridman (2:14:30.640)
and maybe you're right that the rhetoric is like,
Vincent Racaniello (2:14:33.740)
you better take this or you're dumb.
Lex Fridman (2:14:37.140)
It's not the right approach.
Vincent Racaniello (2:14:38.460)
I've seen, actually, it's kind of interesting.
Lex Fridman (2:14:40.220)
I've seen both sides kind of imply that.
Lex Fridman (2:14:42.940)
So the people who are against the vaccine
Lex Fridman (2:14:48.940)
are dumb for not trusting science,
Lex Fridman (2:14:52.260)
and the people who are for the vaccine
Lex Fridman (2:14:55.680)
are called dumb for trusting science,
Vincent Racaniello (2:14:59.380)
the scientific institution.
Lex Fridman (2:15:00.220)
And nobody wins, yeah.
Lex Fridman (2:15:01.820)
And they both kind of have a point.
Lex Fridman (2:15:03.960)
Like, because you can always,
Lex Fridman (2:15:07.740)
it's like, is the glass half full or half empty?
Lex Fridman (2:15:10.260)
Because you can always look at, like, science
Vincent Racaniello (2:15:15.420)
from a perspective of certain individuals
Lex Fridman (2:15:18.160)
that don't represent, perhaps, the not greatest leaders,
Vincent Racaniello (2:15:23.580)
almost like political leaders.
Lex Fridman (2:15:25.380)
There's a lot of, you know,
Vincent Racaniello (2:15:27.620)
yesterday I went on a whole rant against,
Lex Fridman (2:15:31.380)
I said a lot of positive things about Anthony Fauci
Vincent Racaniello (2:15:34.140)
before I went on a rant against him.
Lex Fridman (2:15:36.140)
Because ultimately, you know,
Vincent Racaniello (2:15:40.020)
I think he failed as a leader,
Lex Fridman (2:15:41.980)
and I know it's very difficult to be a leader,
Lex Fridman (2:15:44.260)
but I still wanted to hold him accountable for that
Lex Fridman (2:15:47.340)
as a great communicator of science and as a great leader.
Lex Fridman (2:15:50.700)
What do you think he didn't do right?
Lex Fridman (2:15:52.300)
I'm curious.
Lex Fridman (2:15:55.060)
So the core of the problem is the several characteristics
Lex Fridman (2:16:00.060)
of the way he was communicating to the public.
Lex Fridman (2:16:06.540)
So one is the general inauthenticity.
Lex Fridman (2:16:10.340)
Two is a thing that, it's very hard to put into words,
Lex Fridman (2:16:14.500)
but there's certain ways of speaking to people
Lex Fridman (2:16:18.700)
that sounds like you're hiding something from them.
Vincent Racaniello (2:16:21.740)
That sounds like you're full of shit.
Lex Fridman (2:16:23.980)
That's the authenticity piece.
Vincent Racaniello (2:16:25.500)
Like, it sounds like you're not really speaking
Lex Fridman (2:16:30.620)
to the full truth of what you know
Lex Fridman (2:16:34.460)
and that you did some shady shit in your past
Lex Fridman (2:16:38.420)
that you're trying to hide.
Lex Fridman (2:16:40.860)
So that's a way of communicating
Lex Fridman (2:16:42.820)
that I think the internet and people in general
Vincent Racaniello (2:16:45.020)
are becoming much better at detecting.
Lex Fridman (2:16:46.780)
Yeah, it's like you said, they're good BS detectors.
Vincent Racaniello (2:16:48.620)
Yeah, good BS detectors.
Lex Fridman (2:16:51.500)
But contributing to that is speaking from authority,
Vincent Racaniello (2:16:55.380)
speaking with authority and confidence
Lex Fridman (2:17:01.540)
where neither is deserved.
Lex Fridman (2:17:04.500)
So first of all, nobody's an authority on this new virus.
Lex Fridman (2:17:10.140)
We're facing a deadly pandemic,
Lex Fridman (2:17:12.220)
and especially in the early stages,
Lex Fridman (2:17:15.260)
it was unclear how deadly it would be.
Vincent Racaniello (2:17:17.540)
It was unclear, probably still unclear,
Lex Fridman (2:17:19.660)
fully how it's transmitted.
Vincent Racaniello (2:17:22.140)
The full dynamics of the virus,
Lex Fridman (2:17:24.420)
the full understanding of which solutions work and not,
Lex Fridman (2:17:28.540)
how well masks of different kinds work,
Lex Fridman (2:17:31.220)
how easy or difficult it is to create tests,
Lex Fridman (2:17:34.260)
how many months or years it's gonna take
Lex Fridman (2:17:36.500)
to create a vaccine,
Lex Fridman (2:17:38.780)
how well in history or currently do quarantine methods
Lex Fridman (2:17:43.140)
or lockdown methods work,
Lex Fridman (2:17:45.620)
what are the different data mechanisms
Lex Fridman (2:17:48.060)
that are data collection mechanisms
Vincent Racaniello (2:17:50.740)
that are being implemented,
Lex Fridman (2:17:52.060)
what are the clear plans that need to happen,
Lex Fridman (2:17:55.660)
what the epidemiology that's happening,
Lex Fridman (2:17:58.340)
what is the uncertainty around that?
Vincent Racaniello (2:18:02.340)
Then there's the geopolitical stuff with China.
Lex Fridman (2:18:09.140)
I personally believe there should have been
Vincent Racaniello (2:18:11.460)
much more openness about the origins of the virus,
Lex Fridman (2:18:15.300)
whether they're leaked from a lab or not.
Vincent Racaniello (2:18:17.100)
I think communicating that you're open to these ideas
Lex Fridman (2:18:21.180)
is actually the way to get people to trust you,
Vincent Racaniello (2:18:25.340)
that you are legitimately open to ideas
Lex Fridman (2:18:28.220)
that are very unpleasant, that go against the mainstream.
Vincent Racaniello (2:18:32.540)
Showing that openness is going to get people to trust you
Lex Fridman (2:18:35.740)
when you finally decrease the variance in your uncertainty,
Vincent Racaniello (2:18:40.980)
like decrease uncertainty and have,
Lex Fridman (2:18:42.820)
we still have a lot of uncertainty,
Lex Fridman (2:18:44.420)
but this is the best course of action.
Lex Fridman (2:18:46.460)
Vaccines still have a lot of uncertainty around them.
Vincent Racaniello (2:18:49.660)
mRNA is a new technology,
Lex Fridman (2:18:51.260)
but we have increasing amounts of data,
Lex Fridman (2:18:53.300)
and here's the data sources,
Lex Fridman (2:18:54.940)
and laying them out in a very clear way
Vincent Racaniello (2:18:58.740)
of this is the best course of action that we have now.
Lex Fridman (2:19:01.260)
We don't know if it's the perfect course of action,
Lex Fridman (2:19:04.060)
but it's by far the best course of action.
Lex Fridman (2:19:06.420)
And that would come from a leader
Vincent Racaniello (2:19:09.460)
that has earned the capital of trust from people.
Lex Fridman (2:19:13.060)
I mean, I think in recent history,
Lex Fridman (2:19:15.900)
the worst pandemic is 1918 flu, right?
Lex Fridman (2:19:19.740)
But that's mainly because we didn't know what to do.
Vincent Racaniello (2:19:22.540)
We didn't have many tools at our disposal.
Lex Fridman (2:19:24.420)
And that was tied up with World War I.
Vincent Racaniello (2:19:26.420)
That's right, that's right.
Lex Fridman (2:19:27.900)
So the leadership there, I mean.
Lex Fridman (2:19:30.300)
But I don't know what is a lot of deaths, right?
Lex Fridman (2:19:32.820)
And any one person is someone's family,
Lex Fridman (2:19:35.420)
so to them it's a lot, right?
Lex Fridman (2:19:37.420)
But that logic, we don't apply that logic generally,
Vincent Racaniello (2:19:41.740)
because there's a lot of people suffering
Lex Fridman (2:19:43.420)
and dying throughout the world,
Lex Fridman (2:19:44.860)
and we turn the other way all the time.
Lex Fridman (2:19:47.780)
And that's the story of history.
Lex Fridman (2:19:49.100)
So saying you all of a sudden.
Lex Fridman (2:19:51.580)
What bothers me though, I mean, personally,
Vincent Racaniello (2:19:53.780)
I don't like anyone dying anywhere,
Lex Fridman (2:19:56.180)
but, and especially considering what technology
Vincent Racaniello (2:20:00.100)
we're able to muster, yet we still kill each other.
Lex Fridman (2:20:02.340)
It's just a dichotomy to me.
Lex Fridman (2:20:04.500)
Yeah, but I mean, this is the, what is it, Paul Farmer?
Lex Fridman (2:20:08.940)
There's these great stories.
Vincent Racaniello (2:20:10.140)
I mean, that's the,
Lex Fridman (2:20:11.380)
that's the burden of being in healthcare,
Vincent Racaniello (2:20:17.460)
being a doctor, is you have to help.
Lex Fridman (2:20:23.060)
You can't help but help a person in front of you
Vincent Racaniello (2:20:25.260)
who's hurting, but you also are burdened
Lex Fridman (2:20:28.580)
by the knowledge that you helping them,
Vincent Racaniello (2:20:31.420)
you spending money and effort and time on them,
Lex Fridman (2:20:34.860)
means you're not going to help others,
Lex Fridman (2:20:36.860)
and you cannot possibly allocate
Lex Fridman (2:20:38.540)
that amount of time to everybody.
Lex Fridman (2:20:40.220)
So you're choosing which person lives and which person dies.
Lex Fridman (2:20:44.060)
And you're doing so,
Vincent Racaniello (2:20:45.420)
the reason you're helping the person in front of you
Lex Fridman (2:20:47.740)
is because they're in front of you.
Lex Fridman (2:20:49.460)
And so the reason right now we care a lot about COVID
Lex Fridman (2:20:53.260)
is because the eye of the world has turned to COVID,
Lex Fridman (2:20:56.620)
but we're not seeing all the other atrocities
Lex Fridman (2:20:59.300)
going on in the world.
Vincent Racaniello (2:21:00.460)
They're not necessarily related to deaths,
Lex Fridman (2:21:02.780)
they're related to suffering, human suffering,
Vincent Racaniello (2:21:05.260)
which you could argue is worse than death,
Lex Fridman (2:21:07.420)
prolonged suffering.
Lex Fridman (2:21:08.660)
So there's all of these questions.
Lex Fridman (2:21:11.620)
And the fundamental question here is,
Lex Fridman (2:21:15.740)
are we overreacting to COVID in our policies?
Lex Fridman (2:21:19.340)
So this is the, when we turn our eye
Lex Fridman (2:21:23.700)
and care about this particular thing and not other things,
Lex Fridman (2:21:26.900)
are we dismissing the pain that business owners
Lex Fridman (2:21:29.180)
who've lost their businesses are going to feel?
Lex Fridman (2:21:31.660)
And then the long, talking about long COVID,
Vincent Racaniello (2:21:35.660)
the long term effects, economic effects on the millions
Lex Fridman (2:21:39.380)
of people that will suffer, that suffer financially,
Lex Fridman (2:21:42.460)
but also suffer from their dreams
Lex Fridman (2:21:44.820)
being completely collapsed.
Lex Fridman (2:21:46.660)
So a lot of people seek gain meaning from work.
Lex Fridman (2:21:50.700)
And if you take away that work,
Vincent Racaniello (2:21:52.820)
there's anger that can be born, there's pain.
Lex Fridman (2:21:55.660)
And so what does that lead to?
Vincent Racaniello (2:21:57.180)
That can lead to the rising up of charismatic leaders
Lex Fridman (2:22:01.860)
that channel that anger towards destructive things.
Vincent Racaniello (2:22:05.100)
That's been done throughout history.
Lex Fridman (2:22:06.700)
So you have to balance that with the policies
Vincent Racaniello (2:22:10.220)
that you have in COVID.
Lex Fridman (2:22:12.060)
And then, I mean, very much my main opposition
Vincent Racaniello (2:22:16.220)
to Fauci is not on the details, but the final result,
Lex Fridman (2:22:20.700)
which is I just observe that there's a significant decrease
Vincent Racaniello (2:22:25.020)
in trust in science as a, not the institution,
Lex Fridman (2:22:30.500)
but the very sort of mechanisms of science.
Vincent Racaniello (2:22:32.700)
I think science is both beautiful and powerful.
Lex Fridman (2:22:35.860)
And the reason why we have so many amazing things
Lex Fridman (2:22:38.220)
and such a high quality of life.
Lex Fridman (2:22:40.460)
And distrust in that, that the thing we need now
Vincent Racaniello (2:22:44.020)
to get out of all the troubles we're in,
Lex Fridman (2:22:46.580)
continue getting out of the troubles we're in is science,
Vincent Racaniello (2:22:49.660)
the scientific process, broadly defined like innovation,
Lex Fridman (2:22:53.300)
technological innovation, scientific innovation,
Vincent Racaniello (2:22:55.660)
all of that, distrust in that is totally
Lex Fridman (2:23:00.860)
the wrong thing we need.
Lex Fridman (2:23:02.460)
And so anybody who gets in,
Lex Fridman (2:23:04.780)
who causes a distrust in science to me,
Vincent Racaniello (2:23:12.220)
carries the responsibility of that
Lex Fridman (2:23:14.220)
and should be in, because the response,
Vincent Racaniello (2:23:16.980)
I mean, should be fired, should be,
Lex Fridman (2:23:20.060)
or at least openly have to carry the burden of that,
Vincent Racaniello (2:23:24.380)
of having caused of that kind of level of mistrust.
Lex Fridman (2:23:27.460)
Now, it's maybe unfair to place it on any one individual,
Lex Fridman (2:23:30.460)
but you have to, I think in your pocket said,
Lex Fridman (2:23:34.060)
the buck stops at the top, like the leaders have to.
Vincent Racaniello (2:23:37.660)
No, no, there's a clear leader here, yes, absolutely.
Lex Fridman (2:23:40.980)
So even if it's not directly his fault,
Vincent Racaniello (2:23:44.060)
he has to carry the price of that.
Lex Fridman (2:23:48.340)
Do you think we should at this point say,
Vincent Racaniello (2:23:50.900)
okay, we have vaccines,
Lex Fridman (2:23:53.420)
you can decide whether you take them or not,
Lex Fridman (2:23:55.420)
let's move forward?
Lex Fridman (2:23:57.420)
Maybe you can help me understand this,
Lex Fridman (2:23:59.180)
because it seems like, why is that not the right solution?
Lex Fridman (2:24:04.540)
Completely open society, the vaccines,
Vincent Racaniello (2:24:07.220)
at least in the United States,
Lex Fridman (2:24:09.780)
as I understand are widely available.
Lex Fridman (2:24:14.140)
So this is the American way, you have the decision to make.
Lex Fridman (2:24:18.340)
If you have conditions that make you worried to get COVID
Lex Fridman (2:24:23.260)
and go to the hospital, then you should get vaccinated
Lex Fridman (2:24:26.180)
because here's the data that shows
Vincent Racaniello (2:24:27.820)
that it's much less likely for you to die
Lex Fridman (2:24:31.980)
if you get vaccinated,
Vincent Racaniello (2:24:34.260)
if you don't want to get vaccinated
Lex Fridman (2:24:35.780)
because you're worried about longterm effects of vaccine
Vincent Racaniello (2:24:39.300)
that you don't have to,
Lex Fridman (2:24:40.340)
but then you suffer the consequences of that,
Lex Fridman (2:24:43.100)
and that's it.
Lex Fridman (2:24:44.420)
So here's what I think is driving,
Vincent Racaniello (2:24:47.260)
I think it's all about kids,
Lex Fridman (2:24:50.220)
because they're gonna go back to school in the fall
Lex Fridman (2:24:51.940)
and many of them can't be vaccinated.
Lex Fridman (2:24:53.980)
So if they get infected, they do have less frequency
Vincent Racaniello (2:24:59.060)
of disease, but it's not zero.
Lex Fridman (2:25:01.260)
They do get sick and they can have longterm consequences.
Lex Fridman (2:25:04.740)
And at that age, it would be a shame, right?
Lex Fridman (2:25:09.340)
And not even their choice,
Vincent Racaniello (2:25:10.620)
they can't decide to get vaccinated or not
Lex Fridman (2:25:13.460)
because they can't have access to it.
Lex Fridman (2:25:15.220)
So I think that's what would drive my efforts
Lex Fridman (2:25:19.380)
to try and get more people, at least in schools, vaccinated,
Lex Fridman (2:25:22.540)
but I might be wrong, it may not be that.
Lex Fridman (2:25:24.660)
So can you kind of dig into that a little bit?
Lex Fridman (2:25:26.540)
So there's,
Lex Fridman (2:25:30.740)
so you're saying that there should be an effort
Vincent Racaniello (2:25:33.260)
for increased vaccinations of kids going to school,
Lex Fridman (2:25:37.620)
just not for societal benefit,
Lex Fridman (2:25:39.900)
but for the benefit of each individual kid, right?
Lex Fridman (2:25:42.260)
So right now, kids under 12, right,
Lex Fridman (2:25:46.140)
are not yet vaccinated, is that correct?
Lex Fridman (2:25:48.540)
Yeah, I think so.
Lex Fridman (2:25:49.940)
And it's not gonna be in time for school opening
Lex Fridman (2:25:53.420)
that they get vaccinated.
Lex Fridman (2:25:56.700)
And then, I suppose the teachers
Lex Fridman (2:25:59.700)
are all gonna be vaccinated,
Vincent Racaniello (2:26:01.380)
makes sense for them to do that,
Lex Fridman (2:26:02.780)
but I'm just worried the kids
Vincent Racaniello (2:26:04.100)
are gonna be transmitting it amongst them
Lex Fridman (2:26:05.980)
and many states don't allow mask mandate in school.
Lex Fridman (2:26:08.900)
So I think that's what's driving the larger narrative
Lex Fridman (2:26:14.060)
in the US to protect kids.
Vincent Racaniello (2:26:16.740)
It's kind of what I hear from Daniel Griffin,
Lex Fridman (2:26:18.940)
because increasing numbers of kids
Vincent Racaniello (2:26:21.620)
are being admitted to hospitals now,
Lex Fridman (2:26:23.980)
because they're becoming the major unvaccinated population.
Vincent Racaniello (2:26:28.260)
They're hanging out over the summer
Lex Fridman (2:26:29.620)
and that's just gonna get worse in the fall.
Lex Fridman (2:26:32.260)
And so you could have a lot of kids with long COVID
Lex Fridman (2:26:35.380)
and disabled their entire lives, right, so.
Lex Fridman (2:26:38.300)
And of course, hearing from people who are vaccine hesitant,
Lex Fridman (2:26:42.060)
I hear exactly the kids statement,
Lex Fridman (2:26:44.820)
but they're saying they don't want
Lex Fridman (2:26:47.100)
the long term effects of the vaccine to affect the kids.
Vincent Racaniello (2:26:53.220)
That's of this new vaccine.
Lex Fridman (2:26:56.020)
Which I would say is, as I said before,
Vincent Racaniello (2:26:58.620)
you can't say never,
Lex Fridman (2:27:00.620)
but we do know that long COVID exists.
Vincent Racaniello (2:27:05.900)
We don't know for how long,
Lex Fridman (2:27:06.860)
because we've only looked out six or eight months.
Vincent Racaniello (2:27:09.300)
We know that exists and the frequency is increasing.
Lex Fridman (2:27:12.380)
It certainly exists in young kids
Lex Fridman (2:27:14.260)
and we have no idea about long vaccine effects.
Lex Fridman (2:27:16.540)
So I think they have to make their decision based on that.
Lex Fridman (2:27:22.820)
But yeah.
Lex Fridman (2:27:24.420)
But your question is why don't we just open up society,
Vincent Racaniello (2:27:28.180)
say here we have these vaccines
Lex Fridman (2:27:29.580)
if you wanna protect yourself.
Vincent Racaniello (2:27:30.780)
I think it's mainly the school
Lex Fridman (2:27:32.140)
that's driving the whole narrative, that's my opinion.
Lex Fridman (2:27:35.300)
In which direction, not to open up or?
Lex Fridman (2:27:37.740)
No, to open up, but to try and get their efforts
Lex Fridman (2:27:41.380)
at the federal level to get people vaccinated, right?
Lex Fridman (2:27:43.940)
But see, how high are the risks for kids?
Vincent Racaniello (2:27:45.940)
I mean, my understanding was it's,
Lex Fridman (2:27:48.060)
I mean, yes, it's nonzero, but it's very low.
Lex Fridman (2:27:52.220)
But what is the numbers?
Lex Fridman (2:27:53.620)
Now, 70,000 hospitalizations so far
Vincent Racaniello (2:27:57.660)
in kids as of last week.
Lex Fridman (2:27:59.740)
So yes, it's low, but polio was low.
Vincent Racaniello (2:28:05.380)
Polio was 20, 30,000 kids a year paralyzed.
Lex Fridman (2:28:08.740)
And well, many people have actually argued
Vincent Racaniello (2:28:11.460)
that that vaccine wasn't necessary.
Lex Fridman (2:28:13.540)
Now, that wasn't a substantial enough health problem.
Lex Fridman (2:28:17.300)
But paralyzed is different than hospital.
Lex Fridman (2:28:18.980)
So what does hospitalized mean?
Vincent Racaniello (2:28:20.860)
Long COVID.
Lex Fridman (2:28:21.700)
But this is the long COVID question.
Vincent Racaniello (2:28:23.060)
I mean, this is the open question.
Lex Fridman (2:28:24.540)
It was long COVID in kids.
Lex Fridman (2:28:26.420)
What is that?
Lex Fridman (2:28:27.820)
Well, a lot of the same issues,
Vincent Racaniello (2:28:30.660)
cognitive issues, motor issues,
Lex Fridman (2:28:34.180)
respiratory, GI dysfunction.
Lex Fridman (2:28:37.700)
How long?
Lex Fridman (2:28:39.300)
We don't know.
Vincent Racaniello (2:28:41.100)
I mean, it could end in a year.
Lex Fridman (2:28:43.260)
As you know, there are other post acute infectious sequelae
Vincent Racaniello (2:28:47.460)
that we know about.
Lex Fridman (2:28:48.660)
Chronic fatigue, ME, CFS is thought
Vincent Racaniello (2:28:51.420)
to be a post infectious sequelae,
Lex Fridman (2:28:53.220)
which has gone for many decades now
Vincent Racaniello (2:28:55.140)
in many millions of people.
Lex Fridman (2:28:56.540)
This could be another one of those.
Lex Fridman (2:28:58.740)
So I'm just saying it might be worth erring
Lex Fridman (2:29:02.060)
on the side of not letting the kids get infected.
Vincent Racaniello (2:29:05.860)
Yeah, well, I'm trying to keep an open mind here
Lex Fridman (2:29:09.860)
and I appreciate you doing the same.
Vincent Racaniello (2:29:12.060)
Of course, I lean on definitely not requiring people
Lex Fridman (2:29:18.500)
to get vaccinated,
Lex Fridman (2:29:19.340)
but I do think getting vaccinated
Lex Fridman (2:29:21.540)
is just the wiser choice,
Vincent Racaniello (2:29:24.980)
looking at all the different trajectories before us.
Lex Fridman (2:29:28.460)
Getting vaccinated seems like from the data,
Vincent Racaniello (2:29:33.220)
it seems like the obvious choice, frankly.
Lex Fridman (2:29:35.500)
But I'm also trying to keep an open mind
Vincent Racaniello (2:29:38.100)
because some things in the past that seemed obvious
Lex Fridman (2:29:40.100)
would turn out to be completely wrong.
Lex Fridman (2:29:42.100)
So I'm trying to keep an open mind here.
Lex Fridman (2:29:44.820)
So for example, one of the things,
Vincent Racaniello (2:29:48.100)
I'd love to get your thoughts on this is antiviral ideas.
Lex Fridman (2:29:52.980)
So ideas outside of the vaccine.
Lex Fridman (2:29:56.020)
So ivermectin, something that Brett Weinstein
Lex Fridman (2:30:00.380)
and a few others have been talking about.
Vincent Racaniello (2:30:02.100)
There's been a few studies.
Lex Fridman (2:30:03.180)
Some of them have been shown not to be very good studies,
Lex Fridman (2:30:07.100)
but nevertheless, there seems to be some promise.
Lex Fridman (2:30:11.460)
And I wanted to talk to Brett
Vincent Racaniello (2:30:14.500)
about this particular topic for two reasons.
Lex Fridman (2:30:17.300)
One, I was really bothered by censorship of this.
Vincent Racaniello (2:30:19.940)
That's a whole nother topic.
Lex Fridman (2:30:22.060)
I just, I'm bothered by censorship.
Vincent Racaniello (2:30:25.940)
There's a gray area, of course,
Lex Fridman (2:30:28.700)
but it just feels like that should not have been censored
Vincent Racaniello (2:30:32.180)
from YouTube, like discussions of ivermectin.
Lex Fridman (2:30:34.900)
We can set that aside.
Vincent Racaniello (2:30:36.740)
The other thing I was bothered by
Lex Fridman (2:30:39.260)
the lack of open mindedness
Vincent Racaniello (2:30:42.100)
on exploring things like ivermectin in the early days,
Lex Fridman (2:30:46.780)
especially when at least I thought
Vincent Racaniello (2:30:49.140)
the vaccine would take a long time.
Lex Fridman (2:30:51.660)
I mean, it's not just ivermectin.
Vincent Racaniello (2:30:53.140)
It's really seriously at a large scale,
Lex Fridman (2:30:57.500)
rigorously exploring the effectiveness of masks.
Lex Fridman (2:31:01.340)
And the big one for me is testing.
Lex Fridman (2:31:03.700)
Like the fact that that wasn't explored aggressively
Vincent Racaniello (2:31:07.020)
to lead to mass manufacturing like May, 2020 is absurd.
Lex Fridman (2:31:11.500)
Anyway, so I was bothered by these solutions
Vincent Racaniello (2:31:14.780)
not being explored and not by now
Lex Fridman (2:31:16.860)
having really good ivermectin studies.
Lex Fridman (2:31:19.620)
Can I talk about ivermectin?
Lex Fridman (2:31:20.980)
Yeah, I would love that, yeah.
Vincent Racaniello (2:31:21.820)
Sure, so full disclosure,
Lex Fridman (2:31:23.060)
my wife worked on ivermectin at Merck for 20 years.
Vincent Racaniello (2:31:26.580)
Okay, so they just want people to know,
Lex Fridman (2:31:30.940)
but I don't talk to her all the time about it.
Lex Fridman (2:31:34.580)
And anyway, she hasn't been at Merck for a long time.
Lex Fridman (2:31:37.220)
As you know, ivermectin is a very safe drug
Lex Fridman (2:31:39.900)
used to treat certain parasitic infections, right?
Lex Fridman (2:31:43.580)
And it is approved, it's amazing.
Vincent Racaniello (2:31:47.300)
You can take one dose a year
Lex Fridman (2:31:48.660)
and be protected against river blindness in Africa
Lex Fridman (2:31:51.660)
and certain parts of Africa.
Lex Fridman (2:31:52.700)
It's remarkably effective.
Lex Fridman (2:31:54.660)
And so it's quite a safe drug
Lex Fridman (2:31:57.820)
at the doses that are approved.
Vincent Racaniello (2:32:01.260)
Now, early last year, a study was done,
Lex Fridman (2:32:04.500)
I believe in Australia, which showed in cells in the lab,
Vincent Racaniello (2:32:07.380)
if you infect with SARS CoV2 and then put ivermectin in,
Lex Fridman (2:32:11.100)
it would inhibit the virus production substantially.
Lex Fridman (2:32:13.860)
It was quite clear, right?
Lex Fridman (2:32:16.020)
But the concentrations they were using were rather high
Lex Fridman (2:32:19.660)
and could not be achieved by the approved dosing.
Lex Fridman (2:32:24.660)
So you would need to do a dosing study
Vincent Racaniello (2:32:27.860)
to make sure it's safe.
Lex Fridman (2:32:28.700)
And the reason is that ivermectin binds to receptors
Vincent Racaniello (2:32:32.060)
in your brain and it can have high doses.
Lex Fridman (2:32:34.300)
So some people take high doses inappropriately
Lex Fridman (2:32:37.500)
and they have neurological consequences.
Lex Fridman (2:32:39.660)
So if you needed 10 times more ivermectin,
Vincent Racaniello (2:32:42.660)
you'd have to make sure it would be safe in people.
Lex Fridman (2:32:44.980)
So this is a question of safety too.
Vincent Racaniello (2:32:46.460)
Right, so I think it has always been the case
Lex Fridman (2:32:51.340)
that it should have been properly studied, but it wasn't.
Vincent Racaniello (2:32:54.580)
There were lots of trials here and there,
Lex Fridman (2:32:56.140)
lots of improperly controlled trials
Vincent Racaniello (2:32:58.700)
where someone would just treat some patients
Lex Fridman (2:33:00.780)
and say, hey, they all did fine, but have no control arm.
Lex Fridman (2:33:03.780)
And there were some controlled trials,
Lex Fridman (2:33:05.260)
but they were very small.
Lex Fridman (2:33:06.500)
So right now, a 4,000 person trial is enrolling
Lex Fridman (2:33:12.660)
to test in a randomly controlled trial setting,
Vincent Racaniello (2:33:16.660)
whether it works or not.
Lex Fridman (2:33:17.820)
There's still plenty of cases that you can do that.
Lex Fridman (2:33:20.340)
So you can ask whether there are any side effects.
Lex Fridman (2:33:23.060)
I think that's completely fine.
Lex Fridman (2:33:25.020)
And if it says it works, then we should use it.
Lex Fridman (2:33:28.540)
In the meantime, I always tell people,
Vincent Racaniello (2:33:31.340)
if you wanna use ivermectin, you can do it off label.
Lex Fridman (2:33:33.820)
It's FDA approved.
Lex Fridman (2:33:35.700)
And if your physician says,
Lex Fridman (2:33:36.780)
I'm gonna give you this off label,
Vincent Racaniello (2:33:38.740)
I don't have any objection,
Lex Fridman (2:33:41.580)
but I don't know if it's gonna work.
Vincent Racaniello (2:33:43.780)
Now, a friend of ours last week in New Jersey got COVID.
Lex Fridman (2:33:49.260)
He went to his local hospital
Lex Fridman (2:33:50.540)
and their regimen was remdesivir, dexamethasone, ivermectin.
Lex Fridman (2:33:56.580)
It's written, that's what they do for every COVID patient.
Vincent Racaniello (2:33:59.140)
They just give it to them automatically.
Lex Fridman (2:34:01.140)
And so he recovered.
Lex Fridman (2:34:04.300)
So who's to say it was or was not ivermectin, right?
Lex Fridman (2:34:08.320)
So I don't have any strong ideological opposition.
Vincent Racaniello (2:34:12.820)
I just think it should be tested
Lex Fridman (2:34:14.620)
for what you wanna use it for.
Lex Fridman (2:34:16.660)
And that's being done, and I think that's fine.
Lex Fridman (2:34:19.260)
Is it strange to you that ivermectin
Vincent Racaniello (2:34:23.500)
or other things like it
Lex Fridman (2:34:24.780)
weren't tested aggressively in the beginning?
Vincent Racaniello (2:34:27.660)
From a broad scientific community aspect,
Lex Fridman (2:34:33.940)
I can be a little bit conspiratorial,
Lex Fridman (2:34:35.980)
and this is what people talk about with ivermectin,
Lex Fridman (2:34:39.060)
is with the vaccines,
Vincent Racaniello (2:34:40.420)
there's quite a lot of money to be made.
Lex Fridman (2:34:42.700)
With ivermectin, there's not as much money to be made.
Lex Fridman (2:34:45.660)
Is that too conspiratorial?
Lex Fridman (2:34:48.380)
Like why didn't we try more solutions in the beginning?
Lex Fridman (2:34:51.500)
Well, all the money was put into vaccines, right?
Lex Fridman (2:34:55.580)
Very little was put into antivirals,
Vincent Racaniello (2:34:57.340)
because the decision was made at a very high level,
Lex Fridman (2:34:59.520)
probably involving Dr. Fauci.
Lex Fridman (2:35:01.620)
We're gonna put 24 billion into vaccines, right?
Lex Fridman (2:35:06.220)
And I think part of the reasoning is
Vincent Racaniello (2:35:08.020)
they give you years worth of protection,
Lex Fridman (2:35:10.100)
whereas an antiviral works
Lex Fridman (2:35:11.380)
and you have to keep dosing and so forth.
Lex Fridman (2:35:13.240)
But ivermectin is not trivial in this.
Vincent Racaniello (2:35:16.000)
I agree, it should have been tested early on,
Lex Fridman (2:35:18.620)
but we had a really bad experience with hydroxychloroquine,
Vincent Racaniello (2:35:21.820)
which we can talk about too.
Lex Fridman (2:35:25.380)
Ivermectin is very hard to synthesize.
Vincent Racaniello (2:35:28.740)
Most drugs, you synthesize chemically.
Lex Fridman (2:35:31.620)
You devise a formulation and a synthesis,
Lex Fridman (2:35:34.660)
and they do it, they scale it up, and it's fine.
Lex Fridman (2:35:36.660)
Ivermectin is really hard.
Lex Fridman (2:35:38.340)
And so what they do instead is they take the culture
Lex Fridman (2:35:41.540)
of the bacterium that makes it,
Lex Fridman (2:35:43.820)
and they grow it up, and they ferment it,
Lex Fridman (2:35:45.420)
and then they purify it.
Lex Fridman (2:35:47.180)
And Merck owns the bacteria.
Lex Fridman (2:35:51.380)
A number of years ago, two employees of Merck stole it
Lex Fridman (2:35:55.420)
and left the company and tried to market it,
Lex Fridman (2:35:58.140)
and they were arrested and they got put in jail.
Lex Fridman (2:35:59.980)
So they protect it very carefully.
Lex Fridman (2:36:02.740)
So you can't just make it.
Vincent Racaniello (2:36:05.580)
If you do, it's incredibly expensive.
Lex Fridman (2:36:07.660)
And now India, it's very cheap apparently.
Vincent Racaniello (2:36:10.140)
They use it quite liberally there,
Lex Fridman (2:36:12.540)
and I don't know how they're making it.
Vincent Racaniello (2:36:14.420)
Maybe they've licensed it from Merck and so forth.
Lex Fridman (2:36:16.660)
But that's why it hasn't been tested more widely, I think.
Vincent Racaniello (2:36:21.620)
There's complexities in terms of getting a lot of it
Lex Fridman (2:36:24.140)
and manufacturing a lot of it.
Vincent Racaniello (2:36:25.420)
Yes. Okay.
Lex Fridman (2:36:26.420)
So what was the hydroxychloroquine?
Lex Fridman (2:36:28.420)
So hydroxychloroquine was also shown early on
Lex Fridman (2:36:32.300)
to inhibit virus in cell culture.
Lex Fridman (2:36:36.240)
And that's not surprising.
Lex Fridman (2:36:37.340)
Hydroxychloroquine, of course, is used for malaria.
Lex Fridman (2:36:41.260)
And what it does, when your cell takes up things
Lex Fridman (2:36:46.260)
from the plasma membrane, including viruses,
Vincent Racaniello (2:36:49.620)
it goes through a pathway called the endocytic pathway,
Lex Fridman (2:36:52.140)
which involves a vesicle moving through the cell.
Lex Fridman (2:36:54.100)
And as it moves through the cell, its pH drops.
Lex Fridman (2:36:57.580)
And that lets a lot of viruses out actually.
Lex Fridman (2:37:00.180)
And hydroxychloroquine blocks that.
Lex Fridman (2:37:01.820)
So it blocks infection with a lot of viruses.
Lex Fridman (2:37:06.340)
So the problem with those early studies that were published
Lex Fridman (2:37:10.140)
is that they were done in kidney cells and culture,
Vincent Racaniello (2:37:14.100)
where the only way the virus can get in
Lex Fridman (2:37:16.280)
is through the endosome.
Lex Fridman (2:37:18.820)
And hydroxychloroquine inhibits that,
Lex Fridman (2:37:20.940)
and that's why it inhibits in kidney cells and culture.
Lex Fridman (2:37:24.420)
But lung cells and respiratory cells of humans
Lex Fridman (2:37:28.060)
where the virus reproduces can get in two different ways.
Vincent Racaniello (2:37:31.540)
It can get in from this endocytic pathway,
Lex Fridman (2:37:34.680)
which is inhibited by hydroxychloroquine,
Vincent Racaniello (2:37:37.860)
or it can get in at the cell surface,
Lex Fridman (2:37:40.340)
which is not inhibited by hydroxychloroquine.
Lex Fridman (2:37:43.140)
So when you treat patients, it has no effect in the lung
Lex Fridman (2:37:46.500)
because the virus can just bypass it.
Lex Fridman (2:37:50.160)
And all the usage initially were based on
Lex Fridman (2:37:54.580)
the studies done in kidney cells and culture.
Lex Fridman (2:37:57.220)
So that was just wrong, scientifically incorrect,
Lex Fridman (2:38:00.580)
yet it drove a lot of, and today many people
Vincent Racaniello (2:38:02.980)
still think they should be taking it, but.
Lex Fridman (2:38:04.980)
So that not panning out kind of resulted
Vincent Racaniello (2:38:09.220)
in a loss of optimism about other similar things panning out.
Lex Fridman (2:38:14.060)
Well, that and many other repurposed drugs were tried,
Lex Fridman (2:38:17.860)
and a lot of HIV antivirals were tried.
Lex Fridman (2:38:20.180)
I think the problem with hydroxychloroquine
Vincent Racaniello (2:38:23.460)
influenced the ivermectin narrative.
Lex Fridman (2:38:26.060)
People thought that the data was being hidden
Vincent Racaniello (2:38:29.340)
about hydroxychloroquine, so they said,
Lex Fridman (2:38:30.940)
well, they must be doing the same thing with ivermectin,
Lex Fridman (2:38:33.100)
but with hydroxychloroquine, it just scientifically
Lex Fridman (2:38:36.020)
could not work as an antiviral.
Vincent Racaniello (2:38:39.860)
The other problem that is more broad
Lex Fridman (2:38:42.080)
that is important to point out is that
Vincent Racaniello (2:38:45.820)
when you have COVID and you need an antiviral,
Lex Fridman (2:38:49.580)
it's usually because you can't breathe
Lex Fridman (2:38:50.900)
and you go in a hospital.
Lex Fridman (2:38:52.920)
Because if you're mildly ill,
Vincent Racaniello (2:38:53.940)
you're never gonna go to your doctor
Lex Fridman (2:38:55.340)
and ask for an antiviral.
Lex Fridman (2:38:56.820)
And the problem is when you can't breathe,
Lex Fridman (2:38:58.380)
it's no longer a viral issue.
Vincent Racaniello (2:39:00.380)
It is now an inflammatory issue,
Lex Fridman (2:39:02.260)
and no antiviral in the world is gonna help you.
Lex Fridman (2:39:05.300)
So that's why remdesivir doesn't work very well,
Lex Fridman (2:39:08.980)
because it's mainly given intravenously
Vincent Racaniello (2:39:10.540)
to people who go in a hospital.
Lex Fridman (2:39:13.100)
If you get ivermectin in the hospital,
Vincent Racaniello (2:39:16.740)
it's not gonna do anything for reducing virus,
Lex Fridman (2:39:18.980)
because by that time, you have very little virus
Vincent Racaniello (2:39:20.860)
to begin with.
Lex Fridman (2:39:21.780)
You have an inflammatory problem
Vincent Racaniello (2:39:23.140)
that you need to treat in other ways.
Lex Fridman (2:39:24.860)
So this is why a lot of the antivirals failed,
Vincent Racaniello (2:39:28.900)
because they're used too late.
Lex Fridman (2:39:30.860)
What you need is a pill you take
Vincent Racaniello (2:39:32.980)
on that first positive test,
Lex Fridman (2:39:34.460)
when you have a scratchy throat.
Vincent Racaniello (2:39:36.780)
You get a PCR in 15 minutes, I'm positive,
Lex Fridman (2:39:39.620)
take a pill, boom, that's gonna inhibit it.
Vincent Racaniello (2:39:42.740)
If you wait till you can't breathe,
Lex Fridman (2:39:44.900)
and that's why the monoclonals even don't work
Vincent Racaniello (2:39:47.580)
if you're in hospital that well,
Lex Fridman (2:39:49.140)
because it's too late.
Lex Fridman (2:39:50.140)
And the approach now is if you're in a high risk group,
Lex Fridman (2:39:54.360)
if you're over 65, if you are obese or have diabetes
Vincent Racaniello (2:39:58.900)
or any other comorbidities,
Lex Fridman (2:40:00.700)
your first sign of a scratchy throat positive,
Vincent Racaniello (2:40:03.780)
you get monoclonals, then they might help you.
Lex Fridman (2:40:07.300)
But if you wait till you go in a hospital, it's too late,
Vincent Racaniello (2:40:09.820)
because the viral curve drops.
Lex Fridman (2:40:12.060)
After that first symptom, within three days,
Vincent Racaniello (2:40:15.540)
you're no longer shedding enough virus to transmit.
Lex Fridman (2:40:19.580)
Drops really quickly.
Lex Fridman (2:40:20.700)
So that's the reason a lot of these antivirals failed,
Lex Fridman (2:40:23.180)
because they were tested in hospitalized patients.
Lex Fridman (2:40:25.860)
And we have nothing but remdesivir now, unfortunately.
Lex Fridman (2:40:29.500)
So it was the wrong approach.
Vincent Racaniello (2:40:30.940)
We should have been giving it to people
Lex Fridman (2:40:33.780)
who just tested positive from the start.
Vincent Racaniello (2:40:35.900)
Or just even for preventative and see.
Lex Fridman (2:40:38.140)
You could do that too.
Lex Fridman (2:40:39.660)
But I have to say, the other issue is,
Lex Fridman (2:40:42.040)
this molnupiravir is a drug in phase three now,
Vincent Racaniello (2:40:45.020)
it's an oral antiviral, it looks good.
Lex Fridman (2:40:48.420)
If we go ahead with just one,
Vincent Racaniello (2:40:51.140)
we're gonna get resistance within a few months,
Lex Fridman (2:40:53.320)
and it will be useless.
Vincent Racaniello (2:40:54.360)
We need to have at least two or three drugs
Lex Fridman (2:40:56.860)
that we can give in combinations.
Lex Fridman (2:40:58.820)
And we know that, because that's what took care of HIV,
Lex Fridman (2:41:01.700)
that's what took care of HCV, hepatitis C virus.
Vincent Racaniello (2:41:05.260)
It really reduces the emergence of resistance.
Lex Fridman (2:41:08.980)
Joe Rogan got quite a bit of heat recently
Vincent Racaniello (2:41:11.600)
about mentioning a paper and a broader idea,
Lex Fridman (2:41:16.620)
which I don't think is that controversial,
Lex Fridman (2:41:19.920)
but maybe we can expand on it.
Lex Fridman (2:41:22.820)
And the idea is that vaccines
Vincent Racaniello (2:41:26.180)
create selective pressure for a virus to mutate
Lex Fridman (2:41:32.420)
and for variants to form.
Vincent Racaniello (2:41:37.380)
First of all, from a biological perspective,
Lex Fridman (2:41:40.380)
can you explain this process?
Lex Fridman (2:41:42.100)
And from a societal perspective,
Lex Fridman (2:41:45.680)
what are we supposed to do about that?
Lex Fridman (2:41:47.620)
So let's get the terminology right.
Lex Fridman (2:41:49.580)
So as we talked about earlier,
Vincent Racaniello (2:41:51.860)
viruses are always mutating.
Lex Fridman (2:41:54.060)
So no vaccine or no drug makes a virus mutate.
Vincent Racaniello (2:41:57.660)
Right, that's the wrong perspective
Lex Fridman (2:41:59.460)
in which to look at it, got it.
Lex Fridman (2:42:01.180)
What the immune response is putting pressure,
Lex Fridman (2:42:04.940)
selection pressure on the virus.
Lex Fridman (2:42:07.020)
And if there's one particle with the right mutation
Lex Fridman (2:42:11.500)
that can escape the antibody, that will emerge, right?
Lex Fridman (2:42:15.260)
So that's what happens with influenza virus, right?
Lex Fridman (2:42:17.700)
We vaccinate every year,
Lex Fridman (2:42:20.220)
and there are not a lot of people that get infected,
Lex Fridman (2:42:22.160)
so they get natural immunity.
Lex Fridman (2:42:24.780)
And then the virus is incredibly varied.
Lex Fridman (2:42:28.900)
It mutates like crazy.
Lex Fridman (2:42:30.260)
And in some person somewhere,
Lex Fridman (2:42:32.120)
there's one variant that escapes the antibody,
Vincent Racaniello (2:42:34.380)
which has been induced either by infection or vaccination.
Lex Fridman (2:42:37.100)
It can be both.
Lex Fridman (2:42:38.860)
And that drives the emergence of the new variants,
Lex Fridman (2:42:41.260)
so the next year we need to change the vaccine.
Lex Fridman (2:42:43.860)
So I would say both natural infection and vaccination,
Lex Fridman (2:42:48.960)
sure, select for variants.
Vincent Racaniello (2:42:51.440)
Absolutely, there's no question,
Lex Fridman (2:42:53.500)
because they're inducing immunity.
Vincent Racaniello (2:42:55.420)
Now, what happened last year was at the beginning of 2020,
Lex Fridman (2:43:00.060)
very few people in the world were immune
Vincent Racaniello (2:43:02.340)
as the virus first started spreading.
Lex Fridman (2:43:05.960)
But you can see in the sequences of those isolates
Vincent Racaniello (2:43:09.140)
from the beginning of 2020,
Lex Fridman (2:43:11.040)
you can see all of the changes that are now present
Vincent Racaniello (2:43:14.660)
in the variants of concern at very, very low frequencies.
Lex Fridman (2:43:17.700)
They were already there,
Lex Fridman (2:43:18.700)
but there was no selection for them to emerge.
Lex Fridman (2:43:21.940)
Until November, when we now had many millions of people
Vincent Racaniello (2:43:25.340)
who had mostly been infected, but also some vaccinated,
Lex Fridman (2:43:29.780)
then we saw the alpha variant emerge in England,
Vincent Racaniello (2:43:33.060)
probably because of immune selection.
Lex Fridman (2:43:35.360)
Now, the virus that had the change
Vincent Racaniello (2:43:38.300)
that evaded the antibody had an advantage,
Lex Fridman (2:43:41.980)
and that virus drove through the population.
Lex Fridman (2:43:44.060)
So that's what we're seeing.
Lex Fridman (2:43:45.300)
All these variants are simply antigenic selection.
Lex Fridman (2:43:47.980)
So the variants, the mutations
Lex Fridman (2:43:50.780)
that are at the core of these, quote unquote, variants,
Vincent Racaniello (2:43:55.500)
they were always there all along the vaccine,
Lex Fridman (2:43:58.380)
or the infections did not create them.
Vincent Racaniello (2:44:00.440)
No, the infections don't create them, they're selected.
Lex Fridman (2:44:02.660)
It's like the vaccine wipe out a lot of the variants,
Lex Fridman (2:44:09.020)
and then by making your body immune to them,
Lex Fridman (2:44:13.740)
but some of them survive.
Vincent Racaniello (2:44:15.540)
Yeah, exactly.
Lex Fridman (2:44:16.820)
And then there's another tree that's built,
Lex Fridman (2:44:19.500)
and it's unclear what that tree leads to.
Lex Fridman (2:44:23.880)
I mean, it could make things much worse or much better,
Lex Fridman (2:44:26.980)
and we don't know.
Lex Fridman (2:44:28.340)
Well, with flu, we see year after year the virus changes,
Vincent Racaniello (2:44:31.220)
we change the vaccine, we deal with it,
Lex Fridman (2:44:33.580)
we change it again, there's an unending series.
Lex Fridman (2:44:35.540)
But see, that's a very different story.
Lex Fridman (2:44:37.260)
If, do you think COVID will be with some likelihood,
Vincent Racaniello (2:44:42.260)
like the flu, where it's basically variants,
Lex Fridman (2:44:47.860)
we'll never be able to eradicate it?
Vincent Racaniello (2:44:52.780)
It will never eradicate it in any case, ever.
Lex Fridman (2:44:57.380)
Well, come up with a vaccine
Vincent Racaniello (2:44:59.820)
that makes you immune to enough variants
Lex Fridman (2:45:03.140)
where there's not enough evolutionary room.
Vincent Racaniello (2:45:07.240)
Well, if you cut down the number of infections,
Lex Fridman (2:45:09.100)
then you reduce the diversity, sure, right?
Vincent Racaniello (2:45:12.180)
The problem is if, let's say you're a cynic
Lex Fridman (2:45:15.140)
and you say, well, vaccination is just selecting
Vincent Racaniello (2:45:18.100)
for variants, so let's stop it.
Lex Fridman (2:45:20.020)
But then you're gonna have infection,
Lex Fridman (2:45:21.460)
and that's gonna select for variants.
Lex Fridman (2:45:23.280)
And there, you're more likely to get very sick
Vincent Racaniello (2:45:26.260)
because we know the vaccines are really good
Lex Fridman (2:45:28.620)
at preventing you from dying.
Lex Fridman (2:45:30.060)
So that's why it still makes sense to use vaccines
Lex Fridman (2:45:34.060)
because they prevent you from dying.
Vincent Racaniello (2:45:36.900)
That's the bottom line.
Lex Fridman (2:45:38.180)
But can we ever make a vaccine that deals with all variants?
Vincent Racaniello (2:45:44.560)
Absolutely.
Lex Fridman (2:45:45.580)
And the reason I say that is because people
Vincent Racaniello (2:45:49.240)
who get naturally infected with SARS COVID,
Lex Fridman (2:45:53.420)
they develop COVID, they recover.
Vincent Racaniello (2:45:56.860)
If you give them one vaccine dose,
Lex Fridman (2:45:59.580)
they make an immune response
Vincent Racaniello (2:46:01.460)
that handles all the variants that are around right now.
Lex Fridman (2:46:05.740)
All of them.
Vincent Racaniello (2:46:06.580)
Much better than people who've gotten two doses of vaccine.
Lex Fridman (2:46:10.380)
For some reason, their immune response is suddenly broadened
Vincent Racaniello (2:46:14.340)
after the infection vaccination,
Lex Fridman (2:46:16.860)
and they can handle all the variants that we know of so far.
Lex Fridman (2:46:19.340)
So that tells me we can devise a strategy
Lex Fridman (2:46:22.780)
to do the same thing with a vaccine
Vincent Racaniello (2:46:24.540)
that makes a really broad vaccine
Lex Fridman (2:46:26.620)
that'll handle all the variants.
Vincent Racaniello (2:46:27.940)
Well, you actually, on the virology blog,
Lex Fridman (2:46:30.660)
I don't know if you're the author of that, but.
Vincent Racaniello (2:46:32.340)
I am, I am, yes.
Lex Fridman (2:46:33.900)
Oh, the blog, yes, but there's a particular post
Vincent Racaniello (2:46:36.820)
that's talking about reporting on a paper
Lex Fridman (2:46:39.400)
that a mix and match strategy.
Vincent Racaniello (2:46:40.860)
Oh, yes, that's one of my co writers, Trudy Ray, yeah.
Lex Fridman (2:46:44.180)
Yeah, it's an interesting idea
Vincent Racaniello (2:46:46.620)
that there's some early evidence now
Lex Fridman (2:46:49.380)
that mixing and matching vaccines,
Vincent Racaniello (2:46:52.380)
like one shot of Pfizer and one of like Moderna or something,
Lex Fridman (2:46:56.500)
that creates a much better immunity
Vincent Racaniello (2:47:00.460)
than does two shots of Pfizer.
Lex Fridman (2:47:02.820)
I think that's worth exploring, absolutely.
Lex Fridman (2:47:05.420)
And this is relevant, what we're doing with influenza,
Lex Fridman (2:47:09.100)
you know, instead of having to vaccinate people every year,
Lex Fridman (2:47:11.240)
why can't we devise a vaccine
Lex Fridman (2:47:12.860)
which you'd get once in your lifetime
Lex Fridman (2:47:14.780)
or maybe once every 10 years, okay?
Lex Fridman (2:47:17.420)
So the spike of influenza, it's a long protein,
Vincent Racaniello (2:47:22.440)
kind of like the spike of SARS CoV2,
Lex Fridman (2:47:24.740)
it's stuck in the virus membrane,
Lex Fridman (2:47:26.340)
and the very tip, that's the part that changes every year.
Lex Fridman (2:47:31.340)
This is where the antibodies bind.
Lex Fridman (2:47:33.740)
But the stem doesn't change.
Lex Fridman (2:47:37.540)
And if you make antibodies to the stem,
Vincent Racaniello (2:47:39.860)
they can also prevent infection.
Lex Fridman (2:47:41.660)
It's just that when people are infected
Vincent Racaniello (2:47:44.020)
or with the current vaccines,
Lex Fridman (2:47:45.940)
they don't make many antibodies to that stem part,
Lex Fridman (2:47:48.820)
but we're trying to figure out how to make those
Lex Fridman (2:47:51.380)
and we think they would be broadly protective
Lex Fridman (2:47:53.620)
and you'd never be able to,
Lex Fridman (2:47:55.400)
or more rarely be able to have a variant emerge
Vincent Racaniello (2:47:59.020)
that escaped it.
Lex Fridman (2:48:00.820)
And I think we can do the same thing
Vincent Racaniello (2:48:02.460)
with coronavirus too, for sure.
Lex Fridman (2:48:06.660)
Can I ask you about testing?
Vincent Racaniello (2:48:08.380)
Sure, sure.
Lex Fridman (2:48:10.220)
You mentioned PCR, what kind of tests are there?
Lex Fridman (2:48:13.300)
The antigen test, what are your thoughts on each?
Lex Fridman (2:48:18.160)
Maybe this is a good place to also mention like viral load
Lex Fridman (2:48:22.460)
and the history of the virus as it passes through your body
Lex Fridman (2:48:27.460)
in terms of what's being tested for
Lex Fridman (2:48:31.260)
and all those kinds of things.
Lex Fridman (2:48:33.380)
So the first tests that were developed were PCR,
Vincent Racaniello (2:48:39.100)
polymerase chain reaction.
Lex Fridman (2:48:40.260)
They're basically nucleic acid amplification tests.
Lex Fridman (2:48:43.780)
And they were very first ones.
Lex Fridman (2:48:44.820)
They stuck the swab all the way up into your brain almost.
Vincent Racaniello (2:48:49.260)
I had that done a couple of weeks ago.
Lex Fridman (2:48:50.860)
Oh my gosh, it's really nasty.
Lex Fridman (2:48:53.420)
But now they do an anterior Nares swab.
Lex Fridman (2:48:56.280)
They get a little, they get a bunch of cells
Lex Fridman (2:48:58.940)
and some mucus which has virus and parts of virus,
Lex Fridman (2:49:02.660)
stick it in a test tube and then they run a reaction
Vincent Racaniello (2:49:05.980)
which by the way involves reverse transcriptase
Lex Fridman (2:49:09.020)
because it converts the viral RNA to DNA
Lex Fridman (2:49:11.980)
and then you amplify it.
Lex Fridman (2:49:14.240)
And you can specify what part of the viral RNA
Vincent Racaniello (2:49:18.940)
you wanna amplify and then a machine will detect it
Lex Fridman (2:49:22.540)
and it can be done in 15 minutes.
Lex Fridman (2:49:25.100)
But you're detecting pieces of RNA, not infectious virus.
Lex Fridman (2:49:29.100)
So we're measuring viral RNA loads, right?
Lex Fridman (2:49:32.420)
And a common mistake that many people
Lex Fridman (2:49:36.060)
who should know better, physicians and scientists
Vincent Racaniello (2:49:38.700)
of all kinds, they think that indicates
Lex Fridman (2:49:41.180)
how much virus you have.
Vincent Racaniello (2:49:43.620)
It doesn't.
Lex Fridman (2:49:45.580)
It's a diagnostic of whether you have bits of RNA in you
Lex Fridman (2:49:48.620)
and it probably means you're infected.
Lex Fridman (2:49:51.320)
But you can't use it to shed light on what's going on
Lex Fridman (2:49:55.300)
and I'll tell you why in a bit.
Lex Fridman (2:49:56.880)
But first we have to explain some other things.
Lex Fridman (2:50:01.940)
So until you get to about a million copies of RNA,
Lex Fridman (2:50:06.380)
so you can measure the copy number in this test,
Vincent Racaniello (2:50:08.540)
this PCR test.
Lex Fridman (2:50:10.660)
It's a number called CT or cycle threshold.
Vincent Racaniello (2:50:13.860)
The test, the way the machine works, it goes through cycles
Lex Fridman (2:50:16.420)
and every cycle it amplifies what you put in
Lex Fridman (2:50:19.980)
and the more cycles you need to see something,
Lex Fridman (2:50:23.900)
that means there's not a lot of RNA there.
Lex Fridman (2:50:26.660)
So if you do a test and you have a cycle threshold of 35,
Lex Fridman (2:50:31.100)
you have very little RNA in you.
Vincent Racaniello (2:50:33.660)
Contrary, if you have a cycle threshold of 10,
Lex Fridman (2:50:36.160)
you have a ton of RNA and it only took 10 cycles
Vincent Racaniello (2:50:38.700)
to detect it.
Lex Fridman (2:50:40.700)
And you can extrapolate from that number,
Vincent Racaniello (2:50:42.780)
the number of copies you have per sample, say per swab.
Lex Fridman (2:50:46.100)
And if you don't have a million, you're not infectious.
Vincent Racaniello (2:50:49.120)
You're not gonna infect anyone.
Lex Fridman (2:50:50.740)
So in the early days, no matter what CT,
Lex Fridman (2:50:53.300)
what PCR result you had, they would quarantine you.
Lex Fridman (2:50:56.020)
And that was wrong because you're not shedding.
Vincent Racaniello (2:50:58.340)
You don't need to be quarantined,
Lex Fridman (2:51:00.020)
but wasn't thought through properly, right?
Lex Fridman (2:51:02.740)
And that's where you had like 14 days
Lex Fridman (2:51:04.540)
or something like that.
Vincent Racaniello (2:51:05.380)
14 days, which is now we know is too long
Lex Fridman (2:51:07.900)
because you don't shed for that long in a normal infection.
Vincent Racaniello (2:51:11.580)
Now it's 10 days should be fine.
Lex Fridman (2:51:14.120)
So what happens is you get infected,
Vincent Racaniello (2:51:16.140)
you don't know it of course.
Lex Fridman (2:51:17.820)
The virus starts to grow very quickly.
Lex Fridman (2:51:19.780)
And within four or five days,
Lex Fridman (2:51:21.900)
you reach a peak of shedding.
Vincent Racaniello (2:51:24.660)
You're making a lot of RNA and you may be asymptomatic.
Lex Fridman (2:51:28.220)
You're shedding, you can infect others.
Lex Fridman (2:51:30.040)
And then you may or may not have your symptom onset.
Lex Fridman (2:51:33.940)
So you shed for a couple of days before symptom onset.
Lex Fridman (2:51:36.240)
And then within three days, four days,
Lex Fridman (2:51:38.620)
the viral RNA crashes and you're no longer shedding,
Vincent Racaniello (2:51:41.460)
you're no longer transmitting.
Lex Fridman (2:51:42.940)
So that's the one kind of test we have.
Vincent Racaniello (2:51:44.540)
It can tell you if you're infected at the moment,
Lex Fridman (2:51:47.640)
but it won't tell you
Lex Fridman (2:51:49.020)
if you're gonna be infected tomorrow, right?
Lex Fridman (2:51:51.460)
Cause if you're negative today,
Vincent Racaniello (2:51:52.660)
you could be positive tomorrow.
Lex Fridman (2:51:54.020)
You just might be in a different part
Lex Fridman (2:51:56.140)
of the incubation period, right?
Lex Fridman (2:51:58.300)
So that's one test been used the most.
Vincent Racaniello (2:52:01.060)
You can now get 15 minute versions of them
Lex Fridman (2:52:05.020)
in a walk in or whatever fine.
Vincent Racaniello (2:52:06.860)
Then there are antigen tests,
Lex Fridman (2:52:08.040)
which look for the proteins that the virus is making.
Lex Fridman (2:52:11.620)
So as it's reproducing in your nose,
Lex Fridman (2:52:13.440)
it's not only making genomes, it's making proteins.
Lex Fridman (2:52:16.140)
And so these you can buy in the drug store.
Lex Fridman (2:52:18.340)
And these would have been great if they had,
Vincent Racaniello (2:52:22.140)
Michael Minna last year had the idea
Lex Fridman (2:52:24.300)
that if we could make a little stick,
Vincent Racaniello (2:52:26.460)
a little piece of paper that you would suck on
Lex Fridman (2:52:28.580)
and it would tell you if you're infected or not,
Vincent Racaniello (2:52:30.340)
if this could cost less than a buck,
Lex Fridman (2:52:32.540)
everybody could test themselves.
Vincent Racaniello (2:52:33.980)
Which they can cost less than a buck, by the way.
Lex Fridman (2:52:37.020)
Yeah, but they were never made, right?
Vincent Racaniello (2:52:38.820)
Right, they're never mass manufactured.
Lex Fridman (2:52:42.300)
So his idea is to do like daily tests.
Vincent Racaniello (2:52:44.740)
Yeah, daily and then the kid's going to school,
Lex Fridman (2:52:47.340)
he's positive or she's positive.
Vincent Racaniello (2:52:49.860)
Well, if it's cheap enough, you just take another test
Lex Fridman (2:52:51.820)
because they have a certain error frequency.
Vincent Racaniello (2:52:53.540)
If it's positive twice, you stay home
Lex Fridman (2:52:55.300)
and the next day you try again.
Lex Fridman (2:52:57.180)
And I think this would have revolutionized
Lex Fridman (2:52:59.860)
because the PCR tests are more expensive at the time
Lex Fridman (2:53:02.460)
and they take longer to do and so forth.
Lex Fridman (2:53:05.320)
But that never happened.
Lex Fridman (2:53:07.060)
But now we do have $20 Binax now
Lex Fridman (2:53:09.500)
and others that you can buy and people buy them.
Lex Fridman (2:53:12.420)
But that can still happen, right?
Lex Fridman (2:53:13.980)
And this is the very frustrating thing to me
Vincent Racaniello (2:53:16.020)
because I'm worried about variants,
Lex Fridman (2:53:18.980)
but I'm also worried about future,
Vincent Racaniello (2:53:20.660)
much more deadly pandemics.
Lex Fridman (2:53:23.600)
Like I know we kind of said, yes, COVID, lots of deaths,
Lex Fridman (2:53:28.460)
but like it could be a lot worse too.
Lex Fridman (2:53:31.380)
And so I'm thinking what is going to be the right response
Lex Fridman (2:53:35.780)
for the future pandemic of its kind?
Lex Fridman (2:53:38.580)
And what's the right response
Vincent Racaniello (2:53:39.900)
for continued number of variants
Lex Fridman (2:53:41.640)
and some of the variants might be deadlier
Lex Fridman (2:53:44.620)
or more transmissible?
Lex Fridman (2:53:45.940)
Well, we can, the antigen tests
Vincent Racaniello (2:53:49.980)
will pick up the variants.
Lex Fridman (2:53:51.860)
That's not a question.
Vincent Racaniello (2:53:52.700)
The PCR may be influenced by changes,
Lex Fridman (2:53:55.100)
but you can quickly adapt the primers that you use.
Lex Fridman (2:53:58.500)
So that's what I mean.
Lex Fridman (2:53:59.340)
Like to me, all of these discussions
Vincent Racaniello (2:54:00.980)
about vaccines and so on.
Lex Fridman (2:54:03.300)
Vaccines, we got very lucky that they took so little time.
Lex Fridman (2:54:08.060)
And you have to be aware no matter what
Lex Fridman (2:54:10.540)
that there's hesitancy with the vaccines
Vincent Racaniello (2:54:12.340)
in this country before.
Lex Fridman (2:54:13.780)
I mean, yeah, that's a reality.
Vincent Racaniello (2:54:15.700)
You can't just be like magically saying
Lex Fridman (2:54:17.580)
that you're going to overcome that.
Lex Fridman (2:54:20.420)
And I don't think there's any hesitancy
Lex Fridman (2:54:22.200)
and cheap tests at home.
Vincent Racaniello (2:54:24.040)
I agree.
Lex Fridman (2:54:24.880)
I think if someone, so the question is
Lex Fridman (2:54:27.020)
if someone tested positive, would they stay home?
Lex Fridman (2:54:29.220)
That's the question.
Lex Fridman (2:54:30.060)
What if their job depends on them going in?
Lex Fridman (2:54:32.380)
I mean, that's.
Vincent Racaniello (2:54:33.580)
Well, you have to look at sort of aggregate,
Lex Fridman (2:54:36.660)
how many people would decide.
Lex Fridman (2:54:38.180)
And I think, again, a lot of that is in leadership,
Lex Fridman (2:54:43.060)
but I think a lot of them,
Vincent Racaniello (2:54:45.060)
I would say most people would stay home.
Lex Fridman (2:54:47.140)
I think that Mina had the idea
Lex Fridman (2:54:49.460)
and it would have changed the whole situation for sure.
Lex Fridman (2:54:53.180)
If it could have been made when we talked to him last spring,
Vincent Racaniello (2:54:56.220)
I think, or summer, we would have gotten around
Lex Fridman (2:54:59.900)
a lot of the issues that we're in today
Vincent Racaniello (2:55:01.540)
because I think people would have stayed home
Lex Fridman (2:55:03.060)
and not transmitted.
Lex Fridman (2:55:04.000)
And I think it's still valuable to this day.
Lex Fridman (2:55:06.060)
In the fall, if we don't have vaccine uptake,
Vincent Racaniello (2:55:09.820)
we could just test kids every day
Lex Fridman (2:55:12.380)
and keep them home when they're infected.
Vincent Racaniello (2:55:14.240)
It cuts, and we don't have it.
Lex Fridman (2:55:17.580)
But I think, and I'm not privy to what was going on,
Lex Fridman (2:55:20.620)
but I don't think a lot of emphasis
Lex Fridman (2:55:22.980)
was put on testing early on.
Vincent Racaniello (2:55:25.100)
The CDC developed the first one, it was flawed.
Lex Fridman (2:55:27.940)
They had to recall the kits.
Vincent Racaniello (2:55:29.380)
I mean, that's a fiasco.
Lex Fridman (2:55:30.380)
They should have had 100 companies
Lex Fridman (2:55:32.200)
making the tests initially, right?
Lex Fridman (2:55:34.700)
So for the future, I think what we have learned
Vincent Racaniello (2:55:37.960)
is we need to have a rapid antigen test right off the bat.
Lex Fridman (2:55:42.280)
It's doable.
Vincent Racaniello (2:55:43.700)
You can't do it in a day like you can for PCR
Lex Fridman (2:55:46.220)
because you need to make antibodies
Vincent Racaniello (2:55:49.700)
to the protein that you're looking for
Lex Fridman (2:55:51.180)
and you need to do those in animals.
Lex Fridman (2:55:52.920)
But you can do it in weeks and we should be ready for that.
Lex Fridman (2:55:57.660)
Yeah, because I mean, to me, that's obvious.
Vincent Racaniello (2:56:00.680)
That's obviously the best solution.
Lex Fridman (2:56:02.820)
Second to that, if we understood how well masks work.
Vincent Racaniello (2:56:08.500)
Like, maybe let me ask you this question.
Lex Fridman (2:56:11.300)
Let's put masks aside.
Lex Fridman (2:56:14.040)
How well do we understand how COVID is transmitted?
Lex Fridman (2:56:18.100)
There's droplets of different sizes,
Vincent Racaniello (2:56:22.140)
aerosols, tiny, tiny droplets.
Lex Fridman (2:56:26.500)
It seems like that's a very difficult thing
Vincent Racaniello (2:56:28.480)
to understand thoroughly.
Lex Fridman (2:56:29.840)
So it seems like it's transmitted both ways.
Vincent Racaniello (2:56:33.320)
It's unclear how exactly.
Lex Fridman (2:56:35.640)
So how much do we understand
Lex Fridman (2:56:38.480)
and why is it so difficult to understand fully?
Lex Fridman (2:56:40.680)
Well, I think it's clear that it's transmitted
Vincent Racaniello (2:56:43.080)
through the air mostly.
Lex Fridman (2:56:44.760)
It's not touching.
Vincent Racaniello (2:56:46.240)
We thought initially it would be a lot of touch,
Lex Fridman (2:56:47.920)
but very little of that.
Vincent Racaniello (2:56:50.040)
It's through the air and when you talk,
Lex Fridman (2:56:53.120)
mainly when you talk, you expel a lot of droplets, right?
Vincent Racaniello (2:56:56.640)
Even the plosives that your foam thing here
Lex Fridman (2:56:59.240)
are meant to pee, right?
Vincent Racaniello (2:57:01.560)
That you send out little sprays
Lex Fridman (2:57:03.040)
and those have viruses in them.
Lex Fridman (2:57:05.520)
And the big drops fall to the ground
Lex Fridman (2:57:08.200)
and the little ones can go 100 feet or more, right?
Lex Fridman (2:57:11.280)
But the little ones also have less virus in them.
Lex Fridman (2:57:15.720)
So I'm not sure, well, we certainly do not know
Lex Fridman (2:57:18.720)
how much virus you need to be infected.
Lex Fridman (2:57:21.360)
But it's probably at least several thousand particles,
Vincent Racaniello (2:57:24.920)
if not more.
Lex Fridman (2:57:26.160)
And it could be that for most people,
Vincent Racaniello (2:57:30.320)
the tiny droplets don't have enough virus
Lex Fridman (2:57:32.720)
to infect someone else.
Lex Fridman (2:57:34.200)
But there's one observation about this virus
Lex Fridman (2:57:37.080)
that's really interesting.
Lex Fridman (2:57:38.640)
And that is that 80% of transmissions
Lex Fridman (2:57:42.080)
are done by 20% of the people, of the infected people.
Vincent Racaniello (2:57:46.360)
Not every infected person transmits.
Lex Fridman (2:57:49.840)
That's been borne out in multiple studies.
Lex Fridman (2:57:51.920)
And in fact, there's a study at University of Colorado
Lex Fridman (2:57:55.520)
where they quantified the viral RNA loads
Vincent Racaniello (2:57:58.720)
in all the swabs that had been done of students
Lex Fridman (2:58:01.320)
for like a six month period.
Lex Fridman (2:58:03.760)
And most of the infectious virus,
Lex Fridman (2:58:07.880)
most of the RNA copies were found
Vincent Racaniello (2:58:10.680)
in 15 to 20% of the people.
Lex Fridman (2:58:14.600)
The rest had really low
Lex Fridman (2:58:15.760)
and that's probably why they don't transmit.
Lex Fridman (2:58:18.320)
So those are the ones that might get enough virus
Vincent Racaniello (2:58:22.320)
in the tiny droplets to be able to infect
Lex Fridman (2:58:24.840)
someone at a distance.
Lex Fridman (2:58:26.520)
And I think that's entirely possible.
Lex Fridman (2:58:28.840)
Why is it hard to study?
Vincent Racaniello (2:58:31.040)
You can't do it in real life
Lex Fridman (2:58:32.800)
because you don't know who's infected.
Lex Fridman (2:58:35.360)
And if you do, there's not a controlled environment
Lex Fridman (2:58:37.800)
to measure droplets and so forth.
Vincent Racaniello (2:58:39.240)
You'd have to do it in a laboratory situation.
Lex Fridman (2:58:42.280)
If you use an animal, you just don't know
Lex Fridman (2:58:44.160)
what the relevance of that is to people.
Lex Fridman (2:58:46.520)
You'd have to use human and do challenge experiments.
Lex Fridman (2:58:50.000)
And we don't do that at this point,
Lex Fridman (2:58:51.880)
at least not for this virus.
Lex Fridman (2:58:53.320)
So that's why it's hard to know what's going on.
Lex Fridman (2:58:55.920)
So we have to make inferences
Vincent Racaniello (2:58:58.240)
from epidemiological associations
Lex Fridman (2:59:01.240)
where you're studying, say transmission in a household
Vincent Racaniello (2:59:03.840)
where people are stuck in the same rooms together
Lex Fridman (2:59:06.080)
and you can get an idea of what kind of droplets
Vincent Racaniello (2:59:09.160)
were involved.
Lex Fridman (2:59:10.000)
So that makes it much harder too.
Vincent Racaniello (2:59:11.320)
If you're leaning on epidemiological stuff
Lex Fridman (2:59:14.160)
as opposed to like biophysics
Vincent Racaniello (2:59:15.680)
or something like the mechanic.
Lex Fridman (2:59:17.280)
Very hard.
Lex Fridman (2:59:18.320)
So that makes it really hard to then develop solutions
Lex Fridman (2:59:23.120)
like masks, to ask the question, how well do masks work?
Vincent Racaniello (2:59:26.600)
Because then to answer that question,
Lex Fridman (2:59:28.800)
you can lean on epidemiological stuff again,
Vincent Racaniello (2:59:32.280)
like looking at populations that wear masks
Lex Fridman (2:59:34.520)
versus don't wear masks.
Vincent Racaniello (2:59:36.560)
As opposed to actually saying,
Lex Fridman (2:59:40.320)
like from an engineering perspective,
Vincent Racaniello (2:59:41.840)
like what kind of material and what kind of tightness
Lex Fridman (2:59:46.600)
by which amount decreases the viral load
Vincent Racaniello (2:59:50.440)
that's received on the other end.
Lex Fridman (2:59:52.480)
But some experiments have been done with masks
Lex Fridman (2:59:55.800)
and just droplets with no virus in them, right?
Lex Fridman (2:59:58.680)
And you can measure the efficiency
Lex Fridman (30:04.280)
So if you wanna be really safe and boring,
Lex Fridman (30:06.060)
just make sure everything is cooked.
Lex Fridman (30:07.920)
And now we have a case this week on TWIP
Lex Fridman (30:11.000)
of a young man who went, I forgot where he went,
Lex Fridman (30:14.200)
but he stayed in a hotel.
Lex Fridman (30:15.600)
I think, oh, Oaxaca, Mexico.
Vincent Racaniello (30:18.080)
Stayed in a hotel.
Lex Fridman (30:20.480)
And he came back with diarrhea and fever.
Lex Fridman (30:23.740)
And he said, I don't know where, I stayed in the hotel.
Lex Fridman (30:26.520)
I just ate hotel food, lots of vegetables and fruits,
Lex Fridman (30:30.000)
and probably they weren't washed with clean water.
Lex Fridman (30:32.960)
He got something from that.
Vincent Racaniello (30:34.840)
The bottom line is most of these infections
Lex Fridman (30:38.480)
with parasites can be diagnosed,
Lex Fridman (30:40.180)
and you can be treated, and you'll be fine.
Lex Fridman (30:42.680)
So if you really wanna experience the cuisine,
Vincent Racaniello (30:47.520)
I don't think you should worry about it.
Lex Fridman (30:49.240)
That's what Daniel would say.
Vincent Racaniello (30:50.680)
Let's return to the basics.
Lex Fridman (30:51.960)
We can then jump around all over the place.
Lex Fridman (30:54.840)
What are the basic principles of virology?
Lex Fridman (30:58.720)
Maybe a good place to start is what is a virus?
Vincent Racaniello (31:02.120)
That's great.
Lex Fridman (31:03.600)
I mean, I talk in my first lecture for 20 minutes
Vincent Racaniello (31:05.840)
before I get to that.
Lex Fridman (31:07.520)
But, and I wonder if I should put it up front,
Lex Fridman (31:10.060)
but it's kind of a boring definition.
Lex Fridman (31:12.100)
So if you do that first, people will turn off.
Lex Fridman (31:14.840)
So first you tell them about all the millions and billions
Lex Fridman (31:17.600)
of viruses around.
Lex Fridman (31:18.920)
So a virus, we have a very specific definition
Lex Fridman (31:22.720)
because it's different from everything else on the planet.
Vincent Racaniello (31:26.400)
Because first of all, it's a parasite.
Lex Fridman (31:28.960)
It takes, a parasite means you take something
Vincent Racaniello (31:32.060)
from someone else.
Lex Fridman (31:33.920)
We have human parasites who take money from others, right?
Lex Fridman (31:36.840)
But in biological terms, a parasite takes something
Lex Fridman (31:40.880)
from the host that the host would otherwise use energy
Vincent Racaniello (31:44.280)
or some building block or something.
Lex Fridman (31:46.200)
There's never really a symbiotic relationship
Vincent Racaniello (31:48.560)
between a virus and a host.
Lex Fridman (31:50.440)
Well, there can be.
Lex Fridman (31:52.000)
So that's the dichotomy I think is that we define them
Lex Fridman (31:54.640)
as parasites, yet I just told you 20 minutes ago
Vincent Racaniello (31:58.720)
that many viruses are probably beneficial.
Lex Fridman (32:01.520)
So I think what it means is we, at some point
Lex Fridman (32:04.480)
we're gonna have to change our definition, right?
Lex Fridman (32:06.800)
Because after all, definitions we make are just constructs
Vincent Racaniello (32:12.000)
that make it easy for us to study,
Lex Fridman (32:14.140)
that don't necessarily represent what's right.
Vincent Racaniello (32:16.760)
Yeah, like Pluto was a planet at first
Lex Fridman (32:20.420)
and now it's not a planet anymore
Lex Fridman (32:21.680)
and a lot of people are very upset.
Lex Fridman (32:23.360)
But it's only according to us.
Vincent Racaniello (32:24.700)
There may be another race living somewhere else
Lex Fridman (32:27.020)
who thinks it's a planet, right?
Vincent Racaniello (32:28.500)
Well, maybe that's why viruses are attacking humans.
Lex Fridman (32:30.680)
They're very angry.
Vincent Racaniello (32:31.560)
They're calling them parasites.
Lex Fridman (32:33.980)
So right now our definition includes parasite
Vincent Racaniello (32:38.000)
because a virus cannot do anything without a cell.
Lex Fridman (32:41.400)
If this mug were full of viruses,
Vincent Racaniello (32:44.040)
it would not do anything for years.
Lex Fridman (32:46.360)
It would eventually probably lose its infectivity,
Lex Fridman (32:49.040)
but it's not gonna reproduce here, it needs cells.
Lex Fridman (32:52.040)
And to the first people who discovered viruses,
Vincent Racaniello (32:54.240)
that was astounding that they didn't just reproduce,
Lex Fridman (32:57.360)
divide on their own like bacteria.
Lex Fridman (32:59.640)
So a virus needs to get inside of a cell,
Lex Fridman (33:02.640)
inside the cell, it can't just hang around on the surface.
Vincent Racaniello (33:05.520)
It needs to get in in order to make more of itself.
Lex Fridman (33:09.200)
And so we call it an obligate intracellular parasite
Vincent Racaniello (33:13.080)
because it needs to get in a cell
Lex Fridman (33:15.060)
and then it takes things from the cell
Vincent Racaniello (33:17.320)
in the form of all kinds of molecules
Lex Fridman (33:19.280)
and processes and energy and so forth to make new viruses.
Vincent Racaniello (33:23.640)
Obligate means it's obligated to be inside the cell.
Lex Fridman (33:26.240)
Absolutely, it will not reproduce outside of the cell.
Lex Fridman (33:30.800)
So this mug of viruses can in no way be living,
Lex Fridman (33:35.880)
in my opinion.
Vincent Racaniello (33:36.920)
However, once it gets inside of a cell,
Lex Fridman (33:39.160)
now the cell is a virus infected cell, it's alive.
Lex Fridman (33:42.320)
So a virus, in my view, has two phases, right?
Lex Fridman (33:45.360)
It's this nonliving particulate phase
Vincent Racaniello (33:48.200)
that everyone is used to.
Lex Fridman (33:50.600)
I'll send you, you need a virus for your table.
Vincent Racaniello (33:52.720)
I'll send you a nice model.
Lex Fridman (33:54.560)
I think it would look good here.
Vincent Racaniello (33:55.400)
Which, yes, definitely.
Lex Fridman (33:56.240)
You don't have to go with all this other stuff.
Vincent Racaniello (33:57.800)
Yeah, well, these are all mechanical.
Lex Fridman (33:59.560)
There's no biology here.
Lex Fridman (34:01.240)
So you wouldn't want a virus here?
Lex Fridman (34:02.480)
No, I'd want a virus, of course.
Vincent Racaniello (34:04.000)
No, I'll send you one and then you can look at it.
Lex Fridman (34:06.840)
Because now that we have the three dimensional structures
Vincent Racaniello (34:09.920)
solved by structural biologists,
Lex Fridman (34:12.600)
we take the coordinates and we put it in a 3D printer
Lex Fridman (34:14.720)
and you can make amazing models, right?
Lex Fridman (34:18.040)
Of any virus.
Lex Fridman (34:18.880)
And so there's a huge variety of viruses?
Lex Fridman (34:21.520)
Huge, that we know of,
Vincent Racaniello (34:23.320)
which is only a fraction of what's out there.
Lex Fridman (34:24.840)
What's the categories?
Lex Fridman (34:25.800)
So there's RNA, there's DNA viruses.
Lex Fridman (34:27.840)
What are those, what's DNA and RNA?
Vincent Racaniello (34:30.240)
Two broad categorizations.
Lex Fridman (34:33.920)
RNA, these are genetic material.
Vincent Racaniello (34:37.080)
Can be two different chemicals.
Lex Fridman (34:39.200)
So RNA, everything else on the planet besides viruses
Vincent Racaniello (34:43.120)
is all DNA based.
Lex Fridman (34:44.120)
You and I are DNA based.
Vincent Racaniello (34:45.280)
Everything on the planet today is DNA based,
Lex Fridman (34:47.320)
except some viruses are RNA based.
Lex Fridman (34:50.200)
And that's because, as I mentioned earlier,
Lex Fridman (34:53.120)
the first life that arose on the planet was RNA based.
Vincent Racaniello (34:57.240)
Yeah, so these are like old school viruses.
Lex Fridman (34:59.480)
These are old school.
Vincent Racaniello (35:00.600)
We call relics, yeah.
Lex Fridman (35:02.560)
Relics, and this has got a name,
Vincent Racaniello (35:04.480)
it's called the RNA world, which I think is great.
Lex Fridman (35:06.760)
Is it big still, or are the relics dying out?
Vincent Racaniello (35:09.640)
Oh no, the relics, in my opinion,
Lex Fridman (35:11.520)
are the most successful viruses, the RNA viruses.
Lex Fridman (35:14.880)
And SARS CoV2 is an RNA virus.
Lex Fridman (35:16.680)
We can talk about why they're so successful.
Lex Fridman (35:19.040)
But you have, broadly speaking, viruses with RNA,
Lex Fridman (35:22.720)
genetic information, which are relics.
Vincent Racaniello (35:24.920)
Of course, they're contemporary.
Lex Fridman (35:26.440)
They have adapted to the modern world
Lex Fridman (35:28.920)
and the modern organisms living in it.
Lex Fridman (35:31.160)
And then we have DNA based viruses,
Vincent Racaniello (35:33.240)
which are extremely conservative and slow.
Lex Fridman (35:36.440)
They're very successful.
Vincent Racaniello (35:37.800)
Everyone has a herpes virus infection,
Lex Fridman (35:40.040)
but they don't get the news like the RNA viruses do.
Vincent Racaniello (35:44.520)
The HIVs and the influenza viruses
Lex Fridman (35:46.800)
and the SARS Coronaviruses, they get all the press
Lex Fridman (35:49.880)
and they're RNA based, because RNA lets you change
Lex Fridman (35:52.880)
more so than DNA.
Lex Fridman (35:54.400)
So they evolve much faster, the RNA viruses.
Lex Fridman (35:57.240)
Much faster.
Lex Fridman (35:58.320)
And in fact, I have an lecture on evolution.
Lex Fridman (36:01.920)
I don't know if you've listened to that one.
Vincent Racaniello (36:03.800)
You should, it's really, I think it's really interesting.
Lex Fridman (36:07.760)
RNA viruses exist at their error threshold,
Vincent Racaniello (36:13.720)
which means they can't make any more mutations
Lex Fridman (36:17.120)
when they reproduce, otherwise they're dead.
Vincent Racaniello (36:19.560)
They would go extinct.
Lex Fridman (36:20.880)
They're evolving at their error threshold.
Vincent Racaniello (36:23.600)
DNA viruses are hundreds of times lower
Lex Fridman (36:26.280)
than their error thresholds.
Lex Fridman (36:28.400)
And we know this, we can do an experiment to find that out.
Lex Fridman (36:31.120)
Now, why that is, is a good question,
Lex Fridman (36:33.560)
but that's the reason why RNA viruses
Lex Fridman (36:38.240)
are far more successful.
Vincent Racaniello (36:39.400)
They infect many more hosts and they're very,
Lex Fridman (36:42.920)
I would say slippery.
Vincent Racaniello (36:44.120)
They can change hosts really quickly,
Lex Fridman (36:46.440)
because in any animal harboring an RNA virus,
Vincent Racaniello (36:50.440)
like let's say a bat in some cave somewhere,
Lex Fridman (36:52.960)
it's not just one genome.
Vincent Racaniello (36:55.160)
It's millions of different genomes of all kinds,
Lex Fridman (36:58.680)
all within the framework of, say, coronavirus,
Lex Fridman (37:01.240)
but they're all different.
Lex Fridman (37:02.600)
And one genome in there might just be right
Vincent Racaniello (37:04.760)
for infecting a person if it ever encountered that person.
Lex Fridman (37:08.200)
I mean, that's the thing that.
Vincent Racaniello (37:09.400)
Or there could be a large number.
Lex Fridman (37:11.240)
This is a tiny fraction, but a large number of them.
Lex Fridman (37:15.000)
And they're all operating at the threshold of error.
Lex Fridman (37:18.280)
That's fascinating.
Vincent Racaniello (37:19.120)
It's like little, like it's like startups,
Lex Fridman (37:21.560)
little entrepreneurs, like a startup world.
Vincent Racaniello (37:23.840)
Yes, and many of them fail.
Lex Fridman (37:25.160)
Yeah, many of them fail.
Vincent Racaniello (37:26.000)
Many of the changes fail.
Lex Fridman (37:26.840)
And then there's the DNA viruses that are like the IBM
Lex Fridman (37:29.200)
and the Google. Exactly, exactly.
Lex Fridman (37:30.520)
The big corporations.
Vincent Racaniello (37:31.720)
That's very good, I like that.
Lex Fridman (37:32.560)
They become conservative with the bureaucracies
Lex Fridman (37:34.120)
and all that kind of stuff, so they.
Lex Fridman (37:34.960)
And a lot of baggage.
Vincent Racaniello (37:36.240)
Yeah, yeah, it's expensive for them to reproduce, yeah.
Lex Fridman (37:39.440)
And they don't move quickly.
Vincent Racaniello (37:40.480)
Yes, the RNA viruses are the fast moving members.
Lex Fridman (37:43.760)
So that's what a virus is.
Vincent Racaniello (37:45.400)
We call them ovulated intracellular parasites.
Lex Fridman (37:48.840)
And then I told you there's DNA and RNA,
Lex Fridman (37:50.760)
but then let's go further.
Lex Fridman (37:52.880)
The nucleic acid is not naked.
Vincent Racaniello (37:56.120)
Because naked nucleic acid in the world isn't good.
Lex Fridman (37:59.800)
I mean, it existed in the precellular world,
Lex Fridman (38:03.440)
but there probably weren't a lot of threats to it then.
Lex Fridman (38:07.080)
Naked nucleic acid doesn't last long in the environment.
Lex Fridman (38:09.640)
So they're covered, the nucleic acid is covered.
Lex Fridman (38:12.120)
It can be covered with a protein shell,
Vincent Racaniello (38:13.920)
a pure protein shell, or it can have a membrane around it,
Lex Fridman (38:18.920)
which would be lipids from the host cell.
Lex Fridman (38:22.360)
So lipids, so it's a fatty membrane.
Lex Fridman (38:26.160)
Fatty membrane, yeah, so our cells
Lex Fridman (38:27.760)
are coated with fatty membranes, right?
Lex Fridman (38:30.440)
Our cells, the outer plasma membrane, right?
Vincent Racaniello (38:32.480)
That's the same.
Lex Fridman (38:33.320)
Viruses can be too.
Lex Fridman (38:34.320)
So they're kind of like cells,
Lex Fridman (38:35.720)
but without the ability to do the mitochondria stuff.
Vincent Racaniello (38:38.600)
Some are, they don't have nuclei,
Lex Fridman (38:41.120)
they don't have mitochondria.
Lex Fridman (38:42.760)
But they do have a nucleic acid, they have a membrane,
Lex Fridman (38:45.960)
and then of course there's spikes in the membrane
Vincent Racaniello (38:48.600)
that allow them to attach to cells.
Lex Fridman (38:51.200)
And so that completes our two different kinds.
Lex Fridman (38:53.320)
So they have, they all have like attachment mechanisms,
Lex Fridman (38:55.720)
like ways to, like keys into the cell.
Vincent Racaniello (38:59.240)
They all have to get into cells.
Lex Fridman (39:01.280)
There are a couple of exceptions though.
Vincent Racaniello (39:05.160)
There are viruses of fungi and plants.
Lex Fridman (39:10.560)
So let's do the fungi.
Vincent Racaniello (39:11.920)
Fungi would be like yeast.
Lex Fridman (39:13.520)
The yeast cell wall is pretty hard to get through.
Lex Fridman (39:17.960)
So viruses typically don't attach to a yeast
Lex Fridman (39:21.200)
and get inside.
Vincent Racaniello (39:22.040)
Rather, they just live in the yeast forever.
Lex Fridman (39:24.880)
And they multiply as mostly nucleic acids,
Lex Fridman (39:27.920)
and as the yeast divide, they go into the daughter cells.
Lex Fridman (39:30.600)
And that's how they exist.
Vincent Racaniello (39:31.840)
Plant viruses, also the plant cell wall
Lex Fridman (39:34.920)
would be very hard to get across by binding a protein.
Lex Fridman (39:39.760)
So plant viruses get into plants either by
Lex Fridman (39:43.280)
pests that inject them in, they're sucking sap out,
Lex Fridman (39:48.440)
and they inject virus at the same time.
Lex Fridman (39:49.920)
Or farmers, they have contaminated farm equipment
Lex Fridman (39:52.600)
and they roll over the plants and introduces viruses.
Lex Fridman (39:55.800)
So those fungi and plant viruses,
Vincent Racaniello (39:57.680)
they don't have this specific receptor binding
Lex Fridman (3:00:01.360)
of different mask materials at keeping those in.
Lex Fridman (3:00:04.400)
So if I say that this mask stops 70%
Lex Fridman (3:00:09.880)
of this or larger size droplet,
Vincent Racaniello (3:00:13.760)
that leads to this percent decreased transmission.
Lex Fridman (3:00:18.000)
And also on both the generation
Lex Fridman (3:00:23.040)
and the receiving end and the giving end.
Lex Fridman (3:00:27.520)
Sure.
Lex Fridman (3:00:28.360)
So how well do masks protect you from others?
Lex Fridman (3:00:30.560)
How well do you do mask protect others from you?
Vincent Racaniello (3:00:34.200)
Like all of those things seem like
Lex Fridman (3:00:36.920)
they could be more rigorously studied.
Vincent Racaniello (3:00:40.120)
There's no doubt about it.
Lex Fridman (3:00:41.560)
And now is the time because once this is over,
Vincent Racaniello (3:00:46.120)
nobody's gonna do it.
Lex Fridman (3:00:47.200)
Nobody's gonna care.
Vincent Racaniello (3:00:48.360)
No. Right.
Lex Fridman (3:00:49.200)
But it seems like to me, so tests is one thing,
Lex Fridman (3:00:52.880)
but masks, like the good mask,
Lex Fridman (3:00:57.480)
whatever the good means, whatever that means,
Vincent Racaniello (3:00:59.960)
like some level of quality of material on your face,
Lex Fridman (3:01:04.200)
if it's shown to actually like thoroughly shown to work well,
Vincent Racaniello (3:01:08.960)
that seems like an obvious solution
Lex Fridman (3:01:12.120)
to reopen society with.
Vincent Racaniello (3:01:14.840)
If you have a good understanding of how well they work.
Lex Fridman (3:01:17.920)
Because if you don't have a good understanding,
Vincent Racaniello (3:01:20.040)
if there's a lot of uncertainty,
Lex Fridman (3:01:21.800)
that's when you get,
Lex Fridman (3:01:23.000)
and you have people speaking from authority,
Lex Fridman (3:01:24.960)
that's when you start getting the politicization
Vincent Racaniello (3:01:27.960)
of the solution.
Lex Fridman (3:01:28.800)
Of course, of course.
Vincent Racaniello (3:01:29.640)
No, the data, there are some data,
Lex Fridman (3:01:33.200)
most, they're mostly epidemiological
Lex Fridman (3:01:36.320)
and they show some effect in some countries, right?
Lex Fridman (3:01:39.120)
But they could be way better.
Vincent Racaniello (3:01:40.800)
Yeah.
Lex Fridman (3:01:41.640)
And, but the fact that they're not perfect,
Vincent Racaniello (3:01:44.920)
then people take advantage of and say,
Lex Fridman (3:01:46.800)
well, look, they don't work that well,
Lex Fridman (3:01:48.120)
so I'm not gonna wear it.
Lex Fridman (3:01:49.120)
I think, as you said, people can use it as an excuse.
Lex Fridman (3:01:53.040)
But even if it works, so Daniel always says,
Lex Fridman (3:01:56.200)
a mask will cut down transmission by 50 to 60%,
Lex Fridman (3:02:00.680)
and then distance will do another 30%.
Lex Fridman (3:02:03.480)
Yeah, those numbers are made up though.
Vincent Racaniello (3:02:05.800)
I mean, they're not made up, but they're estimates.
Lex Fridman (3:02:08.360)
Absolutely.
Lex Fridman (3:02:09.200)
And many of them are made based on models, right?
Lex Fridman (3:02:12.720)
Yeah.
Vincent Racaniello (3:02:13.560)
We make this model,
Lex Fridman (3:02:14.400)
and let's say the mask cuts down this much,
Lex Fridman (3:02:16.480)
what will be the effect on it?
Lex Fridman (3:02:17.920)
I mean, yeah, they're models,
Lex Fridman (3:02:19.000)
and it's for the same reason.
Lex Fridman (3:02:20.760)
I don't believe the transmission of the variants
Vincent Racaniello (3:02:25.000)
because it's all based on statistical models as well,
Lex Fridman (3:02:27.280)
not biological experiments done in a lab.
Lex Fridman (3:02:29.520)
So in that sense, vaccine data is much better
Lex Fridman (3:02:32.000)
than mask data.
Vincent Racaniello (3:02:33.200)
For sure, for sure.
Lex Fridman (3:02:34.480)
So my problem with the mask data,
Vincent Racaniello (3:02:37.160)
which I always thought was fascinating,
Lex Fridman (3:02:38.440)
I stopped talking about it.
Vincent Racaniello (3:02:39.600)
I was in a paper about masks.
Lex Fridman (3:02:41.400)
I stopped talking about it
Vincent Racaniello (3:02:42.400)
because what started happening
Lex Fridman (3:02:45.080)
is masks created assholes on both sides.
Vincent Racaniello (3:02:48.000)
The people that were like in Silicon Valley,
Lex Fridman (3:02:50.400)
the friends of mine that were wearing masks,
Vincent Racaniello (3:02:52.520)
the way they look at others who don't is like...
Lex Fridman (3:02:56.160)
Well, that's a whole nother issue, right?
Vincent Racaniello (3:02:58.240)
Yeah, I understand.
Lex Fridman (3:02:59.880)
That happens when you don't have solid science.
Vincent Racaniello (3:03:02.560)
Understood.
Lex Fridman (3:03:03.400)
They now start judging you like you're a lesser human being.
Vincent Racaniello (3:03:07.240)
You're not only dumb, but you're almost like evil.
Lex Fridman (3:03:11.520)
You're doing bad for society by not wearing a mask.
Lex Fridman (3:03:14.280)
And then the people looking in the other way
Lex Fridman (3:03:17.120)
are seeing you for the asshole that you're being
Vincent Racaniello (3:03:19.800)
for judging them unrightly.
Lex Fridman (3:03:22.040)
So they almost wanna say F you by not wearing the mask.
Lex Fridman (3:03:24.480)
And there's this division that's created
Lex Fridman (3:03:26.640)
that was heartbreaking to me because masks like testing
Vincent Racaniello (3:03:30.400)
is a solution that was available early on.
Lex Fridman (3:03:33.400)
And if understood well, it could be deployed
Vincent Racaniello (3:03:35.920)
in a mass scale, and it seems like there's
Lex Fridman (3:03:37.880)
some historical evidence for other viruses
Vincent Racaniello (3:03:40.120)
where it does very well.
Lex Fridman (3:03:41.760)
That's correct.
Lex Fridman (3:03:42.600)
And so like the fact that this was politicized,
Lex Fridman (3:03:47.200)
yeah, it was a little bit heartbreaking.
Vincent Racaniello (3:03:48.760)
You can find in the literature studies,
Lex Fridman (3:03:51.800)
mostly of healthcare workers and influenza,
Vincent Racaniello (3:03:54.560)
where you can actually,
Lex Fridman (3:03:56.240)
because you see the people every day that can sample them,
Vincent Racaniello (3:03:58.440)
you can actually see what masking does.
Lex Fridman (3:04:00.520)
And some of them show an effect and others do not,
Vincent Racaniello (3:04:04.040)
then that's the problem.
Lex Fridman (3:04:05.600)
Like any trial, sometimes if it's not big enough
Lex Fridman (3:04:08.280)
and then people latch onto that, see,
Lex Fridman (3:04:10.360)
it doesn't really work.
Lex Fridman (3:04:11.600)
But I think the main issue is that in January,
Lex Fridman (3:04:15.000)
both CDC and WHO said masks don't work, don't use them.
Vincent Racaniello (3:04:20.000)
That was the kiss of death for masks
Lex Fridman (3:04:22.240)
because when they then changed their mind,
Vincent Racaniello (3:04:25.920)
they didn't say we screwed up.
Lex Fridman (3:04:28.040)
They just said wear masks.
Vincent Racaniello (3:04:29.240)
If they had said we made a mistake, we were wrong,
Lex Fridman (3:04:33.000)
I think more people would have worn masks.
Lex Fridman (3:04:35.400)
But they didn't.
Lex Fridman (3:04:36.600)
And like you said, admitting you're wrong
Vincent Racaniello (3:04:39.080)
is like a real big part of it.
Lex Fridman (3:04:41.440)
And I also think almost the better way
Vincent Racaniello (3:04:43.200)
is not just saying you're wrong,
Lex Fridman (3:04:46.560)
but in January saying,
Vincent Racaniello (3:04:49.760)
like revealing the uncertainty under which we operate.
Lex Fridman (3:04:52.360)
Like actually, like reveal what was done
Vincent Racaniello (3:04:56.440)
with the Spanish flu at the beginning
Lex Fridman (3:04:58.360)
of the previous century,
Vincent Racaniello (3:05:01.080)
because there's a lot of mass controversy then too.
Lex Fridman (3:05:03.240)
It went back and forth.
Lex Fridman (3:05:04.120)
And that was actually the source of a lot of distrust
Lex Fridman (3:05:05.960)
there too.
Vincent Racaniello (3:05:06.920)
So, and then look at influenza,
Lex Fridman (3:05:09.280)
like how is it effective with that?
Lex Fridman (3:05:11.080)
And just reveal this, we don't know,
Lex Fridman (3:05:13.880)
but like with some probability,
Vincent Racaniello (3:05:17.680)
this is the best option we got currently.
Lex Fridman (3:05:20.120)
And then in a month or two, adjust it,
Vincent Racaniello (3:05:23.600)
saying that, you know what,
Lex Fridman (3:05:25.280)
our like uncertainty decreased a little bit.
Vincent Racaniello (3:05:27.840)
We have a better idea.
Lex Fridman (3:05:29.440)
Like that was an incorrect estimate,
Lex Fridman (3:05:32.320)
but reveal that you're struggling.
Lex Fridman (3:05:34.840)
It's not like this weird binary clock
Vincent Racaniello (3:05:36.840)
that goes one direction or the other.
Lex Fridman (3:05:38.440)
You're struggling with uncertainty.
Lex Fridman (3:05:41.200)
And like trusting,
Lex Fridman (3:05:43.240)
people maybe criticize me sometimes for this,
Lex Fridman (3:05:45.040)
but I think most people are actually intelligent.
Lex Fridman (3:05:48.960)
Like trusting the public to be intelligent
Vincent Racaniello (3:05:51.760)
with if you give them, if you have transparent
Lex Fridman (3:05:54.040)
and give them information in a real authentic way,
Vincent Racaniello (3:05:57.680)
like don't look like you're hiding something.
Lex Fridman (3:05:59.560)
I think they're intelligent enough to use that data
Vincent Racaniello (3:06:01.920)
to make decisions.
Lex Fridman (3:06:03.120)
It's the same thing as with the testing,
Vincent Racaniello (3:06:05.080)
is if you put that power in the people's hands
Lex Fridman (3:06:07.600)
to know if they're sick or not,
Vincent Racaniello (3:06:08.640)
they're gonna make unmasked the right decision, I think.
Lex Fridman (3:06:14.240)
The masks and the testing has been a bit heartbreaking.
Vincent Racaniello (3:06:18.000)
I think that's a good point though,
Lex Fridman (3:06:19.440)
that most people don't seem to have an objection
Vincent Racaniello (3:06:21.640)
to testing.
Lex Fridman (3:06:23.040)
It's a good point.
Vincent Racaniello (3:06:23.880)
Yes. Yeah.
Lex Fridman (3:06:24.720)
And then obviously Macamina makes that point brilliantly.
Lex Fridman (3:06:27.960)
And still there's very little excitement around that.
Lex Fridman (3:06:33.320)
But he said he was going to do it.
Vincent Racaniello (3:06:35.000)
I don't understand.
Lex Fridman (3:06:35.840)
I mean, I haven't spoken to him since then.
Lex Fridman (3:06:37.600)
So I don't know why.
Lex Fridman (3:06:38.720)
He's pushing it.
Vincent Racaniello (3:06:39.560)
Well, I mean, but he can't do it alone.
Lex Fridman (3:06:41.640)
He has to get, so one of the resistances,
Vincent Racaniello (3:06:44.680)
FDA doesn't like cheap things.
Lex Fridman (3:06:48.160)
Yeah.
Vincent Racaniello (3:06:49.120)
They don't wanna approve it.
Lex Fridman (3:06:50.240)
So they makes the mass manufacture
Vincent Racaniello (3:06:52.960)
like with the emergency exceptions,
Lex Fridman (3:06:55.120)
all those kinds of things very difficult.
Lex Fridman (3:06:57.440)
And then there's not much money to be made on it
Lex Fridman (3:06:59.560)
without that.
Vincent Racaniello (3:07:00.760)
I don't know.
Lex Fridman (3:07:01.600)
I think there's just economic pressures against it.
Lex Fridman (3:07:04.840)
And because so much investment was placed on the vaccines
Lex Fridman (3:07:10.920)
and obviously there's an incentive mechanism there
Vincent Racaniello (3:07:13.360)
where the companies, lobbyists and all those,
Lex Fridman (3:07:17.200)
there's this machine that says arguing for tests
Vincent Racaniello (3:07:21.440)
is difficult because the thing that's worked
Lex Fridman (3:07:23.240)
for most severe viruses in the past is vaccines.
Vincent Racaniello (3:07:27.160)
Now we have vaccines.
Lex Fridman (3:07:28.320)
Why the hell would you need tests?
Vincent Racaniello (3:07:30.360)
At that time, like why the hell do you need tests
Lex Fridman (3:07:34.440)
when we can be working on vaccines?
Vincent Racaniello (3:07:36.080)
It seems like the obvious thing to be working
Lex Fridman (3:07:37.720)
is the vaccines from their perspective,
Lex Fridman (3:07:40.680)
but it's not obvious at all to me.
Lex Fridman (3:07:43.160)
I think you should have both.
Vincent Racaniello (3:07:44.440)
I think have vaccines and good testing
Lex Fridman (3:07:46.600)
and that covers you really well
Vincent Racaniello (3:07:48.920)
because you're always gonna have people
Lex Fridman (3:07:50.080)
who don't get vaccinated.
Vincent Racaniello (3:07:52.080)
I don't know if you've been paying attention to this.
Lex Fridman (3:07:54.200)
There's a guy named Brett Weinstein.
Vincent Racaniello (3:07:55.720)
There's a guy named Sam Harris.
Lex Fridman (3:07:57.760)
They have good representation.
Vincent Racaniello (3:08:00.760)
I would say of two sides of a perspective on the vaccine.
Lex Fridman (3:08:06.240)
So from Sam Harris's perspective,
Vincent Racaniello (3:08:09.680)
it's obvious that everybody should get vaccinated
Lex Fridman (3:08:13.240)
and it's irresponsible to not get vaccinated.
Vincent Racaniello (3:08:18.560)
I think he represents a lot of people's belief in that.
Lex Fridman (3:08:22.360)
And then Brett talks a lot about ivermectin,
Lex Fridman (3:08:28.520)
but also talks about hesitancy towards the vaccine
Lex Fridman (3:08:32.720)
for people who are healthy,
Vincent Racaniello (3:08:35.040)
for people who are younger, that kind of thing,
Lex Fridman (3:08:38.480)
and saying we should consider longterm effects
Vincent Racaniello (3:08:40.840)
of the vaccine in making this calculation.
Lex Fridman (3:08:45.200)
What do you make about this conversation?
Vincent Racaniello (3:08:47.520)
Some of it happens on Twitter.
Lex Fridman (3:08:49.400)
Some of it happens in the space of podcasts.
Lex Fridman (3:08:54.000)
Do you pay attention to this kind of thing?
Lex Fridman (3:08:56.240)
What's your role in this?
Lex Fridman (3:08:58.240)
What do you hope is the way to resolve this conversation?
Lex Fridman (3:09:02.080)
Do you think it's healthy?
Vincent Racaniello (3:09:04.040)
Well, a conversation is always healthy,
Lex Fridman (3:09:05.760)
but to make definitive statements is not
Vincent Racaniello (3:09:09.280)
because it suggests you have information that you don't have.
Lex Fridman (3:09:12.200)
So we talked about longterm effects.
Vincent Racaniello (3:09:16.880)
I think you need to balance those versus longterm effects
Lex Fridman (3:09:20.360)
of the disease and you can make your decision.
Vincent Racaniello (3:09:22.520)
I don't think you need to tell everybody to get vaccinated.
Lex Fridman (3:09:26.560)
I think you need to present the case.
Vincent Racaniello (3:09:28.760)
You say, here, we made good vaccines.
Lex Fridman (3:09:30.400)
Here are the safety profile.
Vincent Racaniello (3:09:32.240)
Here's the risk benefit balance.
Lex Fridman (3:09:34.400)
And you should decide.
Vincent Racaniello (3:09:35.280)
You're a smart person.
Lex Fridman (3:09:36.160)
You should decide.
Lex Fridman (3:09:37.880)
Now, companies are gonna do differently, right?
Lex Fridman (3:09:41.240)
Companies may say you have to be vaccinated to work here.
Vincent Racaniello (3:09:43.320)
My employer, Columbia, said we have to be vaccinated
Lex Fridman (3:09:46.720)
to work in the fall.
Lex Fridman (3:09:47.560)
And if you wanna be a student, you have to be vaccinated.
Lex Fridman (3:09:49.440)
So you decide whether you wanna go or not.
Lex Fridman (3:09:52.240)
But the idea that you should make a decision
Lex Fridman (3:09:58.000)
based on longterm effects, there is no evidence, right?
Lex Fridman (3:10:02.480)
So how can you make a decision
Lex Fridman (3:10:03.760)
when we don't have evidence,
Vincent Racaniello (3:10:05.200)
whereas we do have evidence
Lex Fridman (3:10:06.280)
that there are longterm effects of getting COVID?
Lex Fridman (3:10:08.440)
So I don't think that's a fair argument
Lex Fridman (3:10:10.200)
and it just makes people scared to say that.
Lex Fridman (3:10:13.640)
But on the other hand, for someone to say
Lex Fridman (3:10:15.000)
it's a no brainer and to denigrate people
Vincent Racaniello (3:10:18.280)
for not being vaccinated, that's not the approach either
Lex Fridman (3:10:20.400)
because they're gonna dig in and say,
Lex Fridman (3:10:23.320)
I'm not doing this because you tell me to, right?
Lex Fridman (3:10:25.680)
I think the middle ground is to say,
Vincent Racaniello (3:10:28.600)
take a bit of both and say, here are the potential issues
Lex Fridman (3:10:33.600)
and here are the benefits and this is what I would do.
Lex Fridman (3:10:37.280)
And you have to just decide on your own.
Lex Fridman (3:10:38.680)
I'd leave it to them.
Vincent Racaniello (3:10:39.520)
I say, you decide.
Lex Fridman (3:10:40.360)
And if you don't want to, it's up to you.
Vincent Racaniello (3:10:42.280)
You don't have to get vaccinated.
Lex Fridman (3:10:44.480)
And you'll probably get infected at some point
Lex Fridman (3:10:46.360)
and maybe you'll be okay.
Lex Fridman (3:10:50.040)
But here's the best available data
Lex Fridman (3:10:51.640)
and it looks like the vaccines are pretty damn smart solution.
Lex Fridman (3:10:56.760)
They seem to work.
Vincent Racaniello (3:10:57.600)
I think you tell people what you did
Lex Fridman (3:11:00.000)
and present both sides calmly.
Lex Fridman (3:11:01.880)
And I think digging in, like in a debate,
Lex Fridman (3:11:04.720)
I don't think that's terribly useful.
Lex Fridman (3:11:06.920)
So that's my view.
Lex Fridman (3:11:08.920)
I mean, people come to me all the time and ask me,
Lex Fridman (3:11:11.440)
I'm worried, what should I do?
Lex Fridman (3:11:14.680)
And I say, what are you worried about?
Vincent Racaniello (3:11:16.120)
Let's talk about it and go through it calmly.
Lex Fridman (3:11:18.960)
And if they want to still take ivermectin,
Vincent Racaniello (3:11:20.720)
I say, it's fine, it's your choice.
Lex Fridman (3:11:22.640)
And I have a problem with that.
Vincent Racaniello (3:11:23.480)
I love that.
Lex Fridman (3:11:24.960)
I love that's the way you think.
Vincent Racaniello (3:11:26.680)
People should definitely listen to This Week in Virology
Lex Fridman (3:11:32.040)
and follow your work, it's brilliant.
Vincent Racaniello (3:11:33.920)
I've been really enjoying it lately.
Lex Fridman (3:11:35.760)
It's like, it's my favorite way to stay in touch
Vincent Racaniello (3:11:38.320)
with the happenings of COVID.
Lex Fridman (3:11:42.160)
Obviously you put in a lot of other stuff in there, but.
Vincent Racaniello (3:11:45.520)
We used to do other viruses before COVID.
Lex Fridman (3:11:47.760)
It was quite interesting.
Lex Fridman (3:11:50.040)
And I'm trying to slip other viruses in
Lex Fridman (3:11:52.520)
because I think they're informative in many ways.
Lex Fridman (3:11:56.120)
And we're gonna do more and more of that.
Lex Fridman (3:11:57.280)
But I have to say I canceled,
Vincent Racaniello (3:11:58.600)
usually I record on Tuesday and Friday
Lex Fridman (3:12:00.840)
and I canceled today so I could be with you.
Vincent Racaniello (3:12:02.960)
It's a huge honor, I appreciate that.
Lex Fridman (3:12:05.040)
No, no, it's fine.
Vincent Racaniello (3:12:06.680)
I think a couple of other people were gonna be away anyway.
Lex Fridman (3:12:10.240)
So I do a lot of different pods.
Vincent Racaniello (3:12:12.040)
They're all on YouTube, but I also do a live stream
Lex Fridman (3:12:15.680)
on Wednesday nights on YouTube, which you can find.
Lex Fridman (3:12:18.480)
And that's where people can come and ask questions.
Lex Fridman (3:12:21.360)
We don't have an agenda.
Vincent Racaniello (3:12:22.440)
We just start and by 30 minutes in,
Lex Fridman (3:12:25.280)
there's 700 people with questions
Vincent Racaniello (3:12:27.440)
that I can't even get through
Lex Fridman (3:12:28.600)
because there's so many of them.
Lex Fridman (3:12:29.600)
And I'm actually astounded
Lex Fridman (3:12:31.720)
that so many people have really good questions.
Vincent Racaniello (3:12:35.640)
Most of them are reasonable and they come back every week.
Lex Fridman (3:12:38.960)
So it's turning into a great forum
Vincent Racaniello (3:12:41.880)
to have a nice discussion.
Lex Fridman (3:12:44.120)
And the YouTube channel is called what?
Lex Fridman (3:12:46.920)
So you could search for my name,
Lex Fridman (3:12:48.960)
which is Vincent Racaniello, it'll turn up.
Vincent Racaniello (3:12:51.280)
Or my handle on YouTube is ProfVRR, P R O F V R R.
Lex Fridman (3:13:00.000)
Have you read The Plague by Camus by any chance?
Vincent Racaniello (3:13:03.040)
Years ago, years ago.
Lex Fridman (3:13:05.800)
I have to read it again.
Vincent Racaniello (3:13:07.160)
That's really relevant.
Lex Fridman (3:13:08.720)
Let me sort of ask you a question about it.
Vincent Racaniello (3:13:10.840)
It describes a town that's overtaken by a plague
Lex Fridman (3:13:14.000)
and it's blocked off from the rest of the world.
Lex Fridman (3:13:16.480)
And it kind of reveals the best, the worst of human nature.
Lex Fridman (3:13:19.480)
That's like how people respond to that.
Vincent Racaniello (3:13:21.240)
Sort of the encroaching, their own mortality,
Lex Fridman (3:13:25.120)
their own death on the horizon.
Vincent Racaniello (3:13:27.240)
I think one of the messages in the book
Lex Fridman (3:13:28.960)
that ultimately like love for others.
Lex Fridman (3:13:34.160)
So like a lot of people want to become isolated
Lex Fridman (3:13:36.800)
and they hide from each other,
Lex Fridman (3:13:38.440)
but ultimately the thing that saves you is love,
Lex Fridman (3:13:42.040)
which is one of the things of just watching this pandemic,
Vincent Racaniello (3:13:46.680)
with the distance, with the masks, that's all fine.
Lex Fridman (3:13:50.560)
But there's a distancing from people of that tension,
Vincent Racaniello (3:13:55.560)
the breaking of the common humanity between people.
Lex Fridman (3:13:59.240)
That's one of the reasons when I came to Austin
Vincent Racaniello (3:14:02.280)
earlier this year just to visit,
Lex Fridman (3:14:05.200)
I fell in love with the city
Vincent Racaniello (3:14:06.440)
because even with the masks and the distance,
Lex Fridman (3:14:09.040)
there was still a camaraderie, like, I don't know,
Vincent Racaniello (3:14:14.600)
just a love for each other,
Lex Fridman (3:14:15.800)
just a kindness towards each other.
Lex Fridman (3:14:18.040)
And that's why I took away from The Plague.
Lex Fridman (3:14:20.840)
Mostly it's told to the story of the doctor
Vincent Racaniello (3:14:23.400)
who basically gives in
Lex Fridman (3:14:27.000)
and just gives himself as a service to others.
Lex Fridman (3:14:30.480)
And that love is the thing that liberates him
Lex Fridman (3:14:33.000)
from his own conception of mortality,
Vincent Racaniello (3:14:34.680)
the fact that he's here, he's going to die.
Lex Fridman (3:14:37.920)
What do you think about the effect of the virus?
Vincent Racaniello (3:14:41.760)
We talked a lot about biology,
Lex Fridman (3:14:43.080)
but the effect of the virus
Vincent Racaniello (3:14:45.280)
on the fabric of the common humanity that connects us.
Lex Fridman (3:14:50.280)
Well, that's what a pandemic does.
Lex Fridman (3:14:54.200)
It really cuts that, right?
Lex Fridman (3:14:56.280)
Because small outbreaks, they're local,
Vincent Racaniello (3:14:58.440)
they don't have global effects.
Lex Fridman (3:15:00.880)
But when you have something this big
Vincent Racaniello (3:15:03.080)
where pretty much nobody escapes,
Lex Fridman (3:15:07.440)
and not just making people sick,
Lex Fridman (3:15:10.200)
it changes your life, right?
Lex Fridman (3:15:12.480)
People lose jobs, they change jobs,
Vincent Racaniello (3:15:14.600)
they move somewhere else.
Lex Fridman (3:15:17.240)
They have all kinds of disruptions.
Vincent Racaniello (3:15:20.000)
You know, kids can't go to school.
Lex Fridman (3:15:22.080)
It really shows you.
Vincent Racaniello (3:15:23.560)
I mean, I always like to say,
Lex Fridman (3:15:25.520)
a tiny virus can bring Earth to its knees.
Vincent Racaniello (3:15:30.240)
A tiny virus that you can't even see them,
Lex Fridman (3:15:31.920)
that most people don't even think about most of the time.
Lex Fridman (3:15:35.240)
And the real effect is not just sickness,
Lex Fridman (3:15:37.720)
it's what it does to people.
Vincent Racaniello (3:15:39.240)
Because in the end, we are animals,
Lex Fridman (3:15:42.800)
and most animals like each other, and they interact,
Vincent Racaniello (3:15:46.040)
they have great social structures,
Lex Fridman (3:15:47.600)
and that makes them do well.
Lex Fridman (3:15:49.960)
And I guess the exception is people in AI, right?
Lex Fridman (3:15:53.320)
They could be on their own.
Vincent Racaniello (3:15:56.600)
Well, that's why you build robots,
Lex Fridman (3:15:57.840)
that you fall in love with.
Vincent Racaniello (3:15:58.960)
That's right.
Lex Fridman (3:15:59.800)
And so I think when a,
Vincent Racaniello (3:16:02.000)
the real story is what it does to society, for sure.
Lex Fridman (3:16:06.040)
Which has ramifications way beyond
Vincent Racaniello (3:16:08.640)
the number of people dying,
Lex Fridman (3:16:10.520)
and the vaccines, and the tests, and all of that.
Lex Fridman (3:16:12.720)
And this one has really made a big rupture.
Lex Fridman (3:16:15.640)
And you could tell, not now so much,
Vincent Racaniello (3:16:17.360)
I think being out and about now,
Lex Fridman (3:16:18.680)
things look pretty normal,
Vincent Racaniello (3:16:21.080)
except for some people wearing masks.
Lex Fridman (3:16:23.760)
You would never know.
Vincent Racaniello (3:16:25.000)
I mean, the airport this morning was completely jammed.
Lex Fridman (3:16:28.200)
People going, and they're all on vacation,
Lex Fridman (3:16:29.680)
they're all wearing shorts, right?
Lex Fridman (3:16:31.480)
So they're back to normal.
Vincent Racaniello (3:16:32.960)
It's August.
Lex Fridman (3:16:34.320)
But last year is really different.
Vincent Racaniello (3:16:36.800)
In New York, where you're used
Lex Fridman (3:16:38.880)
to lots of people on the street, it was eerie.
Vincent Racaniello (3:16:41.160)
It was just quiet.
Lex Fridman (3:16:43.040)
But under it all, people are still,
Lex Fridman (3:16:46.000)
most people help each other when they have to, right?
Lex Fridman (3:16:50.120)
Most people are willing to,
Vincent Racaniello (3:16:52.320)
if something happens to someone,
Lex Fridman (3:16:53.640)
to reach out and help them.
Vincent Racaniello (3:16:56.360)
There are always exceptions where people are mean,
Lex Fridman (3:16:58.840)
and that's just the way animals are.
Vincent Racaniello (3:17:01.880)
We're not the only ones that can be mean to our own species.
Lex Fridman (3:17:05.280)
But I think most of the motivation
Vincent Racaniello (3:17:08.680)
for everything that was done is to help other people.
Lex Fridman (3:17:12.200)
I mean, I do think that the vaccine manufacturers,
Vincent Racaniello (3:17:15.600)
maybe not the leaders, but the people working in the labs
Lex Fridman (3:17:18.120)
really wanted to get this out quickly
Lex Fridman (3:17:20.480)
and help people, right?
Lex Fridman (3:17:22.720)
I think at every level, people who are contributing
Vincent Racaniello (3:17:26.320)
really wanted to help other people
Lex Fridman (3:17:27.920)
and feel proud that they're able to do that.
Lex Fridman (3:17:30.160)
So I view it as we're never gonna be 100% good
Lex Fridman (3:17:35.640)
because animals are not.
Vincent Racaniello (3:17:37.640)
Evolution made us, I mean, we're lucky.
Lex Fridman (3:17:40.440)
We somehow rose above by having incredible brain
Lex Fridman (3:17:43.480)
and so forth, but a lot of our base instincts
Lex Fridman (3:17:45.520)
are animals, and they chase each other
Lex Fridman (3:17:47.920)
and have alpha males and all that stuff,
Lex Fridman (3:17:51.200)
and we always have a little bit of that in us.
Lex Fridman (3:17:53.440)
But we do have some humanity
Lex Fridman (3:17:56.800)
that this really ripped up, it really did.
Lex Fridman (3:18:00.960)
And I think for me, someone who studied viruses
Lex Fridman (3:18:05.160)
for over 40 years, it's just amazing
Lex Fridman (3:18:07.760)
that an invisible thing can do that, right?
Lex Fridman (3:18:11.240)
It goes back to the thing you found fascinating,
Vincent Racaniello (3:18:13.320)
which is a virus affecting human behavior.
Lex Fridman (3:18:15.200)
Yes.
Vincent Racaniello (3:18:16.040)
Or behavior of the organism.
Lex Fridman (3:18:18.680)
Yes, so humans can make weapons and do harm
Lex Fridman (3:18:22.920)
and you can see that, but this you can't even see.
Lex Fridman (3:18:25.280)
Yeah.
Vincent Racaniello (3:18:26.240)
You can't, and look what it has done.
Lex Fridman (3:18:27.640)
And it'll do it again, there'll be more.
Vincent Racaniello (3:18:29.720)
I just, I wish we would be more prepared
Lex Fridman (3:18:32.800)
because we know what to do.
Vincent Racaniello (3:18:34.800)
We know we should be making antivirals vaccines,
Lex Fridman (3:18:38.120)
masks, testing masks, making test modalities
Vincent Racaniello (3:18:42.080)
that we can really quickly redesign.
Lex Fridman (3:18:46.120)
But after SARS one, all that went out the door.
Vincent Racaniello (3:18:49.080)
People didn't do anything,
Lex Fridman (3:18:50.160)
and that's why we're in this situation.
Lex Fridman (3:18:51.880)
So people ask me this all the time,
Lex Fridman (3:18:54.840)
are we gonna be ready for the next one?
Lex Fridman (3:18:57.800)
And I always say, we should be.
Lex Fridman (3:18:59.520)
We have all the information we need to know what to do.
Lex Fridman (3:19:03.000)
But somehow I think people forget.
Lex Fridman (3:19:05.840)
That said, sometimes we really step up
Vincent Racaniello (3:19:12.760)
when the tragedies run in front of us.
Lex Fridman (3:19:14.840)
We do.
Vincent Racaniello (3:19:15.680)
When the catastrophe.
Lex Fridman (3:19:16.520)
So I don't know, somehow humans have still survived.
Vincent Racaniello (3:19:18.720)
The fact that we had nuclear weapons for so many decades
Lex Fridman (3:19:21.080)
and we still have not blown each other up,
Vincent Racaniello (3:19:23.120)
whether by terrorists or by nation is quite surprising.
Lex Fridman (3:19:27.520)
That's always, after reading the Pentagon Papers,
Lex Fridman (3:19:30.640)
it's even more amazing, right?
Lex Fridman (3:19:32.920)
So I don't know how we do it.
Vincent Racaniello (3:19:34.400)
I tend to believe there's that at the surface,
Lex Fridman (3:19:40.280)
you notice the greed, the corruption, the evil,
Lex Fridman (3:19:43.480)
but the core of human nature, the human spirit
Lex Fridman (3:19:46.560)
is one in the scientific realm is curiosity,
Lex Fridman (3:19:50.840)
and more deeply is kindness, compassion,
Lex Fridman (3:19:54.280)
and wanting to do good for the world.
Vincent Racaniello (3:19:56.800)
I believe that desire to do good outpowers
Lex Fridman (3:20:00.160)
all the other stuff by a large amount.
Lex Fridman (3:20:03.000)
And that's why we have not yet destroyed ourselves.
Lex Fridman (3:20:06.960)
There's a lot of bickering.
Vincent Racaniello (3:20:08.320)
There's a lot of wars on the surface,
Lex Fridman (3:20:10.360)
but underneath it all,
Vincent Racaniello (3:20:11.520)
there's this ocean of love for each other.
Lex Fridman (3:20:16.240)
I mean, I think there's an evolutionary advantage to that.
Lex Fridman (3:20:21.280)
And it would be a good explanation
Lex Fridman (3:20:23.640)
why we still haven't destroyed ourselves.
Vincent Racaniello (3:20:25.440)
God, we had so many opportunities.
Lex Fridman (3:20:27.440)
If you look at all the wars in history, so many.
Vincent Racaniello (3:20:29.840)
I was just, my son was telling me
Lex Fridman (3:20:33.360)
about the Ottoman Empire, right?
Vincent Racaniello (3:20:35.880)
I mean, it's just war after war,
Lex Fridman (3:20:39.520)
and then other countries splitting up countries
Lex Fridman (3:20:42.120)
with no regard to who's living where, right?
Lex Fridman (3:20:46.560)
It's just, how can these people do this?
Vincent Racaniello (3:20:49.440)
Yeah, it's fascinating.
Lex Fridman (3:20:50.840)
Human history is fascinating,
Lex Fridman (3:20:52.040)
and we're still young as a species.
Lex Fridman (3:20:54.600)
We have a lot more time to go,
Lex Fridman (3:20:57.360)
and a lot more ways to destroy ourselves.
Lex Fridman (3:21:00.520)
Do you have advice?
Vincent Racaniello (3:21:01.660)
Like you said, you have many decades of research
Lex Fridman (3:21:03.880)
and an incredible career and life.
Lex Fridman (3:21:06.400)
Do you have advice for young people about career,
Lex Fridman (3:21:09.880)
about life, people in high school, people in college,
Lex Fridman (3:21:13.360)
of how to live a life they can be proud of?
Lex Fridman (3:21:17.460)
So what I like to do is tell people,
Vincent Racaniello (3:21:20.000)
don't plan it, because I didn't plan anything.
Lex Fridman (3:21:22.360)
Everything I did was one step at a time.
Vincent Racaniello (3:21:25.000)
You don't have to plan.
Lex Fridman (3:21:26.660)
I just found things that were interesting to me.
Lex Fridman (3:21:30.800)
And so my father was a doctor,
Lex Fridman (3:21:33.440)
and he wanted me to be a doctor,
Lex Fridman (3:21:35.780)
but I was not interested in taking care of people.
Lex Fridman (3:21:39.040)
I learned that, but I couldn't say no to him.
Lex Fridman (3:21:43.160)
So I was a biology major in college,
Lex Fridman (3:21:46.320)
and I graduated, and I didn't have anything to do.
Lex Fridman (3:21:51.660)
So I liked science, so I got a job in a lab.
Lex Fridman (3:21:54.800)
And it was very exciting,
Lex Fridman (3:21:57.720)
and that led to everything else
Lex Fridman (3:22:00.680)
that I've done one step at a time.
Lex Fridman (3:22:02.880)
And I think the most important thing you can do,
Lex Fridman (3:22:05.800)
well, there are two important things.
Vincent Racaniello (3:22:06.960)
You can be really curious all the time.
Lex Fridman (3:22:08.640)
You mentioned curiosity.
Vincent Racaniello (3:22:10.040)
I think curiosity is essential.
Lex Fridman (3:22:12.980)
You have to be curious about everything.
Lex Fridman (3:22:15.580)
And if you are, you're never gonna be bored.
Lex Fridman (3:22:19.240)
And so people who say they're bored,
Vincent Racaniello (3:22:20.920)
I say, you are not curious.
Lex Fridman (3:22:22.520)
You should just think about things
Lex Fridman (3:22:24.200)
and say, look at something and say, how does that work?
Lex Fridman (3:22:27.440)
Or what is it doing, and how do they get there?
Lex Fridman (3:22:29.320)
And you'll never be bored.
Lex Fridman (3:22:30.480)
And the other thing is when you find something,
Vincent Racaniello (3:22:32.840)
which may take time, it's fine.
Lex Fridman (3:22:36.960)
You have to be passionate about it.
Vincent Racaniello (3:22:38.540)
You have to put everything into it.
Lex Fridman (3:22:40.860)
And that's what I did with viruses.
Lex Fridman (3:22:42.920)
So I think they're amazing.
Lex Fridman (3:22:46.240)
And I tell my classes, I love viruses.
Vincent Racaniello (3:22:51.160)
They're amazing, and people think I'm morbid
Lex Fridman (3:22:53.120)
because obviously they kill people,
Lex Fridman (3:22:55.320)
and I shouldn't love something.
Lex Fridman (3:22:56.560)
But that's not the point.
Vincent Racaniello (3:22:57.480)
That's not what I mean.
Lex Fridman (3:22:58.320)
I love them in the way they have emerged
Lex Fridman (3:23:00.520)
and how they work and so forth
Lex Fridman (3:23:03.080)
and all that we don't know about them.
Lex Fridman (3:23:04.240)
So you need to be curious and passionate,
Lex Fridman (3:23:06.240)
and don't plan too much.
Lex Fridman (3:23:07.720)
And just find something that you don't call a job.
Lex Fridman (3:23:12.240)
As someone said on the livestream last week,
Vincent Racaniello (3:23:14.520)
I wish I had a job I liked as much as you.
Lex Fridman (3:23:17.360)
I said, it's not a job.
Vincent Racaniello (3:23:18.440)
I never looked at it as a job.
Lex Fridman (3:23:20.400)
It's my vocation, it's my passion.
Vincent Racaniello (3:23:23.720)
If it's a job, then you're not gonna like it.
Lex Fridman (3:23:25.880)
Yeah, something that doesn't feel like a job.
Lex Fridman (3:23:28.400)
So you said viruses are kind of passive,
Lex Fridman (3:23:33.880)
nonliving, you could say, or even cells are passive.
Lex Fridman (3:23:38.520)
And humans are kind of active.
Lex Fridman (3:23:39.840)
We seem to be making our own decisions.
Lex Fridman (3:23:42.320)
So let me ask you the why question.
Lex Fridman (3:23:44.720)
What do you think is the meaning of this life of ours?
Vincent Racaniello (3:23:47.620)
Oh, there's no meaning.
Lex Fridman (3:23:49.780)
It just happened.
Vincent Racaniello (3:23:51.340)
It's an accident.
Lex Fridman (3:23:53.500)
I think there's no life elsewhere
Vincent Racaniello (3:23:55.020)
because this is just a rare accident
Lex Fridman (3:23:56.740)
that happened in the right conditions.
Vincent Racaniello (3:23:58.660)
I mean, people all think I'm wrong
Lex Fridman (3:24:00.300)
because there are billions and billions
Lex Fridman (3:24:01.700)
of stars out there, right?
Lex Fridman (3:24:02.860)
So there's a lot of opportunity.
Vincent Racaniello (3:24:05.140)
There's no meaning.
Lex Fridman (3:24:06.260)
It's just, what do they call it?
Vincent Racaniello (3:24:10.500)
A perfect storm of events
Lex Fridman (3:24:12.660)
that led to molecules being formed.
Lex Fridman (3:24:14.900)
And eventually, I mean, it took a long time
Lex Fridman (3:24:17.260)
for life to evolve, right?
Lex Fridman (3:24:19.900)
But it's just driven by conditions.
Lex Fridman (3:24:23.980)
If something emerged that worked,
Vincent Racaniello (3:24:25.500)
it would then go on to the next step.
Lex Fridman (3:24:26.980)
There's no meaning other than that.
Vincent Racaniello (3:24:29.140)
The only difference is that we,
Lex Fridman (3:24:32.180)
and I think many other animals can probably,
Lex Fridman (3:24:34.060)
we have the ability, we're sentient, right?
Lex Fridman (3:24:36.020)
We can influence what happens to us.
Lex Fridman (3:24:39.160)
We can take medicines, right?
Lex Fridman (3:24:41.420)
We can alter what would normally happen to us.
Lex Fridman (3:24:44.420)
So we can remove some of the selection pressure.
Lex Fridman (3:24:48.740)
But I think everything else on the planet
Vincent Racaniello (3:24:50.840)
just goes, looks for food and give a lot of offspring
Lex Fridman (3:24:55.180)
so you can perpetuate.
Vincent Racaniello (3:24:56.220)
It's just a natural biological function.
Lex Fridman (3:24:58.740)
Yeah, they're much more directly concerned with survival.
Vincent Racaniello (3:25:01.980)
I think humans are able to contemplate their mortality.
Lex Fridman (3:25:04.620)
We can see that even if we're okay today,
Vincent Racaniello (3:25:08.500)
we're eventually going to die
Lex Fridman (3:25:10.300)
and we really don't like that.
Lex Fridman (3:25:13.020)
So we try to come up with ways to push that deadline
Lex Fridman (3:25:16.140)
farther and farther away.
Vincent Racaniello (3:25:17.060)
Well, we have really, I mean,
Lex Fridman (3:25:18.740)
we used to die in our 30s, right?
Vincent Racaniello (3:25:20.460)
Now it's 70s, 80s.
Lex Fridman (3:25:22.020)
Well, most of us used to die in the first few weeks.
Vincent Racaniello (3:25:26.140)
That's true.
Lex Fridman (3:25:27.260)
Yeah, infant death.
Vincent Racaniello (3:25:29.140)
I always tell people the only thing that's 100% is death.
Lex Fridman (3:25:34.260)
It's the only thing in the world that's 100%.
Lex Fridman (3:25:36.300)
Do you think about your own mortality?
Lex Fridman (3:25:37.700)
No, I never think about it.
Vincent Racaniello (3:25:39.020)
I'm just enjoying day to day and I don't think about it.
Lex Fridman (3:25:42.220)
Really?
Vincent Racaniello (3:25:43.060)
You work on viruses.
Lex Fridman (3:25:44.140)
You don't contemplate your own mortality
Lex Fridman (3:25:47.580)
given the deadliness of the viruses around us?
Lex Fridman (3:25:51.660)
I never thought COVID would kill me.
Vincent Racaniello (3:25:53.580)
No, I never was afraid of that.
Lex Fridman (3:25:55.460)
Not at all.
Vincent Racaniello (3:25:56.460)
I mostly feared for other people getting sick,
Lex Fridman (3:26:00.380)
especially people who could die of it.
Vincent Racaniello (3:26:02.380)
I didn't want that to happen to them.
Lex Fridman (3:26:03.600)
But I always thought that it's obviously
Vincent Racaniello (3:26:06.860)
not a realistic viewpoint not to be worried
Lex Fridman (3:26:10.740)
because many people are.
Lex Fridman (3:26:13.820)
But I've been relatively healthy.
Lex Fridman (3:26:17.100)
They should sequence my genome because it works really well
Lex Fridman (3:26:19.740)
and I have a good immune system.
Lex Fridman (3:26:21.260)
Maybe you'd be the first immortal person.
Vincent Racaniello (3:26:24.100)
There's gotta be a first.
Lex Fridman (3:26:25.820)
I don't think so.
Vincent Racaniello (3:26:27.100)
I think that biologically you just can't,
Lex Fridman (3:26:31.180)
the ends of our chromosomes keep getting
Vincent Racaniello (3:26:32.940)
shorter and shorter and that's eventually what kills us.
Lex Fridman (3:26:37.200)
So you just can't keep going on.
Lex Fridman (3:26:39.580)
But that's fine, I don't need to.
Lex Fridman (3:26:42.220)
I understand from the vampires
Vincent Racaniello (3:26:43.700)
that it's not good to live forever.
Lex Fridman (3:26:47.340)
I guess make the most of the time you got.
Vincent Racaniello (3:26:50.380)
That's the, bacteria live a much shorter time
Lex Fridman (3:26:53.200)
so we got that on bacteria.
Vincent Racaniello (3:26:55.180)
Bacteria are just little bags of chemicals that split.
Lex Fridman (3:27:00.100)
So they have no stake in the matter at all.
Vincent Racaniello (3:27:05.260)
It doesn't bother.
Lex Fridman (3:27:06.540)
I think that you have to go a long ways
Vincent Racaniello (3:27:08.180)
before you get into some kind of consciousness.
Lex Fridman (3:27:12.960)
Yeah, it's weird that this bag of chemicals
Vincent Racaniello (3:27:15.420)
has a stake in the matter.
Lex Fridman (3:27:17.040)
Like our human body, consciousness is a weird thing.
Vincent Racaniello (3:27:21.380)
Not just in us, but they make half of the oxygen
Lex Fridman (3:27:23.540)
on the planet.
Vincent Racaniello (3:27:24.380)
20% of the oxygen comes from bacteria.
Lex Fridman (3:27:27.920)
And they made, in the beginning of Earth,
Vincent Racaniello (3:27:29.900)
they made enough oxygen to start oxygenation going,
Lex Fridman (3:27:34.060)
life going.
Vincent Racaniello (3:27:34.900)
I mean, they have an incredible role.
Lex Fridman (3:27:36.500)
It's all an accident, just happened.
Vincent Racaniello (3:27:40.500)
Well, Vincent, like I told you, I'm a huge fan.
Lex Fridman (3:27:44.660)
It's a big honor that you would talk to me today.
Vincent Racaniello (3:27:47.060)
Thank you so much for coming down.
Lex Fridman (3:27:48.420)
Thank you for spending so much time with me.
Lex Fridman (3:27:51.660)
And thank you for everything you do
Lex Fridman (3:27:53.020)
in terms of educating about viruses,
Vincent Racaniello (3:27:54.900)
about biology, microbiology, and everything else.
Lex Fridman (3:27:57.300)
I can't wait.
Vincent Racaniello (3:27:58.160)
Everybody should check out Vincent's YouTube,
Lex Fridman (3:28:00.540)
watch his lectures, listen to the podcast.
Vincent Racaniello (3:28:03.020)
It's truly incredible.
Lex Fridman (3:28:05.060)
Thank you so much for talking to me, Vincent.
Vincent Racaniello (3:28:06.780)
My pleasure.
Lex Fridman (3:28:08.220)
Thanks for listening to this conversation
Vincent Racaniello (3:28:10.220)
with Vincent Racaniello.
Lex Fridman (3:28:12.260)
To support this podcast,
Vincent Racaniello (3:28:13.380)
please check out our sponsors in the description.
Lex Fridman (3:28:16.540)
And now, let me leave you with some words
Vincent Racaniello (3:28:18.740)
from Isaac Asimov.
Lex Fridman (3:28:20.980)
The saddest aspect of life right now
Vincent Racaniello (3:28:23.140)
is that science gathers knowledge
Lex Fridman (3:28:25.380)
faster than society gathers wisdom.
Vincent Racaniello (3:28:27.720)
Thank you for listening and hope to see you next time.
Lex Fridman (40:00.520)
to get them into the cell.
Lex Fridman (40:01.480)
But everything else, yeah, the virus binds
Lex Fridman (40:03.560)
to something on the surface, very specific.
Vincent Racaniello (40:05.360)
It's taken into the cell because that's what cells do.
Lex Fridman (40:09.000)
When things bind their exterior, they take it in.
Vincent Racaniello (40:12.600)
Because in most cases, it's good.
Lex Fridman (40:14.280)
It's something they need.
Lex Fridman (40:15.800)
And so the virus slips in.
Lex Fridman (40:17.200)
I guess you'd call that a Trojan horse, right?
Vincent Racaniello (40:19.200)
Trojan horse.
Lex Fridman (40:20.040)
It's so hard to not anthropomorphize this whole thing.
Vincent Racaniello (40:23.280)
It is hard.
Lex Fridman (40:24.160)
So obviously, they don't know any of this.
Vincent Racaniello (40:26.960)
It's not an actual Trojan horse.
Lex Fridman (40:29.400)
So they're not getting actually tricked
Vincent Racaniello (40:32.760)
in the way humans trick each other.
Lex Fridman (40:34.600)
No, it's all passive.
Lex Fridman (40:35.720)
And it's just through so many years of evolution,
Lex Fridman (40:38.600)
you select something that works, and it continues.
Lex Fridman (40:42.920)
And what survives then goes on
Lex Fridman (40:44.920)
with perhaps a slightly different approach.
Vincent Racaniello (40:48.280)
I love this idea of passive.
Lex Fridman (40:49.720)
Of course, according to Sam Harris,
Lex Fridman (40:52.040)
so for my sufficiently intelligent alien civilization
Lex Fridman (40:54.840)
observing humans, our behavior might seem passive too
Vincent Racaniello (40:58.080)
because they understand fully exactly what we're doing.
Lex Fridman (41:00.800)
And then there's no free will,
Lex Fridman (41:02.200)
and we're all just operating in the same way.
Lex Fridman (41:04.040)
Could be.
Vincent Racaniello (41:04.880)
A cell does, but just a much higher level of complexity.
Lex Fridman (41:07.760)
Yeah, so I love the distinction between active and passive.
Vincent Racaniello (41:11.760)
I mean, the point is, I think anthropomorphizing
Lex Fridman (41:14.760)
to a certain extent is fine
Vincent Racaniello (41:15.880)
because it helps people understand.
Lex Fridman (41:17.800)
But when you start to say,
Vincent Racaniello (41:19.520)
I think the virus is doing that
Lex Fridman (41:21.040)
because then you're putting a human lens on it,
Lex Fridman (41:24.640)
and you may be wrong.
Lex Fridman (41:26.200)
Yeah.
Vincent Racaniello (41:27.040)
Because you don't know why things happen for a virus.
Lex Fridman (41:30.880)
So right now, we have variants emerging,
Lex Fridman (41:33.400)
and people say, well, I think it's because the antibodies
Lex Fridman (41:35.920)
are selecting for variants.
Vincent Racaniello (41:38.120)
That's a good idea,
Lex Fridman (41:39.080)
but it may not be the only thing that's going on.
Vincent Racaniello (41:41.440)
You start imagining them coming to the table negotiating.
Lex Fridman (41:45.760)
Yeah, you get into trouble with that.
Vincent Racaniello (41:47.920)
That's why I tell my students,
Lex Fridman (41:49.320)
be careful about the anthropomorphizing
Vincent Racaniello (41:51.720)
because you're gonna apply your values to a virus,
Lex Fridman (41:55.880)
and you have different values.
Vincent Racaniello (41:57.040)
You're a human, and you have,
Lex Fridman (41:58.920)
what you think is the reason for this outcome
Vincent Racaniello (42:01.200)
may not be right, that's all.
Lex Fridman (42:02.280)
Just be open minded about it.
Vincent Racaniello (42:04.160)
In both directions.
Lex Fridman (42:05.120)
I actually, one of the things that pushed back
Vincent Racaniello (42:07.680)
on this in the space of robotics,
Lex Fridman (42:10.360)
people, most people in robotics
Vincent Racaniello (42:12.280)
try to not anthropomorphize.
Lex Fridman (42:14.560)
For example, they don't give a gender or a name to robots.
Vincent Racaniello (42:17.480)
They really try to see it as a machine.
Lex Fridman (42:20.000)
And to me, that makes sense in one way,
Lex Fridman (42:23.840)
but it totally doesn't make sense in another.
Lex Fridman (42:25.440)
If that robot is to interact,
Vincent Racaniello (42:27.600)
operate in the human world and interact with humans,
Lex Fridman (42:30.720)
we have to anthropomorphize it
Vincent Racaniello (42:33.880)
in order to understand, as an engineering problem,
Lex Fridman (42:38.880)
how should it operate in a human world?
Vincent Racaniello (42:42.080)
Now, the difference with viruses, the scale of operation,
Lex Fridman (42:46.000)
it doesn't make sense to treat them as humanlike
Vincent Racaniello (42:49.240)
because the scale of operations is much smaller.
Lex Fridman (42:51.560)
But with robots, you're in the same time scale,
Vincent Racaniello (42:54.240)
the same spatial scale.
Lex Fridman (42:55.280)
Of course, in the movies,
Lex Fridman (42:56.240)
they always give them names and personalities, right?
Lex Fridman (42:58.480)
Yeah, well, yeah, that's the,
Lex Fridman (43:00.400)
but that's my argument is we should do the same
Lex Fridman (43:02.960)
when you're trying to solve
Vincent Racaniello (43:03.920)
the engineering problem of robotics too.
Lex Fridman (43:06.280)
It's not just for the movies.
Vincent Racaniello (43:07.760)
Well, let me ask you this,
Lex Fridman (43:08.800)
because you've said, controversially, not really,
Vincent Racaniello (43:12.280)
that viruses are not living.
Lex Fridman (43:17.160)
Defend yourself.
Lex Fridman (43:19.360)
Are viruses alive or not?
Lex Fridman (43:20.600)
So I've seen many people say, oh, they have to be,
Vincent Racaniello (43:22.880)
they have nucleic acids, they evolve, they mutate.
Lex Fridman (43:27.160)
That's all true, but they don't do it on their own.
Vincent Racaniello (43:29.560)
The particles in my mug are just not doing any of that
Lex Fridman (43:32.200)
unless they get into a cell.
Lex Fridman (43:33.960)
So a virus infected cell is alive.
Lex Fridman (43:36.200)
I totally agree with that,
Vincent Racaniello (43:37.800)
because in fact, when a virus gets in a cell,
Lex Fridman (43:40.800)
it converts it into a virus making factory, if you will.
Vincent Racaniello (43:45.280)
It's no longer a cell.
Lex Fridman (43:47.240)
Some people call it a viro cell.
Vincent Racaniello (43:48.920)
I don't really like that, but it's fine.
Lex Fridman (43:51.200)
So that's what I'm talking about.
Vincent Racaniello (43:53.000)
The particle is not alive.
Lex Fridman (43:54.840)
You can have your virus infected cell as alive,
Lex Fridman (43:57.760)
but the particle, it just would not do anything forever
Lex Fridman (44:02.160)
without getting inside of a cell.
Lex Fridman (44:03.840)
But once it's in a cell, it is alive then,
Lex Fridman (44:07.040)
but it's no longer a particle.
Vincent Racaniello (44:08.200)
It's taken apart and nucleic acid is moving
Lex Fridman (44:10.720)
around the cell, it's making proteins.
Vincent Racaniello (44:12.920)
Eventually it makes new particles.
Lex Fridman (44:14.080)
And then those particles released from the cell,
Vincent Racaniello (44:16.440)
they're not living anymore.
Lex Fridman (44:17.960)
So it's kind of, I think it's kind of like a spore,
Vincent Racaniello (44:21.320)
a spore of a, or a seed.
Lex Fridman (44:25.200)
Although the seed just doesn't work because the seeds,
Vincent Racaniello (44:28.120)
the cells in the seed have the ability
Lex Fridman (44:29.840)
to make their own energy and so forth.
Lex Fridman (44:31.920)
But a bacterial spore, and it's the same thing,
Lex Fridman (44:34.400)
doesn't do anything unless you add water and nutrients
Lex Fridman (44:36.520)
and then it starts to divide.
Lex Fridman (44:37.560)
But it doesn't need to get into a cell.
Vincent Racaniello (44:39.040)
It's very different from a virus.
Lex Fridman (44:40.640)
So that's why the particle.
Lex Fridman (44:42.440)
And when people think of virus,
Lex Fridman (44:45.280)
they're always thinking of the particle.
Lex Fridman (44:47.320)
And that's why I say it can't be alive
Lex Fridman (44:49.240)
because the particle can't do anything on its own.
Lex Fridman (44:51.320)
But if you think of a virus as an organism
Lex Fridman (44:53.360)
with a particle phase in a cell,
Vincent Racaniello (44:55.880)
then it makes sense to be alive.
Lex Fridman (44:58.360)
And by the way, when you say particle,
Vincent Racaniello (44:59.880)
you're referring to that structure
Lex Fridman (45:01.160)
that you've been mentioning,
Vincent Racaniello (45:02.000)
some parts of the membrane and not,
Lex Fridman (45:03.440)
that's been called, what is that,
Lex Fridman (45:05.600)
a virion particle or something?
Lex Fridman (45:06.800)
Virion.
Lex Fridman (45:07.640)
So it's what you should have here.
Lex Fridman (45:09.120)
I'll send you one.
Lex Fridman (45:10.280)
And then you can refer to it.
Lex Fridman (45:11.720)
What's the sexiest one to have?
Lex Fridman (45:13.640)
Like what, in terms of particles to have on a table?
Lex Fridman (45:17.920)
Well, unfortunately, the ones that you can 3D print.
Vincent Racaniello (45:21.400)
Oh, they're not going to be super.
Lex Fridman (45:23.520)
They're the ones that we know the structures of, right?
Lex Fridman (45:26.360)
So someone sent me last year
Lex Fridman (45:29.200)
a 3D model of SARS CoV2, and it's beautiful.
Vincent Racaniello (45:32.000)
It's actually cracked open so you can see the RNA
Lex Fridman (45:34.720)
and the spikes are sticking out.
Lex Fridman (45:36.960)
And they even put some antibodies sticking onto the spikes.
Lex Fridman (45:39.760)
And I mean, when I show this on a live stream,
Vincent Racaniello (45:42.760)
people love this.
Lex Fridman (45:43.600)
They go, oh my God, that's beautiful.
Vincent Racaniello (45:45.080)
It is, it's absolutely gorgeous.
Lex Fridman (45:46.640)
I have that.
Vincent Racaniello (45:47.480)
I have my virus that I worked on
Lex Fridman (45:49.520)
most of my career, poliovirus.
Vincent Racaniello (45:50.840)
I have a 3D model of that, which I actually just had made.
Lex Fridman (45:54.200)
It's gorgeous.
Lex Fridman (45:55.040)
And you can have it made in any color you want, right?
Lex Fridman (45:57.600)
What would you say is the most fascinating,
Lex Fridman (46:01.480)
terrifying, surprising, beautiful virus to you?
Lex Fridman (46:05.120)
So of all the viruses you looked at,
Vincent Racaniello (46:08.400)
sometimes when you just sit late at night
Lex Fridman (46:10.920)
with a glass of wine looking over the sunset,
Lex Fridman (46:13.960)
which virus do you think about?
Lex Fridman (46:16.240)
So fulfilling all of those adjectives is hard, right?
Vincent Racaniello (46:21.280)
Fascinating, exciting, terrifying.
Lex Fridman (46:24.920)
Well, the terrifying is an optional one, I think,
Vincent Racaniello (46:27.120)
because maybe that puts a lot of pressure.
Lex Fridman (46:30.200)
See, terrifying, to me, I'm not terrified
Vincent Racaniello (46:34.240)
because I think we can handle most viruses.
Lex Fridman (46:37.560)
As you see with this brand new one that emerged a year ago,
Vincent Racaniello (46:40.720)
we can handle it.
Lex Fridman (46:42.400)
From a virology perspective.
Vincent Racaniello (46:44.120)
Yeah, I mean, the human perspective
Lex Fridman (46:45.600)
is a different story, right?
Vincent Racaniello (46:46.840)
That's always an issue.
Lex Fridman (46:47.840)
But so I think there are a couple of different categories
Vincent Racaniello (46:55.120)
of virus.
Lex Fridman (46:55.960)
You could do the terrifying,
Lex Fridman (46:57.400)
and I think rabies is a terrifying virus
Lex Fridman (47:00.080)
because unless you're vaccinated,
Vincent Racaniello (47:02.360)
100% certainty you're gonna die.
Lex Fridman (47:05.920)
So you get bitten by a rabid raccoon or bat or dog, whatever,
Lex Fridman (47:11.000)
and there's still 70,000 deaths a year of rabies
Lex Fridman (47:15.600)
throughout the world because there are a lot of feral dogs
Vincent Racaniello (47:17.480)
running around that are infected.
Lex Fridman (47:19.080)
Unless you're vaccinated, you're gonna die.
Vincent Racaniello (47:21.720)
There's nothing we can do.
Lex Fridman (47:23.120)
But we do have a vaccine
Vincent Racaniello (47:24.480)
which we can actually give you
Lex Fridman (47:26.440)
even after you've been bitten,
Vincent Racaniello (47:27.800)
which is the only vaccine that works that way.
Lex Fridman (47:31.120)
It's a therapeutic, right?
Vincent Racaniello (47:32.880)
It will treat your illness
Lex Fridman (47:34.840)
because the disease takes so long to develop.
Vincent Racaniello (47:38.720)
Eventually, you get all kinds of neurological issues
Lex Fridman (47:41.240)
and paralysis and so forth, but it takes time,
Lex Fridman (47:44.800)
and you can be vaccinated.
Lex Fridman (47:45.960)
It will prevent that in the meanwhile.
Lex Fridman (47:47.440)
So people always say,
Lex Fridman (47:48.400)
what's the most lethal virus?
Lex Fridman (47:50.280)
Is it Ebola?
Lex Fridman (47:51.120)
I said, no, it's actually rabies.
Vincent Racaniello (47:53.600)
Unless you're vaccinated, it will kill you.
Lex Fridman (47:56.000)
Maybe it's good to linger,
Vincent Racaniello (47:57.800)
because we'll talk about vaccines a few times today.
Lex Fridman (48:01.160)
It's good to linger on cases
Vincent Racaniello (48:04.240)
where vaccines have clearly,
Lex Fridman (48:09.040)
undoubtedly helped human civilization.
Lex Fridman (48:12.280)
And it seems like rabies is a good example.
Lex Fridman (48:15.400)
Oh, rabies is great because everyone knows what happens
Lex Fridman (48:19.000)
when somebody gets rabies, right?
Lex Fridman (48:21.400)
You have fear of water, hydrophobia.
Vincent Racaniello (48:26.160)
Your body becomes spastic and stiff and jerks around,
Lex Fridman (48:31.320)
and you lose consciousness.
Vincent Racaniello (48:33.600)
You can't, no more.
Lex Fridman (48:35.520)
It's not a fun ride to death.
Vincent Racaniello (48:36.640)
It's horrible.
Lex Fridman (48:37.480)
It's a horrible way to die.
Lex Fridman (48:39.200)
So I think most people know that.
Lex Fridman (48:40.880)
It's been popularized enough in media, right?
Lex Fridman (48:44.080)
So that nobody would probably object to getting,
Lex Fridman (48:47.060)
oh, I was just bit by this raccoon and it ran off.
Vincent Racaniello (48:51.000)
Okay, well, we should assume it's rabid.
Lex Fridman (48:53.000)
We should immunize you.
Lex Fridman (48:54.200)
And most people are okay with that,
Lex Fridman (48:56.320)
because they know the consequences.
Lex Fridman (48:57.560)
And it's also pretty rare, right?
Lex Fridman (48:59.880)
It's not like something that you're trying to get
Vincent Racaniello (49:02.120)
into the arms of 250, 300 million Americans.
Lex Fridman (49:06.920)
That's hard.
Lex Fridman (49:07.920)
But the few thousand every year, it's easy.
Lex Fridman (49:11.680)
So the transmissibility is difficult, right?
Vincent Racaniello (49:13.800)
It has to, oh, it's not airborne.
Lex Fridman (49:16.640)
It's not airborne.
Vincent Racaniello (49:17.480)
It's just you have to be bitten.
Lex Fridman (49:19.880)
Although some people claim you could walk into a cave
Lex Fridman (49:24.760)
and the bats breathing out rabies virus could infect you,
Lex Fridman (49:28.340)
but I don't really think that's well substantiated.
Vincent Racaniello (49:32.600)
I think it's a bite.
Lex Fridman (49:33.440)
How would you do a study on that?
Vincent Racaniello (49:34.800)
Yeah, it's very hard to do.
Lex Fridman (49:36.360)
You'd have to collect the vapors in the cave
Lex Fridman (49:38.440)
and show that they're infectious, which,
Lex Fridman (49:40.760)
and by the way, someone emailed me the other day.
Vincent Racaniello (49:43.200)
You'll like this.
Lex Fridman (49:44.260)
They say, why can't we just immunize
Lex Fridman (49:45.760)
all the bats in the world against these viruses?
Lex Fridman (49:49.280)
And I said, well, how would you do that?
Lex Fridman (49:50.500)
There are caves everywhere, right?
Lex Fridman (49:52.320)
Yeah.
Vincent Racaniello (49:53.240)
He said, well, maybe you could just go and aerosolize.
Lex Fridman (49:56.580)
Yeah.
Vincent Racaniello (49:57.420)
It's pretty dangerous.
Lex Fridman (49:58.440)
And then all the bats should have vaccine passports
Vincent Racaniello (50:01.480)
to make sure that they're all.
Lex Fridman (50:02.320)
Yeah, and I said, you have to get their consent
Vincent Racaniello (50:03.840)
before you do it.
Lex Fridman (50:05.340)
But we do immunize wildlife against rabies.
Vincent Racaniello (50:12.060)
We have rabies vaccines for wild animals.
Lex Fridman (50:15.040)
There are a whole bunch of them that get rabies.
Lex Fridman (50:17.400)
And we put it in bait
Lex Fridman (50:19.760)
and drop it from helicopters in the woods
Lex Fridman (50:21.560)
and it drops down the incidence of rabies in people.
Lex Fridman (50:25.160)
People hiking, get bitten and so forth,
Vincent Racaniello (50:27.120)
it drops the incidence.
Lex Fridman (50:28.000)
So we can do that.
Vincent Racaniello (50:29.000)
I didn't know that.
Lex Fridman (50:30.320)
I always wondered how much medical care
Vincent Racaniello (50:32.200)
are we doing for animals in the wild
Lex Fridman (50:34.020)
because I've recently become more and more aware
Lex Fridman (50:37.480)
that animals are living in extreme poverty, right?
Lex Fridman (50:42.000)
Like you don't know, you think like natural, it's great.
Vincent Racaniello (50:45.360)
Like when animals are living on a farm, it's terrible.
Lex Fridman (50:51.800)
But then you also have to compare to like
Lex Fridman (50:53.720)
what life is like in the, or like the zoo.
Lex Fridman (50:56.320)
You have to compare what life is like in the wild.
Vincent Racaniello (50:58.760)
Well, the life in the wild is very tough, I think.
Lex Fridman (51:01.600)
Most animals have to, well, the carnivores anyway,
Lex Fridman (51:03.760)
they have to catch their food every day, right?
Lex Fridman (51:06.160)
And then there's the viruses there.
Vincent Racaniello (51:08.200)
Yeah, viruses as well.
Lex Fridman (51:09.200)
So the rabies immunization is the only one I'm aware of
Vincent Racaniello (51:14.200)
for wild animals.
Lex Fridman (51:17.480)
We do immunize lots of other animals.
Lex Fridman (51:20.640)
So we immunize chickens and pigs and cows,
Lex Fridman (51:24.960)
even fish, farmed fish.
Vincent Racaniello (51:26.600)
We pick each fish up and give it an injection,
Lex Fridman (51:30.080)
you know, when it's a small fish.
Lex Fridman (51:32.520)
But that's mostly so that the farmers get a good yield.
Lex Fridman (51:36.220)
We don't really care about the animals, right?
Vincent Racaniello (51:38.400)
We want a good yield for market.
Lex Fridman (51:41.040)
And then there's some examples where we immunize animals
Vincent Racaniello (51:46.080)
to prevent spillovers into people.
Lex Fridman (51:50.000)
So there's a disease called Hendra in Australia,
Vincent Racaniello (51:53.360)
which was discovered in the 90s.
Lex Fridman (51:57.560)
And it turns out that there are bats, fruit bats,
Vincent Racaniello (51:59.720)
that have this virus, and the bats are fine,
Lex Fridman (52:02.460)
but sometimes they fly into horse stalls
Lex Fridman (52:05.180)
and the horses get infected.
Lex Fridman (52:06.720)
In Australia, it was initially racehorses,
Lex Fridman (52:09.040)
which are very expensive, right?
Lex Fridman (52:11.240)
The horses got infected and they died,
Lex Fridman (52:12.880)
and the humans who would take care of them would die also.
Lex Fridman (52:15.080)
So now they immunize the horses to prevent the,
Vincent Racaniello (52:19.280)
well, to save the horses.
Lex Fridman (52:20.400)
Probably that's the motivation,
Vincent Racaniello (52:21.600)
because these horses are hundreds of thousands of dollars,
Lex Fridman (52:23.880)
right?
Lex Fridman (52:24.720)
And then the people don't get sick
Lex Fridman (52:25.800)
because the horses don't get sick.
Vincent Racaniello (52:27.440)
You don't want to immunize all the people
Lex Fridman (52:29.360)
because it's too rare.
Lex Fridman (52:30.360)
But that approach is called the one world health approach,
Lex Fridman (52:33.960)
which means everything's connected on the planet.
Lex Fridman (52:37.240)
And we have to think of everything in the grander scheme,
Lex Fridman (52:39.320)
not just us.
Vincent Racaniello (52:40.960)
Yeah, so you can immunize some things
Lex Fridman (52:42.920)
along the trajectory that a virus would take.
Vincent Racaniello (52:45.000)
Exactly.
Lex Fridman (52:45.840)
Some living beings.
Vincent Racaniello (52:48.240)
In the Arabian Peninsula,
Lex Fridman (52:49.880)
they have a MERS coronavirus issue every month.
Vincent Racaniello (52:52.640)
There are a couple of cases where a camel
Lex Fridman (52:55.840)
will infect a human, and the human can get very sick.
Vincent Racaniello (52:59.200)
It's a respiratory disease, very much like COVID.
Lex Fridman (53:03.200)
And so camels are very common there.
Vincent Racaniello (53:05.840)
They're raced, they're used as pets, they're eaten.
Lex Fridman (53:10.520)
So there's a lot of human camel contact.
Lex Fridman (53:12.560)
But the number of cases are rare, two a month.
Lex Fridman (53:15.120)
So you don't want to immunize all the humans.
Lex Fridman (53:16.760)
So the idea would be to immunize the camels.
Lex Fridman (53:20.320)
So.
Vincent Racaniello (53:21.160)
I like it.
Lex Fridman (53:22.000)
So, okay, so you put rabies.
Lex Fridman (53:23.720)
But Ebola also is a famously deadly one.
Lex Fridman (53:30.120)
What is it?
Vincent Racaniello (53:30.960)
It kills like, I don't know, 50%, 60% of its.
Lex Fridman (53:33.240)
It could be 50 to 90, but that's in Africa,
Vincent Racaniello (53:37.120)
where the healthcare isn't great.
Lex Fridman (53:38.840)
You saw when the cases of Ebola came to the U.S.,
Vincent Racaniello (53:42.880)
we could take care of it.
Lex Fridman (53:43.800)
We knew how to take care of it.
Vincent Racaniello (53:45.160)
We had fancy hospitals and so forth,
Lex Fridman (53:46.800)
and now we have a vaccine, so we can.
Lex Fridman (53:49.960)
And the vaccine is really good,
Lex Fridman (53:52.280)
but there are many governments in Africa
Vincent Racaniello (53:54.960)
that are suspicious of us,
Lex Fridman (53:56.960)
and they don't want to use our vaccine, so they.
Lex Fridman (53:58.960)
So there's a vaccine for Ebola.
Lex Fridman (54:00.640)
There is, yeah.
Lex Fridman (54:01.480)
And the effectiveness and safety of it,
Lex Fridman (54:04.520)
to how much is understood.
Lex Fridman (54:06.400)
So this is difficult,
Lex Fridman (54:08.480)
because there's not a lot of Ebola, right?
Vincent Racaniello (54:11.880)
It's not a continuous, ongoing thing.
Lex Fridman (54:14.040)
There are sporadic outbreaks here and there.
Vincent Racaniello (54:16.560)
Of a few thousand people.
Lex Fridman (54:17.640)
At most, at most, usually a few hundred.
Lex Fridman (54:19.840)
And the biggest ever, in fact,
Lex Fridman (54:23.000)
this is why we didn't for years have an Ebola vaccine.
Vincent Racaniello (54:25.440)
The U.S. military, together with Canada,
Lex Fridman (54:27.880)
developed an Ebola vaccine for service people, right?
Vincent Racaniello (54:30.560)
They wanted to say, well, we're sending people
Lex Fridman (54:32.120)
into these Ebola areas, we want a vaccine for them.
Lex Fridman (54:34.680)
So they had developed it through all the preclinical,
Lex Fridman (54:38.120)
which means before it goes into people.
Lex Fridman (54:40.960)
And that stopped, because there was no money
Lex Fridman (54:43.240)
to do a phase one and a phase two and a phase three.
Vincent Racaniello (54:46.320)
In fact, for phase two and three,
Lex Fridman (54:47.800)
you need to have infections going on,
Vincent Racaniello (54:49.480)
because you're looking at how well
Lex Fridman (54:50.760)
the vaccine prevents infections, right?
Lex Fridman (54:52.960)
So then there was a West African outbreak in 2015.
Lex Fridman (54:57.000)
2013, 2015.
Vincent Racaniello (54:58.680)
The most cases ever, 25,000.
Lex Fridman (55:00.720)
So they got to test the vaccine.
Lex Fridman (55:03.640)
But they only put it in a few thousand people.
Lex Fridman (55:07.400)
It's not like it's been in hundreds of thousands of people
Vincent Racaniello (55:10.480)
like the COVID vaccines has been.
Lex Fridman (55:12.080)
So it looks like it has high efficacy.
Lex Fridman (55:16.600)
But we'd like to have more data.
Lex Fridman (55:18.560)
Side effects maybe are not so great.
Vincent Racaniello (55:21.440)
There are a couple of different available vaccines.
Lex Fridman (55:23.560)
Some have been tested more than others.
Vincent Racaniello (55:25.840)
I would say this would probably not be widely accepted
Lex Fridman (55:29.760)
in the US.
Lex Fridman (55:31.440)
But then neither would be something over 50%
Lex Fridman (55:36.840)
deadliness of a virus.
Vincent Racaniello (55:38.440)
No, I think if you were, in fact, many physicians
Lex Fridman (55:41.240)
work in countries that have Ebola,
Lex Fridman (55:43.280)
so they get vaccinated, because they understand the choice.
Lex Fridman (55:45.960)
Yeah, right, it's always about the choice.
Vincent Racaniello (55:48.480)
So.
Lex Fridman (55:49.400)
So then one more thing.
Vincent Racaniello (55:50.680)
To answer the interesting,
Lex Fridman (55:53.200)
what are some of the viruses you really are fascinated by?
Vincent Racaniello (55:57.000)
There are a number of viruses that have clearly been shown
Lex Fridman (56:01.240)
to alter host behavior, and that's how they spread.
Vincent Racaniello (56:04.600)
I think those are fascinating.
Lex Fridman (56:05.840)
For example, there are some viruses of plants
Vincent Racaniello (56:11.080)
that are spread by aphids.
Lex Fridman (56:14.920)
And the aphid bites the plant,
Vincent Racaniello (56:16.760)
the virus reproduces in the plant,
Lex Fridman (56:18.880)
and it somehow engineers the plant
Vincent Racaniello (56:21.640)
to give off volatile organics to attract more aphids,
Lex Fridman (56:26.440)
which will spread the virus.
Lex Fridman (56:30.080)
Isn't that amazing?
Lex Fridman (56:31.440)
Yeah.
Lex Fridman (56:32.280)
So that's altering the behavior.
Lex Fridman (56:35.080)
Altering because somehow the virus infecting the plant cells
Vincent Racaniello (56:38.640)
gives off these organics and attracts aphids.
Lex Fridman (56:40.760)
And furthermore, somehow when the aphid bites,
Vincent Racaniello (56:44.720)
it tastes horrible.
Lex Fridman (56:46.280)
So they immediately leave with the virus
Vincent Racaniello (56:48.400)
they've just picked up and go to another plant to spread it.
Lex Fridman (56:51.240)
So they're attracted and then repulsed at the same time.
Lex Fridman (56:53.760)
And obviously you don't want to anthropomorphize this
Lex Fridman (56:55.920)
like a strategy they're taking on.
Vincent Racaniello (56:57.560)
Somehow this worked out.
Lex Fridman (56:58.680)
It worked out this way.
Vincent Racaniello (56:59.840)
It just evolved.
Lex Fridman (57:00.680)
And you know, evolution is sometimes hard to trace, right?
Vincent Racaniello (57:04.280)
Like Darwin famously said,
Lex Fridman (57:06.320)
he could never figure out how an eye evolved
Lex Fridman (57:08.240)
from a single cell, right?
Lex Fridman (57:09.320)
But it did.
Vincent Racaniello (57:11.160)
The more complicated, complex the holistic organism is
Lex Fridman (57:16.120)
that the virus invades,
Lex Fridman (57:18.120)
the less able it is to control that organism, right?
Lex Fridman (57:21.360)
So I wonder if there's viruses
Vincent Racaniello (57:22.600)
that can control human behavior,
Lex Fridman (57:26.800)
you know, to induce more spread of the virus.
Vincent Racaniello (57:32.880)
Well, I don't see why not.
Lex Fridman (57:34.320)
There's not enough humans
Vincent Racaniello (57:35.160)
that's supposed to like evolve through.
Lex Fridman (57:37.080)
Well, we can't do the experiment to test it, right?
Vincent Racaniello (57:39.240)
We have to observe.
Lex Fridman (57:40.080)
And that's always hard when you're observing
Vincent Racaniello (57:41.720)
because there's so many things that can confound
Lex Fridman (57:45.040)
what you're looking at.
Vincent Racaniello (57:45.880)
Yeah, change human behavior, yeah.
Lex Fridman (57:47.520)
I mean, there's so many things that impinge on our behavior,
Lex Fridman (57:50.360)
but yeah, I think it's possible.
Lex Fridman (57:54.960)
I think it's highly possible.
Vincent Racaniello (57:56.520)
If it does it in a plant,
Lex Fridman (57:58.000)
why not change some other organism's behavior?
Vincent Racaniello (58:00.800)
I think it's fine.
Lex Fridman (58:01.640)
Anyway, those fascinate me.
Vincent Racaniello (58:02.480)
There are lots of examples of those that are fascinating
Lex Fridman (58:06.080)
and how they work, people are trying to figure out.
Lex Fridman (58:08.840)
But there's not a lot of money to work on, you know,
Lex Fridman (58:10.680)
insect and plant viruses unless you're going to the USDA.
Lex Fridman (58:13.560)
So they don't get a lot of work moving forward.
Lex Fridman (58:17.120)
Well, is there, if you understand some of those viruses,
Lex Fridman (58:19.800)
is that transferable to human viruses, that understanding?
Lex Fridman (58:23.760)
I think some of it could be, sure.
Vincent Racaniello (58:25.560)
I think the general principles, for example,
Lex Fridman (58:28.160)
how does the virus cause volatile organics to be made?
Vincent Racaniello (58:32.280)
It must be turning on some genes
Lex Fridman (58:34.960)
and you could learn principles from that,
Lex Fridman (58:37.400)
how the virus might do that.
Lex Fridman (58:38.720)
Sure, I think everything is broadly applicable.
Lex Fridman (58:41.320)
So to say it's not useful to study viruses of insects
Lex Fridman (58:46.200)
and plants is just wrong because in science,
Vincent Racaniello (58:49.280)
we probably know this, maybe in your field it's the same.
Lex Fridman (58:52.880)
If you're curious, you're going to run into interesting
Lex Fridman (58:55.040)
things that you never planned on, right?
Lex Fridman (58:57.160)
That's why people like, you can criticize,
Lex Fridman (58:59.680)
why do we want to go on Mars?
Lex Fridman (59:01.280)
Why do we want to colonize Mars?
Lex Fridman (59:03.560)
Well, it's like, why do you want to go to the moon?
Lex Fridman (59:06.600)
The reality is when you do really difficult things,
Vincent Racaniello (59:10.520)
engineering things, like all these inventions
Lex Fridman (59:13.080)
along the way are created.
Vincent Racaniello (59:14.320)
It's kind of fascinating.
Lex Fridman (59:16.080)
Basically just pick a thing that everyone can agree
Vincent Racaniello (59:21.120)
is kind of cool and is really hard and do that.
Lex Fridman (59:24.440)
And then you'll have like thousands of inventions
Vincent Racaniello (59:26.920)
that have nothing to do with the thing.
Lex Fridman (59:28.200)
That's right.
Vincent Racaniello (59:29.040)
I think you should let curious scientists
Lex Fridman (59:32.040)
just follow what they're interested in
Vincent Racaniello (59:34.440)
to a certain extent.
Lex Fridman (59:35.280)
You can't, in science we say we have translational research
Vincent Racaniello (59:38.880)
where we say, okay, here's some money,
Lex Fridman (59:40.200)
go cure cancer or diabetes or heart disease, whatever.
Lex Fridman (59:43.600)
And that's fine.
Lex Fridman (59:44.520)
But that often doesn't work out very well.
Lex Fridman (59:46.680)
What works better is to say, you have a good lab,
Lex Fridman (59:49.840)
you have a good track record,
Vincent Racaniello (59:50.800)
here's some money, here's something.
Lex Fridman (59:52.960)
And that's where PCR, CRISPR, recombinant DNA,
Vincent Racaniello (59:56.840)
all that stuff which has made the field explode,
Lex Fridman (59:59.840)
that's all it came from.
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