back to indexVincent Racaniello: Viruses and Vaccines | Lex Fridman Podcast #216
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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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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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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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It's just actually not my idea.
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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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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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My colleague, Dixon de Palmier, calls viruses 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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Oh, we'll return to that.
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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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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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Birds can give us their viruses that's happened.
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Influenza viruses come from birds mainly.
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So I think those are the three species,
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not species, it's higher than species obviously,
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but those are the three I would worry about
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in terms of getting their viruses.
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And we don't really know what's out there, right?
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We have very little clue about what viruses,
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and I've for years wanted to capture wild mice
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in my backyard and see what viruses they have
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because no one knows.
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We can't ask them, so you mean map,
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like is there a way?
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I can't ask them, yeah.
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No, I would have to sacrifice them and take tissue
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and then bring it in the lab and do genome sequencing.
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So you can do a thorough sequencing
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to determine which viruses.
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Is there a sufficiently good categorization of viruses
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That's a very good question.
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So whenever you do sequence, right?
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You get some environmental sample
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and you extract nucleic acid and you sequence it.
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What you do is you run it past the database.
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The gold standard is the GenBank database
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which is maintained here in the US.
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And you see if you get any hits.
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And then you can say, ah, look,
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this sequence is similar to this virus.
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And you can classify all the viruses you see.
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The problem is 90% of your sequence is dark matter.
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It doesn't hit with anything.
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It's probably a lot of it is unknown viruses.
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And that's gonna be hard to figure out
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because someone's gonna have to go after it
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and sort it through.
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So yes, you can find a lot of viruses
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and the numbers you get are astounding.
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You can find thousands of new viruses
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just by looking in various life forms.
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But there are many more that we don't pick up
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because they're not in the database.
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Maybe this is a good time to take a quick tangent.
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What do you think about Alpha Fold 2?
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I don't know if you've been paying attention to that.
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With them DeepMind solving the protein folding problem
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and then also releasing, first of all,
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open sourcing the code, which is for me
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as a software person, I love.
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And then second of all, also making like 300,000 predictions
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or something like that for different protein structures
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and releasing that data.
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because you're saying there's dark matter.
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Is there something, first, what are your general thoughts,
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level of excitement about their work?
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And second, how can that be applied to viruses?
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Do you think we'll be able to explore
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the dark matter of virology using machine learning?
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Because in all this dark sequence,
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you can translate it and make a protein.
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You can see what a protein looks like.
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It has what we call an open reading frame, right?
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A start and a stop.
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And right now it's just a bunch of amino acids,
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but if we could fold it,
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maybe the fold would be like something we already know,
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some protein fold, which gives you a lot of clues, right?
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Because there are only so many protein folds in biology
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and that dark matter is probably one of them.
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So I think that's very exciting because for years,
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I've followed structural biologists for years
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and in the beginning,
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we couldn't even solve structures of viruses, they're too big.
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We could do small molecules like myoglobin,
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that was the first one done, took years to do that.
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Then as computational power increased,
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then they could start to do viruses,
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but it took a long time.
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X ray crystallography,
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depending on getting crystals of the virus, right?
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And now we can do cryo electron microscopy,
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which is much faster.
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the spike of SARS COVID 2 was solved in two months
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by Jason McClelland here in Austin actually
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at the beginning of the pandemic,
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but you're limited, you can't do huge proteins.
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You can only do moderately sized ones.
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So, or actually you can do viruses,
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but you can't do small proteins.
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So that's speeded it up, but it's still too fast to solve.
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You get a new protein, you wanna solve its structure.
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So if we could predict it,
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and I know from talking to structural biologists,
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this has been their holy grail from day one.
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They wanna be able to take a sequence of a protein,
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put it in a computer and have the structure put out
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without having to do all the experiment.
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So that's why this is very exciting
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that you can predict it.
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That mean it's not finished obviously,
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and there's more to do,
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but I think it will be a day
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where you could take any amino acid sequence
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and predict what it's gonna look like.
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See, but like aren't structural biologists
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So once you have that,
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don't you wanna go more complicated then?
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Don't you wanna go,
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because that's just the first step, right?
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You go from amino acid to the structure,
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then there's like multiple protein interactions.
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Like how do you get to the virus?
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Well, so that's what the ultimate goal
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of getting a structure is that then you can do experiments
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and figure out what the structure means, right?
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So many, in the old days,
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structural biology was a career in itself.
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You worked with people who had a system
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and just solve proteins for them,
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and then you moved on to another one.
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You didn't really do any experiments.
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The other people got to do all the interesting experiments.
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Now, young structural biologists are multifaceted.
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They solve the structure,
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and then they say,
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what happens if we change this amino acid?
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Oh, look, it blocks binding to the receptor.
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This must be the receptor binding interface.
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So that's the exciting stuff, absolutely,
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is doing the experiment.
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Well, I wonder if you can do some kinds of like simulations
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of like, you know, different proteins
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or multi protein systems going to war against each other,
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like to try to figure out, you know,
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reinforcement learning is used in alpha zero, for example,
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to learn chess and go,
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and that's using the self play mechanism
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where the thing plays against itself
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and learns better and better.
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Whether you can, I wonder if you can simulate
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almost evolution in that way
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for primitive biological systems,
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have them in simulation, fight each other,
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and then see what comes out,
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like a super dangerous virus comes out
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or super like Chuck Norris type of thing
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that defends against the super dangerous virus,
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and it's all in simulation.
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So an example would be,
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we have all these variants of SARS COVID 2 arising, right?
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Which look to be selected by immune responses,
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but we know what amino acids are changing in the spike
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and how they block antibody binding.
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You could simulate that.
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You could say, what is the antibody looking at?
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Where antibodies bind on proteins are called epitopes, right?
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You could map them all and change them in a simulation
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one by one and go back and forth
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between the antibody and the virus.
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So all these, evolution is what we call an arms race, right?
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The virus changes and then it evades the host
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and then the host can change.
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The host takes longer to change though, unfortunately.
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It takes geological time, but it can.
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And then the virus can change
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and it can go back and forth.
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And we can see evidence of this in genome sequences
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of both viruses and their hosts.
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And so you can take a protein in a host
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that is a receptor for multiple viruses
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and you can see all the impacts of virus pressure on it.
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And you could simulate that for sure.
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And that's just one thing that you could do.
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You could simulate changes in say an enzyme
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that makes it resistant to a drug
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and predict all the drug resistance.
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But the problem is people like me,
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the experimental virologists
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don't know how to do any of that.
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So we need to collaborate with people, I guess.
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Oh, with other humans.
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We do that, we do that.
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But with people from a field that we're not used to,
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I suppose people who, would it be AI, I suppose?
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Yeah, machine learning people.
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Machine learning people.
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And you would say, look, this is the biological problem.
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Is there a way we can use your tools to attack it?
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The problem is those people are antisocial introverts
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that have a place like this
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and try to hide from other people in the world.
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Very difficult to find in the wild.
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Okay, so outside of doing amazing brilliant lectures online,
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you host and produce five, I would say, related podcasts,
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including my favorite, This Week in Virology,
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also This Week in Parasitism,
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This Week in Microbiology, and so on.
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So you're a good person to ask,
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what are the categories of small things,
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small biological things in this world that can kill you,
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Let's look, you said like most viruses are friendly
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or at least not unfriendly.
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But let's look at the unfriendly ones.
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And viruses and bacteria and those kinds of things.
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When you look at the full spectrum of things
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that can kill you, can you kind of paint a brief picture?
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Yeah, I think the big picture is that
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the things that can kill you are a minority
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of everything that's out there.
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And we're talking about molecules.
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So we have in us proteins that can kill us.
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Preons that are just, it's a protein in us.
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And if it misfolds, it makes all of its other copies misfold
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and then you die of a neurological disease.
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That's pretty rare.
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So there are proteins, there are viruses.
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And as I said, only certain ones can kill us.
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But even if we get those from animals,
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it's not straightforward.
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If you look at SARS CoV2, right?
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This is probably a once in a hundred year pandemic,
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I would say, equivalent to 1918 in its devastation.
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And in between there have been smaller pandemics
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of other viruses, but it doesn't happen all that often.
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So we have a lot of viruses.
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We have a lot of bacteria of various sorts
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that can cause infections in us.
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And it's a limited number, right?
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You're streptococci and staphylococci and clostridia.
link |
We could go on and on, but we know how to handle those.
link |
As long as we have antimicrobials,
link |
it's just that we abuse them and we get resistant.
link |
So that can be a problem.
link |
Then we have fungi, not mushrooms,
link |
but much smaller fungi that multiply sub microscopic
link |
or just at the microscopic level.
link |
They can, in dry climates of the US,
link |
you can inhale their spores and they can grow in your lung
link |
if you're immunosuppressed and so forth.
link |
So those are the tiny guys.
link |
And then we have parasites,
link |
which we do this week in parasitism,
link |
where single cells, even worms of various sorts
link |
can invade you and cause all sorts of problems.
link |
How, I was like kind of terrified to listen to that podcast.
link |
Well, I mean, what you learn is that you can,
link |
you travel somewhere and you can get infected
link |
and bring it back home.
link |
Here in the US, we do have certain kinds of parasites,
link |
but because of our lifestyle,
link |
we more or less have avoided them.
link |
For example, there's a parasite called toxoplasma,
link |
which is infected most of the world, actually,
link |
because a lot of people like to eat raw meat
link |
and you would get it from raw meat.
link |
And we're not as fond of that here in the US.
link |
We like to cook our meat,
link |
but that could be a consequence of eating raw meat.
link |
Is that what leads to, what is it called, toxoplasmosis?
link |
Yeah, so toxoplasmosis, it's mainly,
link |
a big issue is if you're pregnant and you get toxo,
link |
then your fetus is gonna be very badly malformed.
link |
It's gonna have brain defects and so forth.
link |
And animals can get it as well.
link |
So there are a lot of parasites of that nature,
link |
which you often acquire by food,
link |
eating food of different sorts.
link |
And it usually happens elsewhere.
link |
On This Week in Parasitism, we do a case.
link |
So Daniel Griffin is our resident physician.
link |
He's a doctor, a real doctor, right?
link |
And every month, he comes up with a case.
link |
Okay, this is a person I saw.
link |
And last month, this young lady had traveled somewhere
link |
and she ate raw fish.
link |
It was somewhere Southeast Asia or something.
link |
And she ended up with red bumps all over her skin.
link |
And it turned out it was a parasite from the fish
link |
that moved around in her and very easy to cure.
link |
We have, if the right doctors and the right drugs,
link |
you can cure all these things.
link |
What about diagnose, like connect the red spots
link |
to the fact that it's a parasite?
link |
It's very easy if you have the right diagnostics.
link |
Now, Daniel often goes to parts of the world
link |
where they don't have diagnostics
link |
and he has to use other mechanisms.
link |
He may have to take a bit and look at it under a microscope.
link |
And then he may not be able to get the drug
link |
depending on where he is.
link |
But often he sees patients who come back to the US
link |
and they get diarrhea or they have a fever.
link |
And he said, where have you been?
link |
And he can put two and two together.
link |
And so we let our listeners do that.
link |
And they all send in guesses.
link |
And it's wonderful to hear them go through this.
link |
So there are a lot of parasites that can get you.
link |
You have to be careful about eating when you go overseas.
link |
And in parts of Africa, there are parasites in the lakes
link |
that if you go swimming, they can invade you.
link |
And in fact, they can go into your hair follicles
link |
and burrow in and get into your bloodstream.
link |
So Daniel is interesting because he's very adventurous
link |
and he's not afraid of any of this.
link |
So there's a famous lake in Africa, Lake Malawi,
link |
which harbors a lot of these parasites.
link |
And he said, oh yeah, yeah, I just make sure
link |
I towel off vigorously when I get out and get rid of them.
link |
And that was the name of an episode.
link |
But food is, sushi, you can get worms from sushi.
link |
And the solution is to freeze it.
link |
And many sushi restaurants now have liquid nitrogen.
link |
They snap freeze their sushi and that kills all the parasites.
link |
And a study was actually done in Japan
link |
showing that freezing does not alter the taste of sushi
link |
because it's up, you see a big industry there.
link |
Wow, that's brilliant.
link |
Yeah, I was thinking about, I'm so boring and bland
link |
that especially when I am now in Texas here
link |
and I've been eating quite a bit of barbecue,
link |
I realized I really haven't explored the culinary world.
link |
And I've been curious to travel and taste different foods.
link |
Is there something you could say by way of advice,
link |
channeling Daniel, I guess, if you were to travel
link |
in the world, if eating is the thing
link |
that gets you the parasites,
link |
what's a good advice for eating
link |
in strange parts of the world, Mongolia, India, China?
link |
Is there something you could say by way of advice?
link |
I think Daniel would say,
link |
make sure your food is cooked, right?
link |
Cooked, but that's so boring.
link |
Yeah, it's unfortunate.
link |
And he would agree with you
link |
because many vegetables are delicious.
link |
Salads even are delicious, not cooked,
link |
but they can have parasites in them.
link |
Meats, fish, people like to have uncooked fish.
link |
So if you wanna be really safe and boring,
link |
just make sure everything is cooked.
link |
And now we have a case this week on TWIP
link |
of a young man who went, I forgot where he went,
link |
but he stayed in a hotel.
link |
I think, oh, Oaxaca, Mexico.
link |
Stayed in a hotel.
link |
And he came back with diarrhea and fever.
link |
And he said, I don't know where, I stayed in the hotel.
link |
I just ate hotel food, lots of vegetables and fruits,
link |
and probably they weren't washed with clean water.
link |
He got something from that.
link |
The bottom line is most of these infections
link |
with parasites can be diagnosed,
link |
and you can be treated, and you'll be fine.
link |
So if you really wanna experience the cuisine,
link |
I don't think you should worry about it.
link |
That's what Daniel would say.
link |
Let's return to the basics.
link |
We can then jump around all over the place.
link |
What are the basic principles of virology?
link |
Maybe a good place to start is what is a virus?
link |
I mean, I talk in my first lecture for 20 minutes
link |
before I get to that.
link |
But, and I wonder if I should put it up front,
link |
but it's kind of a boring definition.
link |
So if you do that first, people will turn off.
link |
So first you tell them about all the millions and billions
link |
of viruses around.
link |
So a virus, we have a very specific definition
link |
because it's different from everything else on the planet.
link |
Because first of all, it's a parasite.
link |
It takes, a parasite means you take something
link |
from someone else.
link |
We have human parasites who take money from others, right?
link |
But in biological terms, a parasite takes something
link |
from the host that the host would otherwise use energy
link |
or some building block or something.
link |
There's never really a symbiotic relationship
link |
between a virus and a host.
link |
Well, there can be.
link |
So that's the dichotomy I think is that we define them
link |
as parasites, yet I just told you 20 minutes ago
link |
that many viruses are probably beneficial.
link |
So I think what it means is we, at some point
link |
we're gonna have to change our definition, right?
link |
Because after all, definitions we make are just constructs
link |
that make it easy for us to study,
link |
that don't necessarily represent what's right.
link |
Yeah, like Pluto was a planet at first
link |
and now it's not a planet anymore
link |
and a lot of people are very upset.
link |
But it's only according to us.
link |
There may be another race living somewhere else
link |
who thinks it's a planet, right?
link |
Well, maybe that's why viruses are attacking humans.
link |
They're very angry.
link |
They're calling them parasites.
link |
So right now our definition includes parasite
link |
because a virus cannot do anything without a cell.
link |
If this mug were full of viruses,
link |
it would not do anything for years.
link |
It would eventually probably lose its infectivity,
link |
but it's not gonna reproduce here, it needs cells.
link |
And to the first people who discovered viruses,
link |
that was astounding that they didn't just reproduce,
link |
divide on their own like bacteria.
link |
So a virus needs to get inside of a cell,
link |
inside the cell, it can't just hang around on the surface.
link |
It needs to get in in order to make more of itself.
link |
And so we call it an obligate intracellular parasite
link |
because it needs to get in a cell
link |
and then it takes things from the cell
link |
in the form of all kinds of molecules
link |
and processes and energy and so forth to make new viruses.
link |
Obligate means it's obligated to be inside the cell.
link |
Absolutely, it will not reproduce outside of the cell.
link |
So this mug of viruses can in no way be living,
link |
However, once it gets inside of a cell,
link |
now the cell is a virus infected cell, it's alive.
link |
So a virus, in my view, has two phases, right?
link |
It's this nonliving particulate phase
link |
that everyone is used to.
link |
I'll send you, you need a virus for your table.
link |
I'll send you a nice model.
link |
I think it would look good here.
link |
Which, yes, definitely.
link |
You don't have to go with all this other stuff.
link |
Yeah, well, these are all mechanical.
link |
There's no biology here.
link |
So you wouldn't want a virus here?
link |
No, I'd want a virus, of course.
link |
No, I'll send you one and then you can look at it.
link |
Because now that we have the three dimensional structures
link |
solved by structural biologists,
link |
we take the coordinates and we put it in a 3D printer
link |
and you can make amazing models, right?
link |
And so there's a huge variety of viruses?
link |
Huge, that we know of,
link |
which is only a fraction of what's out there.
link |
What's the categories?
link |
So there's RNA, there's DNA viruses.
link |
What are those, what's DNA and RNA?
link |
Two broad categorizations.
link |
RNA, these are genetic material.
link |
Can be two different chemicals.
link |
So RNA, everything else on the planet besides viruses
link |
You and I are DNA based.
link |
Everything on the planet today is DNA based,
link |
except some viruses are RNA based.
link |
And that's because, as I mentioned earlier,
link |
the first life that arose on the planet was RNA based.
link |
Yeah, so these are like old school viruses.
link |
These are old school.
link |
We call relics, yeah.
link |
Relics, and this has got a name,
link |
it's called the RNA world, which I think is great.
link |
Is it big still, or are the relics dying out?
link |
Oh no, the relics, in my opinion,
link |
are the most successful viruses, the RNA viruses.
link |
And SARS CoV2 is an RNA virus.
link |
We can talk about why they're so successful.
link |
But you have, broadly speaking, viruses with RNA,
link |
genetic information, which are relics.
link |
Of course, they're contemporary.
link |
They have adapted to the modern world
link |
and the modern organisms living in it.
link |
And then we have DNA based viruses,
link |
which are extremely conservative and slow.
link |
They're very successful.
link |
Everyone has a herpes virus infection,
link |
but they don't get the news like the RNA viruses do.
link |
The HIVs and the influenza viruses
link |
and the SARS Coronaviruses, they get all the press
link |
and they're RNA based, because RNA lets you change
link |
So they evolve much faster, the RNA viruses.
link |
And in fact, I have an lecture on evolution.
link |
I don't know if you've listened to that one.
link |
You should, it's really, I think it's really interesting.
link |
RNA viruses exist at their error threshold,
link |
which means they can't make any more mutations
link |
when they reproduce, otherwise they're dead.
link |
They would go extinct.
link |
They're evolving at their error threshold.
link |
DNA viruses are hundreds of times lower
link |
than their error thresholds.
link |
And we know this, we can do an experiment to find that out.
link |
Now, why that is, is a good question,
link |
but that's the reason why RNA viruses
link |
are far more successful.
link |
They infect many more hosts and they're very,
link |
I would say slippery.
link |
They can change hosts really quickly,
link |
because in any animal harboring an RNA virus,
link |
like let's say a bat in some cave somewhere,
link |
it's not just one genome.
link |
It's millions of different genomes of all kinds,
link |
all within the framework of, say, coronavirus,
link |
but they're all different.
link |
And one genome in there might just be right
link |
for infecting a person if it ever encountered that person.
link |
I mean, that's the thing that.
link |
Or there could be a large number.
link |
This is a tiny fraction, but a large number of them.
link |
And they're all operating at the threshold of error.
link |
That's fascinating.
link |
It's like little, like it's like startups,
link |
little entrepreneurs, like a startup world.
link |
Yes, and many of them fail.
link |
Yeah, many of them fail.
link |
Many of the changes fail.
link |
And then there's the DNA viruses that are like the IBM
link |
and the Google. Exactly, exactly.
link |
The big corporations.
link |
That's very good, I like that.
link |
They become conservative with the bureaucracies
link |
and all that kind of stuff, so they.
link |
And a lot of baggage.
link |
Yeah, yeah, it's expensive for them to reproduce, yeah.
link |
And they don't move quickly.
link |
Yes, the RNA viruses are the fast moving members.
link |
So that's what a virus is.
link |
We call them ovulated intracellular parasites.
link |
And then I told you there's DNA and RNA,
link |
but then let's go further.
link |
The nucleic acid is not naked.
link |
Because naked nucleic acid in the world isn't good.
link |
I mean, it existed in the precellular world,
link |
but there probably weren't a lot of threats to it then.
link |
Naked nucleic acid doesn't last long in the environment.
link |
So they're covered, the nucleic acid is covered.
link |
It can be covered with a protein shell,
link |
a pure protein shell, or it can have a membrane around it,
link |
which would be lipids from the host cell.
link |
So lipids, so it's a fatty membrane.
link |
Fatty membrane, yeah, so our cells
link |
are coated with fatty membranes, right?
link |
Our cells, the outer plasma membrane, right?
link |
Viruses can be too.
link |
So they're kind of like cells,
link |
but without the ability to do the mitochondria stuff.
link |
Some are, they don't have nuclei,
link |
they don't have mitochondria.
link |
But they do have a nucleic acid, they have a membrane,
link |
and then of course there's spikes in the membrane
link |
that allow them to attach to cells.
link |
And so that completes our two different kinds.
link |
So they have, they all have like attachment mechanisms,
link |
like ways to, like keys into the cell.
link |
They all have to get into cells.
link |
There are a couple of exceptions though.
link |
There are viruses of fungi and plants.
link |
So let's do the fungi.
link |
Fungi would be like yeast.
link |
The yeast cell wall is pretty hard to get through.
link |
So viruses typically don't attach to a yeast
link |
Rather, they just live in the yeast forever.
link |
And they multiply as mostly nucleic acids,
link |
and as the yeast divide, they go into the daughter cells.
link |
And that's how they exist.
link |
Plant viruses, also the plant cell wall
link |
would be very hard to get across by binding a protein.
link |
So plant viruses get into plants either by
link |
pests that inject them in, they're sucking sap out,
link |
and they inject virus at the same time.
link |
Or farmers, they have contaminated farm equipment
link |
and they roll over the plants and introduces viruses.
link |
So those fungi and plant viruses,
link |
they don't have this specific receptor binding
link |
to get them into the cell.
link |
But everything else, yeah, the virus binds
link |
to something on the surface, very specific.
link |
It's taken into the cell because that's what cells do.
link |
When things bind their exterior, they take it in.
link |
Because in most cases, it's good.
link |
It's something they need.
link |
And so the virus slips in.
link |
I guess you'd call that a Trojan horse, right?
link |
It's so hard to not anthropomorphize this whole thing.
link |
So obviously, they don't know any of this.
link |
It's not an actual Trojan horse.
link |
So they're not getting actually tricked
link |
in the way humans trick each other.
link |
No, it's all passive.
link |
And it's just through so many years of evolution,
link |
you select something that works, and it continues.
link |
And what survives then goes on
link |
with perhaps a slightly different approach.
link |
I love this idea of passive.
link |
Of course, according to Sam Harris,
link |
so for my sufficiently intelligent alien civilization
link |
observing humans, our behavior might seem passive too
link |
because they understand fully exactly what we're doing.
link |
And then there's no free will,
link |
and we're all just operating in the same way.
link |
A cell does, but just a much higher level of complexity.
link |
Yeah, so I love the distinction between active and passive.
link |
I mean, the point is, I think anthropomorphizing
link |
to a certain extent is fine
link |
because it helps people understand.
link |
But when you start to say,
link |
I think the virus is doing that
link |
because then you're putting a human lens on it,
link |
and you may be wrong.
link |
Because you don't know why things happen for a virus.
link |
So right now, we have variants emerging,
link |
and people say, well, I think it's because the antibodies
link |
are selecting for variants.
link |
That's a good idea,
link |
but it may not be the only thing that's going on.
link |
You start imagining them coming to the table negotiating.
link |
Yeah, you get into trouble with that.
link |
That's why I tell my students,
link |
be careful about the anthropomorphizing
link |
because you're gonna apply your values to a virus,
link |
and you have different values.
link |
You're a human, and you have,
link |
what you think is the reason for this outcome
link |
may not be right, that's all.
link |
Just be open minded about it.
link |
In both directions.
link |
I actually, one of the things that pushed back
link |
on this in the space of robotics,
link |
people, most people in robotics
link |
try to not anthropomorphize.
link |
For example, they don't give a gender or a name to robots.
link |
They really try to see it as a machine.
link |
And to me, that makes sense in one way,
link |
but it totally doesn't make sense in another.
link |
If that robot is to interact,
link |
operate in the human world and interact with humans,
link |
we have to anthropomorphize it
link |
in order to understand, as an engineering problem,
link |
how should it operate in a human world?
link |
Now, the difference with viruses, the scale of operation,
link |
it doesn't make sense to treat them as humanlike
link |
because the scale of operations is much smaller.
link |
But with robots, you're in the same time scale,
link |
the same spatial scale.
link |
Of course, in the movies,
link |
they always give them names and personalities, right?
link |
Yeah, well, yeah, that's the,
link |
but that's my argument is we should do the same
link |
when you're trying to solve
link |
the engineering problem of robotics too.
link |
It's not just for the movies.
link |
Well, let me ask you this,
link |
because you've said, controversially, not really,
link |
that viruses are not living.
link |
Are viruses alive or not?
link |
So I've seen many people say, oh, they have to be,
link |
they have nucleic acids, they evolve, they mutate.
link |
That's all true, but they don't do it on their own.
link |
The particles in my mug are just not doing any of that
link |
unless they get into a cell.
link |
So a virus infected cell is alive.
link |
I totally agree with that,
link |
because in fact, when a virus gets in a cell,
link |
it converts it into a virus making factory, if you will.
link |
It's no longer a cell.
link |
Some people call it a viro cell.
link |
I don't really like that, but it's fine.
link |
So that's what I'm talking about.
link |
The particle is not alive.
link |
You can have your virus infected cell as alive,
link |
but the particle, it just would not do anything forever
link |
without getting inside of a cell.
link |
But once it's in a cell, it is alive then,
link |
but it's no longer a particle.
link |
It's taken apart and nucleic acid is moving
link |
around the cell, it's making proteins.
link |
Eventually it makes new particles.
link |
And then those particles released from the cell,
link |
they're not living anymore.
link |
So it's kind of, I think it's kind of like a spore,
link |
a spore of a, or a seed.
link |
Although the seed just doesn't work because the seeds,
link |
the cells in the seed have the ability
link |
to make their own energy and so forth.
link |
But a bacterial spore, and it's the same thing,
link |
doesn't do anything unless you add water and nutrients
link |
and then it starts to divide.
link |
But it doesn't need to get into a cell.
link |
It's very different from a virus.
link |
So that's why the particle.
link |
And when people think of virus,
link |
they're always thinking of the particle.
link |
And that's why I say it can't be alive
link |
because the particle can't do anything on its own.
link |
But if you think of a virus as an organism
link |
with a particle phase in a cell,
link |
then it makes sense to be alive.
link |
And by the way, when you say particle,
link |
you're referring to that structure
link |
that you've been mentioning,
link |
some parts of the membrane and not,
link |
that's been called, what is that,
link |
a virion particle or something?
link |
So it's what you should have here.
link |
I'll send you one.
link |
And then you can refer to it.
link |
What's the sexiest one to have?
link |
Like what, in terms of particles to have on a table?
link |
Well, unfortunately, the ones that you can 3D print.
link |
Oh, they're not going to be super.
link |
They're the ones that we know the structures of, right?
link |
So someone sent me last year
link |
a 3D model of SARS CoV2, and it's beautiful.
link |
It's actually cracked open so you can see the RNA
link |
and the spikes are sticking out.
link |
And they even put some antibodies sticking onto the spikes.
link |
And I mean, when I show this on a live stream,
link |
They go, oh my God, that's beautiful.
link |
It is, it's absolutely gorgeous.
link |
I have my virus that I worked on
link |
most of my career, poliovirus.
link |
I have a 3D model of that, which I actually just had made.
link |
And you can have it made in any color you want, right?
link |
What would you say is the most fascinating,
link |
terrifying, surprising, beautiful virus to you?
link |
So of all the viruses you looked at,
link |
sometimes when you just sit late at night
link |
with a glass of wine looking over the sunset,
link |
which virus do you think about?
link |
So fulfilling all of those adjectives is hard, right?
link |
Fascinating, exciting, terrifying.
link |
Well, the terrifying is an optional one, I think,
link |
because maybe that puts a lot of pressure.
link |
See, terrifying, to me, I'm not terrified
link |
because I think we can handle most viruses.
link |
As you see with this brand new one that emerged a year ago,
link |
From a virology perspective.
link |
Yeah, I mean, the human perspective
link |
is a different story, right?
link |
That's always an issue.
link |
But so I think there are a couple of different categories
link |
You could do the terrifying,
link |
and I think rabies is a terrifying virus
link |
because unless you're vaccinated,
link |
100% certainty you're gonna die.
link |
So you get bitten by a rabid raccoon or bat or dog, whatever,
link |
and there's still 70,000 deaths a year of rabies
link |
throughout the world because there are a lot of feral dogs
link |
running around that are infected.
link |
Unless you're vaccinated, you're gonna die.
link |
There's nothing we can do.
link |
But we do have a vaccine
link |
which we can actually give you
link |
even after you've been bitten,
link |
which is the only vaccine that works that way.
link |
It's a therapeutic, right?
link |
It will treat your illness
link |
because the disease takes so long to develop.
link |
Eventually, you get all kinds of neurological issues
link |
and paralysis and so forth, but it takes time,
link |
and you can be vaccinated.
link |
It will prevent that in the meanwhile.
link |
So people always say,
link |
what's the most lethal virus?
link |
I said, no, it's actually rabies.
link |
Unless you're vaccinated, it will kill you.
link |
Maybe it's good to linger,
link |
because we'll talk about vaccines a few times today.
link |
It's good to linger on cases
link |
where vaccines have clearly,
link |
undoubtedly helped human civilization.
link |
And it seems like rabies is a good example.
link |
Oh, rabies is great because everyone knows what happens
link |
when somebody gets rabies, right?
link |
You have fear of water, hydrophobia.
link |
Your body becomes spastic and stiff and jerks around,
link |
and you lose consciousness.
link |
You can't, no more.
link |
It's not a fun ride to death.
link |
It's a horrible way to die.
link |
So I think most people know that.
link |
It's been popularized enough in media, right?
link |
So that nobody would probably object to getting,
link |
oh, I was just bit by this raccoon and it ran off.
link |
Okay, well, we should assume it's rabid.
link |
We should immunize you.
link |
And most people are okay with that,
link |
because they know the consequences.
link |
And it's also pretty rare, right?
link |
It's not like something that you're trying to get
link |
into the arms of 250, 300 million Americans.
link |
But the few thousand every year, it's easy.
link |
So the transmissibility is difficult, right?
link |
It has to, oh, it's not airborne.
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It's not airborne.
link |
It's just you have to be bitten.
link |
Although some people claim you could walk into a cave
link |
and the bats breathing out rabies virus could infect you,
link |
but I don't really think that's well substantiated.
link |
I think it's a bite.
link |
How would you do a study on that?
link |
Yeah, it's very hard to do.
link |
You'd have to collect the vapors in the cave
link |
and show that they're infectious, which,
link |
and by the way, someone emailed me the other day.
link |
They say, why can't we just immunize
link |
all the bats in the world against these viruses?
link |
And I said, well, how would you do that?
link |
There are caves everywhere, right?
link |
He said, well, maybe you could just go and aerosolize.
link |
It's pretty dangerous.
link |
And then all the bats should have vaccine passports
link |
to make sure that they're all.
link |
Yeah, and I said, you have to get their consent
link |
But we do immunize wildlife against rabies.
link |
We have rabies vaccines for wild animals.
link |
There are a whole bunch of them that get rabies.
link |
And we put it in bait
link |
and drop it from helicopters in the woods
link |
and it drops down the incidence of rabies in people.
link |
People hiking, get bitten and so forth,
link |
it drops the incidence.
link |
So we can do that.
link |
I didn't know that.
link |
I always wondered how much medical care
link |
are we doing for animals in the wild
link |
because I've recently become more and more aware
link |
that animals are living in extreme poverty, right?
link |
Like you don't know, you think like natural, it's great.
link |
Like when animals are living on a farm, it's terrible.
link |
But then you also have to compare to like
link |
what life is like in the, or like the zoo.
link |
You have to compare what life is like in the wild.
link |
Well, the life in the wild is very tough, I think.
link |
Most animals have to, well, the carnivores anyway,
link |
they have to catch their food every day, right?
link |
And then there's the viruses there.
link |
Yeah, viruses as well.
link |
So the rabies immunization is the only one I'm aware of
link |
We do immunize lots of other animals.
link |
So we immunize chickens and pigs and cows,
link |
even fish, farmed fish.
link |
We pick each fish up and give it an injection,
link |
you know, when it's a small fish.
link |
But that's mostly so that the farmers get a good yield.
link |
We don't really care about the animals, right?
link |
We want a good yield for market.
link |
And then there's some examples where we immunize animals
link |
to prevent spillovers into people.
link |
So there's a disease called Hendra in Australia,
link |
which was discovered in the 90s.
link |
And it turns out that there are bats, fruit bats,
link |
that have this virus, and the bats are fine,
link |
but sometimes they fly into horse stalls
link |
and the horses get infected.
link |
In Australia, it was initially racehorses,
link |
which are very expensive, right?
link |
The horses got infected and they died,
link |
and the humans who would take care of them would die also.
link |
So now they immunize the horses to prevent the,
link |
well, to save the horses.
link |
Probably that's the motivation,
link |
because these horses are hundreds of thousands of dollars,
link |
And then the people don't get sick
link |
because the horses don't get sick.
link |
You don't want to immunize all the people
link |
because it's too rare.
link |
But that approach is called the one world health approach,
link |
which means everything's connected on the planet.
link |
And we have to think of everything in the grander scheme,
link |
Yeah, so you can immunize some things
link |
along the trajectory that a virus would take.
link |
Some living beings.
link |
In the Arabian Peninsula,
link |
they have a MERS coronavirus issue every month.
link |
There are a couple of cases where a camel
link |
will infect a human, and the human can get very sick.
link |
It's a respiratory disease, very much like COVID.
link |
And so camels are very common there.
link |
They're raced, they're used as pets, they're eaten.
link |
So there's a lot of human camel contact.
link |
But the number of cases are rare, two a month.
link |
So you don't want to immunize all the humans.
link |
So the idea would be to immunize the camels.
link |
So, okay, so you put rabies.
link |
But Ebola also is a famously deadly one.
link |
It kills like, I don't know, 50%, 60% of its.
link |
It could be 50 to 90, but that's in Africa,
link |
where the healthcare isn't great.
link |
You saw when the cases of Ebola came to the U.S.,
link |
we could take care of it.
link |
We knew how to take care of it.
link |
We had fancy hospitals and so forth,
link |
and now we have a vaccine, so we can.
link |
And the vaccine is really good,
link |
but there are many governments in Africa
link |
that are suspicious of us,
link |
and they don't want to use our vaccine, so they.
link |
So there's a vaccine for Ebola.
link |
And the effectiveness and safety of it,
link |
to how much is understood.
link |
So this is difficult,
link |
because there's not a lot of Ebola, right?
link |
It's not a continuous, ongoing thing.
link |
There are sporadic outbreaks here and there.
link |
Of a few thousand people.
link |
At most, at most, usually a few hundred.
link |
And the biggest ever, in fact,
link |
this is why we didn't for years have an Ebola vaccine.
link |
The U.S. military, together with Canada,
link |
developed an Ebola vaccine for service people, right?
link |
They wanted to say, well, we're sending people
link |
into these Ebola areas, we want a vaccine for them.
link |
So they had developed it through all the preclinical,
link |
which means before it goes into people.
link |
And that stopped, because there was no money
link |
to do a phase one and a phase two and a phase three.
link |
In fact, for phase two and three,
link |
you need to have infections going on,
link |
because you're looking at how well
link |
the vaccine prevents infections, right?
link |
So then there was a West African outbreak in 2015.
link |
The most cases ever, 25,000.
link |
So they got to test the vaccine.
link |
But they only put it in a few thousand people.
link |
It's not like it's been in hundreds of thousands of people
link |
like the COVID vaccines has been.
link |
So it looks like it has high efficacy.
link |
But we'd like to have more data.
link |
Side effects maybe are not so great.
link |
There are a couple of different available vaccines.
link |
Some have been tested more than others.
link |
I would say this would probably not be widely accepted
link |
But then neither would be something over 50%
link |
deadliness of a virus.
link |
No, I think if you were, in fact, many physicians
link |
work in countries that have Ebola,
link |
so they get vaccinated, because they understand the choice.
link |
Yeah, right, it's always about the choice.
link |
So then one more thing.
link |
To answer the interesting,
link |
what are some of the viruses you really are fascinated by?
link |
There are a number of viruses that have clearly been shown
link |
to alter host behavior, and that's how they spread.
link |
I think those are fascinating.
link |
For example, there are some viruses of plants
link |
that are spread by aphids.
link |
And the aphid bites the plant,
link |
the virus reproduces in the plant,
link |
and it somehow engineers the plant
link |
to give off volatile organics to attract more aphids,
link |
which will spread the virus.
link |
Isn't that amazing?
link |
So that's altering the behavior.
link |
Altering because somehow the virus infecting the plant cells
link |
gives off these organics and attracts aphids.
link |
And furthermore, somehow when the aphid bites,
link |
it tastes horrible.
link |
So they immediately leave with the virus
link |
they've just picked up and go to another plant to spread it.
link |
So they're attracted and then repulsed at the same time.
link |
And obviously you don't want to anthropomorphize this
link |
like a strategy they're taking on.
link |
Somehow this worked out.
link |
It worked out this way.
link |
And you know, evolution is sometimes hard to trace, right?
link |
Like Darwin famously said,
link |
he could never figure out how an eye evolved
link |
from a single cell, right?
link |
The more complicated, complex the holistic organism is
link |
that the virus invades,
link |
the less able it is to control that organism, right?
link |
So I wonder if there's viruses
link |
that can control human behavior,
link |
you know, to induce more spread of the virus.
link |
Well, I don't see why not.
link |
There's not enough humans
link |
that's supposed to like evolve through.
link |
Well, we can't do the experiment to test it, right?
link |
We have to observe.
link |
And that's always hard when you're observing
link |
because there's so many things that can confound
link |
what you're looking at.
link |
Yeah, change human behavior, yeah.
link |
I mean, there's so many things that impinge on our behavior,
link |
but yeah, I think it's possible.
link |
I think it's highly possible.
link |
If it does it in a plant,
link |
why not change some other organism's behavior?
link |
I think it's fine.
link |
Anyway, those fascinate me.
link |
There are lots of examples of those that are fascinating
link |
and how they work, people are trying to figure out.
link |
But there's not a lot of money to work on, you know,
link |
insect and plant viruses unless you're going to the USDA.
link |
So they don't get a lot of work moving forward.
link |
Well, is there, if you understand some of those viruses,
link |
is that transferable to human viruses, that understanding?
link |
I think some of it could be, sure.
link |
I think the general principles, for example,
link |
how does the virus cause volatile organics to be made?
link |
It must be turning on some genes
link |
and you could learn principles from that,
link |
how the virus might do that.
link |
Sure, I think everything is broadly applicable.
link |
So to say it's not useful to study viruses of insects
link |
and plants is just wrong because in science,
link |
we probably know this, maybe in your field it's the same.
link |
If you're curious, you're going to run into interesting
link |
things that you never planned on, right?
link |
That's why people like, you can criticize,
link |
why do we want to go on Mars?
link |
Why do we want to colonize Mars?
link |
Well, it's like, why do you want to go to the moon?
link |
The reality is when you do really difficult things,
link |
engineering things, like all these inventions
link |
along the way are created.
link |
It's kind of fascinating.
link |
Basically just pick a thing that everyone can agree
link |
is kind of cool and is really hard and do that.
link |
And then you'll have like thousands of inventions
link |
that have nothing to do with the thing.
link |
I think you should let curious scientists
link |
just follow what they're interested in
link |
to a certain extent.
link |
You can't, in science we say we have translational research
link |
where we say, okay, here's some money,
link |
go cure cancer or diabetes or heart disease, whatever.
link |
But that often doesn't work out very well.
link |
What works better is to say, you have a good lab,
link |
you have a good track record,
link |
here's some money, here's something.
link |
And that's where PCR, CRISPR, recombinant DNA,
link |
all that stuff which has made the field explode,
link |
that's all it came from.
link |
Not from people saying, I want to cure genetic diseases
link |
by gene editing, but by saying,
link |
what are these repeated things in this bacterium doing?
link |
Can I ask you a big philosophical question?
link |
So there's these deadly viruses
link |
that are not very transmissible, Ebola, rabies.
link |
And then there's these less deadly viruses
link |
that are very transmissible, like COVID,
link |
I guess kind of borderline.
link |
But why isn't there super transmissible,
link |
super deadly viruses?
link |
I think if you compare SARS one and two,
link |
you get somewhat of an answer, right?
link |
SARS one was more deadly.
link |
In fact, over half of the time when people were infected,
link |
they ended up in the hospital because they were that sick.
link |
And then the peak of virus shedding from them
link |
happened long after they went in the hospital.
link |
So it's easy to contain the infection
link |
when you're in a hospital, right?
link |
There was not much pre symptomatic
link |
or asymptomatic shedding with SARS one.
link |
And shedding means you become infectious.
link |
So in a respiratory virus,
link |
you inhale the droplets with the virus
link |
and they reproduce in your upper respiratory tract,
link |
what we call the nasopharynx, right?
link |
The nose and going back to that little cavity
link |
just above your mouth.
link |
So the virus reproduces really well.
link |
And then as you talk and sneeze and cough,
link |
you expel droplets and then those are inhaled
link |
by other people and then they reproduce.
link |
And for SARS two, we now know there's a lot of reproduction
link |
just before you feel anything, if at all.
link |
So there's a lot of shedding and transmission
link |
before you get symptomatic.
link |
And as many people don't ever get symptomatic, right?
link |
So they spread really easily.
link |
So that explains why some viruses can transmit
link |
a lot better than others.
link |
And if one happens to knock you out,
link |
then you're never gonna transmit
link |
because you're in the hospital like SARS one.
link |
But why can't you have both?
link |
Why can't you just wait a while before it knocks you out
link |
but when it knocks you out, it really kills you?
link |
That is a philosophical question, right?
link |
Because we could talk about why we haven't observed it.
link |
I mean, one issue is that if you're killed too quickly
link |
by a highly lethal virus,
link |
you're not gonna transmit it very well, right?
link |
So Ebola can kill you quite rapidly.
link |
And most of the transmission occurs when people
link |
are being cared for at home or in hospitals.
link |
The doctors and nurses get the virus,
link |
but people walking around, you're not walking around
link |
when you have Ebola, you're too sick.
link |
You know, you have black, bloody diarrhea,
link |
you're vomiting, you're bleeding from your skin
link |
and mucous membranes, you're not walking around,
link |
you're not going to parties.
link |
So I think that's part of it,
link |
that if the infection is too lethal,
link |
you're simply not a good transmitter.
link |
And I think transmission is probably one
link |
of the most powerful selection forces for viruses
link |
because a virus always has to find a new host.
link |
If it doesn't, it's a startup that fails, right?
link |
If it doesn't find a new host, it's gone.
link |
And so anything that makes the virus transmit better
link |
And if killing you, being less lethal is part of that,
link |
So there's a strong selection pressure
link |
against being lethal.
link |
I think there's a strong selection pressure
link |
against being lethal and being more transmissible.
link |
Those two seem to work in opposite ways.
link |
And now we don't have a lot of data to support this.
link |
This is kind of a thought experiment,
link |
but there is one experiment done in Australia
link |
I don't know if you know this, but in the 1800s,
link |
the hunters in Australia imported a rabbit from Europe
link |
so they could hunt it because the native rabbit
link |
in Australia was too fast for them.
link |
They couldn't shoot them.
link |
So they brought in this European rabbit
link |
and they reproduced out of control.
link |
Within a couple of years, they were everywhere,
link |
millions of rabbits in all the watering holes.
link |
And now they had a problem.
link |
So they decided to use a virus
link |
to get rid of these excess rabbits.
link |
And they used a virus, a pox virus called myxoma virus,
link |
which is a natural virus of a different kind of rabbit.
link |
But for these European rabbits, it was quite lethal
link |
and it's spread by mosquitoes.
link |
So they said, okay, let's release this virus.
link |
And the first year, 99.2% of the rabbits were killed,
link |
but that 0.8% that were left had some form of resistance.
link |
They were variants.
link |
Every organism, not just viruses, makes mutants.
link |
And there were some variants of the rabbits
link |
that could survive infection.
link |
And then in subsequent years, the virus became less lethal.
link |
And then the mosquitoes had a better shot
link |
of transmitting it from one rabbit to another
link |
if the rabbit lived longer.
link |
That's the selection probably.
link |
And so in the end, the rabbits lived on.
link |
The virus was there.
link |
It evolved to be more transmissible and less lethal.
link |
So that's the only.
link |
That's the only data. Life on Earth is amazing.
link |
If you take the time to look at it and see what's happened,
link |
It's also humbling that it just makes you realize
link |
humans are just a small part of the picture.
link |
And we're wrecking it, aren't we?
link |
Well, I mean, we're not really.
link |
I mean, viruses are wrecking it some ways.
link |
We're not really wrecking anything.
link |
It's all part of it.
link |
But you know, when the ways that humans exist
link |
encourages viruses to infect us, right?
link |
When we were hunter gatherers,
link |
living in bands of 100 people, very few viruses
link |
because it was hard for the virus to go
link |
from one band to another.
link |
And perhaps a hunter would, one of these humans
link |
would get an animal and bring a virus into camp
link |
and some people would die,
link |
but it would never spread to another.
link |
And then when we started to congregate in cities,
link |
we figured out agriculture and so forth
link |
and how to harvest animals,
link |
then we could get bigger and bigger populations
link |
and the viruses went crazy.
link |
And they went from animals to us.
link |
So measles went from cows to humans
link |
when humans learned to domesticate cows
link |
and started gathering in big cities.
link |
Yeah, but now that humans are able to communicate
link |
and travel globally,
link |
the viruses become more and more dangerous, transmissible.
link |
Thereby, if you look at earth as an organism,
link |
thereby pushing humans to be more innovative,
link |
create alpha fold two and three and four and five,
link |
create better systems and eventually there's rockets
link |
that keep flying from earth.
link |
And eventually the virus is becoming super dangerous
link |
and threatening all of human civilization,
link |
will force it to become a multi planetary species
link |
and its organism starts expanding.
link |
So I think it's a feature, not a bug, I don't know.
link |
Well, I think that we have our early,
link |
probably the most of the,
link |
we're studying viruses since 1900, right?
link |
Most of that time was because of diseases they caused.
link |
The first viruses discovered, yellow fever,
link |
virus, smallpox, polio virus, influenza virus,
link |
those were all because people got sick and they said,
link |
oh, look, this is a virus that's associated with it.
link |
And so we got good at learning how to take care
link |
of these infections, making vaccines and so forth
link |
over the years and it's only in the last 20 years
link |
that we recognize that there are more viruses out there
link |
that are far more interesting, perhaps,
link |
but we've learned how to deal with the bad ones for sure.
link |
So we talked about what is a virus.
link |
We talked about some of the most dangerous
link |
and deadly viruses.
link |
Can we zoom in and talk about COVID 19 virus?
link |
I don't know what your preferred name is, but maybe for this.
link |
Right, the virus is SARS CoV2, which is hard, it's long,
link |
and then COVID 19 is the disease.
link |
So you could say the virus of COVID 19, that's fine.
link |
The virus of COVID 19.
link |
But for the purpose of this conversation,
link |
we'll every once in a while just say COVID.
link |
It's fine, no problem.
link |
What is this virus from,
link |
I don't know how many ways we can talk about it.
link |
I think from a basic structural,
link |
like the variant structure,
link |
biological structure perspective, what is it?
link |
What are its variants?
link |
Can you describe the basics,
link |
the important characteristics of the virus?
link |
So viruses are classified by humans
link |
just to make it easier to keep track of them, right?
link |
So this is a coronavirus, which is because
link |
when they were first discovered,
link |
I think the first ones were animal coronaviruses.
link |
They looked at them in the electron microscope
link |
and it looked like the solar corona,
link |
and that's all there is to it.
link |
And I have to say that early in the outbreak,
link |
the place with the highest seropositivity in the US,
link |
for a while, 68% was a working class neighborhood
link |
in New York City called corona.
link |
Can you beat that, right?
link |
That's crazy, yeah.
link |
So coronaviruses, they have membranes, right?
link |
We talked about membranes,
link |
they have spike proteins in the membrane,
link |
so they can attach to cells.
link |
And inside, they have RNA.
link |
And they are the viruses with the longest RNA
link |
None other comes close.
link |
For some reason, they're able to maintain 30,000,
link |
so SARS, COVID, two RNAs, 30,000 bases of RNA,
link |
and some of the other coronas are even longer, 40,000.
link |
This is a, coronas are family of viruses
link |
that included the one you mentioned before, version one.
link |
So SARS, COVID one, yeah.
link |
COVID one, and I guess other ones as well.
link |
So the first, we first learned of them in animals,
link |
a lot of animals, pigs, and cows,
link |
and horses have coronaviruses.
link |
And then in the 60s, we discovered
link |
a couple of human coronaviruses that just cause colds,
link |
very mild colds that you wouldn't even think twice about.
link |
And then suddenly, in 2003, there's this outbreak
link |
of severe respiratory disease in China.
link |
And it started in November,
link |
and they didn't tell the world until February.
link |
And that was really bad, because it was already spreading
link |
by the time they told people about it.
link |
But this went to 29 different countries.
link |
Only 8,000 people were infected, and then it stopped.
link |
And that was the first time we saw an epidemic coronavirus.
link |
And what they did afterwards is they said,
link |
okay, it looks like it came from the meat markets.
link |
They have live meat markets in Guangzhou,
link |
in the south of China, where you can go
link |
and pick out an animal and the guy will slaughter it for you
link |
and give it to you, and then of course,
link |
there's blood everywhere, and that's how they got infected.
link |
And they figured out that there's this animal
link |
called a palm civet, that was the source of virus.
link |
The palm civets are shipped in from the countryside,
link |
and the palm civets somehow in the countryside
link |
got it from a bat.
link |
So they went looking in caves in the countryside,
link |
and they found in one cave all the viruses
link |
that could make up SARS 1.
link |
And that was 2000, and I would say,
link |
took about five, eight years after that outbreak.
link |
So that was the first hint that bats have coronaviruses
link |
that can infect people and cause problems, right?
link |
And after that, we should have been ready.
link |
So didn't they already start developing
link |
vaccines after then? Yes.
link |
So some people started making vaccines.
link |
They tested them in mice, but they never got into people.
link |
And some people started working on antiviral drugs.
link |
Nothing ever came of them because, you know,
link |
industry, there's no disease, it's gone.
link |
Why should we make vaccines and drugs?
link |
And NIH in the US, you submit a grant,
link |
and they say, ah, it's too risky.
link |
There's none of this virus around.
link |
So people were really shortsighted because I always say,
link |
we could have had antivirals for this, absolutely, for sure.
link |
In fact, the one antiviral that's in phase three,
link |
it's called molnupiravir.
link |
It's the only one that you can take orally.
link |
It looks really good.
link |
That was developed five years ago,
link |
but never taken into humans.
link |
It could have been ready.
link |
So we dropped the ball, and then the next decade, 2012,
link |
MERS coronavirus comes up in the Arabian Peninsula.
link |
This comes from camels and infects people,
link |
but probably the camels got it from bats originally
link |
But that never transmits from person to person, very rarely.
link |
Every new little outbreak is a new infection from a camel.
link |
So that was 2012, and now here we are, 2019,
link |
the new outbreak of respiratory disease in China.
link |
And this one really goes all over the world
link |
where SARS1 could not.
link |
It's a coronavirus.
link |
It's different enough from SARS1
link |
that it has very different properties.
link |
But it still has a membrane.
link |
It still has a very long RNA in the middle,
link |
and then it still has the spike proteins.
link |
What are the things that are,
link |
what are the little unique things
link |
that make it that much more effective?
link |
That make it cause a pandemic of millions of people
link |
as opposed to SARS1?
link |
Well, the genome is 20% different from SARS1, say.
link |
And in those bases, there's some,
link |
there are things that make it different from SARS1.
link |
It binds the same receptor, ACE2, on the cell surface.
link |
So that's remarkable.
link |
It has a lot of the same proteins.
link |
They look similar.
link |
Like if you look at the structure of the spikes,
link |
they look similar,
link |
but there's enough amino acid differences
link |
And what it is, we don't know,
link |
because how do you figure that out?
link |
You need to study animals,
link |
because you can't infect people.
link |
And the animal models aren't great.
link |
So the way you figure that out
link |
is you figure out how those differences,
link |
like how the difference in the amino acids
link |
lead to functional difference of the virus.
link |
Like how it attaches, how it breaks the cell wall.
link |
And how the hell do you figure that out?
link |
Like, I guess there's models of interaction.
link |
First, you need an animal of some kind to infect, right?
link |
People have used ferrets, guinea pigs,
link |
nonhuman primates,
link |
Nonhuman primates are very expensive,
link |
so not many people do that.
link |
And then you can put the virus in the respiratory tract.
link |
But in fact, none of them get sick like people do.
link |
Many people with COVID get a mild disease,
link |
but 20% get a very severe, longer lasting disease.
link |
They can die from it, right?
link |
No animal does that yet.
link |
So we have no insight into what's controlling that.
link |
But if you just wanna look at the very first part
link |
of infection and the shedding and the transmission,
link |
you can do it in any one of several animal models.
link |
Ferrets are really good for transmission.
link |
They tend to have nasal structures like humans
link |
and you can put them in cages next to each other
link |
and they'll transmit the virus really nicely.
link |
So you can study that.
link |
But the other thing that's important that we should mention
link |
is how do you manipulate these viruses?
link |
So these are RNA viruses.
link |
You can't manipulate RNA.
link |
We don't know how to do it.
link |
But DNA, because of the recombinant DNA revolution
link |
that occurred in the 70s,
link |
we can change DNA any way we want.
link |
We can change a single base, we can cut out bases,
link |
we can put other things in really easily.
link |
And if I may give it a personal aspect,
link |
when I went to MIT as a postdoc in 1979,
link |
David Baltimore said, here's what I want you to do.
link |
The moratorium on recombinant DNA experiments
link |
on viruses has just been lifted.
link |
I want you to make a DNA copy of polio
link |
and see if you put that in a cell
link |
whether it will start an infection.
link |
So I made a DNA copy of polio virus.
link |
It's only 7,500 bases.
link |
It's much smaller than corona.
link |
And I took that DNA and I put it in a piece of DNA
link |
from a bacteria called a plasmid.
link |
And you can grow plasmids in many, many bacteria,
link |
make lots of them and purify the DNA really easily.
link |
And I took that DNA and I sequenced it
link |
because we didn't know the genome sequence
link |
of polio at the time.
link |
And that took me a year by the way,
link |
because the techniques we had were really archaic
link |
and nowadays you could do it in 15 minutes, right?
link |
And I took the DNA, I put it into cells and out came polio.
link |
So that's the start.
link |
Now, since then everybody has taken that technique
link |
and used it for their virus.
link |
You can now do it with SARS CoV2.
link |
You make a DNA copy of any RNA virus,
link |
you can modify it and you put it back into cells
link |
and you'll get your modified virus out.
link |
So that's an important part of understanding
link |
the properties of the virus as, say, in an animal.
link |
By changing the virus, you're changing a DNA copy,
link |
you're making the virus then and putting it into the animal.
link |
Can you clarify, so even in the RNA virus,
link |
you can take and turn it into DNA?
link |
And then that allows you to modify it.
link |
What's that mapping?
link |
Well, no, no, no, what's the process
link |
of going from RNA to DNA?
link |
Reverse transcription.
link |
That's reverse transcription.
link |
Oh, so you actually go through the process
link |
of reverse transcription to do this?
link |
Remember, David Baltimore and Howard had discovered
link |
this enzyme in the 70s.
link |
They got the Nobel Prize for that.
link |
And when I went to David's lab at MIT,
link |
he had the enzyme in the freezer.
link |
He said, here, take this and make a DNA copy of polio.
link |
Yeah, I didn't make the connection
link |
that you can use that kind of thing for an RNA virus.
link |
And then modify it.
link |
See, any DNA virus already exists as DNA.
link |
So you can modify it.
link |
But for RNA viruses, it was difficult.
link |
And so then from that point on, for influenza,
link |
every other RNA virus and coronaviruses,
link |
people made DNA copies.
link |
And that's what they use to modify
link |
and ask questions about what things are doing, right?
link |
What's this gene doing?
link |
What if we take it out?
link |
Can you do the same thing with COVID?
link |
Is take the RNA and then.
link |
And in fact, in January 2020,
link |
as soon as the genome sequence was released from China,
link |
the labs all over were synthesizing this 30,000 base DNA
link |
and getting virus.
link |
What can you figure out without infecting anything?
link |
Just turning into, with the reverse transcription,
link |
turning into DNA, modifying stuff,
link |
and then putting it into a cell.
link |
What can you figure out from that?
link |
Oh, well, you could, let's say you can cut out a gene.
link |
You see some genes in the sequence.
link |
I don't know what these genes do.
link |
Let's cut them out.
link |
And then you could cut them out of the DNA.
link |
You put the DNA in cells and maybe you get virus out.
link |
And you go, oh, clearly that gene's not needed
link |
for the virus to reproduce, at least in cells, right?
link |
Or maybe you take the gene out
link |
and you never get any virus, so it's lethal.
link |
Is there a nice systematic ways of doing this?
link |
Do people kind of automate it?
link |
And we, I mean, the problem with SARS, the COVID virus,
link |
is it's 30,000 bases, a lot of stuff there.
link |
And what makes it more difficult is that you have to,
link |
it's been classified as a BSL3 agent, biosafety level three.
link |
And so not everyone has a lab that's capable of doing that.
link |
So it limits the number of people who can do experiments.
link |
You know, we're lucky to have a few in New York City,
link |
but not every place has them.
link |
So you cannot work with a virus just out on the bench
link |
like we do with many other viruses.
link |
You have to wear a suit and have to have special procedures
link |
and containment and so forth.
link |
So it makes it difficult to do basic experiments
link |
But when it's a pandemic, there's a lot of money,
link |
there's a lot of incentive to work on it harder.
link |
And also you don't need to work on the virus.
link |
You can take bits of it and work.
link |
You could take, say, just the spike, right?
link |
And say, can we make a vaccine with just the spike?
link |
Because that doesn't require BSL3, so yes.
link |
So like building a vaccine requires you to figure out
link |
how, or antiviral drugs, how to attack various structural
link |
parts of the virus and the functional parts of the virus.
link |
You have to decide on a target.
link |
Like, I'm gonna make an antiviral,
link |
what am I gonna target in the virus?
link |
And there are a few things that make more sense than others.
link |
Usually we like to target enzymes.
link |
I don't know if you remember your biochemistry,
link |
but enzymes are catalytic.
link |
You don't need a lot of them to do a lot of things.
link |
So they're typically in low concentrations
link |
in a virus infected cell.
link |
So it's easier to inhibit them with a drug.
link |
And the coronas have a couple of enzymes that we can target.
link |
So you have to figure that out ahead of time
link |
and decide what to go after.
link |
And then you can look for drugs that inhibit
link |
what you're interested in.
link |
It's not that hard to do.
link |
There's just something beautiful about biology,
link |
about the mechanisms of biology.
link |
And I kind of regret falling in love
link |
with computer science so much
link |
that I left that biology textbook on the show
link |
and left it behind.
link |
But hopefully we'll return to it now
link |
because I think one of the things you learn
link |
even in computer science that studying biology
link |
and certainly neurobiology,
link |
Here's a mechanism of incredible complexity
link |
that works really well, is very robust,
link |
is very effective, efficient.
link |
It inspires you to come up with techniques
link |
that you can engineer in the machine.
link |
That's what drives a field forward
link |
when people improvise and come up with new technologies
link |
that really make a difference.
link |
And we have a bunch of those now.
link |
What's the difference between the coronavirus family
link |
and the other popular family, influenza virus family?
link |
I mean, if I were, because you mentioned
link |
we should have done a lot more
link |
in terms of vaccine development,
link |
that kind of thing for coronaviruses.
link |
But if I were back then, from my understanding,
link |
the thing we should all be afraid of is influenza,
link |
like some strong variants coming out from that family.
link |
That seems like the one that will destroy human civilization
link |
or hurt us really badly.
link |
I don't know if you agree with this sense,
link |
but maybe you can also just clarify
link |
what to use as the difference between the families.
link |
So it's an interesting difference.
link |
They both have membranes, right?
link |
So then they have spike proteins embedded in them.
link |
And they're different spikes.
link |
In fact, for influenza, there are two main ones.
link |
They're called the HA and the NA.
link |
But what's inside is RNA,
link |
but it's very different RNA.
link |
And here we have to explain that.
link |
So viruses with RNA can have three different kinds of RNA.
link |
They can have what we call plus RNA.
link |
They can have minus RNA,
link |
or they could have plus minus,
link |
actually two strands hybridized together.
link |
The plus RNA simply means that
link |
if you put that plus RNA in a cell,
link |
you know, your cell has ribosomes in it
link |
that make the proteins that you need.
link |
The ribosomes will immediately latch onto the plus RNA
link |
and begin to make proteins.
link |
A minus RNA is not the right strand to make proteins.
link |
So it has to be copied first.
link |
And then the plus minus is both together.
link |
So the SARS coronaviruses,
link |
all the coronaviruses have plus RNA.
link |
So as soon as that RNA gets in the cell,
link |
boom, it starts an infectious cycle.
link |
Same thing with poliovirus, by the way, which I worked on.
link |
Influenza viruses are negative stranded.
link |
So they cannot be translated when they get in the cell.
link |
So that's tough for the virus
link |
because the cell actually cannot make plus RNA
link |
It doesn't have the enzyme to do it.
link |
So the virus has to carry it in inside the virus particle.
link |
And then when the minus RNA is in the cell,
link |
the virus enzyme makes plus RNAs and those get translated.
link |
So it's a big difference.
link |
And then in the influenza viruses,
link |
not only is it minus RNA, but it's in pieces.
link |
It's in eight pieces.
link |
We call that segmented,
link |
whereas the corona is in one long piece of RNA.
link |
So they're like floating separately?
link |
Yeah, so the genes are on separate pieces.
link |
They're all packaged inside that virus particle
link |
of influenza virus, but they're in pieces.
link |
And why that's important
link |
is because if two different influenza viruses
link |
infect the same cell,
link |
the pieces as they reproduce can mix
link |
and out can come a virus with a new assortment of pieces.
link |
And that allows influenza virus
link |
to undergo extremely high frequency evolution.
link |
That's why we get pandemics.
link |
When we have a new flu pandemics
link |
is because somewhere in some animal,
link |
two viruses have reassorted
link |
and made a new virus that we hadn't seen before.
link |
So you're talking about kind of biological characteristics,
link |
but what am I incorrect in my intuition
link |
that are from the things I've heard
link |
that the influenza family viruses is more dangerous?
link |
Like what makes it more dangerous to humans?
link |
Well, it depends on the,
link |
there are many flavors or vintages of influenza virus.
link |
Some are dangerous and some are not, right?
link |
It depends on which one.
link |
Some like the 1918 apparently was very lethal,
link |
killed a lot of people.
link |
But more contemporary viruses,
link |
we had a pandemic in 2009 of influenza.
link |
That wasn't such a lethal virus.
link |
We don't know exactly why,
link |
but it didn't kill that many people.
link |
It transmitted pretty well.
link |
Is that the bird flu one?
link |
They're all deriving.
link |
That one was called swine influenza.
link |
Swine, that's right, swine, yeah.
link |
It seemed to have started in a pig,
link |
but it had bird, it had RNAs from bird influenza viruses.
link |
These viruses are all reassortants of different viruses
link |
from pigs and birds and humans.
link |
But influenza can cause pneumonia
link |
and can kill you as does SARS COVID too.
link |
So it depends on the virus.
link |
So there is another influenza virus
link |
that's currently circulating.
link |
So right now we have the 2009 pandemic virus
link |
that's still around.
link |
And then the 1968 pandemic virus,
link |
which was the one before 2009,
link |
that one is still around too.
link |
And that's more lethal.
link |
And depending on the season,
link |
some seasons the 2009 virus predominates,
link |
some seasons the 1968.
link |
And when the 68 is around, you get more lethality.
link |
So we're living with an influenza family.
link |
We haven't exterminated them.
link |
Right, we never will, never exterminate them.
link |
Because every shorebird in the world is infected with them.
link |
Gulls and terns and ducks and all sorts of things.
link |
Why can't we develop strong vaccines that defend against?
link |
Oh, we could do that, sure.
link |
But that would not eliminate them from humans.
link |
Even if you had the best vaccine,
link |
you would never get rid of it in people
link |
because there would always be someone who's not vaccinated
link |
or in which the vaccine didn't work.
link |
No vaccine is 100%.
link |
Well, you just contradicted yourself.
link |
You said the perfect vaccine.
link |
Imperfect, imperfect.
link |
But then you said, like, even if you had the perfect,
link |
yeah, some people wouldn't get vaccinated.
link |
But I understand what you mean.
link |
But I actually was asking how difficult is it
link |
to make vaccines like that for,
link |
it seems like it's very difficult to do that
link |
for the influenza virus.
link |
So it's really easy to make an old school vaccine.
link |
So the way the first influenza vaccines were made
link |
was actually Jonas Salk worked on them in the 40s.
link |
You just grow lots of virus
link |
and you grow it in eggs, by the way, chicken eggs.
link |
Yeah, chicken, embryonated.
link |
So they get fertilized and there's a 10 or 12 day embryo
link |
in it and you put virus in it, it grows up
link |
and then you harvest it.
link |
You get about 10 mls of fluid.
link |
And then you take that,
link |
you treat it with formaldehyde or formalin
link |
and it inactivates the virus so it's no longer infectious.
link |
And you just inject that into people.
link |
And that was the first flu vaccine.
link |
It was made for the US Army actually.
link |
And then it got moved over to people.
link |
We still use that old school tech today.
link |
So you're taking, can you help me out here?
link |
Okay, so this is a good time to talk about vaccines.
link |
Okay, so you're talking about,
link |
you're taking the actual virus,
link |
you put it in an egg, you let it grow up.
link |
It's very funny that you put it in an egg.
link |
And then how do you make it not infection,
link |
not effective or whatever?
link |
Not infectious, is that the right term here?
link |
So how do you make it not infectious?
link |
You can treat it with any number of chemicals
link |
that'll disrupt the particle so it no longer infects.
link |
So that step of disrupting the particle
link |
is that very specific to a particular variant particle?
link |
No, the same collection of chemicals
link |
you can use for all kinds of,
link |
and which have been used for SARS CoV2 vaccines also.
link |
Okay, so what are, there's several things to ask.
link |
So you called it old school in a way
link |
that's slightly dismissive,
link |
like people talk about Windows 98 or something.
link |
So is there risks involved with it?
link |
Or is it just difficult to produce large amounts?
link |
No, it's only, it's,
link |
I mean, you could do it in cells and culture,
link |
but eggs were convenient.
link |
And in the 1940s, we didn't have cells and culture.
link |
We didn't know how to do that.
link |
So we had to use something else.
link |
but the process of inactivating the virus with a chemical
link |
makes it not the best vaccine you can make.
link |
The flu vaccines that we have today,
link |
which are mostly based on this inactivation,
link |
is called inactivated virus vaccines.
link |
Oh, so like the kind of thing
link |
it presents to the immune system to train on
link |
is not close to the actual virus.
link |
Yes, that's what we think.
link |
So that's why probably the flu vaccines
link |
are just not very good, you know?
link |
60% efficiency at the best, right?
link |
Which is not really good.
link |
What does it mean?
link |
What is the measure of efficiency for a vaccine?
link |
Well, it's how it does in the general population
link |
at preventing influenza.
link |
Illness, not infection.
link |
We usually don't measure infection
link |
when we're testing a vaccine.
link |
We just measure sickness.
link |
That's really easy to score, right?
link |
You do a trial and you say,
link |
if you feel sick, give us a call.
link |
We'll tell you what to do.
link |
So yeah, I mean, what's sickness?
link |
Sickness is the presence of symptoms?
link |
So this is good time to say what a symptom is, okay?
link |
A symptom is what you only can feel.
link |
Only you can feel an upset stomach
link |
or a sore throat or that sort of thing.
link |
It's the lived experience of a symptom.
link |
Whereas a sign is something that someone could measure
link |
and tell that you're infected,
link |
like virus in your nasopharynx or something else, right?
link |
Signs and symptoms.
link |
And so in a vaccine trial, they tell you,
link |
well, if you have any of these symptoms,
link |
they give you a paper with the exact symptoms listed
link |
to make sure you're picking them up, right?
link |
So for flu, it would probably be fever, sore throat, cough.
link |
You call them and then they will do a PCR,
link |
make sure you've got flu and not some other virus
link |
that makes similar symptoms.
link |
And then they would say, are you a vaccine or non vaccine arm
link |
and count up all the infections
link |
and see how the vaccine did, basically.
link |
That's so fascinating because the reporting,
link |
so symptom is what you feel.
link |
And certainly the mind has a ability to conjure up feelings.
link |
Oh yes, absolutely.
link |
And so like culturally, maybe there was a time
link |
in our culture where it was looked down upon
link |
to feel sick or something like that,
link |
like toughen up kind of thing.
link |
And so then you probably have very few symptoms
link |
Absolutely, absolutely.
link |
And now is like much more, I don't know,
link |
perhaps you're much more likely to report symptoms.
link |
Now it's fascinating because then it changes.
link |
Oh, it is definitely a perception because for,
link |
your symptom may be nothing to me or vice versa, right?
link |
And so when you're doing this,
link |
it's a little bit of a imprecise science because,
link |
and even it's a cultural thing in some countries,
link |
something that would make us feel horrible,
link |
they wouldn't even bother reporting.
link |
No, I didn't have any symptoms.
link |
So it's a little bit imprecise and it clouds the results.
link |
So if you can measure things, it's always better,
link |
but you start out with a symptom.
link |
And if you say, if someone tells you this virus,
link |
20% of the people are asymptomatic,
link |
they don't report symptoms,
link |
that number is probably not a constant.
link |
It depends where you did the study.
link |
It could be different in China versus South America,
link |
Europe, et cetera, yeah.
link |
I mean, I was trying to figure,
link |
so I took two shots of the Pfizer vaccine
link |
and I had zero symptoms.
link |
So, and I was wondering, well, see,
link |
but that's my feelings, right?
link |
This is not, because I felt fine, I was waiting.
link |
Did you have pain at the injection site?
link |
No, it was kind of pleasant.
link |
You felt nothing the next day, no?
link |
Nothing, no tiredness, no exhaustion, no.
link |
But see, like I have an insane sleeping schedule.
link |
I already put myself through crazy stuff.
link |
That said, maybe I was expecting something really bad.
link |
Like I was waiting and therefore didn't feel it.
link |
But I also got allergy shots
link |
and those, I was out all next day,
link |
like exhausted for some reason.
link |
So that gave me like a sense like, okay,
link |
at least sometimes I can feel shitty.
link |
That's good to know.
link |
And then with the vaccine it didn't,
link |
but the question is like,
link |
how much does my mind come into play there?
link |
The expectations of symptoms,
link |
the expectations of not feeling well,
link |
how does that affect the sort of the self reporting
link |
I think it's definitely a variable there,
link |
but there's certainly many people that don't feel anything
link |
after the vaccines.
link |
And there's some that have a whole range of things
link |
like soreness and fever, et cetera, yeah.
link |
So okay, you were talking about the old school development
link |
What's better than that?
link |
So then the next generation of vaccines
link |
which arose in the 50s were what we call
link |
replication competent, where the virus you take
link |
and it's actually reproducing in you.
link |
Yeah, that sounds safe.
link |
And it can be somewhat problematic, yes,
link |
as you might imagine,
link |
because once you put that virus in you,
link |
you have no more control, right?
link |
It's not like you have a kill switch in it,
link |
which actually would be a great idea to put in.
link |
Like nanobots, what can possibly go wrong?
link |
No, you could just put something in there.
link |
If you added a drug, you would shut it off, right?
link |
And people are thinking about that
link |
because now we're engineering viruses to treat cancers
link |
and other diseases and we may wanna put kill switches
link |
in them just to make sure they don't run away.
link |
Oh, interesting, so you can deploy a drug
link |
that binds to this virus that would shut it off
link |
in the body, something like that.
link |
Something like that, yeah, that would be the idea.
link |
You'd have to engineer it in.
link |
Anyway, these were, the first one was yellow fever vaccine
link |
that was made because that was a big problem.
link |
And this virus, and the way you do this,
link |
back in the old day was empirical.
link |
So Max Tyler, who did the yellow fever vaccine,
link |
he took the virus, which is a human virus, right?
link |
And he infected, I think he used chick embryos.
link |
And he went from one embryo to another and just kept passing
link |
and he did that hundreds of times.
link |
And every 10 passages, he would take the virus
link |
and put it in a mouse or a monkey, whatever his model was.
link |
And then eventually he got a virus
link |
that didn't cause any disease after 200 and some passages.
link |
And then that was tested in people
link |
and it became the yellow fever vaccine that we use today.
link |
He selected for mutations that made the virus
link |
not cause disease, but still make an immune response.
link |
So those are called replication competent.
link |
We now have the polio vaccine,
link |
which was developed in the 50s after the yellow fever.
link |
Then we had measles, mumps, rubella.
link |
Those are all replication competent vaccines.
link |
And you mentioned is that's a good idea.
link |
They are all safe vaccines.
link |
The only one that has had an issue
link |
is the polio replication competent vaccine.
link |
It was called Sabin vaccine or oral polio virus vaccine
link |
because you take it orally, it's wonderful
link |
because you don't have to inject it.
link |
This is the perfect delivery.
link |
Either intranasal for a respiratory virus
link |
or orally for polio goes into your intestines.
link |
It reproduces and it gives you wonderful protection
link |
However, you do shed virus out
link |
and that virus is no longer a vaccine.
link |
It's reverted genetically in your intestine.
link |
So you can infect others with polio.
link |
Take that virus and put it into an animal and give it polio.
link |
And in fact, the parents of some kids in the 60s and 70s
link |
who were immunized got polio from the vaccine.
link |
The rate was about one and one and a half million
link |
So it's called vaccine associated polio.
link |
And I always argue that
link |
we may not have picked the right vaccine.
link |
There was a big fight in the US and other countries
link |
between the inactivated polio
link |
and the infectious polio vaccines,
link |
which ones we should be using
link |
because we found out that the infectious vaccine
link |
actually caused polio.
link |
And eight to 10 kids a year in the US alone
link |
got polio from the vaccine,
link |
which looking back is really not acceptable in my view,
link |
although the public health community said it was
link |
to get rid of polio.
link |
So now we're close to eradicating polio globally,
link |
but this vaccine derived polio is a problem.
link |
So now we have to go back to the inactivated vaccine,
link |
which is tough because it's injected.
link |
So, okay, so the basic high level,
link |
how vaccines work principle is
link |
you want to deploy something in the body
link |
that's as close to the actual virus as possible,
link |
but doesn't do nearly as much harm.
link |
And there's like a million, not a million,
link |
but there's a bunch of ways you could possibly do that.
link |
So those are two ways.
link |
And now of course we have modern ways
link |
we can make mRNA vaccines, right?
link |
What are the modern ways?
link |
I did, you wanna look, mRNA vaccine.
link |
So that's one of the, that's the most modern,
link |
but even before mRNA vaccines,
link |
we learned that we could use viruses
link |
to deliver proteins from a virus that you wanna prevent.
link |
And so the Ebola vaccine,
link |
we took the spike gene of Ebola virus
link |
and put it in a different virus
link |
and we deliver that to people
link |
and that's called a vector vaccine.
link |
And some of the COVID vaccines are vectors
link |
of different kinds of most famous are adenovirus vectors
link |
carrying the spike gene into the cell.
link |
Can you explain how the vector vaccine works again?
link |
So we have, we take a virus that will infect humans
link |
but will not make you sick.
link |
In the case of adenovirus,
link |
the years and years of people studying it
link |
has told us what genes you could cut out
link |
and allow the virus to infect the cell
link |
but not cause any disease.
link |
So instead of doing selection on it,
link |
you actually genetically modify it.
link |
Yes, you modify the vector, yeah.
link |
So you're much more precise about it.
link |
You're very precise
link |
and then you splice in the gene for the spike
link |
and then you use that to deliver the gene
link |
and it becomes produced as protein
link |
and then you make an immune response.
link |
And vector is the term for this modified.
link |
Right, so we're now using viruses at our bidding.
link |
We're using them as vectors, not just for vaccines.
link |
We can cure monogenic diseases.
link |
That is if you have, if you're born with a genetic disease,
link |
you have a deletion or a mutation in a gene,
link |
single gene, we can give you the regular gene back
link |
using a virus vector.
link |
So cancers too, we can cure cancers with vectors.
link |
Interesting. Yeah.
link |
I think in 10 to 15 years,
link |
most cancers will be treatable with viruses, yeah.
link |
And not only can we put things in the vector
link |
to kill the tumor,
link |
we can target the vector to the tumor specifically
link |
in a number of ways.
link |
And that makes it less toxic, right?
link |
It doesn't infect all your other cells.
link |
But it takes time to develop a vector for a particular thing
link |
because it requires a deep understanding.
link |
Yeah, in fact, we have about a dozen different virus vectors
link |
that have been studied for 20 years.
link |
And those are the set of vaccine vectors that we're using.
link |
So it includes adenovirus, vesicular stomatitis virus,
link |
which is a cousin of rabies, but doesn't make people sick.
link |
Influenza virus is being used as a vector
link |
and even measles virus.
link |
So we're familiar with how to modify those to be vectors
link |
and those are being used for COVID vaccines.
link |
And then of course we have the newest,
link |
which is the nucleic acid vaccines.
link |
So years ago, people said,
link |
why can't we just inject DNA into people?
link |
Take the spike and put it in a DNA and inject it.
link |
So people tried many, many different vaccines.
link |
And in fact, there are no human licensed vaccines
link |
that are DNA vaccines.
link |
Although there is a West Nile vaccine for horses
link |
that's a DNA based vaccine.
link |
So if you have a horse, you can give it this vaccine,
link |
Can you clarify, does a DNA vaccine
link |
only work for DNA viruses?
link |
No, it can work for DNA or RNA.
link |
Because remember, for an RNA virus,
link |
we can make a DNA copy of it.
link |
And it will still, when you put that DNA in a cell,
link |
it goes into the nucleus.
link |
So it's, you're just skipping a step.
link |
For RNA vaccines, you're giving, okay, I got it.
link |
So those didn't work for human vaccines.
link |
And there were many HIV AIDS vaccine trials
link |
that used DNA vaccines, didn't work.
link |
And then a number of years ago,
link |
people started thinking, how about RNA, RNA vaccines?
link |
And I first heard this, I thought, what?
link |
I've worked with RNA my whole career.
link |
If you look at it the wrong way, it breaks.
link |
I mean, that's being facetious, right?
link |
But you have to be very careful
link |
because your hands are full of enzymes
link |
that will degrade RNA.
link |
So I thought, how could this possibly work,
link |
injecting it into someone's?
link |
It's an example of I was skeptical and I was wrong.
link |
It turns out that if you modify the RNA properly
link |
and protect it in a lipid capsule,
link |
it actually works as a vaccine.
link |
And people were working on this years
link |
before COVID came around.
link |
They were doing experimental mRNA vaccines
link |
and there were a couple of companies
link |
that were working on it.
link |
And so at the beginning of 2020, they said, let's try it.
link |
And I was skeptical, frankly,
link |
because I just thought RNA would be too labile,
link |
So this is, as we're saying offline, one of the great things
link |
about you is you're able to say when you're wrong
link |
about intuitions you've had in the past,
link |
which is a beautiful thing for a scientist.
link |
But I still think it's very surprising
link |
that something like that works, right?
link |
Yeah, I am surprised.
link |
So you're just launching RNA in a protective membrane.
link |
And then now one thing is surprising
link |
that the RNA sort of lasts long enough in its structure.
link |
But then the other thing is why does it work
link |
that that's a good training ground for the immune system?
link |
Is that obvious that that should work?
link |
I don't think it's obvious to most people
link |
and it's worth going into it
link |
because it's really interesting.
link |
I mean, first of all, they wrap the RNA in fats,
link |
in lipid membranes, right?
link |
And the particular formulation they test for years
link |
to make sure it's stable,
link |
it lasts a long time after it's injected.
link |
And the two companies that make the current COVID vaccines,
link |
right, Moderna and Pfizer,
link |
they have different lipid formulations to get to the same.
link |
So that's a real part of it.
link |
And it's not simple.
link |
There are quite a few different lipids
link |
that they put into this coding.
link |
And they test to see how long they protect the RNA
link |
after it's injected, say, into a mouse,
link |
how long does it last?
link |
And the way it works is these,
link |
apparently these lipid nanoparticles,
link |
they get injected into your muscle,
link |
they bump into cells and they get taken up.
link |
So lipid fat is sticky.
link |
It's greasy, we like to say.
link |
And so your cells are covered with a greasy membrane also.
link |
So when these lipid nanoparticles bump into them,
link |
they stick and they eventually get taken up.
link |
And they figured this out right at the beginning.
link |
If we put RNA in a lipid nanoparticle,
link |
will it get taken up into a cell?
link |
And the answer was yes, it was just let's try it.
link |
So it's basically experiment.
link |
It's not like some deep understanding of biology.
link |
It's experimentally speaking, it just seems to work.
link |
Yeah, well, they had some idea
link |
that lipids would target this to a cell membrane.
link |
And remember, there's no receptor involved.
link |
Like the virus has a specific protein
link |
that attaches to a receptor.
link |
It's not efficient enough to just bump around
link |
and get into a cell.
link |
That's what these things are doing.
link |
And they probably optimize the lipids
link |
to get more efficient uptake.
link |
But it's not as efficient as a virus would be
link |
to get into a cell.
link |
Right, so you have no specific,
link |
I mean, which is why it's surprising
link |
that you can crack into the safe with a hammer.
link |
I mean, that's kind of surprising.
link |
It's kind of amazing that it works.
link |
But so maybe let's try to talk about this.
link |
So one of the hesitancies around vaccines
link |
or basically around any new technology
link |
is the fact that mRNA is a new idea.
link |
And it's an idea that was shrouded in some skepticism,
link |
as you said, by the scientific community.
link |
Because it's a cool new technology.
link |
Surprising that it works.
link |
What's your intuition?
link |
I think one nice way to approach this
link |
is try to play devil's advocate and say both sides.
link |
One side is why your intuition says
link |
that it's safe for humans.
link |
And what arguments can you see if you could steal man
link |
and argument why it's unsafe for humans.
link |
Or not unsafe for humans,
link |
but the hesitancy to take an mRNA vaccine is justified.
link |
So many people are afraid because it's new technology
link |
and they feel it hasn't been tested.
link |
I mean, in theory, what could go wrong?
link |
This is the nice thing about mRNA
link |
is that it doesn't last forever.
link |
As opposed to DNA, which doesn't last forever,
link |
but it can last a lot longer.
link |
And it could even go into your DNA, right?
link |
So mRNA has a shorter lifetime,
link |
maybe days after it's injected into your arm,
link |
So that's a good thing
link |
because it's not gonna be around forever.
link |
So that would say, okay, so it's sticking around
link |
for your lifetime is not happening.
link |
But what else could happen?
link |
Well, let's see the protein that's made,
link |
could that be an issue?
link |
And again, proteins don't last forever.
link |
They have a finite longevity in the body.
link |
And this one also lasts perhaps at the best a few weeks.
link |
Now this is a protein that's made
link |
after the RNA gets into the cell.
link |
Yeah, so the lipid nanoparticles taken up into a cell
link |
and the mRNA is translated and you get protein made.
link |
And there's also a question, I'm sorry to interrupt,
link |
where in the body, so because it's not well targeted,
link |
or I don't know if it's supposed to be targeted,
link |
but it can go throughout the body,
link |
that's one of the concerns.
link |
Right, so it's injected deep into your deltoid muscle,
link |
right here, shoulder.
link |
And the idea is not to put it in a blood vessel,
link |
otherwise it would then for sure circulate everywhere.
link |
So they go deep in a blood vessel and it's locally injected.
link |
And they did, before this even went into people,
link |
they did experiments in mice
link |
where they gave them a thousand times higher concentrations
link |
than they would ever give to people.
link |
And then when you do that, it can go everywhere basically.
link |
You can find these nanoparticles
link |
in every tissue of the mouse.
link |
But that's at a thousand fold higher concentration, right?
link |
So I think at the levels that we're using in people,
link |
most of it's staying in the muscle,
link |
but sure, small amounts go elsewhere.
link |
Could there be a lot of harm caused if it goes elsewhere?
link |
Like let's say ridiculously high quantities.
link |
I'm trying to understand what is the damage
link |
that could be done from an RNA just floating about.
link |
So the RNA itself is not gonna be a problem,
link |
it's the protein that is encoded in it, right?
link |
This is a viral RNA which has no sequence in us,
link |
so there's nothing that it could do.
link |
It's the protein that I would say you could ask,
link |
what is that gonna do?
link |
And the one property we know about the spike
link |
is that it can cause fusion of cells, right?
link |
That's how the virus gets in in the beginning.
link |
The spike attaches to the cell by this H2 receptor
link |
and it causes the virus and the cell to fuse.
link |
And that's how the RNA gets out of the particle.
link |
But so wait, I'm a bit confused.
link |
So with this mRNA vaccine with the lipids and the RNA,
link |
there's no spike, right?
link |
The mRNA codes for the spike.
link |
Oh, the mRNA codes, so it creates the spike.
link |
And so that spike could cause fusion of cells.
link |
Yes, except they modified the spike so it wouldn't.
link |
They made two amino acid changes in the spike
link |
so it would not fuse.
link |
So they understand enough which amino acids
link |
are responsible for the fusion.
link |
So they could modify it.
link |
So now it's not gonna cause fusion, so that's not an issue.
link |
It's called the prefusion stabilized spike.
link |
So the spike, when it binds ACE2,
link |
that top falls off and the part of the spike
link |
that causes fusion is now exposed.
link |
And that doesn't happen in this mRNA vaccine.
link |
So those are the things that could have happened,
link |
but I think they're ruled out by what we've just said.
link |
But there's no better test
link |
than putting it into people, right?
link |
And doing phase one, phase two, and phase three,
link |
and increasing numbers of people and asking,
link |
Do we have any concerns?
link |
And so now it's been in many millions of people
link |
and we don't see most of the effects you see in a vaccine,
link |
you see in the first couple of months.
link |
Things like the myocarditis with some of the vaccines,
link |
the clotting issues with the AstraZeneca vaccine,
link |
Guillain Barre, you see those relatively quickly.
link |
And we've seen small numbers of those occur,
link |
but other things we haven't seen,
link |
and you never say never, right?
link |
Right, so I mean, this is fascinating, right?
link |
It's like I drink, I put Splenda in my coffee
link |
and it has supposedly no calories,
link |
but it tastes really good.
link |
And despite what like rumors and blogs and so on,
link |
I have not seen good medical evidence
link |
that is harmful to you, but it's like, it tastes too good.
link |
So I'm thinking like,
link |
there's gotta be longterm consequences,
link |
but it's very difficult to understand
link |
what the longterm consequences are.
link |
And there's this kind of like distant fear
link |
or anxiety about it.
link |
Like this thing tastes too good, it's too good to be true.
link |
There's gotta be, there's no free lunch in this world.
link |
This is the kind of feeling that people have
link |
about the longterm effects of the vaccine,
link |
that you mentioned that there's some intuition
link |
about near term effects that you want to remove,
link |
like the diffusion of cells and all those kinds of things,
link |
but they think, okay,
link |
this travels to other cells in the body,
link |
this travels to neurons or that kind of stuff.
link |
And then what kind of effect does that have longterm
link |
that's yet to be discovered?
link |
What do you make me for this vaccine,
link |
but in general in science about making statements
link |
about longterm negative effects?
link |
Is that something that weighs heavy on you?
link |
Is that something we can kind of escape
link |
through just large scale experimentation
link |
with animals and humans?
link |
Well, if you're really, if you're concerned about longterm,
link |
then you have to do a longterm experiment, right?
link |
And maybe you don't see something for 50, 60 years.
link |
So if someone says to you,
link |
there are no longterm effects of the COVID vaccines,
link |
they can't say that
link |
because they haven't done the long experiment, right?
link |
There's always the possibility, but you have to weigh it.
link |
It's always, there's no free lunch, right?
link |
There's always a risk benefit calculation you have to make.
link |
You can have the study, it goes 50 years and then decide,
link |
but I guess what you're doing is just like we said,
link |
I forget which one, with polio, with rabies, I forget,
link |
but you're weighing the side effects.
link |
Yeah, polio, right.
link |
The vaccine versus the effects of the virus.
link |
And like both of them, you don't know longterm effects,
link |
but you're building up intuition as you study,
link |
which what are the longterm effects?
link |
Like there's a huge number of people,
link |
like that have like, I don't want to say experts
link |
because I don't like the word,
link |
but people have studied it long enough
link |
to where they build up intuition.
link |
They don't know for sure.
link |
There's basic science being done, there's basic studies.
link |
But you start to build up an intuition of what might be
link |
a problem down the line and what is not,
link |
biologically speaking.
link |
And so given that map, then considering the virus,
link |
there seems to be a lot of evidence for COVID
link |
having negative effects on all aspects of the body,
link |
not just even respiratory, which is kind of interesting.
link |
So the cognitive stuff is terrifying.
link |
All kinds of systems evolve, yes.
link |
And then you look at the same thing with the vaccine
link |
and there seems to be less of that.
link |
But of course you don't know
link |
if it's some kind of dormant thing that's just going to.
link |
You have to make a judgment.
link |
And for a lot of people they can't, right?
link |
Because they don't have the tools to make the judgment.
link |
I totally understand that.
link |
And we have let people down a few times in medicine, right?
link |
And I know two very specific examples.
link |
The first polio vaccine ever made,
link |
the Salk vaccine was released in 1955.
link |
Immediately within months,
link |
a few hundred cases of paralysis in kids who got it
link |
because it was not properly inactivated.
link |
Now you have to understand,
link |
parents were dying for a polio vaccine
link |
because kids were getting paralyzed every summer,
link |
30,000 kids a year.
link |
And so they went and took it.
link |
They took the word of the medical establishment
link |
that it was safe and it wasn't.
link |
Big letdown, never going to forget something.
link |
Although I think a lot of people today aren't aware of that.
link |
I think that was a big problem that's everlasting.
link |
Then the attenuated vaccine that we talked about,
link |
the infectious causing polio.
link |
Yet parents continued to bring their kids to be vaccinated
link |
because they were said,
link |
this is the right thing to do.
link |
And I have to say,
link |
I was involved in several lawsuits
link |
where parents of a kid who got paralyzed
link |
from the polio vaccine decided to sue the manufacturer
link |
and get some money for their kid.
link |
And so they got mad.
link |
And I think you could not...
link |
The first issue could have been prevented,
link |
could have been prevented by inactivating it properly.
link |
I think the company just did the wrong thing.
link |
The second we had evidence for,
link |
and we should probably have not used that vaccine any longer,
link |
but I think that destroys public confidence.
link |
But those aren't...
link |
They're not long term.
link |
That's a minority of cases.
link |
This is a minority.
link |
This is a very rare event, yeah.
link |
science as an institution didn't make corrections
link |
And so what do you make of that?
link |
I mean, it's very unfortunate
link |
that those few things can destroy trust.
link |
But I don't think that lasts till today.
link |
I think today is a different era, right?
link |
And most people don't know about those stories.
link |
I tell them to you because that's what could happen.
link |
I think it could happen today.
link |
If you look at the history of the polio vaccine,
link |
the US Public Health Service wanted kids to be vaccinated.
link |
So they did things that probably weren't correct
link |
to get the vaccine back online.
link |
But they did it and they pushed it through.
link |
So the question is, what do we do today?
link |
So I can look at, as we just said,
link |
I can look at what might happen
link |
and I can make reasonable decisions
link |
about the likelihood of them happening.
link |
And I can also say, I don't wanna get COVID of any kind
link |
because I've seen how nasty it can be.
link |
And I decide I'm taking the risk,
link |
whatever small of a long term effect,
link |
I'm gonna take the risk.
link |
My family took the risk and many other people did.
link |
Of getting vaccinated.
link |
Because I think it's very small.
link |
But I understand where people can't make that decision.
link |
And that begs the question,
link |
what would they need to make a decision?
link |
So if you're concerned about an effect in 40 years,
link |
we're not gonna know for 40 years.
link |
Yeah, so I think if I were to speak,
link |
because I talked to, like I mentioned offline to Joe Rogan
link |
and his podcast yesterday,
link |
I talked to him all the time about this.
link |
I think the concern is less about the long term effects
link |
It's more about the, like people like Anthony Fauci
link |
and people at the top are simply misrepresenting the data
link |
or like are not accurately being transparent.
link |
Not collecting the data properly.
link |
Not reporting on the data properly.
link |
Not being transparent.
link |
Not representing the uncertainties.
link |
Not openly saying they were wrong two months ago.
link |
Like in a way that's not like dramatic,
link |
but revealing the basic process of science
link |
when you have to do your best under uncertainty.
link |
Just also just being inauthentic.
link |
There's a sense, especially with like a younger generation
link |
now, there's a certain way on the internet.
link |
Like the internet can smell bullshit
link |
much better than previous generations could.
link |
And so they see there's a kind of inauthenticity
link |
that comes with being like representing authority.
link |
Like I am a scientist.
link |
I have four decades of work.
link |
Therefore everyone should listen to me.
link |
And somehow that maps to this feeling of,
link |
well, what are they hiding?
link |
If they're speaking from authority like this,
link |
if everyone is in agreement like this,
link |
that means they all have emails between each other.
link |
They said, we're gonna tell this.
link |
This is the message we're gonna tell the public.
link |
Then what is the truth, the actual truth?
link |
Maybe there's a much bigger uncertainty.
link |
Maybe there's dead people in the basement
link |
that they're hiding from bad mRNA vaccine experiments.
link |
Maybe they're, and then the conspiracy theory
link |
starts to grow naturally
link |
when there's this kind of mistrust of that.
link |
So it's less about kind of like a deep concern
link |
about longterm effects.
link |
It's a concern about longterm effects
link |
if we find out that there's some secret stuff
link |
that we're not being told.
link |
It all lands on that.
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So what the heck, I mean, so I put the blame
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not on the data, but basically on the leaders
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and the communicators of the science at the top.
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Well, to that I would say all the data,
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as far as I know, are made public.
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So you can dive into it.
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And I know a lot of people ask me questions
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and I just say, it's right here in the data.
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And I know a lot of people can't do that.
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They can't dive into it.
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But that's one solution for people who are able.
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Now you could argue, well,
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maybe they've left data out.
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Well, then not even I can help
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because then they're hiding it from me too.
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And I think that's highly unlikely.
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I think for the most part,
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the FDA requires the release
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of all the clinical trial data, right?
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So, okay, so this clinical trial data, that's one thing.
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So that's the data that we should be focusing on, right?
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So there's a lot of different data sets here.
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So there's preclinical data,
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which is everything that was done in the lab
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before this vaccine ever went into a human arm.
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It's all the cell culture work
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that we talked about a little, experiments in animals.
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All of that is publicly accessible.
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Most of it gets published.
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And then there's the initial drug filing,
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which is huge, the books of,
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you can get that and look at it, right?
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This is me sort of asking sort of difficult questions here.
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So there's a lot of money to be made by makers of the vaccine.
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So for these companies, and obviously there's a distrust
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of those folks too.
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They've done a lot of really good things in this world,
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but the incentives are such
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that you wanna sweep stuff under the rug
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if you're not 100% pure in your ethics.
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And how hard is it for that data to be fabricated,
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manipulated, like what's your intuition
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for the pre trial stuff?
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I think when you start fabricating,
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then you get inconsistencies,
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which are pretty easy to pick up.
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When you're talking about some large scale things
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Because then you can look through the data very,
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you're gonna, I mean, we require looking very carefully,
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but you will see inconsistencies from one trial to another.
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And that might ring a bell that something's been done.
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Yeah, it's like the moon landing thing.
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Sometimes like going to the moon is easier than faking it.
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In the sense it might be easier to do a large scale trial
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and get an effective vaccine versus faking it.
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But when you brought up the for profit issue,
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I think that is always been an issue.
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I've always felt that having your health depend
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on for profit industry may not be the best solution.
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And I don't know how else to do it.
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People tell me I'm a dreamer that thinking that,
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all medicines could be nonprofit.
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But I also think that the world should have one health
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system that takes care of everyone, right?
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Because there's some countries that can't
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and other countries have an excess like us.
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So I wish we could do that.
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Well, the argument is the speed of which the vaccines
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for COVID were produced would never happen
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in a nonprofit system,
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would never happen in a non capitalist system.
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Oh, I could set up a vaccine production institute
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in the US that would get the vaccines done
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because you just need to put money into it.
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That's what made these vaccines get done money.
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They poured billions of dollars and they got it done quickly.
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But if I set up a nonprofit institutes of vaccines
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throughout the US staffed with really talented people,
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pay them well, keep them motivated,
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you'll get your vaccine.
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No, but that's the thing with capitalism is that
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the selection of who to hire a good,
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when you say good people,
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capitalism has a machine that fires people
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who are not good and selects people that are good.
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Coming from the Soviet Union,
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the dream of communism is similar
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to what you're saying broadly defined.
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It certainly doesn't work in the broads.
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The question of whether it works in the healthcare space,
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there is some aspect to the machine of capitalism
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being the most effective way to select for good people
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and to effectively produce the thing.
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But then of course, a lot of people would argue
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the current, even the current healthcare is not
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with like regulations, there's some weird mix
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where there's a lot of opportunities for inefficiencies.
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There's a lot of opportunities for bureaucracy.
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So you have like the worst of all worlds.
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Can't there be some intermediate that works
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because I mean, the other issue that we haven't mentioned
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is that politics gets thrown into this
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and that really messes up
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and it should never be mixed with healthcare,
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but it is because a lot of funding comes from the government
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so that's another confounding factor.
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But I really think I could make a vaccine institute
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that if someone didn't do well, I'd fire them.
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No, you're not gonna stay if you can't do your job
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and do it well, you don't give them incentives,
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but it doesn't have to be the two extremes I think.
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There has to be a solution that people don't have
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this mistrust for a company making huge profits
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But you know what, it's funny,
link |
it seems that vaccines and antivirals bear the brunt
link |
of this criticism yet there are many other pharmaceuticals
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that people rely on of all sorts.
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They don't seem to question and have issues
link |
with those and they have far more side effects than vaccines.
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It's a very strange how we're picking that way,
link |
but I should also say that if you have one big
link |
vaccine institute, one of the other sets
link |
of vaccine conspiracies, I mean, I would say they're
link |
a little farther out into the wild side of ideas,
link |
but there's one way to control the populace
link |
is by injecting substances into them, right?
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People, I mean, part of that, funny enough,
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it probably has to do with needles
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versus something you put in your mouth,
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but there's something about the government,
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especially when it's government mandated injection
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of a substance into you.
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I don't care what the science says,
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if it's 100% effective, 100% safe,
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there's a natural distrust of what,
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like even if this is effective and safe,
link |
giving the government power to do this,
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aren't they gonna start getting ideas down the line for,
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I think that they can barely govern.
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I don't think they're gonna do that,
link |
but you don't have to take, unless you're a federal employee,
link |
you don't have to take a COVID vaccine.
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Yeah, but that largely has to do, not largely,
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but there is an individualistic spirit
link |
to the American people.
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There's this, like, you're not gonna take my gun away
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from me, you're not going, and I think that,
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that's something that makes America what it is.
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Just coming from the Soviet Union,
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there's a power to sort of resisting
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the overreach of government.
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That's quite interesting, because I'm a believer,
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I hope that it's possible to have,
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to strive towards a government that works extremely well.
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I think at its best, a government represents the people
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and functions in the similar way that you're mentioning,
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but that, like, pushback,
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even if it turns into conspiracy theory sometimes,
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I think is actually healthy in the long arc of history.
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It can be frustrating sometimes,
link |
but that mechanism of pushing back against power,
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against authority, can be healthy.
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I agree, I think it's fine to question the vaccines.
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What I have issue with is that many people
link |
put out incorrect information,
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and I'm not sure what their motivations are,
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and it's very hard to fight that,
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because then it's my word versus theirs,
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and I'm happy to talk with people
link |
about any of their concerns,
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but if you start getting into the stuff
link |
that just isn't true, then we have a problem.
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The thing I struggle with is conspiracy theories,
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whatever language you want to use,
link |
but sort of ideas that challenge
link |
the mainstream quote unquote narrative,
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given our current social media and internet,
link |
like the way it operates,
link |
they can become viral much easier.
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There's something much more compelling about them.
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Like I have a secret about the way things really work.
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That becomes viral, and that's very frustrating,
link |
because then you're not having
link |
a conversation on level ground.
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When you're trying to present scientific ideas,
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and then there's conspiracy theories,
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the conspiracy theories become viral much faster,
link |
and then you're not just having a discussion
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That's the frustrating part,
link |
that it's not an even discussion.
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Can I just say one more thing?
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I mean, the internet is here to stay,
link |
so we're gonna have to figure out
link |
how to deal with it, right?
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But from my perspective,
link |
I was skeptical that any COVID vaccine
link |
would be ready within a year.
link |
Plus, the way I look at the mRNA vaccine as a scientist,
link |
it's gee whiz to me.
link |
It's amazing that it worked,
link |
and I think the data are great, so I want it.
link |
As a scientist, I want it.
link |
One of the really sad things, again,
link |
with me, too, as a scientist or as an admirer of science,
link |
I don't know if it's politics,
link |
but one of the sad things to me about the previous year
link |
is that I wasn't free to celebrate
link |
the incredible accomplishment of science with the vaccines.
link |
I was very skeptical that it's possible
link |
to develop a vaccine so quickly.
link |
So it's unfortunate that we can't celebrate
link |
how amazing humans are to come up with this vaccine.
link |
Now, this vaccine might have long term effects.
link |
That doesn't mean this is not incredible.
link |
Why couldn't you celebrate?
link |
Because I would love to inspire the world
link |
with the amazing things science can do.
link |
And when you say something about the vaccines,
link |
they're not listening to the science.
link |
A lot of people are not listening to the science.
link |
What they hear is, oh, you're a Republican
link |
or you're a Democrat, and you're social signaling,
link |
doing some kind of signaling.
link |
No, I think that the vaccine,
link |
you're talking about injecting something into you,
link |
and maybe you're right that the rhetoric is like,
link |
you better take this or you're dumb.
link |
It's not the right approach.
link |
I've seen, actually, it's kind of interesting.
link |
I've seen both sides kind of imply that.
link |
So the people who are against the vaccine
link |
are dumb for not trusting science,
link |
and the people who are for the vaccine
link |
are called dumb for trusting science,
link |
the scientific institution.
link |
And nobody wins, yeah.
link |
And they both kind of have a point.
link |
Like, because you can always,
link |
it's like, is the glass half full or half empty?
link |
Because you can always look at, like, science
link |
from a perspective of certain individuals
link |
that don't represent, perhaps, the not greatest leaders,
link |
almost like political leaders.
link |
There's a lot of, you know,
link |
yesterday I went on a whole rant against,
link |
I said a lot of positive things about Anthony Fauci
link |
before I went on a rant against him.
link |
Because ultimately, you know,
link |
I think he failed as a leader,
link |
and I know it's very difficult to be a leader,
link |
but I still wanted to hold him accountable for that
link |
as a great communicator of science and as a great leader.
link |
What do you think he didn't do right?
link |
So the core of the problem is the several characteristics
link |
of the way he was communicating to the public.
link |
So one is the general inauthenticity.
link |
Two is a thing that, it's very hard to put into words,
link |
but there's certain ways of speaking to people
link |
that sounds like you're hiding something from them.
link |
That sounds like you're full of shit.
link |
That's the authenticity piece.
link |
Like, it sounds like you're not really speaking
link |
to the full truth of what you know
link |
and that you did some shady shit in your past
link |
that you're trying to hide.
link |
So that's a way of communicating
link |
that I think the internet and people in general
link |
are becoming much better at detecting.
link |
Yeah, it's like you said, they're good BS detectors.
link |
Yeah, good BS detectors.
link |
But contributing to that is speaking from authority,
link |
speaking with authority and confidence
link |
where neither is deserved.
link |
So first of all, nobody's an authority on this new virus.
link |
We're facing a deadly pandemic,
link |
and especially in the early stages,
link |
it was unclear how deadly it would be.
link |
It was unclear, probably still unclear,
link |
fully how it's transmitted.
link |
The full dynamics of the virus,
link |
the full understanding of which solutions work and not,
link |
how well masks of different kinds work,
link |
how easy or difficult it is to create tests,
link |
how many months or years it's gonna take
link |
to create a vaccine,
link |
how well in history or currently do quarantine methods
link |
or lockdown methods work,
link |
what are the different data mechanisms
link |
that are data collection mechanisms
link |
that are being implemented,
link |
what are the clear plans that need to happen,
link |
what the epidemiology that's happening,
link |
what is the uncertainty around that?
link |
Then there's the geopolitical stuff with China.
link |
I personally believe there should have been
link |
much more openness about the origins of the virus,
link |
whether they're leaked from a lab or not.
link |
I think communicating that you're open to these ideas
link |
is actually the way to get people to trust you,
link |
that you are legitimately open to ideas
link |
that are very unpleasant, that go against the mainstream.
link |
Showing that openness is going to get people to trust you
link |
when you finally decrease the variance in your uncertainty,
link |
like decrease uncertainty and have,
link |
we still have a lot of uncertainty,