Latest / Wellness, Actually with Emily Oster & Perry Wilson, MD / What's the deal with mRNA vaccines?

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What's the deal with mRNA vaccines? · Wellness, Actually with Emily Oster & Perry Wilson, MD

0:00
Speaker 1: Emily. One of the things that is really interesting about
0:05
Speaker 1: the mRNA vaccines, at least is that people have really
0:08
Speaker 1: different responses to them. So I want to know if
0:12
Speaker 1: you're one of the lucky ones who gets an mRNA
0:15
Speaker 1: vaccine for COVID or whatever and like goes about their day,
0:19
Speaker 1: or if you're the type like me whose body seems
0:23
Speaker 1: to think they're under assault from some kind of alien chemical.
0:27
Speaker 2: Yeah.
0:27
Speaker 3: I was in bed for a day after my early
0:32
Speaker 3: COVID vaccines, and I am not a person who spends
0:36
Speaker 3: time in bed, so I had a pretty extreme reaction,
0:40
Speaker 3: I think, like, but my husband had like nothing.
0:43
Speaker 1: Yeah, yeah, I'm so jealous. You know, I don't track
0:46
Speaker 1: things very much, like I have a fitness watch or
0:49
Speaker 1: whatever that I never look at, but I definitely noticed
0:53
Speaker 1: my sleep score went from like, you know, ninety to
0:57
Speaker 1: twenty or something like. It was insane the night after
1:01
Speaker 1: I got one of these shots.
1:03
Speaker 3: So the other person who has no I know who
1:05
Speaker 3: I had no reaction to this is my father. My
1:07
Speaker 3: father has gotten a COVID booster every year. He must
1:09
Speaker 3: have gotten fifty COVID vaccines by now, and he has
1:12
Speaker 3: never had any reaction to them. And I wonder if
1:16
Speaker 3: like people who have a better immune system have more
1:19
Speaker 3: of a reaction. That's how I'm explaining the difference of
1:21
Speaker 3: me and me and my husband. Yeah, validate me.
1:25
Speaker 1: I had thought the same thing because I wanted to
1:27
Speaker 1: be like, ooh, I'm I'm so sweaty. I this must
1:30
Speaker 1: this must be good. And I actually did dig into
1:33
Speaker 1: the data a little bit and honestly, like, there's not
1:35
Speaker 1: that much correlation between your symptoms post vaccine and your
1:39
Speaker 1: antibody levels or anything like that.
1:41
Speaker 3: SOO okay, well that's true.
1:44
Speaker 1: But that is just scratching the surface of this amazing
1:48
Speaker 1: molecule called RNA, which I'm so excited to talk to
1:52
Speaker 1: you about today.
1:53
Speaker 3: I can't wait. I'm Emily Astro, I'm an economist and
1:59
Speaker 3: a data x.
2:00
Speaker 1: And I'm Perry Wilson. I'm a medical doctor.
2:02
Speaker 3: It's Thursday, July second, twenty twenty six. And this is wellness.
2:07
Speaker 1: Actually, because you're getting a staggering amount of health and
2:11
Speaker 1: wellness information nowadays from every source imaginable, and some of
2:15
Speaker 1: it is awesome.
2:16
Speaker 3: And some of it is well actually both Fortunately we
2:21
Speaker 3: are both people who know how to read studies, how
2:24
Speaker 3: to parse the data, and can tell you what's worth
2:26
Speaker 3: thinking about and what you can safely ignore.
2:29
Speaker 1: But before we dig in, a note that this podcast
2:32
Speaker 1: is for educational purposes and should not be construed as
2:34
Speaker 1: medical advice. We don't know your unique situation, so talk
2:38
Speaker 1: to your doctor for personal health decisions.
2:40
Speaker 3: This week we're asking what's the deal with RNA? Harry
2:45
Speaker 3: and I will give the official smasher pass, and then
2:47
Speaker 3: we'll get to your question of the week. But first,
2:49
Speaker 3: let's do the health news roundup after the break, and
3:04
Speaker 3: now for the health news of the week. First up, Perry,
3:07
Speaker 3: the FDA has dropped their enforcement action against Whoop for
3:13
Speaker 3: its blood pressure feature. I have a Whoop. I have
3:17
Speaker 3: never used it to record my blood pressure, but I'm
3:20
Speaker 3: curious what is going on here and how do you
3:22
Speaker 3: feel about it?
3:23
Speaker 1: As a real doctor, So always good to talk about WOOP.
3:28
Speaker 1: I know that you're a fan, And as I've disclosed before,
3:32
Speaker 1: Whoop actually funded a study from our lab a while ago,
3:35
Speaker 1: So bit of a conflict of interest to disclose that
3:38
Speaker 1: said blood pressure measurement using things that don't squeeze your
3:42
Speaker 1: arm or your wrist is sort of fraught. Like there
3:47
Speaker 1: are a lot of devices on the market that promise
3:49
Speaker 1: to do this like non squeezy things, and watches are
3:51
Speaker 1: clearly one of them. The data on their accuracy is
3:54
Speaker 1: generally not great. But that's not what got Woop and trouble.
3:57
Speaker 1: What got Whoop in trouble is that you cannot diagnose
4:00
Speaker 1: a disease if the if you haven't gotten FDA clearance,
4:04
Speaker 1: and because they said your blood pressure was in the
4:06
Speaker 1: red zone, if it was greater than systolic, greater than
4:09
Speaker 1: one hundred and forty or whatever, the FDA was like,
4:11
Speaker 1: that's hypertension. You're diagnosing a disease. That's a no no.
4:16
Speaker 1: What I love is how Weop got around this, which
4:18
Speaker 1: is that they I don't know if you saw this
4:20
Speaker 1: on your whoop, if your woop was like equipped with
4:23
Speaker 1: the blood pressure thing or not. But the graphic had
4:27
Speaker 1: like originally was like green, yellow, red, So there were
4:30
Speaker 1: three zones, right, and the red zone was hypertension. That's
4:33
Speaker 1: no go. So what they did they changed it to
4:35
Speaker 1: like a gradient, so it like changes from green to
4:37
Speaker 1: yellow to red, but without a defined cup point. So
4:40
Speaker 1: now they're not diagnosing a disease anymore. It's just like
4:44
Speaker 1: a wellness Like how good you like? Qualitative action thing
4:48
Speaker 1: and uh, and so the FDA has dropped its concerns.
4:52
Speaker 3: What I find so interesting about that is, in general,
4:55
Speaker 3: these cutoffs are always very stupid, Like.
4:59
Speaker 1: We should always are arbitrary. Yeah, we should always.
5:01
Speaker 3: Be thinking about things as a continuum. So as a
5:03
Speaker 3: reporting mechanism, that's great, of course, as a way to
5:07
Speaker 3: find your blood pressure things, as you point out, things
5:10
Speaker 3: that live on your wrist are not as good as
5:12
Speaker 3: things that squeeze your arm, which is actually how we
5:14
Speaker 3: measure that.
5:15
Speaker 1: Can I like make Emily Oster mad for a second,
5:18
Speaker 1: because I was reviewing some of the literature on these
5:24
Speaker 1: cuffless blood pressure machines and the ones that really do
5:27
Speaker 1: our measured blood pressure, like pass through FDA clearance, the
5:30
Speaker 1: whole deal, and one of the studies I saw that
5:33
Speaker 1: god FDA clearance, this is the design, Emily, tell me
5:36
Speaker 1: what the problem is here. You come to the mall,
5:38
Speaker 1: you sit down, they measure your blood pressure. You sit down,
5:41
Speaker 1: They measure a blood pressure with a cuff. Okay, that's
5:43
Speaker 1: the gold standard.
5:44
Speaker 3: Okay.
5:44
Speaker 1: Then they put on their little device on your wrist
5:47
Speaker 1: and they calibrate it okay to the measured blood pressure. Okay.
5:51
Speaker 1: So they're like Okay, your blood pressures one three, five
5:53
Speaker 1: or seventy five. We're calibrating this thing to risk. Okay,
5:55
Speaker 1: now you go and walk around the mall for a while.
5:58
Speaker 1: Come back an hour later. They met your blood pressure
6:00
Speaker 1: with the cuff thing again and they see what the
6:03
Speaker 1: watch reports and they say, oh, look they're very similar,
6:07
Speaker 1: Like the watch is very similar to the blood pressure cuff,
6:11
Speaker 1: which Emily, Yeah, what's the problem here.
6:16
Speaker 3: There are a lot of problems. There's a lot of problems.
6:20
Speaker 3: What's the problem you most want to identify.
6:22
Speaker 1: I want to say that if my watch did nothing
6:26
Speaker 1: more than just report out whatever the original value you
6:30
Speaker 1: calibrated it to was, it would do great because most great,
6:34
Speaker 1: most people's blood pressure doesn't change that much over an
6:37
Speaker 1: hour when they're sitting down, right, Like, this is not
6:40
Speaker 1: a test. You could just have an algorithm that's like
6:42
Speaker 1: I always just say one three, five or seventy five
6:44
Speaker 1: or whatever you calibrated me to originally.
6:46
Speaker 3: Totally it would be just as It's just as good
6:48
Speaker 3: basically as an algorithm that's like we took the blood
6:50
Speaker 3: pressure measurement and then we just said that was your
6:52
Speaker 3: blood pressure, yes, and then it's about right on average
6:55
Speaker 3: it's going to be right. It's going to be right
6:57
Speaker 3: on average most.
6:57
Speaker 1: Of the time. So anyway, I'm suspicious these cuff lists
7:00
Speaker 1: blood pressure cuffs. Moving on, Emily, there is some concerning
7:05
Speaker 1: news about baby formula. When isn't there news about baby formula?
7:09
Speaker 1: But this time it's botulism. I guess what's going on?
7:12
Speaker 3: Yeah, So in the past year there have been two
7:17
Speaker 3: outbreaks of botulism in baby formula. There was one last
7:21
Speaker 3: fall in like October, in a formula called buy Heart.
7:24
Speaker 3: A bunch of babies got sick, like over fifty babies.
7:27
Speaker 3: None of them died, thank goodness. Botulism is treatable, but
7:30
Speaker 3: it can be quite serious. I think some of these
7:32
Speaker 3: babies have d long term consequences. This was the first
7:36
Speaker 3: time there was ever a bochelism outbreak a baby formula.
7:39
Speaker 3: Boulism gets in because if bacteria gets in and it
7:42
Speaker 3: produces these botulism spores, it is not something we have
7:47
Speaker 3: traditionally tested for in formula because we haven't seen it,
7:49
Speaker 3: and so you know, this was a surprise. And then
7:54
Speaker 3: a few weeks ago there was another bochulism case in
7:58
Speaker 3: a different formula. Another three cases identified and I think
8:02
Speaker 3: It really caused a lot of people to say, you know,
8:04
Speaker 3: oh my god, is there just botulism in all formulas.
8:07
Speaker 3: It's an issue with baby formula that it just gets
8:10
Speaker 3: botulism more than we thought, and we should be sort
8:12
Speaker 3: of worried about all of this. The thing that came
8:16
Speaker 3: out towards the end of last week and over the
8:18
Speaker 3: weekend is that, in fact, this is basically the same outbreak.
8:22
Speaker 3: So both of these companies were using the same provider
8:28
Speaker 3: of the organic whole milk that they were using the
8:31
Speaker 3: same milk provider, the same drying plant. That was not
8:35
Speaker 3: obvious from earlier reporting. Let's put aside why, but it
8:40
Speaker 3: does seem like, actually, there is like one thing that
8:43
Speaker 3: happened in one plant in Nevada where some botulism got
8:47
Speaker 3: into this powdered organic milk, and both companies used it.
8:49
Speaker 3: So on the one hand, I don't know how reassuring
8:52
Speaker 3: it is, but I think it's a little bit reassuring
8:54
Speaker 3: to suggest that in fact, this is like one specific
8:57
Speaker 3: thing that happened.
8:58
Speaker 2: We still need more regulatory oversight, but.
9:01
Speaker 1: Yeah, that's super concerning. Botulism causes like a flaccid paralysis
9:05
Speaker 1: in kids. You know, it's botox, right, Like, this is
9:07
Speaker 1: the toxin that botulism secretes is botox. And that's fine
9:11
Speaker 1: if you're injecting into tiny amounts into small muscles in
9:14
Speaker 1: your face and you're an adult. It's not great if
9:16
Speaker 1: it's getting systemic in your body.
9:19
Speaker 3: So that's that. Okay, Let's turn to something a little
9:23
Speaker 3: uh weirder, which is that stat News has been reporting
9:28
Speaker 3: that there was a request by the White House for
9:34
Speaker 3: compassionate use of Eli Lilly's new weight loss drug, which
9:38
Speaker 3: is called retruit to Tide.
9:40
Speaker 1: Is I'm saying that retat true Tide, which.
9:44
Speaker 3: Is a very it's a GLP one but reportedly in
9:47
Speaker 3: the trials like enormously effective, superpotent. It has not yet
9:51
Speaker 3: been approved, but things that are not yet approved can
9:54
Speaker 3: be requested for compassionate use in some circumstances. This would
9:58
Speaker 3: be an unusual circum stance. But the stat news is
10:02
Speaker 3: speculating that the patient was Trump. Yeah, wtf, Perry, I
10:08
Speaker 3: can't even understand what's going on here.
10:09
Speaker 1: Okay, Yeah, for people not in this space, like, let
10:14
Speaker 1: me first of all say that stat news is no rag, like,
10:17
Speaker 1: this is a really.
10:19
Speaker 2: Excellent not Bob's speculative blog.
10:22
Speaker 1: I mean, it's like a real, real news organization with
10:25
Speaker 1: real reporters. So the facts of the case that we
10:29
Speaker 1: have is that there's been one approval for compassionate use
10:33
Speaker 1: for retatritide, and the reason that there's only one is because, like,
10:37
Speaker 1: why would a GLP one be used for compassionate use,
10:40
Speaker 1: Like that's not you know, usually these are drugs like
10:42
Speaker 1: for end of life, like late stage cancers, you know,
10:44
Speaker 1: like last ditch, hail married types of things. Okay, fine,
10:47
Speaker 1: we know it was done in April for a seventy
10:49
Speaker 1: nine year old patient. We know that. I'm not sure
10:53
Speaker 1: it was the White House, but there were top health
10:56
Speaker 1: officials involved, including a senior clinician at the NIA whose
11:00
Speaker 1: name is Ranganath Muniyappa, who requested the drug to treat whoever.
11:06
Speaker 1: This patient was for refractory obesity with obstructive sleep APNE
11:09
Speaker 1: and pulmonary hypertension, which is a complication of severe obesity,
11:13
Speaker 1: and that the patient had previously tried to zeppetite, which
11:16
Speaker 1: is munjaro so it was like and it had been ineffective.
11:21
Speaker 1: So okay, fine, there are lots of seventy nine year
11:25
Speaker 1: olds in April in Washington, DC, I like what I'm
11:30
Speaker 1: just could it be Trump?
11:32
Speaker 4: Sure?
11:33
Speaker 1: But like what it strikes me and I don't want
11:35
Speaker 1: to get conspiratorial that they must have some other sourcing
11:40
Speaker 1: here than just like oh, a seventy nine year old man,
11:42
Speaker 1: and like Trump seems like he's overweight, Like right.
11:46
Speaker 3: I agree, there's something going on behind this that we
11:49
Speaker 3: don't understand, and I don't know how much we will learn,
11:52
Speaker 3: although I will say that there are people in the Senate.
11:55
Speaker 3: Maggie Hassen in particular, is like trying to get our
11:58
Speaker 3: fea junior to like revee who this.
12:00
Speaker 2: Person is that got this special access.
12:03
Speaker 3: Yeah, I don't know. Like everything in this space, there
12:06
Speaker 3: are so many like messed up incentives and distrust and
12:10
Speaker 3: anger on all sides. It's very difficult to understand what
12:13
Speaker 3: is actually going on.
12:16
Speaker 1: And honestly, I couldn't even parse this right. Like, I
12:19
Speaker 1: guess if Trump wants to take a GLP one, great
12:22
Speaker 1: for Trump. If it were Trump, the only scandal kind
12:26
Speaker 1: of would be I mean sure, I guess it's like
12:29
Speaker 1: pulling the levers of power to you know, get something
12:31
Speaker 1: special for yourself. But a lot of people.
12:33
Speaker 3: Are getting from like Tom Hounty pharmacies and child already anyway, So.
12:37
Speaker 1: Exactly, I think more it would be that they made
12:41
Speaker 1: such a big show of releasing his quote unquote health
12:44
Speaker 1: records and was like the healthiest person in the world.
12:46
Speaker 1: So if it turns out that he has severe obstructive
12:49
Speaker 1: sleep apnea that's led to pulmonary hypertension, you sort of
12:53
Speaker 1: want to know problem why that wasn't reported.
12:56
Speaker 3: But anyway, we'll keep you updated on this really really
12:59
Speaker 3: weird story as we come. And that is it for
13:02
Speaker 3: the Health News of the week. After the break, What's
13:04
Speaker 3: the deal with RNA? All right, we're back and we're
13:13
Speaker 3: going to talk about what is the deal with RNA?
13:17
Speaker 3: And before we get into it, before we start talking
13:19
Speaker 3: about vaccines and controversies and Jeffrey epscene and other important
13:25
Speaker 3: topics in this space, I think it's important to return
13:29
Speaker 3: to high school biology. I'm very up to date on
13:32
Speaker 3: this because I have a person who just finished high
13:34
Speaker 3: school biology, so I basically know everything. But I think
13:39
Speaker 3: we want to set the stage here for people and
13:41
Speaker 3: explain what is RNA and when I say m RNA
13:44
Speaker 3: in particular, which is what a lot of this conversation
13:46
Speaker 3: is going to focus on. What are we talking about So,
13:51
Speaker 3: although I have recently finished a course in ninth grade biology, Perry,
13:54
Speaker 3: I'm going to turn this over to you.
13:56
Speaker 2: As a person who is a scientist.
13:59
Speaker 1: Sure, So, there are three elements that we need to
14:04
Speaker 1: know here, DNA, RNA, and protein. DNA gets transcribed into rna,
14:10
Speaker 1: RNA gets translated into protein. Let me explain what those
14:13
Speaker 1: words mean. So DNA lives in the nucleus of the cell.
14:15
Speaker 1: And think of DNA as like a big cookbook, Like
14:19
Speaker 1: it's got a recipe in there for every single thing
14:22
Speaker 1: that any cell could make, like a really good cookbook, Okay,
14:26
Speaker 1: And it's all there, and it's bound really nicely, you know,
14:29
Speaker 1: leather bindings. It smells of rich mahogany, and it's very protected.
14:33
Speaker 1: The nucleus is like the holiest of holies of the cells.
14:37
Speaker 1: It's very difficult to get things in and out of
14:39
Speaker 1: the nucleus. They need special signaling and all kinds of stuff.
14:41
Speaker 1: So that's DNA. You don't want to mess with that,
14:44
Speaker 1: right we know if you mess with DNA too much
14:46
Speaker 1: and get cancer or other problems. So that's kept very sacred.
14:50
Speaker 1: But then you've got to get the recipes out to
14:51
Speaker 1: the cell to tell the factories of the cell, like
14:54
Speaker 1: what to build today, right, I'm a you know, if
14:56
Speaker 1: you're a white blood cell and you need to make
14:58
Speaker 1: antibodies or whatever, it is, your job is to make
15:00
Speaker 1: so that DNA gets transcribed into RNA. So DNA, you'll remember,
15:07
Speaker 1: has four bases, like four letters. Essentially, that is the
15:11
Speaker 1: genetic code. And so just like AGCD like whatever, in
15:14
Speaker 1: different combination of those letters, that's what makes you human.
15:17
Speaker 1: And it's billions of billions and billions of base pairs long.
15:20
Speaker 1: And mRNA also has four letters, although one of them
15:24
Speaker 1: is different than the DNA letters doesn't even matter. But RNA, now,
15:30
Speaker 1: which is a single helix as opposed to DNA's double helix,
15:33
Speaker 1: is allowed to exit the nucleus. It special permission. It
15:36
Speaker 1: leaves the nucleus and goes into the cytoplasm of the cell.
15:40
Speaker 1: In the cytoplasm of the cell, RNA docks with these factories,
15:44
Speaker 1: which are called ribosomes, which reads that code, and every
15:49
Speaker 1: three letters of code corresponds to one amino acid. If
15:55
Speaker 1: you go back to our protein episode, you will remember
15:58
Speaker 1: that proteins are just long chain of amino acids, and
16:01
Speaker 1: there's something like twenty two amino acids. So we've got
16:03
Speaker 1: to change these four letters in various combinations into twenty
16:06
Speaker 1: two amino acids plus codes that say stop, you know,
16:10
Speaker 1: stop working and you're done and things like that. And
16:14
Speaker 1: this is like, like we know what all this is.
16:16
Speaker 1: It's kind of amazing, Like we know that if you
16:19
Speaker 1: have you know, AAA, like that corresponds to this specific
16:23
Speaker 1: amino acid, and if you have ACA, and it responds
16:27
Speaker 1: to this specific amino acid, and so that code gets
16:32
Speaker 1: translated into a chain of amino acids, and those amino
16:35
Speaker 1: acid chains grow and then fold and become a big
16:38
Speaker 1: sticky glob. That's what we call a protein, and that's
16:40
Speaker 1: how cells work.
16:42
Speaker 3: I just want to pause here because I think when
16:44
Speaker 3: we talk about this biology, like it is easy to
16:47
Speaker 3: just listen and be like, okay, you're right. Like they
16:49
Speaker 3: come out and they turn it in and it turns
16:51
Speaker 3: all the amino acids insurance into protein. But I would
16:54
Speaker 3: like us to retain in this conversation a sense of wonder, Yeah,
16:58
Speaker 3: which is like how amazing is that that? Like we
17:02
Speaker 3: have these things And then the RNA comes out and
17:05
Speaker 3: it like just clicks along and it makes all the
17:08
Speaker 3: little legos and it puts them together, like holy, and
17:12
Speaker 3: then it becomes all the things you need and it
17:14
Speaker 3: turns into these protein and it makes your body. Like
17:16
Speaker 3: that is really really really incredibly cool.
17:20
Speaker 1: It's just really really cool.
17:22
Speaker 3: It's just cool.
17:23
Speaker 1: It's it's super cool. And what's I think additionally fascinating
17:27
Speaker 1: to me is that proteins are so complicated, right, Like
17:29
Speaker 1: there's a million proteins, like proteins that make your hair,
17:32
Speaker 1: and proteins that you know, make lungs, you know, mucus,
17:36
Speaker 1: and like all these different kinds of proteins and you know,
17:40
Speaker 1: in millions fascinating combinations, and all of it can be
17:44
Speaker 1: represented by just like a single chain of these four
17:48
Speaker 1: letters in a very specific order. That is very important.
17:51
Speaker 1: It's it's amazing.
17:53
Speaker 3: It's really cool. Okay, So when we talk about m RNA,
17:57
Speaker 3: in what way is that different from the RNA or
18:00
Speaker 3: that is the RNA.
18:02
Speaker 1: So mRNA is a subtype of RNA. So RNA is
18:07
Speaker 1: any of these single helix molecules that have these four
18:10
Speaker 1: unique base pairs in a chain. And mRNA is certainly
18:14
Speaker 1: the one that you're learning about in high school biology.
18:16
Speaker 1: It stands for messenger RNA. It is the message coming
18:19
Speaker 1: from the DNA in the nucleus out into the cytoplasm,
18:22
Speaker 1: and like, here's what you need to do, sell like,
18:24
Speaker 1: please produce this protein for me.
18:26
Speaker 3: I think, in your in your like beautiful cookbook example,
18:30
Speaker 3: this is a recipe. So it is if we took
18:32
Speaker 3: we opened up the cookbook, we copied like xerox one
18:36
Speaker 3: of the pages and sent that recipe out in the
18:38
Speaker 3: cell and said, okay, now you know you make like
18:41
Speaker 3: chickpeas and tomatoes sheet pan meal. And then the thing
18:46
Speaker 3: puts together the thing into the chickp and tomato sheet
18:48
Speaker 3: pan meal protein and folds it up and sends it
18:51
Speaker 3: to make your hair or whatever. But and then, and
18:54
Speaker 3: I think importantly, after that recipe is made and the
18:57
Speaker 3: chickpea protein leaves, the page just goes away. It just
19:04
Speaker 3: gets trashed.
19:05
Speaker 1: Your cells are absolutely lousy with substances that break down RNA.
19:12
Speaker 1: When I did I'm a clinical researcher now, so I
19:15
Speaker 1: work with humans, which which is much more fun than
19:17
Speaker 1: being in a wet lab. But when I did work
19:19
Speaker 1: in a wet lab way back in college and stuff
19:22
Speaker 1: and was working with RNA, it was like DNA. I'll
19:25
Speaker 1: just say it's super hardy, right, you can, like you
19:28
Speaker 1: can extract it from amber and clone dinosaurs like you
19:31
Speaker 1: can do less.
19:32
Speaker 3: And actually, okay, just people that doesn't actually work, don't
19:35
Speaker 3: try it.
19:36
Speaker 2: Don't try it.
19:37
Speaker 1: I mean it goes poorly, It does go poorly. But
19:40
Speaker 1: no DNA you know, can last for centuries whatever. It's
19:43
Speaker 1: super easy, doesn't matter RNA. When we were working with RNA,
19:46
Speaker 1: it was like, okay, clean everything off the off the
19:48
Speaker 1: bench top, and like wipe it down with all these
19:50
Speaker 1: special things, and like don't breathe on it. Wear a
19:53
Speaker 1: mask because you have RNAs is in your breath and
19:55
Speaker 1: your sweat and everything you touch. It's just like so ephemeral.
20:00
Speaker 1: And that's really important actually because you know, to stick
20:03
Speaker 1: with our recipe analogy. It's like you photocopy, you know,
20:06
Speaker 1: something from your cookbook for a plate of brownies, and
20:10
Speaker 1: like you want that to be done right. You don't
20:12
Speaker 1: want the dumb factory to just be like brownies, brownies
20:15
Speaker 1: bodies bound patties forever. It has to degrade and it
20:19
Speaker 1: does not to mention, there are a bunch of pathogens
20:22
Speaker 1: viruses where RNA is their nuclear material. It's the same
20:26
Speaker 1: RNA that we have, like we're all earthlings. We all
20:30
Speaker 1: have the same code, which is kind of weird and
20:32
Speaker 1: cool in and of itself, but we've evolved to fight
20:37
Speaker 1: those things off. An RNA your body sees in general
20:41
Speaker 1: as a hostile force, which means when you inject RNA
20:47
Speaker 1: into someone, your body responds generally quite robustly.
20:51
Speaker 3: Okay, this is great background. Now I want to talk
20:55
Speaker 3: about why this is such an interesting path for potential
21:01
Speaker 3: doing various health related things in your body. And I
21:03
Speaker 3: think in some sense it's quite simple, which is the
21:06
Speaker 3: proteins that you make are doing like everything, that's all.
21:10
Speaker 3: The huge share of what your body is doing is
21:12
Speaker 3: being You are your proteins, right, you are your proteins.
21:16
Speaker 3: And so let's say I wanted to do something different.
21:19
Speaker 3: I wanted to make a more of something or less
21:23
Speaker 3: of something, or something new that I wanted to introduce
21:28
Speaker 3: the idea in principle that I could give me something injected,
21:32
Speaker 3: like in some way treat a person and tell their
21:35
Speaker 3: body make this protein you weren't making before feels incredibly powerful,
21:39
Speaker 3: or we'll get to this maybe at the end, like
21:41
Speaker 3: don't make this protein anymore. Right, So there's the sort
21:44
Speaker 3: of control of your protein idea here, which feels like
21:49
Speaker 3: conceptually in some ways very straightforward, and most of the
21:54
Speaker 3: issues that people encounter. The reason that mRNA is a
21:58
Speaker 3: relatively new technology is your body like does not want
22:01
Speaker 3: you to do that. Like it is a very very
22:04
Speaker 3: poor idea for your body to just be like, give
22:06
Speaker 3: me some RNA, I'll make whatever. Like your body's like no, no, no.
22:09
Speaker 3: I came up with the plan. I had these things.
22:11
Speaker 3: I was going to make these proteins. I'm not going
22:13
Speaker 3: to make the other protein. You know, I'm not going
22:16
Speaker 3: to make other proteins that you don't.
22:17
Speaker 1: I mean, that's like viruses. Whole deal is they're like, hey, man,
22:20
Speaker 1: here's some here's some RNA, Like, can you make more
22:22
Speaker 1: of me?
22:22
Speaker 5: Please?
22:23
Speaker 1: And in general, your body doesn't want to do that,
22:26
Speaker 1: and the successful viruses obviously I've figured out ways to
22:29
Speaker 1: get around that, and now and now so of weight.
22:32
Speaker 3: But evolving in yeah, but evolving in a world full
22:34
Speaker 3: of viruses, we are like we have developed a lot
22:37
Speaker 3: of ways to not allow our external RNA forces to
22:41
Speaker 3: control our cells. And so most of the research that
22:45
Speaker 3: allowed the creation of the mRNA vaccines and many of
22:49
Speaker 3: the other things that are now potential are things that
22:52
Speaker 3: allow us to better control how our body deals with proteins.
22:56
Speaker 1: Yeah, yeah, and we don't have to go into too
22:59
Speaker 1: much detail about like how we fixed the RNA the
23:02
Speaker 1: central RNA problem. But there are two Nobel prizes here,
23:04
Speaker 1: which I always feel like if there's some Nobel prizes,
23:06
Speaker 1: we should at least give a hat tip for two technologies.
23:10
Speaker 3: I don't have any. So yeah, neither of us have any.
23:13
Speaker 1: So let's talk about not yet, Emily.
23:15
Speaker 4: Not yet.
23:17
Speaker 1: So the one that I think most people will have
23:20
Speaker 1: heard of because it is directly relevant to the COVID
23:22
Speaker 1: vaccine was Catalan Kirico and her colleague Drew Weissman, who
23:27
Speaker 1: got the Nobel Prize in twenty twenty three. They figured
23:30
Speaker 1: out that swapping one of these letters uridine in RNA
23:34
Speaker 1: for a very slightly modified chemical called pseudo uridine, it
23:38
Speaker 1: looks almost the same, eliminates a large proportion of that
23:44
Speaker 1: intense immune response to RNA. So without that, like any
23:49
Speaker 1: RNA that comes in your body, unless it's packaged in
23:52
Speaker 1: a virus or something that's like has its own techniques
23:54
Speaker 1: to avoid detection, is just getting chewed up like before
23:58
Speaker 1: it hits the floor. So major advance there. That was,
24:01
Speaker 1: by the way, they got the prize in twenty twenty three,
24:03
Speaker 1: but they developed that in two thousand and five, which
24:05
Speaker 1: is really the start of human mRNA technology. There's another
24:09
Speaker 1: Nobel prize in this area that will go that attaches
24:13
Speaker 1: to inhibitory RNAs, which you had alluded to the idea
24:16
Speaker 1: of like telling your cells not to do something, which
24:18
Speaker 1: is even more mind blowing to some extent, which we'll
24:21
Speaker 1: get to you later on.
24:22
Speaker 3: The second innovation that has been incredibly important here is
24:25
Speaker 3: how you get the m RNA into the cell. The
24:28
Speaker 3: cell does not want you to be putting mRNA into it,
24:33
Speaker 3: and they basically figure it out how to like surround
24:37
Speaker 3: it with a lipid that allows it to be coming
24:42
Speaker 3: into the cell, and then the lipid goes away and
24:44
Speaker 3: they delivered the mRNA to the cell.
24:48
Speaker 1: Yeah, so it was a long time coming. It was
24:51
Speaker 1: an idea, Like, this wasn't a crazy idea. People have
24:53
Speaker 1: talked about this for decades and decades and decades. It
24:55
Speaker 1: just took some technology to make it feasible.
24:58
Speaker 3: But once it was feasible, this is incredibly cool and
25:02
Speaker 3: I think changer, game changing, and I think it's worth
25:06
Speaker 3: like talking about it in the context of the covid vaccine,
25:11
Speaker 3: So just the covid vaccine, the mRNA covid vaccines, these
25:15
Speaker 3: are the Maderna and Pfizer vaccines work in a very
25:19
Speaker 3: specific way. They introduce mRNA, which codes for a spike
25:26
Speaker 3: protein on the covid virus, and that is a particular
25:31
Speaker 3: protein on the outside of the virus. And what this
25:34
Speaker 3: does is it tells your body to make this protein.
25:37
Speaker 3: And then because this protein is not a protein that
25:40
Speaker 3: you've identified, your body makes antibodies to that protein. And
25:44
Speaker 3: then if you are have the actual covid virus arrives,
25:48
Speaker 3: you already have antibodies to this. And this is actually
25:51
Speaker 3: very different than traditional vaccines because a traditional vaccine would
25:55
Speaker 3: introduce either a killed form of the virus in which
25:58
Speaker 3: you would then create antibodies to that virus structure overall,
26:05
Speaker 3: or there are some protein based vaccines which would actually
26:08
Speaker 3: introduce the protein completely. But this is harnessing your body's
26:13
Speaker 3: own cells to make the effectively make the vaccine. So
26:19
Speaker 3: it's like incredibly cool and it is incredibly fast. So
26:25
Speaker 3: a typical traditional vaccine development takes what Perry like ten
26:31
Speaker 3: or fifteen years on January tenth of twenty twenty, they
26:36
Speaker 3: publish the first stars Kobe two genome online, like somebody
26:40
Speaker 3: had sequenced the genome of this virus, which is the
26:42
Speaker 3: thing we can do, and they put it up online.
26:44
Speaker 1: Remember, yes, cast your mind back to January ten, twenty twenty.
26:48
Speaker 3: You didn't know about coviding. You didn't know about you know,
26:50
Speaker 3: we're not thinking about it.
26:51
Speaker 1: Was like a China thing. It's March where we get lockdown, right, So, okay, January,
26:56
Speaker 1: we've got the January ten.
26:58
Speaker 3: On January thirteenth of twenty twenty, they had the sequence
27:05
Speaker 3: locked in to produce the vaccine. They could effectively print
27:09
Speaker 3: the vaccine three days after they had this. That is
27:13
Speaker 3: absolutely insane, bananas. The first human phase one injections of
27:18
Speaker 3: this were March sixteenth, twenty twenty, which is basically the
27:25
Speaker 3: day that we locked down. So it was like the
27:28
Speaker 3: first day we had lockdowns, we already had We were
27:30
Speaker 3: already not only do we have the vaccine, we were
27:32
Speaker 3: putting it in people.
27:33
Speaker 2: Yep.
27:34
Speaker 3: And then it was December when there was an emergency
27:36
Speaker 3: use authorization issued at the end of you know, so
27:39
Speaker 3: almost all of that time, the vast, vast majority of
27:43
Speaker 3: the time was just doing trials, which of course is
27:47
Speaker 3: you can't really make any faster because that's how trials work.
27:51
Speaker 1: They Involvedeah, you got to recruit people, you give some place,
27:54
Speaker 1: some get the vaccine.
27:55
Speaker 5: Yep.
27:56
Speaker 3: It's just like it's just absolutely like it's astonishing, Yeah,
28:02
Speaker 3: it is.
28:03
Speaker 5: You know.
28:04
Speaker 1: I think one of you alluded to the fact that, Okay,
28:07
Speaker 1: the code that was being used that they had three
28:10
Speaker 1: days to take the entire genome of SARS CoV two
28:13
Speaker 1: and decide which component of that they wanted to put
28:15
Speaker 1: in the vaccine, and they chose the spike protein, which
28:18
Speaker 1: is appropriate because that is in SARS viruses. That's the
28:21
Speaker 1: thing your body generates antibodies too. We already know that's
28:24
Speaker 1: like the thing it likes to fight against. So great
28:26
Speaker 1: spike protein. You could ask, okay, why not just produce
28:30
Speaker 1: a bunch of spike protein and inject people with that
28:33
Speaker 1: instead of mRNA. And the reason is that proteins are sticky, gross,
28:38
Speaker 1: complicated things that have to fold in a very particular
28:40
Speaker 1: way to work and require these incredibly sensitive conditions, and
28:45
Speaker 1: are chains of twenty two amino acids, and all of
28:48
Speaker 1: those are difficult to work with and mRNA is just
28:51
Speaker 1: four letters, and you said, you know, could be printed,
28:54
Speaker 1: and yeah, I mean that's it's it's literally like writing
28:58
Speaker 1: a computer program. Let me give you a way to
29:02
Speaker 1: put this in context. So, like if you think of
29:06
Speaker 1: the flu vaccine, which is a vaccine we produce every year. Obviously,
29:11
Speaker 1: the flu vaccine, the way that works is you infect
29:14
Speaker 1: fertilized chicken eggs, so that you give the poor embryonic
29:18
Speaker 1: chickens the flu and they get a bunch of flu
29:21
Speaker 1: virus in the chicken eggs, and then you crack the
29:24
Speaker 1: chicken eggs and blend them up and then you inactivate
29:26
Speaker 1: the flu virus. So you kill the flu virus in
29:29
Speaker 1: all those chicken eggs, and that's what you get injected
29:32
Speaker 1: into you. And so you need yeah, five hundred million
29:35
Speaker 1: eggs a year to do that for an mr ANDA vaccine.
29:42
Speaker 1: If you have a ten liter bioreactor, so ten liters
29:47
Speaker 1: is so five of those coke bottles. Okay, a ten
29:51
Speaker 1: liter bioreactor can make a few million doses a day
29:55
Speaker 1: of mRNA vaccine. There is absolutely no contestan We can
30:00
Speaker 1: talk about efficacy and all that stuff, but like in
30:02
Speaker 1: terms of sheer, scaleability and rapidity. That is what makes
30:07
Speaker 1: MR and A really really special.
30:09
Speaker 2: Yeah, it is really really cool.
30:13
Speaker 3: And I think printing is the analogy that these guys,
30:15
Speaker 3: when you talk to these guys about making the printing
30:17
Speaker 3: is the analogy to sort of tell the thing, Okay,
30:19
Speaker 3: make this one and then like it bakes this one
30:22
Speaker 3: in the bio reactor and then you have and then
30:24
Speaker 3: you have it and.
30:25
Speaker 1: Then you have it. And what's weirder is it actually worked.
30:28
Speaker 1: Like I you know, those initial randomized trials that came
30:33
Speaker 1: out for the initial version of the vaccine, the vaccine
30:36
Speaker 1: efficacy against infection was above ninety percent, which was was
30:40
Speaker 1: was nuts. Now did that persist over time? It definitely
30:44
Speaker 1: did not. The virus mutates, we have to keep up
30:47
Speaker 1: with various strains, the spike protein changes. There's a lot
30:51
Speaker 1: of issues with that, as there are with all vaccines,
30:55
Speaker 1: and COVID is one that has been tricky to.
30:57
Speaker 5: Keep up with.
30:58
Speaker 1: But I will say the most the latest studies, including
31:03
Speaker 1: that that our friend doctor j. Bodicharia suppressed from CDC,
31:08
Speaker 1: still demonstrates moderate efficacy against hospitization and severe illness.
31:13
Speaker 3: And in the first I mean again, I think it's
31:16
Speaker 3: like to return to both the wonder and also the
31:20
Speaker 3: moments early in COVID, like the protective like this saved
31:24
Speaker 3: literally millions of people, and having the vaccine in December
31:28
Speaker 3: rather than in you know, December of twenty thirty or whenever, Like,
31:33
Speaker 3: it's just that that is millions and millions and millions
31:35
Speaker 3: of people who did not die, and that is just
31:38
Speaker 3: really yeah important.
31:41
Speaker 1: It's really important also to point out the difference between
31:44
Speaker 1: an mRNA vaccine, which is causing yourself to generate one protein,
31:48
Speaker 1: and most vaccines like the flu vaccine and even some
31:50
Speaker 1: of the non mRNA based COVID vaccines, which use the
31:53
Speaker 1: whole virus. You know, COVID has twenty seven twenty nine
31:59
Speaker 1: proteins in it, so COVID's RNA codes for twenty nine
32:03
Speaker 1: different proteins. And the way it works when you get
32:05
Speaker 1: an infection is it matches onto your cell and it
32:08
Speaker 1: injects all its RNA into your cell, and your cell
32:11
Speaker 1: starts making those twenty nine proteins, and those twenty nine
32:13
Speaker 1: proteins come together and create a new COVID virus, and
32:16
Speaker 1: your cell gets filled up with those COVID viruses until
32:19
Speaker 1: it bursts and spreads it throughout the rest of your
32:21
Speaker 1: body until your immune system can get a hold of it.
32:23
Speaker 1: And so you know, when we think about vaccination, there's
32:27
Speaker 1: a real argument that mRNA is kind of the cleanest
32:31
Speaker 1: form of vaccination, Like you're exposing your body to more
32:34
Speaker 1: or less the minimal amount of substance that you need
32:37
Speaker 1: to generate an immune response as opposed to like the
32:40
Speaker 1: entire virus. For what it's worth.
32:42
Speaker 3: So I will say again, I think this is like,
32:45
Speaker 3: there is so much wonder here, and I think that
32:49
Speaker 3: when people were first encountering this, that wonder was much
32:53
Speaker 3: more dominant than it has become over time. And we're
32:56
Speaker 3: going to talk about like some of the conspiracy theories
32:59
Speaker 3: in some of the stuff that sort of came out
33:02
Speaker 3: of all of this crazy discussion, but it is also
33:07
Speaker 3: worth before we get into that, talking about whether there
33:10
Speaker 3: are well documented, non conspiratorial risks that are associated with
33:14
Speaker 3: this particular approach to vaccines as opposed to these other approaches.
33:19
Speaker 3: I think the one that is a real risk that
33:22
Speaker 3: is worth discussing is the risk of myocarditis, particularly in
33:28
Speaker 3: young men. Yeah, yeah, that's real, So let's talk about
33:33
Speaker 3: that before we Let's start with that, because I do
33:36
Speaker 3: think people should hear that piece of it, and then
33:38
Speaker 3: we'll talk about the rest of the stuff, which is
33:40
Speaker 3: much less, much less well supported.
33:43
Speaker 1: Yes, Okay, So myocarditis is inflammation of heart muscle cells,
33:47
Speaker 1: and it can obviously be caused by a wide variety
33:51
Speaker 1: of things. There are autoimmune forms of myocarditis, there's infectious
33:55
Speaker 1: forms of myocarditis. Covid itself can cause milcarditis. But there
33:58
Speaker 1: is vaccine associated my Cardnite is associated with the mRNA vaccines.
34:03
Speaker 1: The cause is a little bit unclear. The thought, the
34:10
Speaker 1: sort of leading hypothesis is that the spike protein bears
34:15
Speaker 1: some similarity to a protein that lives on heart cells.
34:20
Speaker 1: It's like a potassium channel on the heart cells, you know,
34:22
Speaker 1: they sort of they're like they just happen to kind
34:25
Speaker 1: of have similar shapes, and so in some people, if
34:27
Speaker 1: you're generating antibodies against spike protein, you those antibodies might
34:33
Speaker 1: cross react with some of the heart cells. It's quite
34:36
Speaker 1: clear that estrogen is protective against this, and that testosterone
34:42
Speaker 1: makes this worse, which is one of the reasons I
34:45
Speaker 1: think we see a higher risk in young men than
34:48
Speaker 1: in other populations. So there's clearly a risk, right so
34:52
Speaker 1: the question, as you know, will always come up with
34:55
Speaker 1: every medical decision that anyone ever makes, is the benefit
34:59
Speaker 1: worth the risk?
35:00
Speaker 3: Yeah, and I think you know, here if we kind
35:03
Speaker 3: of look at the numbers, you know, in a million,
35:07
Speaker 3: these estimates suggests in a million vaccines, you'd expect something
35:10
Speaker 3: like forty myocarditis cases. But you know, the number of
35:15
Speaker 3: hospitalizations and and you know, potential serious illness that might
35:19
Speaker 3: be prevented by that is actually quite significantly in excessive.
35:22
Speaker 3: That and that's particularly was particularly true early on, in
35:25
Speaker 3: the early on in the pandemic. You know, we we
35:28
Speaker 3: have arrived at a place where COVID boosters have become
35:31
Speaker 3: a much less common thing for healthy adults and for kids.
35:35
Speaker 3: And so at this point, most people with teenage boys
35:38
Speaker 3: are not getting them an additional COVID booster, and the
35:41
Speaker 3: groups that are having the most significantly should be engaging
35:45
Speaker 3: with the boosters. I think at this point, in my view,
35:47
Speaker 3: are older adults for whom myocarditis is actually not a
35:50
Speaker 3: significant not a significant risk, perhaps because their testosterone is
35:55
Speaker 3: not so good anymore.
35:56
Speaker 1: Yeah, that would be really interesting to see if the
35:58
Speaker 1: people now that testosterone self limitation is having its moment like,
36:01
Speaker 1: what's going to happen. There's going to be an interaction. Yeah,
36:04
Speaker 1: I mean it's not I don't want to say that
36:06
Speaker 1: there's a recommendation for teenage boys not to get the
36:08
Speaker 1: COVID vaccine.
36:09
Speaker 5: It is.
36:10
Speaker 1: It is worth having a discussion with a healthcare provider
36:13
Speaker 1: about the risks and benefits because it's going to differ
36:15
Speaker 1: a bit based on your own susceptibilities.
36:18
Speaker 4: You know.
36:19
Speaker 1: The thing we don't know, I think is that in
36:22
Speaker 1: the initial phase of the pandemic, many of us had
36:24
Speaker 1: never been exposed to spike protein at all. Right, it
36:29
Speaker 1: was brand new. It was the novel coronavirus and cove
36:32
Speaker 1: if you remember when it just got started. Now we're
36:35
Speaker 1: in an era where basically everyone has been infected at
36:38
Speaker 1: least once. Many people have you been vaccinated, if not once,
36:43
Speaker 1: multiple times, and so there is obviously we haven't reached
36:48
Speaker 1: a state of herd immunity because people are still getting infected,
36:51
Speaker 1: but the severity of infections have decreased even among people
36:55
Speaker 1: who weren't vaccinated. You know, back in the original days.
37:01
Speaker 1: I remember, so I was on service in April of
37:05
Speaker 1: twenty twenty, and I instead of being a kidney doctor
37:08
Speaker 1: I got plucked out to be a COVID doctor because
37:11
Speaker 1: that's what was happening to everyone. And I remember this, like,
37:14
Speaker 1: thirty five year old guy totally healthy coming in with
37:18
Speaker 1: COVID was on cardiopulmonary bypass because that's how bad it was.
37:21
Speaker 1: And these things do still happen with COVID, but it's
37:24
Speaker 1: not the same, and in part it's not the same
37:26
Speaker 1: because we do we have been exposed before, and you know,
37:30
Speaker 1: there's just a fundamental difference between being exposed to a virus,
37:33
Speaker 1: even a mutated form that you've been exposed to previously,
37:36
Speaker 1: and one that is your immune system is completely unprepared for.
37:39
Speaker 1: So there's some really interesting questions about how to proceed
37:42
Speaker 1: with vaccination. I certainly agree that the benefits outweigh the
37:47
Speaker 1: risk for the vast majority of people. My only sort
37:51
Speaker 1: of question is in this young male group who tend
37:54
Speaker 1: to do pretty well with the virus if they get it.
37:57
Speaker 2: Yeah.
37:58
Speaker 3: So I think one really important point is, regardless of
38:02
Speaker 3: how you feel about the COVID vaccine, at this point,
38:05
Speaker 3: you know, I think there are people here are going
38:06
Speaker 3: to be like, look, I've had COVID six times, I'm
38:09
Speaker 3: not getting any more boosters. I'm not boostering my kids.
38:11
Speaker 3: It's like just if I look out at the world,
38:14
Speaker 3: that is where a large share of people are. But
38:17
Speaker 3: this conversation about mRNA is still incredibly important because there
38:24
Speaker 3: are many other things, other vaccines that we might want
38:28
Speaker 3: to use mRNA for, other things like cancer treatments, which
38:31
Speaker 3: we'll talk about in a second. And so yeah, I
38:34
Speaker 3: actually I want to make sure that we're we're sort
38:37
Speaker 3: of stepped out of the particular COVID COVID thing and
38:40
Speaker 3: keep thinking about the mRNA the potential of this technology.
38:44
Speaker 3: So in leading into that, it is probably worth debunking
38:48
Speaker 3: some of the conspiracy.
38:49
Speaker 2: Theories that I think really arose around COVID.
38:53
Speaker 3: So look, let me just the way I would like
38:55
Speaker 3: to do this is I'm just going to give you
38:56
Speaker 3: the theory, and you're going to tell me yes or no,
39:00
Speaker 3: science or vibes on this theory. Okay, okay, true or false? Perry,
39:06
Speaker 3: mRNA changes your DNA false.
39:10
Speaker 1: I think this is okay, wait, I'm sorry you said
39:13
Speaker 1: one thing. I think this is the uber conspiracy theory.
39:16
Speaker 1: I think part of the reasons, aside from the fact
39:19
Speaker 1: that COVID was just like we all had free time
39:21
Speaker 1: on our hand to bake conspiracy theories. And that's where
39:24
Speaker 1: mRNA got started. I think because it sounds like DNA,
39:27
Speaker 1: and that sounds like gene editing, and like it just
39:30
Speaker 1: it fosters this. And I just want to reiterate that
39:34
Speaker 1: the nucleus of the cell where the DNA lives is
39:36
Speaker 1: this highly highly protected inner sanctum. It is very difficult
39:42
Speaker 1: for RNA to get into the nucleus. That requires special codes,
39:46
Speaker 1: special transporters, and even then it's extraordinarily hard for RNA
39:53
Speaker 1: to get reverse transcribed to DNA and get put into DNA. Remember,
39:59
Speaker 1: there's a whole set of viruses that their trick is
40:03
Speaker 1: that they bring with them reverse transcriptase to make RNA
40:06
Speaker 1: go into DNA instead of vice versa, HIV being the
40:10
Speaker 1: best example of this. Retroviruses like that, like this is
40:14
Speaker 1: their trick. It's like, oh, we're going to get the
40:16
Speaker 1: RNA into your DNA. They had to evolve an entire
40:19
Speaker 1: system to do that. RNA itself is like deliberately excluded
40:25
Speaker 1: from the nucleus and the DNA.
40:27
Speaker 3: Okay, great, we also have a couple of clips, so
40:30
Speaker 3: that's like the uber thing. Then there are some more
40:32
Speaker 3: specific things. So we're going to play these We're gonna
40:34
Speaker 3: play these clips.
40:35
Speaker 5: So where was walking around with a jab that got
40:37
Speaker 5: a little bit of Epstein in them?
40:38
Speaker 6: No way.
40:39
Speaker 5: Epstein's main funder of the mRNA him Bill Gates Fauci,
40:43
Speaker 5: And what he did was he put a little bit
40:44
Speaker 5: of his own gena code in each one of the jabs.
40:47
Speaker 5: But yeah, how did he pull that off? It's all
40:49
Speaker 5: in the files. Man. He was doing experiments and funding
40:52
Speaker 5: that chrisper and that mRNA technology back in the day.
40:55
Speaker 5: And he said in the same document that he wanted
40:57
Speaker 5: to have his code in all of it. So anytime
41:00
Speaker 5: with anybody in jets, they've got a piece of him
41:02
Speaker 5: inside of them. Is that his consciousness being transferred to
41:04
Speaker 5: what exactly just a little code? It's a little ego thing.
41:06
Speaker 5: You know, how much of an effect is it going
41:08
Speaker 5: to have on a person who knows But for him consciously,
41:11
Speaker 5: it's like I'm in everybody, every single person's out here,
41:14
Speaker 5: I'm inside of it. Off the population, right sick?
41:16
Speaker 3: Okay, Perry, what about that one.
41:21
Speaker 1: DNA, Epstein's DNA in the RNA vaccines. You know, Epstein's
41:27
Speaker 1: DNA is in a lot of places but not there,
41:31
Speaker 1: not there.
41:34
Speaker 3: Yeah, we're gonna leave that one. Uh, and then we
41:38
Speaker 3: have this deep population.
41:42
Speaker 2: Well I'm just going to play it for you.
41:44
Speaker 6: The mRNA depopulation technology that was in the COVID vaccines
41:48
Speaker 6: is now in our food supply. And who has this
41:51
Speaker 6: been sponsored by? This is sponsored by yours only, Bill Gates.
41:55
Speaker 6: Bill Gates funded toront of Biosciences is now moving to
41:59
Speaker 6: reprogram life itself. They are planning to spray synthetic mr
42:03
Speaker 6: and A pesticides on your crops, on your vegetables, on
42:07
Speaker 6: your fruits, on your meat, on everything in the food chain.
42:10
Speaker 6: As revealed by doctor Mike Eden, who has been vice
42:13
Speaker 6: president of Pizer for sixteen years, that this mrnay technology
42:17
Speaker 6: is depopulation technology and they have been doing this for
42:19
Speaker 6: a long time now. They have been trying to sneak
42:21
Speaker 6: it into our food supply. And finally he wants that
42:24
Speaker 6: this ammerine technology is intentionally manufactured to cause infertility and
42:28
Speaker 6: to kill human beings. Now, this is not something new
42:31
Speaker 6: if you look at it, depopulation technology.
42:34
Speaker 3: Okay, it's in our food supply.
42:37
Speaker 1: What, dude, what I want to ask some of the
42:42
Speaker 1: conspiracy do you remember early on, They were like, everyone
42:44
Speaker 1: who's getting one of these shots is going to be
42:46
Speaker 1: dead within thirty days, and like, why does it?
42:51
Speaker 4: Do you know?
42:52
Speaker 3: Check?
42:52
Speaker 1: Hey, I'm still here.
42:55
Speaker 3: Yeah, So look, I mean I think the best this
42:59
Speaker 3: is now the universe of conspiracy theories about mRNA. There
43:03
Speaker 3: are a million crazy things. Either. The best defense about
43:06
Speaker 3: them from an individual standpoint is just understanding the basic
43:09
Speaker 3: biology of what this is and what it does, which
43:12
Speaker 3: demystifies the whole situation. So if you are still the
43:16
Speaker 3: next time you hear one of these crazy conspiracy things,
43:19
Speaker 3: just go back and listen to like the first six
43:20
Speaker 3: minutes of this deep dive and make yourself feel better.
43:24
Speaker 3: And that is very important because there are some incredibly
43:29
Speaker 3: cool possible things that may come down the line with mRNA.
43:32
Speaker 3: The most interesting, well, the one we are furthest along on,
43:37
Speaker 3: I would say right now is the idea that this
43:40
Speaker 3: may actually be a cancer vaccine. So that is incredibly cool,
43:47
Speaker 3: and I think the basic idea, and then maybe you
43:50
Speaker 3: can tell us how far we have gotten along with this,
43:52
Speaker 3: is that if I have a tumor and I biopsy
43:57
Speaker 3: the tumor, that tumor may have specific antigen sort of
44:01
Speaker 3: specific characteristics that I could in principle have antibodies to fight,
44:07
Speaker 3: and if I could make a vaccine that would effectively
44:11
Speaker 3: create antibodies to your particular tumor, that may actually be
44:17
Speaker 3: a path to treatment.
44:18
Speaker 2: And because mRNA is perfect.
44:21
Speaker 1: But it takes ten to fifteen years to make a vaccine, Emily,
44:24
Speaker 1: you don't have that kind of time.
44:25
Speaker 3: And because mRNA is programmable and we can do it
44:28
Speaker 3: in a short period of time, it may actually be
44:31
Speaker 3: feasible at an individual level in this kind of personalized
44:34
Speaker 3: medicine way that really hasn't been possible with our existing technology.
44:39
Speaker 1: Yeah, I mean this is where we get to the
44:41
Speaker 1: future and why RNA's so much more than COVID vaccines
44:46
Speaker 1: or flu vaccines and things that are getting developed. So, yeah,
44:49
Speaker 1: this is real. I'll give you a study that appeared
44:52
Speaker 1: in the Lancet in twenty twenty four. So this was
44:55
Speaker 1: a trial one hundred and fifty seven patients. They had
44:59
Speaker 1: relatively high stage stage three B to four cutaneous melanoma,
45:03
Speaker 1: so skin cancer, melanoma, skin cancer, pretty serious. They were
45:07
Speaker 1: randomized to get pemberlysium AB, which is that immune therapy
45:10
Speaker 1: that's really transformed melanoma over the past decade. That's what
45:14
Speaker 1: like Jimmy Carter got, which kept him alive for so long.
45:17
Speaker 1: Great drug that was the standard. Or they got pemberlelysm
45:21
Speaker 1: ab plus an mRNA vaccine and this was like a
45:25
Speaker 1: custom printed mRNA vaccine for their specific tumor. So they
45:30
Speaker 1: took the biopsy, they figured out what proteins were different
45:34
Speaker 1: than their normal cells, and they made an mRNA for them.
45:37
Speaker 1: And again you can do this in like a matter
45:39
Speaker 1: of weeks, which is just insane. So they gave the
45:44
Speaker 1: patients there. The primary outcome was recurrence of melanoma or death.
45:49
Speaker 1: Forty percent of people in the pemberlysim mab alone group,
45:52
Speaker 1: that's the Jimmy Carter standard of care, forty percent had
45:55
Speaker 1: recurrence of melanoma or death. That's actually a good outcome
45:59
Speaker 1: for this stage melanoma. It's obviously advanced melanoma is very serious,
46:05
Speaker 1: versus twenty two percent in the combo group. So it
46:08
Speaker 1: essentially cut in half the new melanoma and death rate
46:13
Speaker 1: in this disease. And it's totally personalized medicine. This is
46:16
Speaker 1: the real promise of RNA technology.
46:21
Speaker 3: Yeah, and I mean it feels like there are many
46:23
Speaker 3: kinds of cancers for which this would be potentially would
46:26
Speaker 3: be every.
46:27
Speaker 1: Every kind of cancer. I mean, like I challenge every
46:30
Speaker 1: cancer has mutations compared to your ordinary cells otherwise or
46:34
Speaker 1: otherwise it would be your ordinary cell. So there's always something,
46:37
Speaker 1: you know, whether it's targetable with antibodies is just about
46:41
Speaker 1: revving up your immune system. That's why pemberlesum mab works.
46:44
Speaker 1: But now we can say, like, not only just rev
46:46
Speaker 1: up the immune system on the whole, we can be
46:48
Speaker 1: like and specifically for cells that you know, look like
46:52
Speaker 1: this so cool?
46:53
Speaker 3: And I think you know, part of what makes this
46:56
Speaker 3: kind of treatment so exciting is that many of are
47:00
Speaker 3: existing A huge sure of our existing cancer treatments. Basically,
47:03
Speaker 3: most of chemotherapy works by killing, you know, all of
47:06
Speaker 3: your fast like targeting flies on you half fast they
47:10
Speaker 3: produce and so, and that's why you lose your hair,
47:12
Speaker 3: you lose your fingernails, your people have gut issues, all
47:15
Speaker 3: kinds of other stuff. If you can find a way
47:18
Speaker 3: to target only the cancer things, that's obviously a path
47:21
Speaker 3: to a much lower side effect, much more effective treatment.
47:25
Speaker 3: Were there significant either side effects or downsides in that
47:28
Speaker 3: Lancet trial.
47:29
Speaker 1: Not really, I mean the side effects were associated primarily
47:32
Speaker 1: with pemberlesim mab. You get like autoimmune types of conditions
47:35
Speaker 1: in other organ systems. But the vaccine related side effects
47:39
Speaker 1: were what we've come to expect from RNA vaccines, which
47:41
Speaker 1: is like, you don't feel great for a day or so,
47:43
Speaker 1: but you're probably willing to accept that in this scenario
47:47
Speaker 1: for sure.
47:48
Speaker 3: Okay, so before we go, let's talk about one other
47:50
Speaker 3: like promised thing, which is SI rna.
47:55
Speaker 1: This is so sci fi, very sci fi.
47:58
Speaker 3: So we've been talking a lot about about RNA treatments
48:01
Speaker 3: that tell your body, okay, make more of this protein.
48:06
Speaker 3: But the idea here is to make less of a protein.
48:09
Speaker 1: It's so cool. Yeah, So I guess what you need
48:13
Speaker 1: to know about SI rna is that your body has
48:16
Speaker 1: a built in mechanism, multiple built in mechanisms to degrade mRNA. Remember,
48:21
Speaker 1: we don't want to keep making the brownies over and
48:22
Speaker 1: over and over again. So you've got all sorts of
48:24
Speaker 1: proteins and enzymes and things that are out there being
48:27
Speaker 1: like degrade mRNA, like don't let it be used too
48:30
Speaker 1: many times, which is important and good, and we want
48:33
Speaker 1: that one of the mechanisms and the Andrew fire and
48:37
Speaker 1: Craig Mellow got the Nobel Prize in two thousand and
48:40
Speaker 1: six for discovering this mechanism. Is there's a protein in
48:44
Speaker 1: your cell that targets mRNAs and choose them up. That's
48:47
Speaker 1: its job. It's a garbage, garbage eating protein. But the
48:50
Speaker 1: protein itself has a binding pocket for RNA and that
48:56
Speaker 1: RNA tells the protein what RNA to look for and digest.
49:00
Speaker 1: So like it's a programmable it like the protein is
49:04
Speaker 1: programmable to look and target for specific mRNAs, which like
49:09
Speaker 1: why we have something like that, I mean, evolution, it's amazing,
49:12
Speaker 1: it's unbelievable, but we can exploit that. And that's what
49:15
Speaker 1: sRNAs are. They are these custom designed RNAs that bind
49:18
Speaker 1: to this special protein and say, look for this mRNA
49:21
Speaker 1: and chew it up. And what that means is that
49:23
Speaker 1: if there's a protein you don't like, you can tell cells, hey,
49:28
Speaker 1: chew up. Any any copy of that recipe, any brownie
49:32
Speaker 1: recipes you see, chew them up. I don't even want
49:33
Speaker 1: to see it get made, right, I don't want a
49:35
Speaker 1: single brownie coming out of this cell. And what this
49:38
Speaker 1: lets you do.
49:39
Speaker 2: See totally totally bananas.
49:42
Speaker 1: Is totally bananas, is give someone an injection that treats
49:48
Speaker 1: them for months at a time, six months at a time.
49:53
Speaker 1: For example, there's a drug called enclysseran which targets a
49:59
Speaker 1: protein called pa CSK nine. So you inject this drug,
50:02
Speaker 1: it's an sRNA drug. It makes your liver cell not
50:04
Speaker 1: produce this PCSK nine protein that's a major component of
50:09
Speaker 1: the cholesterol synthesis cascade. There are other drugs that you
50:12
Speaker 1: take once a day that target PCSK nine, but this
50:17
Speaker 1: drug you get injected once and for six months. In
50:21
Speaker 1: this trial, the LDL level was fifty percent lower in
50:26
Speaker 1: the treatment group than the placebo group. One injection six
50:29
Speaker 1: months long, and everyone was on max dose statins. Every
50:33
Speaker 1: single person the trials on max dose statins. And then
50:36
Speaker 1: you get one drug. There's another. There's another drug called zilbsaran.
50:40
Speaker 1: This was in the New England Journal twenty twenty three,
50:43
Speaker 1: which is a twice yearly blood pressure medication. So it
50:47
Speaker 1: targets a protein called angiate tensinogen which raises your blood pressure.
50:50
Speaker 1: Basically suppresses that protein for six months at a time,
50:53
Speaker 1: and on average, compared to placebo people had a fifteen
50:57
Speaker 1: to twenty millimeter of mercury drop in system blood pressure.
51:00
Speaker 1: That's the number on top one injection six months of
51:03
Speaker 1: blood pressure control. Now, as a doctor, I'm like, that
51:06
Speaker 1: makes me a little nervous because like what if you
51:07
Speaker 1: get sick and have diarrhea and stuff, like maybe you
51:09
Speaker 1: want a little blood pressure. I don't know, cholesterol I
51:11
Speaker 1: feel better about. But like, from a technological standpoint, there's
51:15
Speaker 1: a future out there where instead of every morning you
51:18
Speaker 1: wake up and brush your teeth and take your six pills,
51:21
Speaker 1: you like go twice a year and you get a
51:24
Speaker 1: couple of injections and you're good to go. Absolutely nuts.
51:28
Speaker 3: That is totally, just completely insane. So you talked about
51:34
Speaker 3: blood pressure. This is potentially like an incredibly rich technology.
51:40
Speaker 3: So early in my career I worked a lot of
51:41
Speaker 3: hunting dis disease. I was doing a lot of work
51:44
Speaker 3: with people. Huntingdons is a degenerative neurological disorder. It's a
51:48
Speaker 3: genetically caused is totally totally devastating, runs through families and
51:55
Speaker 3: there within the last year or two there has been
51:58
Speaker 3: probably the most significant step forward in treatment of this disease,
52:02
Speaker 3: which relies on this kind of technology effectively limiting production
52:07
Speaker 3: of this protein. This is a disease where you produce
52:09
Speaker 3: too much of this protein and that leads to to
52:11
Speaker 3: generation and so again, turning off the potential for producing
52:15
Speaker 3: that protein has slowed disease progression like seventy five percent
52:19
Speaker 3: over several years in indosing. So it's just just a
52:23
Speaker 3: technology with unbelievable amounts of potential going forward.
52:27
Speaker 1: Yeah, it's so exciting. It's good that people are starting
52:30
Speaker 1: to learn about it, and hopefully learning about it in
52:32
Speaker 1: a broader way than what you might see on social media.
52:36
Speaker 3: Totally okay. My goal in this episode, I will be
52:40
Speaker 3: just totally upfront, was to deliver a sense of wonder.
52:43
Speaker 3: I mean, I think these technologies are incredibly exciting and
52:48
Speaker 3: I really hope we do not stop researching them because
52:51
Speaker 3: people did not like the COVID vaccine, which feels like
52:55
Speaker 3: really throwing away you know, what is potentially one of
52:59
Speaker 3: the most significant innovations of the past many decades because
53:04
Speaker 3: you didn't like one specific you know, kind of lockdown
53:07
Speaker 3: or whatever. So more mRNA research would be great. I
53:12
Speaker 3: think we could smash your pass.
53:14
Speaker 1: Let's do it.
53:14
Speaker 3: Let me guess, Perry, are you a smasher pass on
53:18
Speaker 3: RNA technologies?
53:19
Speaker 1: I am a huge smash on RNA technologies. These will
53:25
Speaker 1: transform medicine. Mark my words, it's a major paradigm shift. Emily,
53:30
Speaker 1: smash your pass.
53:31
Speaker 3: I'm also smash on these. I am incredibly excited about them,
53:34
Speaker 3: and I just I just really hope we keep pushing
53:38
Speaker 3: this stuff forward. All Right, that's it for RNA your
53:41
Speaker 3: mailback question of the Week after the break.
53:49
Speaker 4: Hi, Emily and Perry. This is Melissa from the Seattle
53:52
Speaker 4: area and am listening to your sleep episode and I
53:55
Speaker 4: have a couple questions that maybe you can diagnose me
53:57
Speaker 4: and figure out if I'm okay. The first is that
54:02
Speaker 4: I believe that since I was in middle school or
54:05
Speaker 4: high school, maybe a few times a year I'll have
54:08
Speaker 4: a really bad dream where I am being either chased,
54:12
Speaker 4: where someone is hurting me, and I'm aware that it's
54:14
Speaker 4: a dream, but in my dream or in real life,
54:16
Speaker 4: I guess I can't breathe, and the only way that
54:18
Speaker 4: I wake up is from screaming. And I'm a side sleeper,
54:22
Speaker 4: and if I fall back asleep in the same side,
54:25
Speaker 4: the dream immediately comes back, or if I flee my body,
54:28
Speaker 4: it goes away. But again, I can't breathe in my sleep,
54:32
Speaker 4: and the only way for me to wake up from
54:35
Speaker 4: the stream that I know is a dream but it's
54:36
Speaker 4: really scary is from screaming. And I think my twin
54:40
Speaker 4: sister sometimes has the same thing. Any idea with that is.
54:44
Speaker 4: Another thing that has happened a few times is that
54:50
Speaker 4: I have bit my husband on the arm in the
54:53
Speaker 4: middle of my sleep because I'm having a dream that
54:55
Speaker 4: I need to bite into something harder. And I also
54:58
Speaker 4: do the same thing with my three year old sun
55:00
Speaker 4: when we were sharing a bit on vacation. I bit
55:02
Speaker 4: his finger and luckily you woke up before anything bad happened.
55:07
Speaker 4: But yeah, can you diagnose me? What's going on?
55:11
Speaker 5: Thanks?
55:11
Speaker 4: Guys?
55:12
Speaker 2: Oh Man?
55:14
Speaker 3: Okay, Perry, what do you think?
55:17
Speaker 1: Yeah? Okay, So, first of all, really sorry you're going
55:20
Speaker 1: through this. This sounds both scary, you know, and if
55:25
Speaker 1: not outright traumatizing. I mean, I do need to say,
55:28
Speaker 1: because I'm a medical doctor that like I can't despite
55:32
Speaker 1: being asked, I can't diagnose you from AFAR. I don't
55:35
Speaker 1: know your medical history or anything like that. But I
55:39
Speaker 1: appreciate that you heard some things on the sleep episode
55:42
Speaker 1: that seem to be resonating. I agree that you know
55:47
Speaker 1: there's some stuff that you mentioned that sounds like it's
55:51
Speaker 1: worth discussing with a sleep medicine doctor. In particular, the
55:56
Speaker 1: like acting out of dreams that we talked about in
55:58
Speaker 1: the episode can be associated with a condition called REM
56:02
Speaker 1: behavioral disorder our AM behavioral disorder that the real terrors
56:07
Speaker 1: that are happening could sound a little bit like night terrors.
56:10
Speaker 1: There is a really clear test for this, so there's
56:14
Speaker 1: a special kind of sleep study called video polysomnography, so
56:18
Speaker 1: it's not only your conventional sleep study that would detect
56:21
Speaker 1: things like sleep apnea. You mentioned something about position being important,
56:25
Speaker 1: so that also leads to the question of sleep apna.
56:27
Speaker 1: But a video polysymnography records you during sleep, and this
56:30
Speaker 1: is critical for REM sleep disturbances because the eg on
56:36
Speaker 1: your brain knows you're in REM and if you listen
56:38
Speaker 1: to our sleep episode, remember you're supposed to be paralyzed.
56:41
Speaker 1: When you're in REM sleeps, you don't act out your dreams,
56:44
Speaker 1: and so the video can then be correlated with that
56:46
Speaker 1: to see if paralysis is working as intended. So this
56:50
Speaker 1: is definitely something to check out, especially if you've hurt
56:53
Speaker 1: or come close to hurting a loved one who shares
56:56
Speaker 1: the bed with you.
56:57
Speaker 3: Yeah, And I would just let me just say one
57:00
Speaker 3: thing about this and all these sleep questions, which is like,
57:03
Speaker 3: if there is an issue in your sleep that is
57:05
Speaker 3: affecting that is affecting your life, you should try to
57:08
Speaker 3: get help with it. I think actually sleep is a
57:10
Speaker 3: place where people underinvest in trying to figure out what
57:14
Speaker 3: the help would be, in part because it's not so clear,
57:16
Speaker 3: like well, what are you going to do? And I
57:18
Speaker 3: think the answer and that answer made it very clear,
57:20
Speaker 3: is like, here's the thing. You probably didn't know about this,
57:22
Speaker 3: but here's a thing that you would do in this situation.
57:24
Speaker 3: If you go to someone and say, you know, I'm
57:26
Speaker 3: having this problem with my sleep, here is the issue.
57:29
Speaker 3: It is really affecting my life. There is probably something
57:33
Speaker 3: that can at least help you figure out more about
57:35
Speaker 3: what could be done or what's going on. So don't suffer,
57:39
Speaker 3: don't suffer in silence.
57:40
Speaker 1: Yeah, don't mess with sleep. Well, that's it for us today.
57:46
Speaker 1: Stick with us next week when we'll ask what's the
57:48
Speaker 1: deal with cortisol?
57:51
Speaker 3: Wellness Actually is produced in association with iHeartMedia. Our senior
57:56
Speaker 3: producer is Tamar Avishai, our executive producer at iHeart is
58:00
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58:03
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58:21
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58:23
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58:26
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58:27
Speaker 3: We'll let the influencers have the last word.
58:30
Speaker 4: Radio. These are to days. This is the long distance call.
58:39
Speaker 1: The way the camera follows us, sloan mode, the way
58:43
Speaker 1: we look too