Speaker 1: Pushkin from Pushkin Industries. This is Deep Background, the show
Speaker 1: where we explore the stories behind the stories in the news.
Speaker 1: I'm Noah Feldman. Coronavirus cases are surging across the country.
Speaker 1: Cities and states are responding with new regulations on social gatherings,
Speaker 1: but another potential solution is at least on the horizon
Speaker 1: and maybe a little closer than that. Last week, the
Speaker 1: drug company Visor announced in a press release that it's
Speaker 1: coronavirus vaccine seems to work. According to a preliminary analysis,
Speaker 1: Visor's vaccine is ninety percent effective at preventing COVID nineteen.
Speaker 1: Maderna's vaccine, which operates on similar principles, has produced similar
Speaker 1: numbers reported by that company as well. To discuss the
Speaker 1: science behind these developments and what's going to happen in practice,
Speaker 1: we are joined by doctor Paul Offen. He's a professor
Speaker 1: of vaccinology and pediatrics at the University of Pennsylvania. He's
Speaker 1: also importantly a member of the FDA's Vaccine Advisory Panel.
Speaker 1: Among his other distinctions, he is also the co inventor
Speaker 1: of the rhodavirus vaccine. Paul, thank you so much for
Speaker 1: joining me. The immediate impetus for our conversation is the
Speaker 1: good news that mRNA vaccines like Visors and Maderna's shows
Speaker 1: efficacy in trials. So let's just start with the very
Speaker 1: basic question. The Visor vaccine is an RNA vaccine. There's
Speaker 1: never been one of those that worked before. Why is
Speaker 1: this appear to be working? So what we think we
Speaker 1: know is we think we know that we want to
Speaker 1: make antibodies to the protein that emanates from the surface
Speaker 1: of the virus that is responsible for attaching the virus
Speaker 1: to cells. If you can then make antibodies to that protein,
Speaker 1: you can prevent the virus from attaching the cells. In
Speaker 1: the past, when we've wanted to make an about it
Speaker 1: to the spike protein, we would do things like give
Speaker 1: sort of a whole killed form of the virus which
Speaker 1: would have the spike protein on it, or we would
Speaker 1: give a live we can form of the virus which
Speaker 1: would have the spike protein on it, or we would
Speaker 1: purify the spike protein, or we would use recomment at
Speaker 1: DNA technology to make the spike protein. What we're doing
Speaker 1: now is we're saying we're not going to do any
Speaker 1: of that. We're going to take a small gene that
Speaker 1: essentially codes for that spike protein, and then we'll inject
Speaker 1: that and hope that it gets into muscle cells and
Speaker 1: will then be translated to the spike protein. So, in
Speaker 1: other words, the person makes the spike protein, then the
Speaker 1: person makes in about it's the spectro protein. We've never
Speaker 1: done that before. Just like you said, there's no commercial
Speaker 1: equivalent for that for any vaccine. It should theoretically work,
Speaker 1: we just never knew that it could. That was a
Speaker 1: spectacularly clear explanation. I want to just dive into a
Speaker 1: specific part of it. The part I want to dive
Speaker 1: into is the idea that historically, the way we've done
Speaker 1: vaccines and by Weime and you the scientific community, is
Speaker 1: by introducing a version of the spike protein in this
Speaker 1: case that we want to block, and then having the
Speaker 1: body produce antibodies to it. And that what makes the
Speaker 1: mRNA approach, which is characteristic of the Fiser approach and
Speaker 1: of the Maderna approach, distinctive, is that it actually introduces
Speaker 1: a genetic code to produce the spike protein, which the
Speaker 1: body then produces, which we don't want in principle a
Speaker 1: body to produce. But then the body produces antibodies to
Speaker 1: the spike protein that the body has produced. So you're
Speaker 1: saving a step, as it were, you don't have to
Speaker 1: introduce the spike protein in some form from the outside.
Speaker 1: First of all, am I getting that right? That's exactly right.
Speaker 1: But if for example, you gave a live attenuated viral vaccine,
Speaker 1: that virus would then enter the cell, reproduce itself, and
Speaker 1: it would make the spike protein inside that cell. So
Speaker 1: it's not like a complete long shot. And we certainly
Speaker 1: have a wealth of experience using live weakened viruses to
Speaker 1: induce immune response, starting in the mid nineteen thirties with
Speaker 1: yellow fever vaccine. And is it a good thing that
Speaker 1: by encoding for the spike protein without introducing the virus,
Speaker 1: the virus actually doesn't in principle have a chance of
Speaker 1: arising within the cell with this kind of vaccine, correct,
Speaker 1: because we're not encoding for the virus, just encoding for
Speaker 1: the spike protein. That's right. It's just you're being infected,
Speaker 1: if you will, with one protein, so that's not the virus,
Speaker 1: that's right. So when we think about potential negative side effects,
Speaker 1: when we think about live attenuated viruses or killed viruses,
Speaker 1: sometimes we worry that they might produce, at least in
Speaker 1: some people, symptoms of the actual virus or the bad
Speaker 1: consequence of the actual virus. Is it correct to say that,
Speaker 1: at least in principle, the mRNA vaccine can't do that
Speaker 1: because there is no virus introduced into the system. There's
Speaker 1: just the genetic code for the spike protein, which is
Speaker 1: not itself the virus. Yeah, this is not sours cob
Speaker 1: two virus. This is just one protein from the virus
Speaker 1: that you will make. Therefore, the signs and symptoms that
Speaker 1: you develop will not resemble those of SARS cob two infection.
Speaker 1: So one of the best things about an RNA vaccine,
Speaker 1: if indeed it works, is that it avoids some of
Speaker 1: the potential downsides of more traditional vaccination. That's correct. Yes,
Speaker 1: Sometimes it's been said in the media and by the
Speaker 1: companies that it's easier to produce large numbers of doses
Speaker 1: of an mRNA vaccine than it is to produce large
Speaker 1: numbers of doses of a traditional killed or attenuated virus vaccine.
Speaker 1: Is that so, And if it is so, why is
Speaker 1: it so? I think there's a couple advantages for these
Speaker 1: genetic approaches. The so called genetic plug and play approaches
Speaker 1: are fast because they're very easy to construct. You just
Speaker 1: take the gene and in the case of mRNA, you
Speaker 1: give the gene, or in the case of some of
Speaker 1: these other so called viral vectors, you just insert the
Speaker 1: gene into that viral vector. So it's really very fast
Speaker 1: to be able to construct it, and then it's very
Speaker 1: easy to scale up rapidly. So MESSERNA, it's essentially synthetic.
Speaker 1: You're just manufacturing it, so it can be scaled up
Speaker 1: very quickly. I mean, I think Visor said that they
Speaker 1: would have fifty million doses by the end of twenty twenty,
Speaker 1: that they would have one point three billion doses in
Speaker 1: the year twenty twenty one. You mentioned the viral vector
Speaker 1: vaccines also sometimes called trojan horse vaccines. The Astroxenica approach,
Speaker 1: the Oxford approach is one of those. Could you describe
Speaker 1: how that works in relationship to the mRNA approach, right,
Speaker 1: So it's a little different. So the so called replication
Speaker 1: defective adnovirus vectors, which is the approach that's being used
Speaker 1: by Johnson Johnson, the approach that's being used by Astroxenica,
Speaker 1: the approach is being used by Russia. The approach is
Speaker 1: being used by Chin in part is the adnovirus is
Speaker 1: a human virus that can cause a variety of diseases.
Speaker 1: But by engineering the virus so that it's replication defective,
Speaker 1: that means that it cannot reproduce itself, that means that
Speaker 1: it cannot cause disease. But it's also genetically engineered so
Speaker 1: it has the gene that codes for the spike protein.
Speaker 1: So then you inoculate this replication defective viral vector into
Speaker 1: the person. It's taken up into muscle cells, and then
Speaker 1: that replication of vectivirus enters the cell nucleus, where then
Speaker 1: that gene that codes for the spike protein is transcribed
Speaker 1: into messenger rna, and then the messenger rna then enters
Speaker 1: the cytoplasm and then makes the protein, and then you
Speaker 1: make the protein. So it's sort of like a step
Speaker 1: back from the messenger RNA strategy, but essentially it's the
Speaker 1: same strategy. It's ultimately getting the cell to make sours
Speaker 1: covie to spike protein. And the reason that it's sometimes
Speaker 1: called the trojan horse vaccination approach is that the adnovirus
Speaker 1: is another virus that does in fact, in effect the cell,
Speaker 1: though not with the possibility of replication. And once it's
Speaker 1: in there, it delivers the genetic code for the spike
Speaker 1: protein exactly right, and then the human body makes the
Speaker 1: spike protein and then develops the antibodies to it, and
Speaker 1: we're off to the races, as it were, off to
Speaker 1: the races. Are those viral vector vaccines just as easy
Speaker 1: to produce in large numbers of doses as the mRNA
Speaker 1: vaccine is. Well, the mRNA is synthetic at some level,
Speaker 1: so it's in that sense easier to make, but it
Speaker 1: can be rapidly killed up. And there's a lot of
Speaker 1: experience actually with replication effective add and ofvirus vectors, which
Speaker 1: was used actually as one of the e bowl of
Speaker 1: vaccines by Johnson and Johnson, the so called replication effective
Speaker 1: ad ofvirus twenty six, So millions of doses were administered
Speaker 1: in West Africa associated with that outbreak. Plus, interestingly, I
Speaker 1: think many people don't realize this that product who had
Speaker 1: to be maintained on dry ice and it was successfully
Speaker 1: maintained on dry ice in West Africa, because that's going
Speaker 1: to be also the story with the Fiser vaccine. So
Speaker 1: we'll see how this plays out, but there is at
Speaker 1: least some experience, some commercial experience with this approach. I'm
Speaker 1: glad you raised the temperature issue, which seems like it's
Speaker 1: going to be an important one going forward. The Fiser
Speaker 1: folks are saying that their vaccine needs to be kept
Speaker 1: at negative seventy degrees centigrade, which is around ninety four
Speaker 1: degrees below zero fahrenheit. Why does it have to be
Speaker 1: kept at that cold temperature? So? People who work with
Speaker 1: messenge drying in a laboratories usually stored in liquid nitrogen,
Speaker 1: which is like minus seventy to minus eighty degrees centigrade
Speaker 1: in order to be able to make sure that that
Speaker 1: molecule doesn't break down at least the fives are construct.
Speaker 1: You have to ship it and store it at minus seventy,
Speaker 1: which means that for the people who are taking care
Speaker 1: of it, they have to constantly replenish the dry ice,
Speaker 1: which is a lot to ask. And it gets worse
Speaker 1: than that. Then what happens is when you've thought it
Speaker 1: out and you put it in the refrigerator, that concentrated
Speaker 1: form of Messenger RNA can only stay in the refrigerator
Speaker 1: for twenty four hours. After twenty four hours you have
Speaker 1: to throw it out. Also, if you reconstitute it and
Speaker 1: it's just reconstituted with just a normal as salt water solution,
Speaker 1: after you reconstitute it, you have six hours to give it.
Speaker 1: So that's a lot to ask and I think when
Speaker 1: you do these trials, it's forty four thousand person trial,
Speaker 1: you can be sure that the company was very good
Speaker 1: about making that these study centers that were doing these
Speaker 1: trials knew exactly how to do it, and we're good
Speaker 1: at doing it. When a thing gets out into the
Speaker 1: real world, you worry that people are going to be
Speaker 1: as good at making sure they kept this ultra cold
Speaker 1: chain going as we did into trials, and that the
Speaker 1: efficacy may be a little less in a real world center.
Speaker 1: Because messenger RNA breaks down very quickly. It decentegrates very quickly,
Speaker 1: and although that would not be an issue, I think
Speaker 1: in terms of safety, it would definitely be an issue
Speaker 1: in terms of potency. Why does it break down so quickly?
Speaker 1: If in the human body, mRNA is tremendously necessary, and
Speaker 1: of course the human body is not negative seventy degrees centigrade, right,
Speaker 1: it does break down quickly in the human body, but
Speaker 1: you're constantly making messenger RNA and it's constantly breaking down.
Speaker 1: I mean, one thing, it's interesting just from a nerdy
Speaker 1: virologious standpoint, when you're infected with this virus, you usually
Speaker 1: shed infectious virus for about a week, meaning live virus
Speaker 1: for about a week, but you can be PCR positive
Speaker 1: for three months. Which interesting about that is when you're
Speaker 1: PCR positive, what that means is is that the virus
Speaker 1: gene is being detected in the back of your throw,
Speaker 1: so it's not the live virus necessarily, it's just the
Speaker 1: virus genome. Well, if messenger RNA breaks down so quickly,
Speaker 1: and it does, why is it that you're positive for
Speaker 1: three months after you're no longer making effect as virus.
Speaker 1: I mean, shouldn't the mRNA breakdown very quickly? And the
Speaker 1: answer as it does. So the only explanation for this
Speaker 1: is that the virus continues to make messenger rna, continues
Speaker 1: to make its genome, but doesn't make whole virus particles,
Speaker 1: which would be the first virus at least that I
Speaker 1: know about, has ever done something like that. It's just
Speaker 1: a very strange virus, this bad coronavirus. Can you think
Speaker 1: of any adaptive advantage genetically for an organism to continue
Speaker 1: to make its genome, maybe if it's not making the
Speaker 1: thing that enables it to spread in the population. That
Speaker 1: doesn't sound super efficient from a sort of classic evolutionary
Speaker 1: advantage standpoint. I know, I can't think of a reason,
Speaker 1: but you know what, I'm going to assume the virus
Speaker 1: is smarter than I am, and it's doing it for
Speaker 1: a reason, because why would it expand the energy that's
Speaker 1: needed to make message RNA unless there was some advantage
Speaker 1: to its survivability. Fascinating of the viral vector vaccines, the
Speaker 1: ones that Johnson and Johnson and Astra Zeneca are producing,
Speaker 1: will those also have to be kept at a comparable
Speaker 1: level of coldness. You mentioned that the vaccine that was
Speaker 1: used in Africa was stored on dry eye, so that's
Speaker 1: at the same kinds of low temperatures. My understanding is
Speaker 1: it's they'll be either kept at freezer or refrigerator temperatures,
Speaker 1: so they're not going to nearly require the kind of
Speaker 1: issues that are going to be required at least with
Speaker 1: the Fiser vaccine. Which interesting is that the modernist vaccine
Speaker 1: is also an mr anda vaccine, but it doesn't have
Speaker 1: to be shipped in stored at minus seventy to Minusa.
Speaker 1: It can be shipped in stored at minus twenty degrees centigrade,
Speaker 1: which is basically freezer temperature. They're both mr Anda vaccines.
Speaker 1: The gene sequence that determines the so called receptor binding
Speaker 1: domain on the Saurus CoV two spy protein is identical,
Speaker 1: but they are different. I mean, Fiser's vaccine is given
Speaker 1: at thirty micrograms per dose in two successive doses. Madernas
Speaker 1: is a hundred micrograms and two successive doses, And they
Speaker 1: don't have the same so called ducleoside analog, so they're
Speaker 1: not the same molecule. Obviously, there's there's stability differences, physical
Speaker 1: chemical differences between those two products, and I'm not sure
Speaker 1: exactly why, because obviously I'm sure if Fizer could ship
Speaker 1: in store at freezer temperature, which is much more doable,
Speaker 1: they would, so will that potentially turn out to be
Speaker 1: a determinative factor for governments that are making specific orders
Speaker 1: or for healthcare systems that are making specific orders. I mean,
Speaker 1: I'm sitting in I don't know, the Massachusetts Department of
Speaker 1: Health and Human Services, and I'm trying to figure out
Speaker 1: which one should I buy? Would that be ir relevant
Speaker 1: consideration for me? I'd rather buy the one, for example,
Speaker 1: that can be shipped at a slightly higher temperature or
Speaker 1: stored at us slightly higher temperature. You would think that
Speaker 1: the degree of ease, the degree to which administration and
Speaker 1: storage is idiot proof, it would be attractive what is
Speaker 1: currently required for the Fiser vaccine, which is, you know
Speaker 1: that you can't keep in the refrigerator from more than
Speaker 1: a day once we constuted, can't be kept for more
Speaker 1: than six hours, that you constantly have to replace with
Speaker 1: dry ice. I can't imagine how that is going to
Speaker 1: be done in a large retail pharmacy. I can't. I
Speaker 1: can't imagine how it's going to be done at our hospital, frankly, so,
Speaker 1: so then how would it be done? One way would
Speaker 1: be to have a series of centers that are distributed
Speaker 1: throughout a city that are like a testing center sept
Speaker 1: here that are specifically devoted to giving the vaccine. That
Speaker 1: would be one way to do it, and that may
Speaker 1: be the way it's going to be done. So yes,
Speaker 1: I think you're exactly right. How operationally or we get
Speaker 1: a vaccine that has these kinds of requirements out there.
Speaker 1: When you just described that you're not even sure your hospital,
Speaker 1: which is one of the best hospitals in the country
Speaker 1: and indeed in the world, could do it, that actually
Speaker 1: makes me wonder about viability altogether. I mean, you describe
Speaker 1: setting up these centers in different cities. That might be
Speaker 1: all well and good in big cities that have lots
Speaker 1: of resources, but it sounds like it would be hard
Speaker 1: to do in lots of parts of the United States,
Speaker 1: and definitely very hard to do in lots of parts
Speaker 1: of the world where such centers don't exist, and would
Speaker 1: then have to be built from scratch. From the way
Speaker 1: you formulated it there, I almost thought you were hinting
Speaker 1: that unless there is no other choice, the Fiser approach
Speaker 1: doesn't sound like it's going to be doable at scale.
Speaker 1: I think it's doable, and I think it's doable at scale.
Speaker 1: I just think it's going to require an enormous effort,
Speaker 1: which means an enormous expenditure as well as time. Yes,
Speaker 1: I think that's right, And understandings in the United States
Speaker 1: has contracted to by one hundred million doses of the
Speaker 1: Fiser vaccine, which means that they could vaccinate fifty million people.
Speaker 1: Now that the number of people that have been considered
Speaker 1: sort of first tier responders meaning essential workers like healthcare workers,
Speaker 1: people in transportation, law enforcement, etc. People over sixty five,
Speaker 1: people who have certain high risk medical conditions, added up
Speaker 1: to about one hundred and fifty million American adults, which
Speaker 1: is roughly half the adult population. This vaccine to be
Speaker 1: given exclusively at least for that hundred million, doses to
Speaker 1: the United States would be about a third of that.
Speaker 1: So the only way we're going to vaccinate the American
Speaker 1: population is if there's more than one vaccine. That's going
Speaker 1: to have to be true. We'll be right back. When
Speaker 1: I try to picture a center, a newly created center
Speaker 1: that becomes the vaccination center in a city, I guess
Speaker 1: we're down at getting into the nitty gritty, But I
Speaker 1: guess you have to set up appointments for people. You
Speaker 1: can have fifty million people lining up and waiting for vaccines,
Speaker 1: among other things, they would probably be too proximate to
Speaker 1: one another and that might spread the virus, right, and
Speaker 1: you have to identify whether or not these people really
Speaker 1: are the first tier for whom the vaccine is recommended.
Speaker 1: Because I think there are a lot of people who
Speaker 1: were going to get it who are not necessarily in
Speaker 1: that first tier group. So how do you identify who
Speaker 1: they are? How do you make sure they come back
Speaker 1: twenty one or twenty eight days letter depending on the vaccine,
Speaker 1: so to make sure they got their second dose. If
Speaker 1: you look at shing ricks, which is probably the best
Speaker 1: equivalent for this, which is an adult vaccine that's given
Speaker 1: in two doses roughly separated by a month, what percentage
Speaker 1: of people come back for that second dose. The answer
Speaker 1: is it's pretty high. It's about eighty five percent or
Speaker 1: so ninety percent. But still, you know, one out of
Speaker 1: ten or more people don't come back for that second
Speaker 1: dose because, first of all, the first dose of a
Speaker 1: shingles vaccine does cause side effect, as these vaccines will
Speaker 1: for different reasons. Mess Darna is an adgement. By adgement,
Speaker 1: I mean it stimulates the immune system so that you
Speaker 1: can give a lesser quantity of the active ingredient. And
Speaker 1: so you may get a first US and think, yeah, hey,
Speaker 1: this wasn't fun. I had fever, including high fever, I
Speaker 1: had headaches, chills, muscle eggs. I'm not signing up for that. Seconds,
Speaker 1: which really is the shingle story. I mean, it's certainly
Speaker 1: nothing compared to what the benefit is, which is preventing
Speaker 1: a disease that could kill you. So it's certainly worth it.
Speaker 1: But you know, for some people, they may think, you know,
Speaker 1: I'm young and healthy, I'm probably not going to die
Speaker 1: from this, so I really have to go back for
Speaker 1: that second dose. This wasn't much fun. The fact that
Speaker 1: mRNA it can be used as an adjument, namely something
Speaker 1: that stimulates your immune system, does that mean that a
Speaker 1: high percentage of the population who takes the vaccine will
Speaker 1: have those kinds of quasi flu leg symptoms in response
Speaker 1: to taking the vaccine. Yes, I think that's right. I
Speaker 1: think probably as much as half of people will have fever,
Speaker 1: including high fever, and then the symptoms associated with fever, headache, chills,
Speaker 1: muscle as I think that's likely. And how long do
Speaker 1: those symptoms typically last When you've administered just an agement
Speaker 1: a day or two. I mean, it'll go away again.
Speaker 1: So people will know they don't have COVID because they've
Speaker 1: just taken the vaccine, but they may be a little
Speaker 1: nervous about it. Well, the same thing actually applies for
Speaker 1: the vaccine trials. In theory, the participant doesn't know whether
Speaker 1: they're getting vaccine or placebo. But because the mRNA vaccines,
Speaker 1: and actually also true for the replication effect of adenovirus
Speaker 1: vaccines for a different reason, that too had a fairly
Speaker 1: high side effect profile. So if you didn't have side effects,
Speaker 1: you probably did have a placebo, and if you did
Speaker 1: have side effects, you probably did have the vaccine. So
Speaker 1: most people probably do know which they got. Interesting. Interesting.
Speaker 1: The second question I wanted to ask about that scenario
Speaker 1: is if one hundred and fifty million people aren't being
Speaker 1: described as first responders, and as you say, that's half
Speaker 1: of the US adult population, that on some level that
Speaker 1: first responder categorization isn't that meaningful, and it's going to
Speaker 1: have to be more narrowed down, especially if let's say
Speaker 1: we have fifteen million doses to begin with, and even
Speaker 1: among that there's the question of the order in which
Speaker 1: it will be given. Do you have a view about
Speaker 1: what would be plausible ways to narrow it down beyond that,
Speaker 1: or do you think that the governments involved are just
Speaker 1: going to duck the issue because it's so difficult to
Speaker 1: do allocation processes like this in a way that seems
Speaker 1: fair to people. I think you're exactly right. I think
Speaker 1: it is going to be difficult to do that, But
Speaker 1: I don't think they're going to duck the issue. I
Speaker 1: think both the Advisor Community for Communization Practice to the
Speaker 1: CDC and the National Category Medicine, which have been charged
Speaker 1: with trying to figure out exactly how these tiers are
Speaker 1: going to work out who's in the top top tier,
Speaker 1: who's just below that top tier, they won't duck it.
Speaker 1: The question is how it then is going to play
Speaker 1: out in the real world when the rubber meets the road,
Speaker 1: and we'll see I'm sure that the healthcare workers will
Speaker 1: be right up at the top, as will people who
Speaker 1: are older. For in terms of people who are over
Speaker 1: sixty five, we do need data to prove that the
Speaker 1: vaccine is effective in that age group. Hopefully we'll have
Speaker 1: enough people in these fisor trials, and we're during the trials,
Speaker 1: which are going to be the first ones to go
Speaker 1: through the FDA, we'll have enough data to be able
Speaker 1: to make that statement. Because although you know, obviously you
Speaker 1: want to make sure that both genders weekly represented, you
Speaker 1: want to make sure that there's an adequate representation of
Speaker 1: racial and ethnic minorities. There's no reason to believe that
Speaker 1: there would be really differences in the ability to respond
Speaker 1: with the accept for someone older and people who have
Speaker 1: various medical conditions, like you know, say obesity or diabetes.
Speaker 1: So that needs to be clear or as we do this.
Speaker 1: I thought of that specifically because I heard an interview
Speaker 1: on the radio with one of the fiser's spokespeople who
Speaker 1: was asked, of your forty four thousand people in your trial,
Speaker 1: were their elderly people? And the spokesperson responded by saying
Speaker 1: the trial group was demographically broad, which was not a
Speaker 1: direct answer, and of course it didn't say anything about
Speaker 1: whether the ninety percent efficacy level is you know, nearly
Speaker 1: one hundred percent of young people are finding it working
Speaker 1: and a very substantial number of older people are not
Speaker 1: discovering that it works. Do you have an instinct about that?
Speaker 1: I mean, would it be ordinarily the case that if
Speaker 1: you looked at a natural variation across a population, that
Speaker 1: older people would have a much harder time having the
Speaker 1: vaccine effectively generate successful protections for them, just because their
Speaker 1: immune systems are less responsive as they get older. Yes,
Speaker 1: and that's the flu story. I mean, influenza vaccine works.
Speaker 1: It's about sixty to sixty five percent effective to say,
Speaker 1: people less than eighteen years of age, but it's barely
Speaker 1: effective in people over sixty five. On the other hand,
Speaker 1: is shingles vaccine in those over seventy eighty years old
Speaker 1: works extremely well. So there are horses for courses. As
Speaker 1: they say at the track, I think we'll find that
Speaker 1: there are vaccines that may work well in one group
Speaker 1: but not another. And I thought, of you. I thought
Speaker 1: that the press release was pretty cajry. I think it
Speaker 1: made a statement that they had X number of people
Speaker 1: over fifty five, but it's really over sixty five that
Speaker 1: you care about. And I'm not just saying that because
Speaker 1: I'm over sixty five. Okay, I am saying that because
Speaker 1: I'm over sixty five. But you know you can't forget
Speaker 1: about us. Well, I don't think anyone is going to
Speaker 1: forget about people over sixty five. In the context of
Speaker 1: responding to a disease where most of the people whom
Speaker 1: it has killed were not just over sixty five, but
Speaker 1: over seventy or over seventy five, I think people are
Speaker 1: going to be extremely concerned about this. I guess there's
Speaker 1: the answer. Then we just have because of your horses
Speaker 1: for courses point, there's just no way we're going to
Speaker 1: know anything about this until we see the data. We
Speaker 1: can't assume what it's going to look like. The challenges here.
Speaker 1: If you look at that forty four thousand person trial
Speaker 1: and then you look at the instance of infection, it's
Speaker 1: actually much less than you would have predicted based on
Speaker 1: what the instances of outbreaks were as these trials were progressing.
Speaker 1: Which makes you wonder whether the people who were participants,
Speaker 1: because they may be more attentive to their health, were
Speaker 1: more likely to wear a mask, more likely to social distance,
Speaker 1: and therefore less likely to have been infected than an
Speaker 1: otherwise group. In other words, as compared to if they say,
Speaker 1: did the trials with bikers in Sturge of South Dakota
Speaker 1: who didn't wear masks, or you know, people who go
Speaker 1: to the Trump rallies or go to Rose Garden ceremonies,
Speaker 1: you know that you'd be more likely to have a
Speaker 1: higher rate of infections. And that matters because masks aren't
Speaker 1: one hundred percent effective, and so it may be that
Speaker 1: you were exposed to a lesser inoculum than someone who
Speaker 1: was less careful about their care. And you know, there's
Speaker 1: definitely an anoculum effect. The greater the enocuum, the more
Speaker 1: likely to have some modern secure disease. So there's a
Speaker 1: lot to work out. I don't think we're going to
Speaker 1: work a lot of it out before these vaccines are
Speaker 1: already introduced, because we have two hundred and forty thousand
Speaker 1: people that died of this virus this year. You're not
Speaker 1: going to do huge long term trials. You're not, and
Speaker 1: there's going to be whenever you do subsets, there's always
Speaker 1: going to be a loss of statistical strength, and so
Speaker 1: you're just going to take your best guests. I'm on
Speaker 1: the FDAs Vaccine Advisor Committee. These are the questions that
Speaker 1: are going to come before us, probably in the next
Speaker 1: few weeks when we're asked to approve these products through EUA,
Speaker 1: and I think we're going to be looking to approve
Speaker 1: both fisor in Maderna soon. And the other thing is
Speaker 1: I think although ninety four cases was reported by fives
Speaker 1: are in this press release, my sense was they're going
Speaker 1: to have at least one hundred and sixty by the
Speaker 1: time that our committee looks at this and it may
Speaker 1: be also drew from Maderna. So just to clarify the
Speaker 1: EUA as the emergency use authorization, your committee is a
Speaker 1: crucial step because the head of the FDA has said
Speaker 1: they're not going to issue an emergency use authorization unless
Speaker 1: your committee says go for it. So you're an important
Speaker 1: choke point in that structure. When you talk about the
Speaker 1: number ninety four or the number one hundred and sixty,
Speaker 1: clarify what that number refers to for us, Right, So
Speaker 1: what fives are said press releases that they had ninety
Speaker 1: four illnesses among participants and that the vaccine was ninety
Speaker 1: percent effective roughly, So we don't really know the numbers, yeah,
Speaker 1: but let's make them up. Let's assume then that there
Speaker 1: were eighty six cases in the placebo group in eight
Speaker 1: cases in the vaccine group, so that would be ninety
Speaker 1: percent protection. And just to clarify, that's out of forty
Speaker 1: four thousand people, twenty two thousand of whom got the vaccine,
Speaker 1: twenty two thousand of whom did not get the vaccine.
Speaker 1: Because it has to have been evenly divided, right, at least,
Speaker 1: that's a normal practice, that's right, so of forty four
Speaker 1: thousand people, twenty two thousand get the vaccine, eight of
Speaker 1: them get sick roughly on this reconstruction, and only eighty
Speaker 1: six people get the virus of twenty two thousand people
Speaker 1: who are not vaccinated. I mean that is stunningly small
Speaker 1: degree of the number of people, isn't it weirdly small?
Speaker 1: That's why I sort of had mentioned before that they
Speaker 1: may be much more likely to protect themselves by it. It
Speaker 1: It means because we're not helpless here, I mean hygienic
Speaker 1: measures who work, so that maybe that's what's going on.
Speaker 1: If that were true, if your hypothesis were correct, then
Speaker 1: maybe this vaccine is a lot less than effective. That's
Speaker 1: a good point. I think it was your point. I
Speaker 1: didn't mean it to you my point. Then I agree
Speaker 1: with my point. Let's assume, just theoretically, that there were
Speaker 1: eight people in the vaccine group who got sick. Those
Speaker 1: are the people you learn the most from, because you'll
Speaker 1: know whether or not they had an immune response what
Speaker 1: you thought was going to be an adequate immune response
Speaker 1: to the vaccine, if they didn't, if they had didn't
Speaker 1: have a very good neutralizing handibody response I e. And
Speaker 1: antibody response that neutralized virus and effectivity. Then you may
Speaker 1: have an immunological marker. You can say that, look, if
Speaker 1: you don't have this sort of level of immunity in
Speaker 1: response to the vaccine, you may not be protected. On
Speaker 1: the other hand, they may have had an a perfectly
Speaker 1: adequate neutralizing antibode response, in which case you can say,
Speaker 1: maybe the immune response that we thought was associated with
Speaker 1: protection isn't clearly associated with protection. And then it's a
Speaker 1: matter of looking at who those people were the god sick.
Speaker 1: Were they more likely to be over sixty five, did
Speaker 1: they have other healthcare problems, were they of a particular
Speaker 1: racial or ethnic background. That's where you learn the most
Speaker 1: people that got the vaccine still got sick. Should we,
Speaker 1: on the more positive front, have a pretty good indication
Speaker 1: of the lack of bad side effects if twenty two
Speaker 1: thousand people have gotten the vaccine, because presumably if there
Speaker 1: were any really meaningfully bad side effects, we would have
Speaker 1: seen them in this population. That's right. And if you
Speaker 1: look historically at the side effects that have been associated
Speaker 1: with vaccines, whether it's sort of polio from the ro
Speaker 1: polio vaccine or so called vicerotropic disease, which is to say,
Speaker 1: yellow fever following the yellow fever vaccine, or Gambera syndrome,
Speaker 1: which is the ascending paralysis that occurs very rarely after
Speaker 1: flu vaccine, and all of which are extremely rare, and
Speaker 1: they all occur really within six weeks of getting a dose.
Speaker 1: So and the way these trials are now being set
Speaker 1: up is that you can't get in EUA unless you
Speaker 1: follow at least half of the population who was vaccinated
Speaker 1: at least two months after dose two. So what that'll
Speaker 1: tell you is that at least as far as you
Speaker 1: know that you don't have a relatively uncommon severe side effect.
Speaker 1: But twenty thousand people isn't twenty million people. I once
Speaker 1: you put the vaccine out there in twenty million people,
Speaker 1: there may be a very rare side effect that the
Speaker 1: cursent say one in a million people or one in
Speaker 1: five hundred thousand people, that you're not going to pick
Speaker 1: up pre approval. But the good news is there are
Speaker 1: systems in place, like the Vaccine Adverse Events Reporting System,
Speaker 1: or like the Vaccine Safety Data Link, which will pick
Speaker 1: that up and have picked that up in the past.
Speaker 1: So I think people can be reassured that you're looking
Speaker 1: to remember a choice not to get a vaccine. It's
Speaker 1: not a risk free choice. It's just a choice to
Speaker 1: take a different risk. And the question is when do
Speaker 1: you know enough to say that I think that we
Speaker 1: have mitigated a critical amount of risk associated with this vaccine.
Speaker 1: Should I feel better say, as an over sixty five
Speaker 1: year old that ten thousand people are five thousand people
Speaker 1: who are three thousand people who've been vaccinated with the
Speaker 1: vaccine safely knowing that if I get infected with this virus,
Speaker 1: I have a higher chance of dying. It's always a
Speaker 1: matter of risk benefit, and I don't think people see
Speaker 1: it that way. They think that I'm just going to
Speaker 1: take the conservative thing and I'm just going to wait,
Speaker 1: And you know, while you're waiting, you may get infected. Now,
Speaker 1: as you wait, more and more people will get vaccinated,
Speaker 1: and then you have a much bigger platform in which
Speaker 1: to say, I think there really isn't a safety issue here,
Speaker 1: but while you wait, you might suffer the consequences. You've
Speaker 1: just replicated the conversation I have had with my parents recently,
Speaker 1: who are definitely over sixty five. And so I want
Speaker 1: to ask you if you're willing to share what your
Speaker 1: view is of the cost benefit here. I mean, my takeaway,
Speaker 1: and this is what I said to my parents, is
Speaker 1: that because you're in an age group, and they also
Speaker 1: live in New York where if you were to become infected,
Speaker 1: your health outcomes are not great, even with the new
Speaker 1: treatments that are available. I mean, I said it more
Speaker 1: bluntly like that. I said, you know, if you're infected
Speaker 1: and you're over this age, the danger that you could
Speaker 1: become sick and even die is really very high. Therefore,
Speaker 1: I argued, being conservative and waiting in this instance would
Speaker 1: make no sense at all measured by cost benefit, because
Speaker 1: although it's nice in general to be cautious about healthcare,
Speaker 1: in this instance, the side effects have not been shown
Speaker 1: to be particularly bad, and if they were in existence,
Speaker 1: they would be of tiny probability, and it would be
Speaker 1: of very very very minuscule probability that you could be
Speaker 1: so ill as to die from those side effects, whereas
Speaker 1: if you get the virus the possibilities are much greater.
Speaker 1: So that was my argument. I'm wondering was I right?
Speaker 1: I mean, I hope I was right, But if I wasn't,
Speaker 1: I want to know that. So I can take it back.
Speaker 1: What would you say to someone in that situation. No,
Speaker 1: I agree with you completely. I think that's exactly the argument.
Speaker 1: You know, when you do vaccine trials and you go
Speaker 1: from phase one trials of twenty two hundred people to
Speaker 1: face through trials of several hundred people, to face three
Speaker 1: trials of tens of thousands of peach people. Every time
Speaker 1: you do that, you mitigate risk, you lessen the risk.
Speaker 1: You never eliminate the risk, you never know everything. I mean,
Speaker 1: one of the real dangers here is that we could
Speaker 1: have a scenario where we have a pretty darn good
Speaker 1: vaccine that's pretty darn safe, and yet there's some significant
Speaker 1: part of the population that refuses to take it. I
Speaker 1: think what's going to happen Because this vaccine, it's not
Speaker 1: going to be recommended for the general population. Initially, it'll
Speaker 1: be recommended for certain groups like healthcare workers and transportation workers, etc.
Speaker 1: Those groups will start to get that vaccine, and then
Speaker 1: you'll see millions of people have been vaccinated, and then
Speaker 1: you'll see that they're happy they've been vaccinated, that there's
Speaker 1: no serious side effect. You may start to see an
Speaker 1: instance of cases and hospitalizations and deaths start to decrease,
Speaker 1: and people will see that the vaccine is having a
Speaker 1: positive effect, and that, I think, which assure people that
Speaker 1: there doesn't seem to be a problem, and there'll be
Speaker 1: more and more confident in getting the vaccine overtime. So
Speaker 1: that's the happy story, and I desperately hope that you're right.
Speaker 1: One of the reasons I always think that anti vaccination
Speaker 1: people manage to have the effect that they do have
Speaker 1: is that they're often free riding. You know that, in effect,
Speaker 1: there are some diseases that are the prevalences which is
Speaker 1: so low as a result or broad vaccination that some
Speaker 1: people say, well, I'm not going to get the vaccine
Speaker 1: and watch, I'm not going to get sick, And they
Speaker 1: might not get sick because the vaccine has effectively reduced
Speaker 1: the prevalence of the disease such that they're not very
Speaker 1: likely to be exposed. Is there a danger of that
Speaker 1: kind of a perceived free rider effect if the first
Speaker 1: responders and others and healthcare workers get the vaccine, if
Speaker 1: numbers start to go down, and then some people say, well,
Speaker 1: now that it's going down, I don't need to be vaccinated.
Speaker 1: I mean, we eliminated measles in the United States. By
Speaker 1: the year two thousand, it's come back because a critical
Speaker 1: number of parents have chosen not to vaccinate their children
Speaker 1: for just that reason. I think they figure, what the
Speaker 1: hell everybody around me is being vaccinated, Why should I
Speaker 1: take the risk and I'll still be protected. When enough
Speaker 1: people make that decision, then the virus thrives. And you
Speaker 1: had a handful of children who were in the Intensive
Speaker 1: care Union in New York hospitals because of severe measles,
Speaker 1: because the parents had made the decision to frankly put
Speaker 1: their children unnecessary risk. And you know, you are a
Speaker 1: member of society. I don't think it's your right to
Speaker 1: catch and transmitted potentially fatal infection. I think you owe
Speaker 1: it not only to yourself or to your children eventually,
Speaker 1: but to the people with whom you come in contact.
Speaker 1: We're remembering that there's five hundred thousand people in this
Speaker 1: country who can't be vaccinated. There can't be vaccinated because
Speaker 1: they're getting cancer chemotherapy, and then some instances now they're
Speaker 1: not going to be vaccinated because they're too young. They
Speaker 1: can't be vaccinated because they're getting biologicals for their chronic diseases.
Speaker 1: So do you have a responsibility to them the answer
Speaker 1: to I mean, in our hospital Children's Hospital of Philadelphia,
Speaker 1: every year we ask our healthcare workers to get a
Speaker 1: flu vaccine. Not just healthcare workers, anybody who could walk
Speaker 1: in the room, dietary, environmental services, anybody. Because you are
Speaker 1: working in a hospital of vulnerable children and it is
Speaker 1: therefore your responsibility to make sure that you protect them. Well,
Speaker 1: you could make the same argument in society. As a
Speaker 1: member of society, it's your obligation to protect those around.
Speaker 1: Could you just say a word about the half a
Speaker 1: million people who we can't vaccinate and what the reasons are,
Speaker 1: what's not safe for them to have their vaccine. Five
Speaker 1: hundred thousand people in this country are receiving biologicals, you know,
Speaker 1: things like monoclonal antibodies, because they have chronic disease, because
Speaker 1: they have psoriasis or arthritis or whatever. And a lot
Speaker 1: of people who are on chemotherapy for cancer, they too
Speaker 1: can't get vaccines because it wouldn't work in them because
Speaker 1: their immune systems are suppressed. Some people are born with
Speaker 1: immune systems that don't work. So that involves about five
Speaker 1: hundred thousand people in this population. Roughly three hundred and
Speaker 1: thirty million, And they depend on the herd. They depend
Speaker 1: on those around them to protect them. And when the
Speaker 1: herd says I don't care about you, they're the ones
Speaker 1: who are often the first to suffer these diseases. Last,
Speaker 1: but not least. What's it kind of feel like in
Speaker 1: the room when your committee meets? What does it usually
Speaker 1: feel like when you're committee meets. I guess it'll be
Speaker 1: virtual because of COVID. Well, we've never had a meeting
Speaker 1: like this, I mean normally, what does it feel like
Speaker 1: in the room. Normally it's it's a group of sort
Speaker 1: of you know, nerdy virologists like myself sitting around talking
Speaker 1: about what flu strange we're going to pick for the
Speaker 1: vaccines for next year. So we haven't at least in
Speaker 1: the last couple of years, licensed a new vaccine that's
Speaker 1: going to be what's happening here, and it's opened to
Speaker 1: the public. Anybody can come to those meetings. But if
Speaker 1: you went to our flu meeting, you'd be bored to death.
Speaker 1: Most likely. We don't have big crowds there. On the
Speaker 1: other hand, when we had our first meeting of the
Speaker 1: FDA's Vaccine Advisor committee regarding these vaccines. It was on
Speaker 1: October twenty second, just to see what criteria we would
Speaker 1: be happy with for approving a vaccine under emergency use authorization,
Speaker 1: and that was televised. I mean, that was on c
Speaker 1: SPAN because there was a lot of interest in seeing it.
Speaker 1: And here again, when we meet, and I suspect we're
Speaker 1: going to be in December, and I suspect we're going
Speaker 1: to be meeting more than once in December and January,
Speaker 1: that too will be televised and people can have public comment,
Speaker 1: because that's true of any federal advisory committee meeting. Those
Speaker 1: have to be open to the public, which is great
Speaker 1: because I think then the public will see the data
Speaker 1: in the same way we see the data, so it
Speaker 1: shouldn't be an issue of transparency. Paul, I just want
Speaker 1: to thank you for your important work with you luck
Speaker 1: in these meetings, and really I just deeply appreciate the
Speaker 1: clarification and the listeners do too, so thank you. Thank
Speaker 1: you very much. That was fun. I appreciate it. I
Speaker 1: learned many fascinating things in the course of my conversation
Speaker 1: with doctor Offitt. The first had to do with the
Speaker 1: basic science, which we've talked about before on this podcast.
Speaker 1: To me, they takeaway here is that mRNA vaccines like
Speaker 1: visors and madernas do not pose the traditional risk of
Speaker 1: actually infecting people with the virus because they're not introducing
Speaker 1: the virus at all into the human system. That seems
Speaker 1: like a very positive fact. Simultaneously, it is true that
Speaker 1: these vaccines may have the side effect on many people
Speaker 1: of giving them twenty four hours of fever and chills,
Speaker 1: and we need to be aware of that and recognize
Speaker 1: that will not be a symptom of COVID. To the contrary,
Speaker 1: it's a symptom that the vaccine is actually doing its work.
Speaker 1: Another crucial takeaway is that the difficulty of delivering at
Speaker 1: least the Fiser vaccine, which has to be stored at
Speaker 1: seventy degrees below zero centigrade, will be very significant. The
Speaker 1: practical difficulty of administering a vaccine that has to be
Speaker 1: kept so cold is going to require, according to doctor Offit,
Speaker 1: the development of new delivery systems and potentially even new
Speaker 1: facilities for doing this. Mr Anda vaccines can be produced
Speaker 1: extremely fast, but their distribution is going to be a
Speaker 1: more subtle matter. A further consequence of my conversation with
Speaker 1: Doctor offit is that I learned that there are half
Speaker 1: a million people in the United States. I didn't know
Speaker 1: that number who are not able to take a vaccine
Speaker 1: of any kind, and therefore are dependent on the rest
Speaker 1: of us to make sure that we take the vaccine,
Speaker 1: to reduce the prevalence of the virus, and to protect
Speaker 1: them via protection of the herd. Last, but by no
Speaker 1: means least, is Doctor Office assessment that if the data
Speaker 1: turn out to be what we've heard from the press release,
Speaker 1: the cost benefit analysis will indicate clearly that people should
Speaker 1: take the vaccine, and that that will be especially true
Speaker 1: of older people who would be very vulnerable to serious,
Speaker 1: serious illness and even death should they catch the stars
Speaker 1: Cove two virus. For me and from my family, that
Speaker 1: takeaway is hugely significant, and I intend to repeat it
Speaker 1: to anyone who will listen. We at Deep Background will
Speaker 1: be taking a Thanksgiving break, so we won't have an
Speaker 1: episode for you next week, but we will be back
Speaker 1: after Thanksgiving. Until the next time I speak to you,
Speaker 1: be careful, be safe, and be well. Deep back Ground
Speaker 1: is brought to you by Pushkin Industries. Our producer is
Speaker 1: Lydia Gencott. Our engineer is Martin Gonzalez, and our showrunner
Speaker 1: is Sophie Crane mckibbon. Theme music by Luis Gera at Pushkin.
Speaker 1: Thanks to Mia Lobell, Julia Barton, Heather Faine, Carlie mcgliori,
Speaker 1: Maggie Taylor, Eric Sandler, and Jacob Weisberg. You can find
Speaker 1: me on Twitter at Noah Arfeld. I also write a
Speaker 1: column for Bloomberg Opinion, which you can find at bloomberg
Speaker 1: dot com slash Feldman. To discover Bloomberg's original slate of podcasts,
Speaker 1: go to Bloomberg dot com slash podcasts, and if you
Speaker 1: liked what you heard today, please write a review or
Speaker 1: tell a friend. This is deep background