FDA vaccine advisory committee member Dr. Paul Offit returns to address our biggest questions on the new COVID vaccines.

We talk about the new mRNA vaccines from Pfizer and Moderna and their safety and efficacy, how they work, their effect on human DNA, the risk of antibody dependent enhancement, whether Phase 3 trials are enough data to feel comfortable with these vaccines, whether we should immunize those who’ve previously been infected, the volunteer bias in these trials, how the vaccine might be better at creating immunity than just getting infected with coronavirus, why antibody levels are misleading when it comes to immunity, why treating a fever is BAD, why we shouldn’t mandate these vaccines yet for healthcare workers, the use of human fetal tissue stem lines, why immunize at all, why wear masks and social distance after vaccination, what we should do about children, and much more.

Watch all our videos with Paul here.

Transcript below!

Dr. Z: Hey guys Dr. Z, the legendary, God of all vaccines, Paul Offit. Welcome back to the show. My intro has gotten shorter and shorter for you over time. Thanks for coming back, you’ve been all over the news. You’re a vaccine researcher. Your credentials, you’ve been on the show a bunch of times. Here’s the bottom line we’re all wondering, we’re looking to you Paul, and again when we start asking scientists to be all over, our shows it means that we’re probably in the apocalypse. And so as an apocalypse, does this have an end date? Are these vaccines looking exciting to you?


Dr. Offit: It’s pretty amazing, really. I mean, there was an article published in Science in January of 2020, which was the SARS-CoV-2, genetic sequence. That’s when we had the virus in hand and we had the sequence. So, we knew the sequence that then coded for the coronavirus spike protein. I think if you asked a 100 scientists in January, do you think that by the end of the year, we will have done two large prospective placebo-controlled trials of 30,000, 40,000 people using a technology we’ve never used before, which is to say messenger RNA. And have the kind of efficacy that you’re seeing at least the top line data. I mean, it’s all press releases. So, I’m on the FDA’s advisory committee, Vaccine Advisory Committee, so we’ll be looking at these data on December 10th and 17th. But, that 90% to 95% effective, virtually 100% protective against severe disease, virtually 100% effective in people over 65 years of age. No one would have believed that. I mean, it’s remarkable.


Dr. Z: Paul, it’s crazy, ’cause you’re on the FDA advisory committee, so you’re gonna look at this raw data, at which point I’m gonna come back to you and be like, okay, between you and me and about two million people that are watching, would you take this vaccine? But even before that, remember the conversations we had early on in the pandemic, where you and I were both like so tell me, what’s the feasibility of this thing happening within the next year, and the skepticism was through the roof.


Dr. Offit: Definitely though, I’ve been like pretty much consistently wrong, which has been amazing me why for have me back on your show. It’s like when Christian Amanpour right at the beginning of March, we were having our first deaths from COVID. I mean, I got on her show and CNN International and said, I just can’t imagine we’re gonna have like the same number of deaths we had last year from flu, which was 60,000 deaths. So I said, I can’t imagine, you could be wrong, be wrong in front of millions of viewers on international television. That’s the way to go. Don’t Just tell your friends something is wrong.


Dr. Z: I wanted it but this is why I love you, because we share something in common. We are often wrong, but yet are learning from the errors as new data comes out and coming out, and still saying, instead of doubling down on the errors, right? And I think that’s the difference between science, which is always trying to find truth and learning and everything else. And so let’s dig into this more now because, okay, both of us are pleasantly amazed, I wouldn’t even say surprised, amazed at the speed of this, and we have to give credit where it’s due. It seems like Operation Warp Speed’s was effective as a public private partnership to help take some of the risk out of developing the vaccines that would normally have taken multiple years. And I wanna ask you about that, but the followup to that is, what do you say to people who are like, well, this was too fast then because, if it normally takes 20 years and a billion dollars and we did it in a year, how can it possibly be safe? And I’d love to hear how you think about that.


Dr. Offit: Right, so the trick is to do a phase three trial. As long as you do a phase three trial, you’re then holding this vaccine to the same standard you want every other vaccine. So, if that’s true, if we’ve done a phase three trial and the Pfizer case, 44,000 or the majority case 30,000 the sum would be close to 60,000. I mean, that’s the size of any vaccine trial. So that’s true. Why are we doing this through emergency use authorization? Why are we doing this way we always do which is submit a biologics license application, have a licensed product and then go to the aid of the CDC for recommendation. And the reason is that the FDA, I think would never license a product that was tested for this shorter period of time. So then the question becomes, how risky is it? So there’s two ways to look at this first say which is what most people care about, the good thing that happened here, the thing that was most worried about actually was that Commissioner Hahn, would not stand up to the administration. That really scared me, because you saw what happened with hydraulic support. You saw what happened with convalescent plasma, where it looked like the FDA which was just seeding to the whim of the administration. And not standing up for the American public and making sure we got products that were safe and effective because neither of those products have been shown to be effective yet they were approved through the emergency use. So then you come to vaccine. So two vaccines are tested these big trials, safety wise, when commissioner onset we need to have two months of safety data after dose two. At least two months of safety data after dose two, then you knew that this vaccine was not gonna be approved before the, before election day. When he did that and he got an enormous pushback from the administration still showed up for that, that was great. Because, if you look at the serious side effects of vaccines the vaccines can have serious side effects. They all occur within six weeks of any dose. So safety wise, I feel pretty good that you can say at least you don’t have any relatively uncommon severe side effects. So then the issue becomes efficacy. You’re gonna be able to say that this vaccine was effective for a couple of months. That’s what you’re gonna be able to say. How big of a risk is that? If you say something 90 to 95% effective for a couple of months, does that mean it’s not gonna be effective at six months or a year or two years. But the truth is you’re not gonna do a two year study with this vaccine before you release it. I mean, more than 260,000 people died this year, you’re just, that’s a risk that you’re taking. I think it’s a small risk because I think if something is 90 to 95% effective in two months, it’s likely to be highly effective six months later, or a year later, we’ll see. The key, by the way, the questions I wanna ask when I’m at the FDA vaccine advisory committee on the 10th is, do they have have data on the frequency of memory being T cells? ‘Cause that’s what you really wanna see. If you have a high frequency of memory, then you can feel pretty good that you’re gonna have fairly long lasting immunity, meaning usually a year, two, three years. The antibody titer itself, per say, doesn’t bother me as much, it’s the frequency of memory beatings. And we’ll see whether the companies have those then.


Dr. Z:  Okay, a few things, this is great. So, phase three trial with 30,000 people, or more are depending on the trial and you have Pfizer you have Madrona. These are the leading mRNA vaccine candidates. What you’re saying is they compressed this sort of 10, 20 year period into a shorter period. But the business end of that period is always the phase three trial. That phase three trial is looking for safety and efficacy signal in a significant number of people with a true placebo control. And that appears to be what’s happening. You’re gonna look at the primary data as part of the committee. That appears to be what’s happening with these two leading candidates from Moderna and Pfizer. And that being said, the major safety signals that you’re concerned about will show up usually within six weeks. We’re gonna have at least two months probably longer of trial data to show serious adverse and unusual adverse reactions. And that is enough for you Paul, if you looked at that data, you know the efficacy data, you’ve seen it and you’ve had maybe two, three months of safety data. Would that be enough to convince you to get the vaccine or give it to your family?


Dr. Offit: Yes.


Dr. Z: Yeah,


Dr. Offit: It would, I’m, if the data are as good as they look, I mean just truth be told we have already received our package, from the FDA. So we’re looking through it now,


Dr. Z: Yeah


Dr. Offit: The public will see what we’re seeing on December eight. So the public will see two days before the FDA advisory committee, what we’re looking through now sort of a massive amount of data, but we’re looking through it. So, it’s always transparent, you can see what we see.


Dr. Z: So, this is important because it’s not like you’re just gonna get all this data on the 10th, you have the data and you’re looking through it, it takes time and all your resources are aimed at this thing. So you’re gonna have something for the public by that time. And that’s, I mean, again, it’s just amazing that it’s all come together in that cohesive way, now again we’ll see what the final data shows and I think that’ll be interesting to see. So you’re gonna look at safety signal. Now, to get into that, and I think this is important. We should talk a little bit about these mRNA vaccines. I did a show recently describing how mRNA vaccines would work, but I really wanna talk to you about this. So, because this is a new technology platform, although it’s been in development in some way worked on since at least 2005, right? Can you kind of walk us through how the mRNA process works?


Dr. Offit: Now that’s exactly right, it’s been, I mean, and me too, I mean you’ll always just see this described as a new technology but it’s been at least, 10 plus years in the work, People like Drew Weissman actually at the University of Pennsylvania is one of the sort of leading researchers. And this has been working on this for a couple of decades. The way it works is, so messenger RNA, is just a small piece of genetic material which we have in our bodies all the time. Our cells are making messenger RNA all the time because that messenger RNA is then translated to proteins, which then are excreted from the cell. So, that’s how we make proteins. So it’s a very common molecule that is in your body all the time. Here the piece of messenger RNA codes for the coronavirus spike protein. So that’s the protein that emanates from the surface of the cell. That’s the protein that’s responsible for binding the virus to the cell. So the thinking is if you can make antibodies to that protein then you can prevent the virus from binding themselves, which is basically the way we make hepatitis B vaccine, the Human Papillomavirus vaccine which would you make antibody responses to that surface proteins? So, here, the trick, the hard part here is getting it into the cytoplasm of the cell. I mean, messenger RNA is a very labor molecule. We all have in our body, something called Ribonuclease which if I just did not circulated your muscle with messenger mRNA, you would break down that messenger RNA in moments, it would never get inside a cell. So to get it inside the cell, they put it into this sort of this like complex lipid capsule, it’s like a little tiny capsule, a little nanoparticle into which then this messenger RNA on is it, sits. That’s story, when the cells will then when this lipid sort of layer that surrounds the messenger mRNA hits the surface of the cells will then take it up. And then the lipid layer sort of dissolves, the messenger RNA now goes into the so-called Ribosomal system where it’s translated to a protein. And then at that protein is either essential in the surface of the cell or its excreta from the cell. That’s how it works. And it’s not just the muscle cells that’ll do this, it’s also partly even more importantly the antigen presenting cells. Like so-called macrophages dendritic cells which will then present this this protein to the immune system so you can get not only antibodies but also get so-called T helper cell, cytotoxic T cells. So that’s all important, I think, in in preventing or treating or preventing this disease.


Dr. Z: Perfect and it so, what’s interesting about the mRNA approaches, part of the way they were able to make this platform work is they were able to stabilize the mRNA, through a synthetic nucleoside process. Where normal, viral mRNA appropriately, not only generates an inflammatory response itself ’cause it’s a foreign thing but it’s broken down by the enzymes that you mentioned, the ribonuclease et cetera. So there’s two things, they modify the nucleus sides and they create this lipid nanoparticle protection. Are these artificial, nucleosides something we should worry about? Because I can already hear the anti-vaccine voices in my head. You’ve synthetically created something and you’re injecting it into me.


Dr. Offit: Well, so again, it’s messenger RNA is itself an adjunct. Meaning stimulates the immune response, simulate your innate immune system as the thing from your adaptive immune system which is kind of being more part of your Immune system. It stimulates the innate part of your immune system specifically the so-called Toll-like receptors, three, seven, and eight. So they’ve modified it. So it really can’t do that. That’s good. So it don’t really have adjutant activity. So that’s good. In the nucleoside analogs that they’re using it the nucleosides will be normally at, it’s not like they got them from Krypton and brought them in and then put them in, so it’s natural. The question I get asked the most though is, will it alter our own genetics?


Dr. Z: Yes


Dr. Offit: I mean, that’s what we’re really worried about so, it, I can’t emphasize enough how hard it is to get something into the nucleus.


Dr. Z: Yeah


Dr. Offit: So, for example, if you look at DNA vaccines, which are, again like mRNA, instead of being sort of so-called naked strand of messenger RNA, it’s a naked strand of DNA. And order to get that DNA vaccine into the nucleus you use something called an electroporation device which is a gun, it’s made, it’s just like what it sounds electro, it’s an electric shock that causes the the nuclear cell membrane to become porus. It’s hard to get DNA into the nucleus. And the mRNA never gets into the nucleus. Although it’s always interesting to me that people say, when they’re worried that you’re gonna sort of alter their genetic material and then they’re gonna get like autism or diabetes and multiple causes. Nobody ever thinks maybe I’ll have X-ray vision. No one ever thinks that why can’t be a good thing.


Dr. Z:  You know what it is a conspiracy theorists are always glass, half empty kind of guys. Paul, I mean, for me, I would think immediately, or I can see to Mars instantly, or become invisible. So, okay, this is a very important point. I did a whole video kinda debunking what Christiane Northrup this obstetrician was saying about this incorporating into our DNA, the adjuvant, the metal adjuvants causing us to become 5G antennas. None of which are true. And so, this is, we’ve kinda gone through this territory and it’s fun and enjoyable until people believe it. And then you’re like, my gosh, help us. So back to the mRNA, the nucleosides they’re using are the same sort of modified nucleosides that we would naturally make. So what are they methylated or what’s the dirt on that?


Dr. Offit: Yeah, no, I think they’re just what you would normally find in nature. So, I mean, since that seems to be the word that appeals to everyone, it’s not it’s although there’s a synthetic molecule, I mean, it’s made in the lab, it’s not using materials that you wouldn’t normally find a nature.


Dr. Z:  Got it, so it’s not like we’re growing it in yeast and it’s biologically produced. We’re actually synthesizing these nucleosides because they’re relatively simple compounds.


Dr. Offit: Right and that’s actually the beauty of this. The hardest part of this process is not the synthesizing, the mRNA, that’s not hard at all. It’s, mass producing that little lipid capsule. I mean, that’s where Pfizer has got into trouble. I don’t know if you saw that they said that they were lower on the sort of just certain materials, certain raw materials, that’s what they’re talking about, the lipid…


Dr. Z:  Is see, it’s the lipid nanoparticle.


Dr. Offit: So I saw a friend of mine, who was actually the head of manufacturing work once said, “When this all first started,” he said, “This lipid particle has never been scaled up before.” And that, was really what people were initially worried about. But it’s, we’ll, it’s, when you think about it, so what’s the dose. The dose worked for Pfizer is 30 micrograms. A microgram is a million of a gram. But you can make kilogram. Those in the kilogram is a 1’000 grams. So there’s a billion micrograms in a kilogram. which is to say you really can scale this up to inoculate the world. You can, once they get rolling.


Dr. Z: So it’s a really good platform for that, because number one you don’t have to rely on culture or biological organisms to spin it up, you can synthesize it. It, all you need is the code of the virus and you can start working on it. It, the mRNA codes specifically only for that spike protein. So you’re not making spurious proteins. And assuming that once it’s transcribed and conforms, it actually looks like the real viral spike protein. So you don’t get a side effect like something you were talking about before antibody dependent enhancement. Can you tell us about that real quick in terms of a concern?


Dr. Offit: Yeah, so antibody dependent enhancement is that when you’re infected so sort of dengue viruses for example you’re infected with one single type of dengue. And then when you’re a challenged with say a second different single type, the antibodies that you generated from your first infection instead of neutralizing the virus, instead of making it so that it can’t enter cells actually binds to the virus, doesn’t neutralize it and actually helps it get into the cell and sort of this Trojan horse manner. It actually facilitates viral entry into cell. There’s nothing about this virus that makes me think that’s gonna happen. Although it happened with SARS-CoV-1 in experimental animal models. There’s no evidence that happens experimental animal models here. If you look at animals, in fact, the SARS-CoV-1 and then reinfected, with SARS-CoV-1, you do not have this AB antibody dependent enhancement phenomenon, the convalescent plasma didn’t do that. None of the vaccine extra animal vaccine trials have shown that. I don’t think that’s gonna be a problem with this, as more information comes out, I don’t think it will be probably, I think in an earlier show, I had said, we’re worried about something certainly people are gonna look for. But as the more information comes out, I don’t think it’s gonna be an issue.


Dr. Z: That’s very important because you would have seen a signal of antibody dependent enhancement in this huge phase three trial, ’cause you would have seen people getting sicker potentially in the vaccine group than not in theory, but there’s other, like you said there’s the animal studies, there’s convalescent plasma which has all this mix of antibodies. And still, you don’t see anybody dependent enhancement of this Trojan horse sucking this virus in, by binding to non-business and parts of the virus. Now, I have a question about this since this is a messenger RNA molecule and a synthetic lipoprotein or I’m sorry, a lipid nanoparticle. Is there a chance that immune system is going to mount a response to those particles in a way that generates an auto-immune crossover?


Dr. Offit: Well, not the lipid. I mean, it may, I mean you’ll make an immune response to the SARS-CoV-2 spike protein, in SARS-CoV-2 spike protein, some cell be expressed on the surface of the cell. So it is possible that those myocytes, the muscle cells that have that on the surface will then be destroyed by say cytotoxic T cells, that’s possible. And when you see, say one of the things I actually, remember that in these trials I think for both Pfizer and Moderna, those researches have not excluded people who’ve been naturally infected. So in other words, if you’ve been infected and you have antibodies at the start of the trial you still are part of this trial. So we will have those data too.


Dr. Z: Perfect because—


Dr. Offit: We have people were not infected who were then vaccinated.


Dr. Z: And we’ll know who those people are, theoretically based on their testing results. So that’s excellent, ’cause that’s another question was if you’ve already been infected, should you get this vaccine? And the data will bear out whether it’s safe and effective to do that. And we’ll talk about why you might wanna do that anyways or might not, but so, so back to that so, yes of course the muscle cells that took up this mRNA that are now expressing the spike protein on their surface or inside or nearby could be the target of an immune response. And that may explain some local redness and that kind of thing that people get. But a question that I had is, there are these exuberant reports. And again, I haven’t seen the primary data, it’s all press release stuff of, you know muscle aches, headache, fever, that seemed pretty strong sort of effects. Is that an example of the adjuvant effects of the virus the lipid nanoparticle, or is it just a natural response to spike protein antibodies being made and the immune response to that? Or are we missing something?


Dr. Offit: I think it’s probably both, but I do think that the immune system needed, needs a better public relations team working for it because all this means is it’s like I hate the term sort of adverse event. It’s not an adverse event. I mean, when your immune system, is stimulated because of natural infection, because of vaccination you make a series of proteins so-called cytokines that are associated with these symptoms, low grade fever and then the symptoms associated with low grade fever headache, chills, muscle aches, et cetera, joint pain. That’s okay. I mean that means your immune system is working. I have a friend actually from who’s in North Carolina, who volunteered for the Pfizer trial. And so right, he doesn’t know whether there’s gonna get vaccine or placebo. So after he gets the, the second dose, he wakes up the next morning, he’s got headache, he’s really pretty fatigued, and significant fatigue. And he turns over to his wife and he goes, “I got the vaccine, yes,” says that’s the right attitude.


Dr. Z: It’s a super power. Well so, and that relates to another question about this, if so and two questions but the first is important. I want to make sure we talk about this. The Februal, the fever response, not just to vaccine, but to infection. Isn’t that a favorable response in general to create a scenario where immune system works better, the molecular of the body works better at those higher temperatures. I mean, that may be the evolutionary reason for a fever. Is there danger to actually treating that fever with Tylenol, ibuprofen, et cetera? When you’re trying to maximize immune function and response.


Dr. Offit: Absolutely, it sort of breaks my heart a little bit. When you read these, the details of these trials that they offer, you know fever reducing medicines like Tylenol or acetaminophen or ibuprofen for people who have, so there’s clear data in children’s, two huge studies, showing that when you get a vaccine, and you start to develop fever, you anticipate there’s going to be a fever and treat with anti fever medicines. Then you lessen the immune response, because as you’ve said, I mean, why do we all make fever? Why are we all willing to spend this metabolic cost for having fever? And the answer is because our immune system works better at a higher temperature, white cells kill bacteria more efficiently, B cells and T cells or B cells make antibodies more efficiently, T helper cells, help B cells make antibodies more efficiently. We should, fever is our friend. You know what I’m saying? And if you look actually at the detail of the response, I think this has been published. And I say this I think it has been published, but the people who are over 65 actually have left less reactive to these vaccines than do people less than 65, because their immune system is more sense.


Dr. Z: That’s absolutely fascinating. I need to tell this right to camera. Fever if you can tolerate it is a good thing for your immune system and your response, especially and it’s interesting as you said it breaks your heart that to see that they’re prophylactically treating for fever or whatever. But what’s interesting is at least they did that, which is what the public’s gonna do. And so we still get data based on what real-world application would be. And it’s still quite efficacious. It’s really interesting because again we’ve been taught, cool people down, treat their fever, et cetera. But this is part of the response relating to that. So, men seem to get so much sicker from everything. I mean, I am a victim of man flu, every time I get sick, I don’t get sick very often but when I do, I’m unconscious whereas my wife just brushes it off, my two daughters brush it off. Is there a component of how men’s cytokine response is different, that they feel all these sort of flu likely symptoms and muscle aches and fevers more?


Dr. Offit: Yeah, it’s true almost across the board for infectious diseases that men do worse than women that’s it with the weaker sex. I mean as I think it was Murphy Brown, who right called it that silly little Y chromosome, I think she got it right. So I’m not sure why, although it’s interesting in this, there was a couple of papers in science for SARS-CoV-2 showing that when you’re infected with this virus men were showed the women will make antibodies against their own interferon. So interferon is a protein made by our immune system to interfere with viruses ability to infect cells, which is why at least these two papers were postulating that men might do worse. Or this is one weird virus, by the way. I mean that it has the capacity to make you induce antibodies against interferon is remarkable to me,


Dr. Z: This is amazing because It means that if the wild type virus can induce antibodies at least in men to interferon that could actually make you sicker because you don’t have the same immune response that would imply then that the vaccine, which is more focused on the spike protein, is more effective immunity than actually wild-type exposure to the virus in theory.


Dr. Offit: That’s right, people have possibly have that. I mean, it may very well be true that vaccination is better than natural infection, which is why, by the way you’re getting to your earlier question for people who’ve already been infected and go, I don’t need the vaccine. I think first of all, programmatically, I can tell you in our hospital, we are not gonna be screening people to see whether they were infected or not.


Dr. Z:  Right


Dr. Offit: We’re just, everybody who’s frontline respond to the vaccine. And so programmatically, it doesn’t work. But secondly, I think you could make an argument just biologically that you may be better off getting a vaccine than having been natural, on yourself.


Dr. Z: So again, and it gets to that question of, okay, so there’s not really, we’re gonna see if there’s any downside to getting vaccine after you’ve been infected based on the data. Because again, there will be people there in that trial that had that and there is a theoretical advantage to being vaccinated, which then goes into that next sort of logical question which is, duration or reinfection ability with this virus. Now, I think before we talked about this idea that like something like RSV, Respiratory Syncytial Virus that really sickens a lot of people around the world and they had a lot of trouble making a vaccine partially because of antibody dependent enhancement. I think that was a vaccine. And you can correct me when I’m done ranting. And the second problem is that RSV incubation period is very short, which means this we’ll get into how does memory immunity work, when you get reinfected? ‘Cause people get so confused. Can you walk me through this and help me understand, say the difference between a short incubation like RSV and something medium, like SARS-CoV-2, where it’s more like six days, min incubation time.


Dr. Offit: Great, so take measles, measles has an incubation period at more like 10 to 14 days. That’s because viremia, meaning spread of viruses into the bloodstream, and then to distant sites after it initially enters your nose and throat it takes longer actually to develop measles. So, that’s good for your immune system ’cause it gives, now you’ve been immunized against measles. You know that when you’re exposed to measles, it’s gonna take a fairly long time for that virus to do what it needs to do, to then cause disease. So that’s plenty of time for activation and differentiation of memory cells to become, say antibody producing cells, which protects you. That’s why that kind of virus you can actually get sterilizing immunity to that, because it’s a long incubation period. And when there were outbreaks between ’89 and ’91, in the United States, where there was, like 50,000 hospitalizations and a number of deaths, there were a lot of number of children who didn’t have antibody circulating antibodies at the time, but were completely protected because they had immunological memory. That’s all you need is immunological memory. If you take the short incubation period diseases, where it’s like one or two days, three days, I mean something like rotavirus, the virus that we worked on or flu can have an incubation period as short as 18 hours. There, it’s not a lot of time for the activation and differentiation of memory B and T cells to protect. It usually takes about three to five days so that happens. So there, and those kinds of diseases, what you see as you see incomplete protection, meaning you get usually protected against moderate to severe disease, but not so much mild disease. This virus is in between those, this virus, just, as you said it’s about an incubation period of six days. That’s a lot of time actually. And I think that as long as you have immunological memory, I think you’re fine. I hope the companies did those studies, because there there was just, I don’t know if you were listening to a Twitter this week in virology, they had a virologist named, an immunologist named Shane Kelly there recently who studies coronaviruses and that was his point. And I think he’s absolutely right.


Dr. Z: That’s absolutely fascinating because, so many people are stressed out well, is the imminent, is the immunity going to last. And the truth is, again this may be another compelling reason for vaccination even if people who’ve had COVID before, because then you get a more specific, is almost a booster, and if you’re gonna get reinfected, if it’s somewhere in between, maybe at least you don’t get severe disease. And maybe that’s a way masks work a little bit too, just by reducing inoculum, so you have less out the bad that you have to react to, less of an inoculum off the bad. And it really makes you think that this sort of, it’s almost a hysteria that, well this thing’s not gonna last, you’re gonna get reinfected, there is no hope, what’s the point, let it rip through the population is just not correct. I mean, is that how you feel about it?


Dr. Offit: Yes, I think the notion of, first of all, there’s never been a no virus has ever eliminated itself from immunity induced by natural infection. None, zero never happened. So when Scott Atlas gets up in front of the American public and says, “Let’s just let it burn.” I don’t know what he’s talking about. The only time we’ve ever eliminated viruses with a vaccine. I mean, we eliminated smallpox by vaccine. We eliminate two or three serotype of polio with a vaccine. And only vaccines can do that. One of the people get hung up on, the antibody titers, just to getting back to the, we were just saying, look antibodies seem to fade antibodies, antibodies for high and low. I know you think we’re focusing on the wrong thing. I think the question is what is the frequency of these memory cells? That’s gonna be the key. One other point by the way, is in terms of reading through some of these data, I think what the companies are gonna need to answer for me anyways is one question is, if you look at the placebo recipients, depending on whether it’s the Pfizer or Moderna trial, it looks like about the infection rate or not the infection rate, the disease rate in the placebo group was depending on which study was like either 0.7% or 0.85%, that’s surprisingly low.


Dr. Z: Yeah.


Dr. Offit: You would have expected it to be more like, three and a half percent just given where these studies were being done. So why was it low? And I think that the when you worry a little bit of so-called volunteer bias. Meaning that they who volunteers for these kinds of trials, certainly a lot of healthcare people volunteer for this trial. So this may be people who are more attentive to their health, more likely to wear a mask, more likely to social distance, and therefore more likely to be exposed to a smaller inoculum. That what we’re looking at in these trials is protection against a smaller inoculum. And then when it gets out there into the real world, when you’re being asked to protect against larger inoculant and there’s clearly a relationship between the amount of virus that you’re exposed to and the severity of your disease that it may act differently. So I think that that’s one question that’s gonna need to be answered in these meetings


Dr. Z: Man, that’s so important. I wanna say that again in a slightly different way. So, what you’re saying is, because these trials were kind of the optimal population of people who care about their health and maybe the healthcare workers. There, it’s gonna show maybe a higher efficacy and a lower infection rate in general which is what we did see a lower infection rate than what you might predict. And so that is yet more compelling reason to answer a question that I would have been thinking about myself, which is, why would you wear a mask and social distance after you’ve been vaccinated? And the answer is quite clear that no vaccine is perfect and even if the trial says 95% efficacy, that’s a trial the real world is gonna be different. And I think that’s very important. And, again, correct me if there’s anything I just said, that’s wrong there. Was there anything that you disagree with?


Dr. Offit: No, you’re absolutely one of the things that is that we don’t know what this vaccine protects against better. We know that meaning which is to say asymptomatic that reuse can still shed virus and be contagious. We know that it protects against disease. We know that, we don’t know whether it protects against infection.


Dr. Z: That’s what I wanted to ask. So we could still have infection. I think this happens with influenza vaccine as well. You can be infected, potentially asymptomatic. Don’t know about shedding, but even though you don’t get sick and it may be the vaccine helps you not get sick, but you can still infect others. So this idea of, at least in the short run, continuing to be precaution, it’s not panic, it’s not hysteria. It’s just pragmatic science from your standpoint, yeah?


Dr. Offit: Yeah, so you could argue if you wanna be completely selfish again, you should be like look, I got the vaccine. I have a 90 to 95% chance of being protected against disease associated with infection but I still may get infection and still shed the virus but who cares as long as I’m protected against disease, I’m good. This just means that other people who come in contact with me, will get infected and the hell with them, let them get vaccinated. But first of all, not everybody can be vaccinated that no vaccine is 100% effective. You do live in this society where you actually should care about your neighbors. So they, really should still wear masking and distance. But I think it’s gonna be hard. It’s hard enough to get people to do that now without a vaccine.


Dr. Z:  Exactly, and now so I wanna get back to speaking of like libertarian ideology, let’s get back to the herd immunity thing and like the atlases and so on. One question I had relating to that, you may not eliminate virus with natural herd immunity but natural infection, because now we’re talking about maybe what a quarter of Americans we don’t know the exact number may have already been exposed and infected at some point, whether asymptomatic or not. Will that help lower the overall threshold of vaccination requirement to reach a stable herd immunity in the community?


Dr. Offit: Yes, it’s a high price to pay for that, but there are definitely people who are much less likely to get diseases associated with exposure. I think you’re right. I think, although I think the numbers are like 12 or 13 million. That is all quite at least a factor of five and maybe a factor as high as eight, so that is true.


Dr. Z:  If is there’s a price, now, so that gets to my follow up question to that which is let’s say we have an infection fatality rate across the board for this thing in the US and I’m making this number up a little bit based on, hearing different things. Let’s say 0.3 to 0.5. So, and again, I don’t know what the exact IFR is, I don’t think anyone really knows, but Infection Fatality Rate, meaning of all the people out there infected and we haven’t necessarily tested them but they’ve been infected. What’s the fatality rate? A 0.3 people will push back and say why should I take a vaccine that may have a one in a million side-effect, when I’m reasonably healthy, the IFR is quite low. Why should I do that? How do you, how do you think about that?


Dr. Offit: Well, it’s virus, doesn’t just kill you. I mean, you, flu is more like that, flu you live or you die but, this virus causes vasculitis. It causes inflammation of your blood vessels because every organ in your body has a blood supply, therefore every organ can be affected. I mean, I there’s, I have to give a talk tomorrow actually, with a guy who’s with the army and this is army sort of fitness thing that, but he’s taken care of a number of young healthy adult males who have heart disease associated with having been infected with SARS-CoV-2. So the virus can cause strokes, heart attacks, kidney disease, liver disease is long-termers. So, the so-called long haulers, sorry, or they in part may be associated with what is a bachelorette phenomenon. We had a kid who came with a child who came into our hospital, who had pneumonia a teenager. You looked at that chest X-ray it looked like lupus. I mean, it looked like a vasculitis. It didn’t look like a typical inner so-called interstitial pneumonia that we normally see. This is a scary virus. I mean, you don’t have to die as your only outcome. This can cause a longer term problem. I mean, think about it when it causes changes in taste and smell is because the virus enters the brain. That’s why it does that.


Dr. Z:  You know what’s crazy Paul is, when we had our first conversation way back in the spring, we were like, you know this thing feels a little more fluish. Like we’re panicking, we’re shutting down schools, we’re turning everything inside, out, ripping the fabric of society apart for basically, an IFR that’s not gonna be that high and so on. And as we’ve learned more, it’s clear that and something you’ve said is very important here. This is a, this may be an auto-immune phenomenon of being exposed to wild type virus. In other words, that virus is more complex than just the spike protein something’s happening because there’s only 1% of people I think are actually viremia actually have blood viral replication of the virus in the blood. So, how is a virus that lives in the oral pharynx, the epithelium and the lung upper respiratory and lower respiratory system. How is that causing systemic vasculitis? And the answer is it’s got to be an immune reaction possibly, is that how you think about it?


Dr. Offit: No, people there was a false notion actually early on that the virus could infect endothelial cells to cells that line blood,


Dr. Z: Right


Dr. Offit: That’s not true. I mean, it’s not by remit less than 1% of the time, so you’re right. It induces your immune response to affect endothelial cell. That’s one of its many horrors. And this has only been out there for a year. We’re still learning about the unusual clinical and pathological changes associated with this virus. This is a scary virus. I mean, that’s why I’m most scared of it. Not that I think I’m likely to die, it’s that I think I’m likely to have this vasculitis which can cause a variety of difficult symptoms.


Dr. Z: I have to say, because I’ve been very sympathetic to the arguments that our response to the virus is potentially more harmful than the virus itself. I think I might be willing to change that or modify that approach, seeing data on actual numbers and impact of this post viral syndrome that we’re seeing. And it is true as young people are having strokes and but then the question is what are the numbers? And is it significantly different than say Coxsackievirus or something that we know can cause cardiomyopathy is this something novel in a sense that it’s doing these things to a degree that we don’t see typical viruses doing? What’s your intuition on that?


Dr. Offit: Yeah, I mean, I don’t understand this virus. I’ll be perfectly honest with you. It’s this bad coronavirus that clearly does things in us that we haven’t seen before. I think we haven’t really worked out the mechanisms by which that happens. What is the mechanism for, this multi-system inflammatory disease of children. I don’t know. I, and then people are worried about the vaccine because they think won’t that trigger this. And my honest answer is don’t know, because you don’t really know what the basis of that is. I mean, when we talk about it being like Kawasaki’s disease or toxic shock syndrome with the kind of profile that you see, it’s the cytokines and even those are not really the same as those. It’s just a different virus.


Dr. Z: This is interesting because now it gets to the question of we don’t know that the vaccine is gonna cause these effects, we will get good safety data for at least two to three months from these trials. So we’ll have a sense, but of course you can never know. But that gets to the question of mandating the vaccine, say for healthcare workers. Now these are people that are, we have patient contact et cetera. We often will mandate a flu vaccination, at least for a purposes of employment. That dog is so cute, Oh! my God.


Dr. Offit: She’s had a for a year and a half, so don’t worry about it. she’s good. Right rose, you’re good? Actually, we’ve been working on this, I just got this. Is it Timmy Rose is Timmy fallen in the well, okay, am done ask your parents about.


Dr. Z: I forget what I asked Paul, what did I ask you? The dog’s so cute, look at it. It was a question about, Oh, mandating vaccines. So do you think we need, are we gonna, is it ethical to mandate? I mean, what do you think about this?


Dr. Offit: Well, practically there’s not enough vaccine out initially. So you can’t mandate something that is incredibly short supply. Two is, I honestly don’t think you can mandate this until you feel very comfortable that you don’t have a rare side effect. I mean, this is a novel technology. It’s, combating a virus that is continuing to surprise us. I think we have to be humble here. And we always are maybe things we’re gonna learn over the next year that we don’t know now that we wish we knew now. I don’t think you can mandate. We’re not mandated in our hospital for those two reasons.


Dr. Z: Right, and that makes perfect sense. And I am a bit of a libertarian at heart and I don’t think Mandate, I think there’s enough people that are gonna wanna take it. And there are people who with this information that we’re talking about we’ll do a risk benefit analysis on themselves. Look, Paul I’m 47 but I have a factor five Leiden and prothrombin 202, 108, heterozygous mutations that I found that on a 23 and me, genetic survey. So I have a reasonable genetic risk of clotting. We know this virus can cause clots. I’m also a healthcare professional. So I would elect with a one in a million risk of serious adverse events, say, let’s just make that up. I would elect to take the vaccine because my chances of an adverse event from natural wild type infection are in my mind a little bit more scary and higher and I’m gonna do that risk analysis. But there are gonna be some people who just don’t wanna get it, and whether they end up getting wild type and generating immunity that way, I think eventually we’ll get to the goal without having to force people to take a vaccine or any of that, do you agree?


Dr. Offit: Agreed and people that come and get it and I’m just thinking it’s off is, do you think because so many people are scared of this and actually we’ll never be able to inoculate enough people to induce herd immunity that stops spread. I don’t think that’s gonna be the issue at all. I mean, I think if this vaccine holds up in terms of the percentage efficacy that we’re seeing, I mean if it holds up in terms of safety regarding, remember the first group that’s gonna get this, is roughly 24 million people that comprise, healthcare workers and residents and staff of long-term care facilities. We’re gonna have 20 million doses, 20 million people inoculated, before we ever get even close to the general population ’cause then you have to go to the central workers, then you have to go to greatest 65 and healthcare people who have various health problems. If you’re gonna have tens of millions doses out there before you ever get to the general population. So I think that should be very reassuring to people. To me, it’s the Beanie Baby phenomenon. And it’s the value of the limited edition vaccine. I mean, that happened in 2004 with the flu vaccine, there were companies that had trouble making it. So there was a limited amount of flu vaccine that was a highly sought after vaccine. I think at some level that’s gonna be this.


Dr. Z: I remember that, yeah, I think you’re right. I think you’re absolutely right. And that gets to a couple of questions. Why to, let’s say Pfizer, Moderna, two shots, weeks apart, why? Why do we need to do that?


Dr. Offit: That’s what it is the best thing for this response. I mean, the Johnson’s a single dose vaccine because that was good enough. I think Astrazeneca thought they can get away with a dose but then they realized they needed a second dose. And so now they have some problems with regard to whether it’s half dose or full dose. That, we’re not gonna be taxing for, I think for a while in this country, I could be wrong.


Dr. Z: We will do another show about that vaccine because I was just looking at that going, wait, what? ‘Cause we’re just not there yet, but during our Pfizer. And so the two doses best immune response. So what happens if you get one and you flake on the second?


Dr. Offit: Well, we’ll also it’s the question is was there any of you that didn’t just have just one dose? There is an answer to that. That answer is actually in the the materials that I’ve seen. We will soon know that. The country will soon know that.


Dr. Z: I love it.


Dr. Offit: If it goes through pharmaceutical companies, I’m sorry, if it goes through a pharmacy retail pharmacies, they’re very good at letting you know that they want you back. If my iPhone is any example of that, your prescription is ready.


Dr. Z:  That’s true, and we, I don’t think we’ll get into like the storage of these new vaccines and how they have to be at -70 for the Pfizer and minus what is it? Four or something for the Moderna.


Dr. Z: Oh, I see, okay.


Dr. Z:  Yeah, so distribution is gonna be tricky. Where do you think, and we talked about, I know there was actually an interesting contrary and opinion I heard from somebody on the CDC committee who was saying we shouldn’t be giving it to people in nursing homes and older people, because what we’re gonna see is a temporal correlation. Those people are more likely to die or get something serious anyways. And the public is gonna conflate, just like in flu vaccine, I took the flu vaccine and then I got flu. Well, no, you didn’t and this is what’s going on. He was worried, the same thing would happen with elders. I mean, how do you think about that, in terms of distribution?


Dr. Offit: I think… I think the person who said that, it was a heartfelt, serious concern that she had. I just think that the, that her concern was that there hadn’t been really, she worried about the safety in this older age. First of all of the most impact you have in a nursing home is actually to vaccinate the staff. I mean, even more so than the nursing home residents themselves, but 40% of the deaths occur in nursing homes. So you got to immunize people in nursing homes. We do, we will have a lot of data on the greater than 65 year old and the greater than 70 year old. So, I mean, there are those data. And I just think that, you never know everything before you launch a product, the question is, when do you know enough to say that the benefits outweigh, what are the present theoretical risks? And I think we were there, if you will we’ll see how this this meeting goes on the 10th and the 17th, but it Certainly looks good. We actually had a practice session today for that meeting. I mean, we’re so nervous about that meeting because it’s open to the public and we wanna know, how can we communicate with each other? How can we communicate with the chairman of the meeting? And how’s this all gonna work? ‘Cause I think it will be picked up it’ll be shown on news, the news and stuff. They just wanna make sure that we don’t screw up.


Dr. Z: I’m so glad you’re in that meeting, Paul. This is like, what you’ve been called to do for your whole career is like, here we go. Now you get to give this gift of wisdom and experience and humility to the public. I have no doubt you’ll crush it and do the right thing and interpret that data and one thing I wanted to just cause a lot of people are concerned about these things, human cell lines, from legally aborted fetuses in the 60’s or whatever. They’re not used in the mRNA a vaccine production.


Dr. Offit: Not in the mRNA, but the Astrazeneca vaccine uses this so-called, HEK 293 cell, at one point which is human embryonic, kidney cells and Johnson they’re a replication defective add 26. They use the so-called Percy six cells, which was I think retinal cells. All these are elective works that were performed. One I think it was in 75, the other one was in 82. So this is it’s an old cell line, but


Dr. Z: Right


Dr. Offit: They’re used in research and so on.


Dr. Z: That’s right, they’re more or less cell lines and the Pope himself weighed in on this I believe and said, the goods of vaccinations out does the moral injury of the original abortion in Catholic dogma. So, and I did a separate video on this, but yeah so that take that off the table. And the other thing is people are saying the vaccine makers have no liability. So, they don’t care about safety. What do you have to say to that?


Dr. Offit: Well, I actually don’t know you shouldn’t actually be a lawyer like to recent to your program. She’s amazing. And she really understands the law about this much better than I do. It’s not to the advantage to a pharmaceutical company to make a product that is dangerous. I mean, it doesn’t help them. These are multinational companies as a general rule. If they put a product out there that is unsafe, they will suffer that. So I but I don’t know, I mean, I’m not sure whether there is federal, whether this is gonna be like the vaccine injury compensation program where there’s sort of a federal umbrella here. Which was basically the way it worked with the swine flu program in 1976. That was that then, I don’t know how this was working now, I don’t.


Dr. Z: Right, so it’ll be different, but yeah, I imagine it’ll be made safer for the vaccine companies just because of the tremendous liable liability risk if there is some, undetected, serious side effect that’s gonna happen adverse event later. Children,


Dr. Offit: Oh, one thing I think if you look at the roster of people that are on the FDA vaccine advisory committee, it’s really an amazing group of people. So Arnaud Monto and Haley Gans, and others are just these brilliant caring, researchers. And, so it’s just you should be glad all those people on this committee there, that’s an amazing group who really wants to get it right. It’s a no blink to see that people like, or in this country.


Dr. Z: I that’s important to say the other thing I was, and you guys wait, you’re all vaccines. You’re all pharma shills, as far as I’m concerned, Okay, Paul, I mean, every last one of you. But the other thing is this is one of those few pharmaceutical products that every single person technically might be getting, right? So everybody’s, skin’s a little bit in the game. Like, it’s not some evil pharma Lord in his office going well even if we kill everybody, it will be rich. It’s like, well, no Smithers you are gonna be getting this vaccine probably too.


Dr. Offit: And petting the cat…


Dr. Z: And petting the cat like excellent, well we’ll fire the vaccine. Related to that, children, so, and I know you gotta run in a second and teach a thing. Children, I know Pfizer expanded its study to include all the way down now to 12 years old. But how do we think about kids. ‘Cause kids can still, I mean I think it killed about as many people as influenza killed so far in terms of children.


Dr. Offit: I think we need a vaccine for children just for that reason. If we have a flu vaccine, it’s the same roughly the same number of children, 120, 130, 140 as COV-SARS is gonna be two and flu. And it causes, these this multi-system inflammatory disease in children. It affects children. If you can prevent, you can prevent that disease safely and effectively then to do it. The Moderna also just announced that they were gonna do this 3,000 person placebo control trial in children. Also going down to 12 years of age and we’ll do what we normally do. Sort of work our way down in age to see this.


Dr. Z: Okay


Dr. Offit: So I think that’ll help, but yeah, so yes, I think on it.


Dr. Z:  Got it, yeah. And then the last thing, so you, when are you gonna know whether you and me are gonna team up and get this vaccine live on TV?


Dr. Offit: I’m happy to the way this will play out is December 10, the FDA will make a determination within a day or two, the ACRP will. And then by December 15, Pfizer’s vaccine is probably gonna be shipped and use. And then a week later, December 17th is when the dermis, will be looked at by the FDA, within a day or two ACI people who’ve got and then December 22nd. So I think December 15th and December 22nd are the dates those two go out. I think we’re gonna be vaccinating people in our hospital by the end of December. So I am, I’d have direct patient care, if I’m not in that first-line group, sort of ed people, who work in ed. But, I’m should be right there and that should what? Beginning of the second line group. So yeah, I’m happy to get I’m happy to have somebody get a little iPhone and take me getting that vaccine.


Dr. Z: I love it, I’ll have to fly out and give you COVID and do it together. Man, Paul, I know you gotta run. This has been so helpful. Our audience is gonna get so much out of this. This is a gift that you give so freely of yourself, educating and entertaining in the process with that dog. I mean, it’s really not you, Paul it’s the dog that was just stole the show. Thank you and man we’re all rooting for you on this panel and everybody all the great people on the panel to do, look at that data science the crap out of it and let us know what you think, because I’m gonna wait to see what you think. Look at the data and then make a recommendation to my own audience. So thank you, thank you, thank you, thank you, thank you. And I’ll see you. Hopefully you’ll be back?


Dr. Offit: Love to, thanks ZDogg, look forward to.


Dr. Z: Thanks brother.


Dr. Offit: Take care.


Dr. Z: All right, guys please share the show and that’s it. Just share the show. We are out, peace.

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