What happens if we rush Phase 3 trials for a coronavirus vaccine? A world expert on vaccine development returns to weigh in.

Dr. Paul Offit is Professor of Pediatrics at Children’s Hospital of Philadelphia, co-inventor of the rotavirus vaccine, and director of the Vaccine Education Center at Children’s Hospital of Philadelphia.

We discuss the timeline and status of current vaccine trials, what the government has done to accelerate the clinical trials, the dangers of rushing Phase 3 trails, different types of immunity, the role of interferon and monoclonal antibodies, the nature of herd immunity, the duration of coronavirus immunity, can people be reinfected, the politicization of science currently, mask efficacy, should we return to school, what we both got wrong early in the pandemic, and much more.

Watch our prior episodes with Dr. Offit here.

Transcript:

  • Hey everyone, it’s Dr. Z, welcome to the show. Today I have again, one of my favorite guests of all time and favorite humans of all time, Dr. Paul Offit. He’s the Director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. Is that right, Paul? Welcome back to the show.
  • Paul: That’s it, thanks for having me back.
  • I think everybody knows you’re a luminary of vaccine science, the person that I trust on vaccines and immunology and all the related stuff. So, you’ve been on the show three times now, and every time, my audience has come away woke and enlightened, so let’s just cut right to the chase. Everybody’s thinking about this right now. What’s going on with the vaccines? What are your concerns? Where are we heading, and just, just fill us in, brother, ’cause we’re lost.
  • Paul: Okay, so, so I think people are worried by a lot of the language that surrounds this, words like, you know, race to make a vaccine, who are the five finalists, warp speed. I mean, those, those are not reassuring terms. It gives you the sense that corners are being cut, and so here’s what I would say. The fastest vaccine ever made, meaning having the strain of virus in hand, to actually having the commercial product, was the mumps vaccine. Strain in hand, 1963, commercial product, 1967, four years. This vaccine will be made in a year and a half. It will. I mean, we had the strain in hand, SARS-CoV-2, in January. I really do think we will have a commercial product that is available to the United States by the middle of next year. I do. So that’s a year and a half.
  • That’s exciting.
  • Paul: So, people are worried. Yeah, it’s good. I, so here’s, here’s what I think you should and shouldn’t be worried about. Typically, when you make a vaccine, you start with preclinical trials. So you, you have an animal model, whether it’s a mouse or a monkey or a ferret or a Syrian hamster, whatever it is, you inoculate it with the virus you’re interested in, and then the animal gets sick in a manner similar to the way humans get sick. Okay, good, now you have an animal model. Then you try the vaccine that you think could work, whatever it is, whether it’s a whole killed virus or a live attenuated virus, or a, just a part of the virus, and then you inoculate the animal with your, the virus and you see whether they’re protected. And most importantly, you can sort of literally, dissect out the immune response to see what’s associated with protection. What part of the immune response and where does it need to be to be protected? And so now you have a concept that you think works, and you think, and you have the part of the immune response that you think is critical. These are just animal models, so you don’t know. I mean, it’s, you know, as I always, as the old line goes in the world of animal model research, mice lie and monkeys exaggerate, that’s true. So, now you go to phase one, which has been done by all these companies. They all do phase one. Phase one typically is 20 to 100 participants that get so-called the dose ranging trial. So now you’re not sure what those to use in humans, so, you know, you try a variety of doses, three doses, five doses. Then you pick the dose that when given to a two, usually less than a hundred people, induced an immune response that you think is protective safely. Then you go to phase two, which is pretty much skipped in, in this particular scenario. Phase two involves hundreds of people who are given that dose so that you can say, “Well, at least it doesn’t have a common severe side effect problem, and it’s consistently immunogenic. They’ve pretty much skipped to phase three. The reason they can do that is that the, the government has taken the risk out of it. I mean, companies, when companies move forward with a vaccine or something, they think is a vaccine, they move slowly because they don’t wanna make the big bet yet. They wanna keep reassuring themselves that things look safe and things look effective before they ever get to mass producing it. So the phase two is, there’s, in making a vaccine and was associated with the team at Children’s Hospital, Florida, they made one vaccine, but when making a vaccine, there’s a lot of go-no-go decisions, 40, I would say, per vaccine. Okay, now we can still go. Can still goes, can still go, you know, looks like a prob, we’re gonna, we’re gonna bail. So, so because the government’s taken the risk out of it, but we’re paying for it. We’re gonna pay for phase one. We’re gonna pay a phase two. We’re gonna pay for, for phase three. So, so they just skipped to phase three. So now they don’t know whether or not this vaccine yet, has a relatively common, severe side effect, and they don’t know in any sense, whether it’s effective. They don’t know that, so they go, they say, “Okay, we’ll just figure it out. We’ll go right to phase three”, which are usually very expensive studies, hundreds of millions of dollars. That’s why you do phase two, but because the government’s taken the risk out of it, they just go right to phase three, which the government is also paying for. So now you do, they’re doing, they’re doing it the right way. They’re doing 30,000 person studies, whether it’s 15,000 vaccines, 15,000 placebo or 20,000 vaccine, 10,000 placebo, to see whether the vaccine, at least doesn’t have an uncommon side effect, and at least is effective for a certain period of time, usually a short period of time, at a certain level of efficacy. So when the vaccine, and in addition what they’re doing, which no one ever does in the world of vaccine manufacturers, they’re mass producing the vaccine at the same time they’re doing the phase three study. I mean, who does that? Right? I mean, if you, usually companies, not surprisingly, wait to make sure that it’s safe, and wait to make sure it’s effective before they mass produce it, but the government says, “We’ll pay for that.” So fine, and that’s all great. And that’s warp speed. Warp speed is a manufacturing issue.
  • So okay, let me see if I can, this is really new to me. Let me see if I can summarize what you said, and you can correct me where I’m wrong. So basically normally, we have these phase two trials, which help establish safety and efficacy at a level that then assuages a company that they’re willing to spend the big dollars on phase three, because there aren’t warning signs. There aren’t stop signs. There aren’t, like you said, those 40 checkpoints. You haven’t met at many of those where you’re like, “You know what, I don’t wanna invest in this phase three because there’s a good chance it might not work or there’s even a small chance it might not work, but our bet is so expensive.” You’re saying the government’s paid for this now. So they’re saying, “Okay, we’ve taken that risk off the table, go right to phase three.” See if you can get the phase three done, and the government will pay for that piece of it, and at the same time, they’re gonna pay for starting to manufacture this vaccine, so that takes that, some of that risk out of it, and so it’s changed the dynamic and the timeline quite a bit. Did I get that right?
  • Paul: Yeah, the only small modification is phase two is, is safety and immunogenicity. You don’t know efficacy because it’s not a controlled trial. So it’s just 200, 300, 400 people, a thousand people get that vaccine because you wanna make sure it’s consistently immunogenic, even though you don’t know whether that immune response is protective, you don’t know that yet, and at least it’s safe, at a certain level. Then you go to phase three.
  • I see, I see. So immunogenicity in the terms of maybe it makes neutralizing antibodies that you can measure, but we don’t really know whether those are protective and that’s the efficacy you’re measuring in phase three, presumably, is that right?
  • Paul: Right, right, exactly. What companies do when they go to phase three is that’s, that’s the proof. That is a prospective placebo control trial where typically 20,000 people get vaccine, 10,000 people get placebo or 15,000, 15,000, but that’s the only way that you can prove whether a vaccine works and it’s, and, and at least that you can say that it’s, let’s say 70% effective for four months, for six months. You can say that. And you can say, if you would say in 20,000 people that it’s, at least it’s safe in 20,000 people. So it doesn’t have an uncommon, serious side effect problem. Now, 20,000 people, isn’t 20 million people. So, you know, you may find out only rare side effects after licensure, and you can only say it’s effective for so long. You don’t know whether it’s effective for a whole year or two years or three years, but that’s the way everything is always done. The human papillomavirus vaccine was a 30,000 person trial before licensure. The conjugate pneumococcal vaccine was a 35,000 person trial before licensure. That’s all okay. So even though the government has taken the risk out of it and the government basically made it, so you could skip phase two and the government made it so that you could actually mass produce vaccine during phase three, which would never normally happen. and the reason they’re doing that make sense. If one or more of these vaccines is shown to work, and I think that’s likely, then what’ll happen is you can just roll it off the assembly line, into people’s arms immediately after you find that out. So that’s if, as long as the government’s willing to pay for that, I think that’s fine. What worries me in all this is that the government wouldn’t let phase three trials go to completion because you have an election coming up, and I think that, you know, for this administration, if they can pull their, put their hand into the warp speed bucket, pull out a couple of vaccines and say, “Look, we’ve tested it in 5,000 people and it’s safe. It induced an immune response, which is excellent. Although, you know, that, that does necessarily mean it’s protective. You don’t know that yet until you do, finish your phase three, and that they would then put it out there as an October surprise. So that’s where the stock market goes up. It helps the, Donald Trump’s re-electability and-
  • Got it and, and I think that’s a valid concern. Let’s clarify a few things, ’cause I think it’s so important. The fact that they’re warping through phase two does not mean that this vaccine is not gonna have appropriate safety and efficacy studies because that’s what really happens in phase three. The main reason for phase two is to mitigate risk for the companies. So let’s be very clear, because you can imagine anti-vaccine proponents would say, “See, they skipped a whole phase of the trial and now they wanna stick this in everyone’s arms.” No, but what you did say that would raise risk is, if phase three weren’t completed, so you don’t get enough data, you rush it out there as whether it’s political, and this is the thing Paul like, everything right now is political on all sides of this. So, it is a valid concern because whether it’s hydroclorothi, or hydroxychloroquine that’s been politicized or the masks that have been politicized, it doesn’t matter on all sides of it. This is such an emotionally charged thing, and science and reason seemed to be a side note in this. So is that a concern now with phase three? Do you think that will happen or are you just, you’re just putting that out there to say, let’s make sure that doesn’t happen?
  • Paul: I’m not the only one who’s worried about this. There were a number of people who are close to this situation that are worried about this. They’re worried because one, I think the administration has, as you said, been willing to perturb the science, take your pick. They, they’ve taken the environmental protection agency and, and convinced them to take the phrase, “Climate change” off their website. They convinced the national weather services to somewhat alter the, the map regarding how this, this storm that hit the Southeast, where it went because Donald Trump had said, “It went into Alabama” and it didn’t. Then they just wanted to cover his butt on that. They were willing to, you know, to ask the FDA to approve hydroxychloroquine when the FDA should never have done that. There were, there were no data suggesting that, that hydroxychloroquine can work. There were abundant data showing that it had a cardiac toxicity. Arrhythmia is a side effect. They should have waited for that, those trials to be done, and it wasn’t that hard. I mean, those Remdesivir trials, which involved more than a thousand people, the antiviral, Remdesivir, was done very quickly. You could have done this trial very quickly too. There’s a lot of people out there with this infection, but they didn’t, and so see, that’s what worries me. To me, that was the warning shot. They were able, through the so-called, Emergency Use Authorization Act to, to bend their will or to impose their will onto the FDA to make them do something. Now, there are a lot of people who have been working through the congressional committees, trying to get Stephen Hahn, who’s the key player here. Stephen Hahn is the FDA Commissioner. He has to approve this through EUA. He has to say, “It’s okay with me that you’re doing that.” So, people have asked him this question at committee hearings, more than once, are you going to allow phase three trials to be completed before you, you offer an EUA, and hasn’t been clear, and you know, it’s what they did, the FDA, and I trust the FDA. I trust the NIH. I trust the CDC. It’s the administration I’m having trouble with. I mean, what the FDA did was, they put out what was called their guidelines. So the document, which was like a 30 page document, said FDA Guidelines for the Licensure of COVID-19 Vaccines. Great. The problem is, these are not gonna be licensed products. They’re gonna be approved through the Emergency Use Authorization. So you have to go to page 19 of that document to see what are the rules for Emergency Use Authorization, and it’s, it’s not clear. And there was a great presentation by an FDA person this week, Wednesday, with Doran Fink actually, who’s wonderful at the FDA, presented what the difference is between licensure and approval through, licensure through the FDA and approval by the FDA through EUA, and it’s just vague. At one point that the quote that Doran used was, “May be effective” What does that mean? So, I do worry there’s a lot of leeway in the EUA that would allow for this.
  • Can you can, for people who don’t know, can you define what EUA is.
  • Paul: I’m sorry, so Emergency Use Authorization, in a time of crisis that you, that you allow for certain products to be used, that you wouldn’t necessarily go through the normal process. The normal process for licensure through the FDA is a year. You can get an expedited review in eight, eight or nine months, and that’s not, that’s too long. I mean, we have 500 to 1000 people dying a day, so we do need to move things quickly, and I think we’ve done it. I actually think everything up to this point has been done, done the right way. I think Dr. Fauci has had a heavy hand in this, and we’ve been doing it the right way. The Moderna vaccine, the mRNA vaccine, is an NIH vaccine. The NIH researchers are the one who basically invented that construct. They then gave it to, to Moderna to make this so-called messenger RNA vaccine. That’s right now gonna probably be the first vaccine that we’re gonna learn about, ’cause that’s, that got the earliest start for phase three.
  • Right and for people who wanna learn more about that whole process, watch our previous videos with Dr. Offit. So this is interesting because again, if you look at how everything has been politicized now, and I have to say, half of my audience is quite conservative. Half is quite liberal, but we all share this goal of trying to actually improve human flourishing, right? So we have to actually, ’cause I think what’s gonna happen is people will say, “Okay, now we’re getting political about this and we’re accusing Trump of this and that.” But the truth is, you have to look at how the science is done. I think we share this concern, which is, if you get this wrong, you not only harm lives directly by a vaccine that isn’t properly studied, right? And then you give credence to all the people over the years, the conspiracy types and others who have felt that, that were not trustworthy in terms of doing the science. And the truth is, it’s because you have to do the science right, and that’s what you’re advocating for, and a lot of your colleagues as well. There was recently an op-ed in “Stat News” by one of your colleagues saying the same thing. I’m forgetting his name, basically saying, “We don’t want to rush this, and we’re relying on the FDA to do the right thing. And if they don’t, if they, if they bow to any political pressure and rush something through, it could cause harm that reverberates through generations, because the amount of distrust that would be sewn from a vaccine that’s maybe neither safe, nor effective, or one or the other is missing, it is gonna give validity to people’s worst concerns about the science of these things.” And then, and then in the setting of all this, Paul, there’s this concern that immunity doesn’t last. What, what are your thoughts on these studies showing antibody levels dropping and that sort of thing? We’ve done some videos on this. I’d love your thoughts on that.
  • Paul: I’m not sure what it means. We certainly know that this virus does a lot of strange things. One thing it does is suppress interferon, so it does have an anti-immune system effect. It’s the, the issue there becomes, to what extent are memory cells important? I mean, this is an incubation period, meaning from the time when you were first exposed to the time you develop symptoms of about six days. That may be enough time for activation and differentiation of memory cells, for example, memory B cells to make antibodies. So that even though you don’t have circulating antibodies, you still have some degree of protection. So, that is unknown. We’ll know that when we do these, these, these vaccine trials. So, I think the phase three trials will tell all, and, and I would like to say again, I actually applaud the administration for doing it this way. I think that they’ve done it exactly right. I just don’t want it to be perturbed at the end, because you don’t have to get lucky. You don’t have to be lucky. And I think that if we put the vaccine out there too early, we’re asking to be lucky and you don’t have to do that. You can, you can mitigate the risk by saying, “I know that in a phase three trial, at least I know this much.” And then when you, when you roll out the vaccine, you can manage expectations. You can say, “Look, we have, we know it’s safe in 20,000. We’re gonna determine whether it’s safe in 20 million. We know that it’s effective for this long. We’ll see whether it lasts eight months or 12 months or two years.” We don’t know that, so be honest with the public, be transparent with the public. And that’s the other advantage actually, of a typical vaccine licensure process, because typically it goes through the FDA’s so-called VRBPAC committee, which is the FDA’s vaccine advisory. I’m actually on that committee. It goes through that committee, so the public can see it. I mean, those are public meetings, so the public can sit there if they want, and I think it may even be online and you can see what the data are, so you can make a decision. You know, ABC conducted a poll where they asked people, “Would you get a COVID-19 vaccine?” About two thirds said, “Yes” and a third said, “No”. I would’ve said, “No”. I mean, I’m not, I don’t know whether I’d get it. I mean, it’s a theoretical vaccine. Let me see what the data looked like, then I’ll tell you would I get the vaccine. And this was sort of handled by the, the press like, you know, a third of the public doesn’t wanna get the vaccine. I was surprised two thirds of the public was willing to get it, sight unseen, that they trusted the process.
  • They’ve asked me the same thing, Paul, and I have said, “No, absolutely not, unless I’m comfortable with the data and people I trust are comfortable with the data.” So for example, if I asked Paul Offit on the show, “Hey, would you get this vaccine now that you’ve seen all the phase three data?” And he says, “Yes, I would, on balance, this is what I’d do.” Then I would do it because I trust your expertise. However, if you were concerned, then I would say, “Okay, we need more data.” One question to follow up on that. So in phase three, a common trope of sort of people who resist vaccines is that these aren’t placebo control, sort of studies. Are phase three trials that we’re gonna do now, you mentioned earlier, I think, a placebo group. Is there a placebo, and what is that exactly?
  • Paul: So the placebo group is an inert substance, probably saline something like, it’s not another vaccine. Sometimes we do other vaccines as the placebo group, because ethicists argue reasonably that you can’t give people nothing. At least give them something from which they would benefit, but it’s interesting that the anti-vaccine people will often say, “You don’t have placebo controlled.” So, it’s meaning using an inert substance. There are about 40 studies that have been placebo controlled, roughly, in the world of vaccines. We actually have the, those all on our website, if people wanna see it.
  • Yeah, that’s, that’s important. What’s your website by the way?
  • Paul: I’m sorry, so it’s the vaccine education center. It’s vaccine.chop.edu.
  • Perfect, yeah. Great, great resource for people. I send a lot of people there as well. So, the other question that came up, we talked about new, you know, antibodies. You talked about memory B cell response. So in other words, even if you don’t see circulating antibodies in people, they have this memory B cell population that can be activated within the timeframe of the infectious parameters of this virus. So, that is not a direct reason to believe that there’s not gonna be an effective vaccine or effective long-term immunity to this from people who’ve been exposed. What’s your take on the anecdotes of people who have gotten reinfected? Do you have any thoughts on that?
  • Paul: Yeah, that’s an important question. I mean, I think you know, that you can make an effective vaccine as long as natural infection protects against disease associated with re-exposure. The virus hasn’t been out there long enough, I think, to answer this question. The people you, you don’t wanna hear, or you don’t wanna hear what’s happening is that somebody got moderate to severe disease associated with natural infection. They got completely better, then six months later, they got moderate disease to severe disease associated with, with again, infection. That’s worrisome. If natural infection doesn’t protect against disease associated with re-infection, then you’re you’re in trouble. I mean, that’s the strep throat story. That’s the gonorrhea story. So, you wanna avoid that. I don’t think we’re there. I mean, the human challenge studies done, at least with human coronavirus was back in the early nineties, showed that you could get protection, but again, this is a bat coronavirus. This is a different virus.
  • You know, by the way, bat coronavirus sounds like some kind of evil superhero thing, you know, and that reminds me at some point, I’m gonna pitch you my idea for a show with you. The vaccine shark tank, where you’re one of the judges and all these companies pitch you, and you, you turn around in your chair when you think the data is actually compelling, but so, so relating to that, you know, this idea that if you get reinfected and you get moderate to severe disease, again, that is concerning, whereas you could get reinfected in theory. In other words, re-exposed even to a slightly different strain, get mildly sick again and get better, but that might actually be expected within the parameters of the immunity you had developed, correct?
  • Paul: That’s exactly right. I mean, I think what you would expect from this, which is a respiratory virus, I mean, it’s similar, in the sense to human coronaviruses, you would expect that, that with reinfection, that what a vaccine should do is what natural infection probably does was, protect you against moderate to severe diseases associated with reinfection, which means that you may still get asymptomatic reinfection. You may still get mild disease associated with reinfection, and you may even shed virus to some extent, but at presumably, a lesser extent, and that all needs to be considered. I think we’re, we’re, it’s going to be a while ’til we abandon hygienic measures. Even when we start to vaccinate the population, I think there’s still gonna be some shedding, so we, they still need to use this, the hygienic measures.
  • A really important point, I wanna really put an emphasis on, so even if you’re vaccinated, even if you’ve been infected, the idea that you abandon social distancing, hand-washing and potentially, masks is not, does not follow from that, because of the reasons you mentioned. So there still can be viral shedding. Even if you’re reinfected, you can infect, in an asymptomatic way, others and who are at risk, who haven’t been vaccinated, or haven’t had the disease, correct?
  • Paul: Correct also, the question is what percentage of the population would you need to vaccinate to stop spread? By stop spread, I mean, the sort of R-naught, which is the contagiousness index, gets to less than one. So, R-naught just means that, the R-naught of this virus is supposedly around two. So, if I’m infected and I’m shedding the virus, and I just live my normal day and everybody I come in contact with is susceptible, I’ll infect two more people. So the, to figure out what percentage of the population needs to be vaccinated, you need to know two variables. One is the, R-naught, and two, the effectiveness of the vaccine. There’s actually a formula for this. If the vaccine were, if this vaccine were 75% say, effective at preventing shedding or a significant amount of shedding you, and the R-naught is two, you would need to vaccinate about two thirds of the American population to stop spread.
  • Mm-hmm, and this is the number that’s come up, this magic herd immunity threshold of around that 60 odd percent. Let me ask a question. So there was recently a piece in “The Atlantic” citing work out of Glasgow, looking at innate resistance to coronavirus mediated disease in a population, presumably T cell humorally or cell mediated immunity in, in populations that then would create a pool of people that are less susceptible at baseline and therefore, lower the herd immunity threshold to as low as 20%. Do you have thoughts on this at all?
  • Paul: Yeah, I think actually Bob Gallo had a piece in the “New York Times” about this and it’s, it’s this old notion of power immunity. In other words, where you’re infected with one virus that, that makes you, at least for a period of time, less susceptible to infection with other viruses. So people have looked at these sort of live attenuated or viral or bacterial vaccines to ask the question, if I give BCG, which is a live attenuated bacterial vaccine, or I give oral polio vaccine, which has a live attenuated polio virus, or I give measles containing vaccine, which is a live attenuated measles virus, am I inducing, it seems to be interferon centered. Am I inducing interferon at levels that can protect me against this virus? And the answer is probably yes, it’s and shockingly, the interferon lasts for awhile. And the other thing is, so, so do I think this of value? Sure, except I think we can make a specific vaccine and these are, these would be nonspecific vaccines, so I do think we can do that. The other thing that’s interesting, actually, it just reminded me when you said it, is that, it is true that this virus seems to suppress your capacity to make interferon. So, now there’s a group in South Hampton in England that actually give interferon as a way of treating this, and there is some success with that, which makes sense, but if the virus does suppress the interferon response, it is possible you may be able to make a vaccine which induces an immune response, which is better than natural infection, because the vaccine won’t suppress interferon.
  • Oh that’s fascinating. So, actually better than wild type virus, because you don’t get the para-viral effect of suppressing the immune response through interferon. That, that’s really interesting, and actually this whole interferon idea is interesting. And the idea that there are other mechanisms of immunity, apart from simple neutralizing antibodies that are at play, that then make this dynamic assessment of where is the herd immunity threshold, and what is the effect of MMR vaccination, ’cause you mentioned there, there was recently this sort of thing going around about people who’ve had MMR, seemed to be in a correlatory fashion, somewhat protected from COVID. Is that based on the same proposed mechanism as what you’re saying here?
  • Paul: Yeah well, people have also proposed that there may be some sequence homology between sort of measles virus surface proteins and this virus. So that, measles may be a little different than, than this, but I don’t think, I don’t think nonspecific immunity is gonna be the way to go here. We have actually, I’m on the NIH’s active group, A-C-T-I-V, which is something that Francis Collins put together, about 30 of us, to try and facilitate and accelerate the development of a vaccine. That was brought up actually by Dr. Gallo, who’s brilliant, and the, frankly co-discoverer of HIV as the cause of AIDS. He has pushed for that. I don’t, I don’t think we need to do that, but we’ll, we’ll see. It’s largely as a temporizing measure. Probably the best temporizing measure would be monoclonal antibodies. I mean, now you can make monoclonal antibodies with sort of long FC receptors so that you can have months really, of protection, as distinct from the few weeks that you would get with, you know, the older kinds of monoclonal antibodies. So, I mean that, and that could also teach you about what level of neutralizing antibodies you need to protect, I think, as well, that kind of study. So, I think we may start to see those studies, pending a vaccine, but you know, Dr. Fauci yesterday, when he was in front of Congress, said he thought that we could have a vaccine by the end of the year. I think that’s remarkably optimistic. I can’t see how that happens. You have a two dose vaccine. We’re just starting these trials, right? Pfizer and Moderna, both mRNA vaccines are starting these trials. They’re so, this is almost August, right? Tomorrow is August, so assume people, not everybody, not all 30,000 people get vaccine or placebo on day one. Why do we assume that? That it’s gonna take the month to get the first dose. So, it can take another month to get the second dose. It’s going take two weeks after the second dose to get really an adequate boost in your immunity. So you’re already in the middle of October, you know, and now you have to accrue enough people in your placebo group who are sick, not just infected, but sick, to be able to say, you can prevent moderate to severe disease. I don’t see that happening by the end of the year. I hope I’m wrong. I hope he’s right, but we’ll see.
  • Man, hey that’s tough because there’s just simple, you know, it’s like the speed of light can’t be exceeded. There’s certain rules that, like you said, just the straight timeline of it makes it tough to imagine how that’s gonna happen, but again, I think, I hope we’re both wrong about that, and I think we’re both optimistic about a vaccine ultimately working. It’s just, in the meantime, there’s so much that we’re doing wrong, that’s costing potentially lives. So, what are your thoughts on masks and the data around masks now? I’d been very resistant to masks early on and I’ve started to alter my feeling about it, seeing as data emerges.
  • Paul: No, I agree, I think masks work. You know, it’s, Dr. Fauci was suspicious about that initially, but I think as we look over time, masks do work. I mean, they’re not perfect obviously, because you can sort of breathe through the sides of them and, but I think they definitely dramatically reduce your chance of transmitting and catching this infection. So that, hand-washing, social distancing, I think does work.
  • Do you think that infectious dose being reduced by masks? So in other words, you get sick, but your inoculum is lower. Does that affect outcomes in these patients?
  • Paul: Definitely. I mean, there’s, there’s, it’s the old varicella chickenpox story. I mean, it’s the second child in the home that gets much sicker because they’re exposed to much more virus, so that’s exactly right.
  • Ah, that’s fascinating. I forgot about that ’cause we’re, you and I are both from the era of 10,000 hospitalizations from varicella, and I remember I was the first in my home to get chicken pox naturally, and then my two, my brother and sister got it. And they were so sick and I never thought, so now another thing to feel guilty about in my family dynamics. Thank you, Paul Offit for that. So, this is interesting because I did a video about this. I think people were concerned, okay, listen, the masks don’t work, you’re breathing around the sides, they’re forcing you to touch your face. They’re giving you a false sense of security and violating social distance, but if they drop the inoculum, even by, you know, 50%, your chances of getting so sick that you’re intubated on a ventilator and dying are much less than that’s worth, that, that in itself is worth doing just for you. Forget about the altruism of protecting others, correct or am I reading that wrong?
  • Paul: No, you’re exactly right. I mean, it protects you and others. It’s, it is of value.
  • Yeah and do you, so you and I, in the past have, have talked about the dangers, the unanticipated, or actually anticipated, but unfactored dangers of our response to this pandemic, in terms of economic shutdowns and closing schools. Now have your, has your thinking on schools or economic shutdowns or all that, how has that evolved over time? And what, what are you thinking about it now, especially for schools?
  • Paul: Yeah, I was fooled by this. I mean, when, when you and I first talked initially, I, I never imagined this, this virus would be as bad as flu this . Flu caused whatever, 780,000 hospitalizations, more than 60,000 deaths in the United States. I never thought we’d be that bad, and the reason is, I kept comparing us to other countries. I looked at like, China and Japan and Singapore and South Korea, and I thought, look, I mean, these, these are here’s, you know, China had 3000 deaths. They’re five times bigger than us. You know, why do we think we’re gonna get 62,000 deaths a year? I was wrong, we were much worse at this. I mean, we are, we have basically 4% of the world’s population and 25% of the world’s deaths. I mean, we’re awful at this.
  • We, you know, you and I share the same mea culpa in the sense that we trusted our country to do the right thing in the way that others were doing it. When I saw China’s response, I actually publicly said, “I don’t think the U.S. can be this draconian. We just don’t have the culture or the apparatus for it, but at least we have a head start, so we can actually do the, as soon as we get cases, we do contact tracing.” Everything fell apart, and so I was feeling the same thing. Saying the flu is much worse because, because it’s already out of the bag and this thing, we can actually respond the way other countries have. Wrong, wrong, wrong, wrong, wrong, and I think some of that again, comes down to our own sense of exceptionalism, our own, we have a particular kind of anti-scientific chutzpah in this country, which I, sometimes I share, honestly Paul, because I’m a bit of, I have a bit of a libertarian streak in me, and I’m like, you’re not gonna put, put a mask on Americans. You’re not gonna do this, but then we do suffer the consequences of that, 150,000 dead. If you would have told us that in Jan, in March or April, whenever we talked, we would’ve, our jaws would’ve dropped, right, ’cause we couldn’t-
  • Paul: Absolutely.
  • Yeah.
  • Paul: I completely agree.
  • Well, so what do you think about, now I’m very concerned about schools. Like I, I actually was with the American Academy of Pediatrics saying, you know, I think children are best served in schools, and I worry about domestic abuse. I worry about educational abuse at home. I worry about my own kids losing their minds. Paul, they are bouncing off the walls neurotic, and then we put them in the safest camps we could imagine, and their whole mental status shifted with the socialization with other kids, with the structure, with being back with this kind of environment, and so what are your, what’s your thinking on schools now?
  • Paul: Right well, I mean, I agree with the CDC. I think that, I mean, you look at a country like Denmark and I don’t know why I continue to compare ourselves to other countries since I always make the mistake of doing that. I mean, Denmark, you know Denmark sent their kids back to school and didn’t have a blip, but they had very strict criteria for how that was gonna happen. You know, kids came in shifts so that all parents weren’t gathered together. When they ate in the cafeteria, they stayed six feet apart. They tried to wear masks where they could. I mean, all that was done, and so the CDC came up with those criteria here, and you know, the administration said, “Let’s go back to school. Forget about these criteria. It’s too expensive. Let’s not do it that way.” It’s just, it was just ill informed. So I think, in areas where they were on fire, I mean like, you know, Florida or Texas or Arizona or Southern California, that’s gonna be harder, I think, to go back to school until things settle down a little bit, but I think there’s no reason not to go back to school for all the reasons you’re saying. I mean, for the mental health of children, for children who are currently in domestic or, or child abuse situations were often identified in schools, many showing their best meal during the day is at school. There’s so many good reasons to go back to school, but we just should do it the right way, and I just, you know, at least in some places, I don’t see that happening. You know, we don’t think like a society. We think as individuals, and I think that’s, that’s what distinguishes us from a lot of these European countries.
  • You kind of nailed it. I was actually thinking about this quite a bit because I just finished Steven Pinker’s book, “Enlightenment Now” on audio book, and he, in that book, he makes the case for advancing humanistic ideas like, science, reason and the values of humanism, which involve using science and reason to actually promote human flourishing. In the United States, we are actually a little late to that game compared to say, New Zealand or the Europeans, in terms of that tension between collective good and individualism. I think we, we favor individualism. The country was kind of like, kinda built on that idea, and then, we do pay some costs for that in terms of our health care system, having some of the worst outcomes in the world, yet being the most expensive. Our public health apparatus, despite wonderful, well-intentioned people in it, having very little power to actually influence change and the very debate between, hey, you know, even if you show me all the data that a mask would actually help, I’m not gonna wear it because you don’t tell me what to do. It’s a challenge, and honestly, I feel the tension in myself because I have that streak of oppositional defiant disorder. I am a contrarian, and yet, when I look at, you know, what the Europeans have done or what the Taiwanese or the Hong Kong-ers have done and, you know, and then you see the press that comes out and it’s like, “Oh, everything was wrong about what Hong Kong did because they have another hundred cases.” It’s like, a hundred cases like, we are having how many tens of thousands of new cases per day-
  • Paul: 70,000 I think yesterday now.
  • In a day, so we really need to also have some degree of humility, which again, we also tend to lack as a people, to be able to address this. And I, do think it’s all out of the bag now, or do you think we’ll just go through this, reach some kind of collective herd immunity between infection and vaccination where we’re then, we’re then through this? I mean, where do you think this is going for the U.S.?
  • Paul: So I don’t, I don’t think you can get herd immunity through natural infection. I mean, I don’t think you can do that. I mean, measles is a perfect example. I mean, I was a child of the fifties. I had measles and every year two to three million people would get measles and, and about 50,000 would be hospitalized and 500 would die every year. There was always a susceptible group. Now when I had measles, that meant I was protected for the rest of my life. I mean, sterilizing immunity. That’s an amazing natural infection. You’re, everybody who gets measles is protected for the rest of life, assuming you’ve lived through measles, but still every year, two to 3 million cases. I think that’s true here too, especially with this kind of immunity, which is not sterilizing immunity. I mean, it’s sort of an incomplete, short-lived immunity, basically, meaning incomplete, meaning just moderate to severe short-lived, meaning probably a year or two, but not, not a lot longer. So I think it’s gonna be a combination of natural infection and vaccination and, and hygienic measures. The vaccine’s not gonna be a wonder drug. It’s not like we’re gonna have the vaccine, and the next day, this virus is gonna be gone, even though I think people think of it that way, that we’re still going to need to use hygienic measures, but you’re right, I mean, we, we are so individualistic that we basically consider it our right to catch and transmit a potentially fatal infection. You know, don’t tell me I can wear a mask or not. You know, in many ways there’s parallels to the anti-vaccine people. The anti-vaccine people will say, you know, “What do you care?” Or the worst thing they say, as far as I’m concerned, is they say, “What do you care what I do, you’re vaccinated”, which assumes that vaccines are a hundred percent effective, which isn’t true, and it also assumes everybody can be vaccinated, which also isn’t true. It’s the same thing with masks. I mean, you know, you’re, you choose not to, if somebody else is wearing a mask, that doesn’t mean they’re a hundred percent protected.
  • That’s exactly correct, and that, and that’s the problem. Like, it requires a buy in of a lot of people to make this work. If we had say, universal masking, universal vaccination, you know, a lot of these problems would be much more soluble. And you know, when people look at the Swedish example too, and they say, “Well, but look, see they, they did it the way we’re trying to do it in America. Just, you know, herd immunity”, and no, that’s not exactly what they did. They actually voluntarily, as a people, distanced, cut down on large gatherings, did a lot of things and they still suffered a higher mortality rate than their European neighbors, although lower than the UK. So, you could say for the Swedish people, maybe that was a good compromise for their culture and their people, and they were okay with that. And, but we haven’t even done that. We’re at a totally different level of nonadherence to, and do you think there’s a, you said a few things that I know I’m gonna see. I see the comments. I’m like somebody who sees dead people like, Bruce Willis in “The Sixth Sign”. I see comments, Paul Offit, so as we’re talking, I see the comments scrolling and the comments are this. “I don’t trust Fauci, he’s a liar. He’s trying to make money. I don’t trust Offit. I don’t trust Damania, he’s a shill. All of them are liberals.” Which of course for me, isn’t even true. “They’re all politically motivated and such, and I don’t trust them because the experts think they know everything, but they’re just arrogant, and that includes Fauci and the CDC, and everybody we mentioned.” There’s a mistrust of expertise that’s happened, and what do you think is the root of that? You’ve written about this. You’re a thinker on this. What, what are your thoughts?
  • Paul: That’s exactly it. Tom Nichols has a book on this, right? “The Death of Expertise”, which is great. You’re right, I mean, I think it’s this, it’s just this incredible hubris I, that I trust my, my experience and my ability to think and reason, so that, that what I believe is, is as valuable as anybody else, independent of their level of experience or expertise. It is just this remarkable hubris, which is not uniquely American, but it is definitely a big part of who we are. I think, I think Donald Trump is able to appeal to that. You know, these sort of these eggheads, these elites, you know, forget about them. I mean, we’re just as good. We’re just, you know, we’re plain folk and we can figure it out too. We don’t need them to tell us what to do, just go with our instincts.
  • You know what’s funny is, I watch, so I read what Trump writes sometimes and I’m like, “Oh, this guy has got a, is he educated at all?” But then when you watch him actually perform what he’s doing, there is a very deep part of me that’s like, finally, somebody’s just saying it like it is. He’s able to resonate with this unconscious Americanism, honestly, and I think that’s where a lot of his power is. And that’s why Paul, honestly, I think, especially with my audience, I’m very sympathetic to why people resonate with that, why they’re suspicious and these other issues. It’s actually understandable by me, but that means that when we message and when we talk about it, we have to use those same sort of, kind of tools of persuasion and understanding, and actually compassion for different views when we’re communicating, and that’s a challenge for a lot of scientists because we do have this kind of like, well, I went to all those school and I studied this and I do this, and I think people are very put off by that, and it might even be understandably put off. I mean, curious your thoughts.
  • Paul: Yeah, I mean, it’s, you’re exactly right. He, he is interesting in some ways. I mean, for example, the hydroxychloroquine story. I mean, he brings that hydroxychloroquine story up and he believes this to be true. He takes, he said he took hydroxychloroquine, and he didn’t get sick. That, which to him, I think is the proof. I really think that to him is the proof, and so he couldn’t let it die, right? He’s gotta again, in the last couple of days, trumpet hydroxychloroquine by using a woman, this Dr. Immanuel or something from overseas who, who as it turns out, also believes that alien DNA is in vaccines and that vaccines make you make you immune from religion. And that if you, if you have uterine problems, it’s because you’ve, you’ve dreamt of having sex with demons and stuff, which you know, is a little concerning, although the most interesting part of that, as an aside, is so aliens have DNA. That’s interesting, I mean, right? It’s, it’s like it’s still predominately the same four nucleotides. I mean, so how do you know it’s alien? I just wanna dig down on that.
  • You know, and that’s so earth centric, Paul. I mean, honestly, like it’s so alien-a-phobic to just assume that it’s, it’s a kind of a DNA appropriation is what’s going on here. No, it’s true, I did a piece on that and you know, what’s interesting is when I talked about that, I did it in a way that I thought was nonpolitical because I don’t really care about the politics, except when doctors dress up in white coats, funded by a political organization and go on the steps of a political organization and say that they’re experts on this and confuse correlation with causation and make a lot of mistakes about the literature on hydroxychloroquine. Nobody wants hydroxychloroquine to work more than me. Cheap, relatively nontoxic. It doesn’t based on anything that we’ve seen that is of any quality, right? That isn’t just an observational crazy, you know, a poorly designed study. So, when I talked about it, I mentioned all those things, and man, if you look at the comments, it’s like a cesspool. Oh, I used to have respect for you, ZDogg. I thought you understood. Well that’s because whatever science that I demonstrate that politically aligns with what you believe, then you’re on my side, but the minute it doesn’t, I’m getting angry messages from doctors who had followed me for years saying I’m withdrawing my support, because how can you silence these doctors? What? it’s a really frustrating place to be.
  • Paul: No, the thing that’s most amazing, the science really is in no sense political. It isn’t. It doesn’t matter what I believe or what you believe. The only thing that matters is what quality data show. That’s all it matters. I think it’s the, the scientist who says it doesn’t matter what you think. Science is not a belief system. I forget how it actually goes, but-
  • Yeah, yeah, exactly right.
  • Paul: But yet it’s become that. You know, that if you, if you support hydroxychloroquine, it’s because you believe that that the President, you know, you believe in the President. You know, it’s just like, it’s become this dividing line for left and right, hydroxychloroquine. It’s just weird.
  • You know, science is not political. Absolutely, but politics is the application of what we learn in good science to conflicting interests that humans have. So, maybe we find out that, you know, hydroxychloroquine, you know, works a little bit, but not enough, what’s the cost balance? Well, now politics has a role to say, “Okay, I’m willing to spend public money to fund this. I’m not willing to spend public money to fund.” Okay, that’s the role of politics. The role of politics is not to differentially interpret data in such wildly different ways to support a preexisting belief, and this occurs on the left as well. It’s not entire, in fact, I mean, Paul, you’re already aware, like, I think a function of the kind of new age left is an anti-vaccine sanctity versus degradation, don’t put this in my body, toxins, big pharma corporation. So, it’s not isolated to the right. It just seems to be flaring right now because of the divide currently around this stuff, but yeah, with hydroxychloroquine, this is such a great example. Good people that I know are smart are so inflamed by this. And it means that we’re thinking with our reptile brains now, instead of our rational minds. We can’t even have a conversation, and honestly, I fall into those patterns sometimes too, and I have to check what my bias is ’cause my bias is actually sort of trans-party. Sometimes I’m really with the left on this. Sometimes I’m with the right on that. Sometimes I’m just off the rails. That’s most of the time, but yeah, I mean, it’s tough.
  • Paul: Yeah, but it was Neil deGrasse Tyson. That’s what I was trying to think of. He said, “The beauty of science is, it doesn’t matter what you believe.” And then, that’s true. I mean, people say, you know, “I believe in vax.” It’s not a belief system. It’s like believing in gravity. I mean, you know, you, these things are just facts.
  • Exactly right, well yeah, and I think, oh yeah, that, that’s right. That’s the example was with the protests, the mass protests, I think, a lot of scientists came out and said, “That’s fine, go and protest, it’s okay.” And I think a lot of people on the right were very upset saying this is a double standard. You’re saying to stay home, but when it’s socially appropriate in your belief system to go out and protest, then it’s okay. And yeah, there are masks and there’s social distancing, so you can make arguments, but still, I think it is very tough to distinguish now, reason from emotion in such a charged and scary time, and I think, I think people who communicate science, it’s incumbent on them to try to see all sides of that.
  • Paul: I agree completely.
  • Awesome, man Paul, so can I ask you a favor? We’re all nervous about vaccine, timing and getting it safely out there. When the next big announcement is, will you come back on the show to walk us through what you think, because I think many people believe in, and trust in you.
  • Paul: Count me in. Thank you.
  • That’s awesome. Thank you, Paul Offit. Thank you, Z-Pak. Do me a favor, subscribe to the show if you haven’t, share this episode. We try to do our best to be as rational and level-headed as we can. Sometimes we get it right, sometimes we don’t. Leave us feedback. I love you guys stay well and we are out, peace.

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