WEBVTT - What We Know about the COVID-19 Vaccines 0:00:15.396 --> 0:00:21.916 Pushkin from Pushkin Industries. This is Deep Background, the show 0:00:21.956 --> 0:00:25.276 where we explore the stories behind the stories in the news. 0:00:25.756 --> 0:00:30.756 I'm Noah Feldman. Coronavirus cases are surging across the country. 0:00:31.396 --> 0:00:35.396 Cities and states are responding with new regulations on social gatherings, 0:00:36.156 --> 0:00:39.876 but another potential solution is at least on the horizon 0:00:40.196 --> 0:00:43.276 and maybe a little closer than that. Last week, the 0:00:43.356 --> 0:00:46.676 drug company Visor announced in a press release that it's 0:00:46.716 --> 0:00:51.756 coronavirus vaccine seems to work. According to a preliminary analysis, 0:00:52.236 --> 0:00:57.756 Visor's vaccine is ninety percent effective at preventing COVID nineteen. 0:00:58.476 --> 0:01:02.836 Maderna's vaccine, which operates on similar principles, has produced similar 0:01:02.916 --> 0:01:06.116 numbers reported by that company as well. To discuss the 0:01:06.156 --> 0:01:09.116 science behind these developments and what's going to happen in practice, 0:01:09.436 --> 0:01:12.556 we are joined by doctor Paul Offen. He's a professor 0:01:12.596 --> 0:01:16.636 of vaccinology and pediatrics at the University of Pennsylvania. He's 0:01:16.636 --> 0:01:20.956 also importantly a member of the FDA's Vaccine Advisory Panel. 0:01:21.596 --> 0:01:24.276 Among his other distinctions, he is also the co inventor 0:01:24.476 --> 0:01:32.316 of the rhodavirus vaccine. Paul, thank you so much for 0:01:32.396 --> 0:01:36.476 joining me. The immediate impetus for our conversation is the 0:01:36.516 --> 0:01:41.796 good news that mRNA vaccines like Visors and Maderna's shows 0:01:41.836 --> 0:01:46.196 efficacy in trials. So let's just start with the very 0:01:46.196 --> 0:01:51.156 basic question. The Visor vaccine is an RNA vaccine. There's 0:01:51.156 --> 0:01:54.156 never been one of those that worked before. Why is 0:01:54.196 --> 0:01:57.996 this appear to be working? So what we think we 0:01:58.116 --> 0:02:01.076 know is we think we know that we want to 0:02:01.076 --> 0:02:03.636 make antibodies to the protein that emanates from the surface 0:02:03.676 --> 0:02:06.516 of the virus that is responsible for attaching the virus 0:02:06.556 --> 0:02:09.396 to cells. If you can then make antibodies to that protein, 0:02:09.516 --> 0:02:11.836 you can prevent the virus from attaching the cells. In 0:02:11.916 --> 0:02:14.596 the past, when we've wanted to make an about it 0:02:14.636 --> 0:02:16.876 to the spike protein, we would do things like give 0:02:17.356 --> 0:02:19.276 sort of a whole killed form of the virus which 0:02:19.276 --> 0:02:21.036 would have the spike protein on it, or we would 0:02:21.076 --> 0:02:22.836 give a live we can form of the virus which 0:02:22.836 --> 0:02:24.876 would have the spike protein on it, or we would 0:02:24.916 --> 0:02:27.636 purify the spike protein, or we would use recomment at 0:02:27.676 --> 0:02:31.036 DNA technology to make the spike protein. What we're doing 0:02:31.116 --> 0:02:32.916 now is we're saying we're not going to do any 0:02:32.956 --> 0:02:35.836 of that. We're going to take a small gene that 0:02:35.996 --> 0:02:39.476 essentially codes for that spike protein, and then we'll inject 0:02:39.516 --> 0:02:42.276 that and hope that it gets into muscle cells and 0:02:42.956 --> 0:02:45.356 will then be translated to the spike protein. So, in 0:02:45.356 --> 0:02:47.876 other words, the person makes the spike protein, then the 0:02:47.956 --> 0:02:50.276 person makes in about it's the spectro protein. We've never 0:02:50.276 --> 0:02:52.436 done that before. Just like you said, there's no commercial 0:02:52.436 --> 0:02:56.756 equivalent for that for any vaccine. It should theoretically work, 0:02:56.876 --> 0:02:59.236 we just never knew that it could. That was a 0:02:59.316 --> 0:03:03.156 spectacularly clear explanation. I want to just dive into a 0:03:03.236 --> 0:03:05.276 specific part of it. The part I want to dive 0:03:05.316 --> 0:03:08.276 into is the idea that historically, the way we've done 0:03:08.316 --> 0:03:11.916 vaccines and by Weime and you the scientific community, is 0:03:12.396 --> 0:03:15.716 by introducing a version of the spike protein in this 0:03:15.756 --> 0:03:18.236 case that we want to block, and then having the 0:03:18.236 --> 0:03:21.836 body produce antibodies to it. And that what makes the 0:03:21.996 --> 0:03:25.196 mRNA approach, which is characteristic of the Fiser approach and 0:03:25.276 --> 0:03:29.836 of the Maderna approach, distinctive, is that it actually introduces 0:03:29.876 --> 0:03:34.196 a genetic code to produce the spike protein, which the 0:03:34.196 --> 0:03:36.316 body then produces, which we don't want in principle a 0:03:36.316 --> 0:03:39.476 body to produce. But then the body produces antibodies to 0:03:39.516 --> 0:03:42.116 the spike protein that the body has produced. So you're 0:03:42.156 --> 0:03:43.796 saving a step, as it were, you don't have to 0:03:43.796 --> 0:03:46.316 introduce the spike protein in some form from the outside. 0:03:46.716 --> 0:03:49.596 First of all, am I getting that right? That's exactly right. 0:03:49.876 --> 0:03:53.036 But if for example, you gave a live attenuated viral vaccine, 0:03:53.116 --> 0:03:55.916 that virus would then enter the cell, reproduce itself, and 0:03:55.956 --> 0:03:58.556 it would make the spike protein inside that cell. So 0:03:58.596 --> 0:04:01.276 it's not like a complete long shot. And we certainly 0:04:01.756 --> 0:04:06.076 have a wealth of experience using live weakened viruses to 0:04:06.116 --> 0:04:08.716 induce immune response, starting in the mid nineteen thirties with 0:04:09.196 --> 0:04:12.396 yellow fever vaccine. And is it a good thing that 0:04:12.836 --> 0:04:17.036 by encoding for the spike protein without introducing the virus, 0:04:17.516 --> 0:04:20.116 the virus actually doesn't in principle have a chance of 0:04:20.156 --> 0:04:23.196 arising within the cell with this kind of vaccine, correct, 0:04:23.196 --> 0:04:25.276 because we're not encoding for the virus, just encoding for 0:04:25.316 --> 0:04:28.036 the spike protein. That's right. It's just you're being infected, 0:04:28.076 --> 0:04:31.196 if you will, with one protein, so that's not the virus, 0:04:31.236 --> 0:04:34.916 that's right. So when we think about potential negative side effects, 0:04:34.916 --> 0:04:38.396 when we think about live attenuated viruses or killed viruses, 0:04:38.636 --> 0:04:41.756 sometimes we worry that they might produce, at least in 0:04:41.796 --> 0:04:45.796 some people, symptoms of the actual virus or the bad 0:04:45.796 --> 0:04:48.196 consequence of the actual virus. Is it correct to say that, 0:04:48.236 --> 0:04:51.036 at least in principle, the mRNA vaccine can't do that 0:04:51.236 --> 0:04:53.676 because there is no virus introduced into the system. There's 0:04:53.716 --> 0:04:56.156 just the genetic code for the spike protein, which is 0:04:56.156 --> 0:04:58.636 not itself the virus. Yeah, this is not sours cob 0:04:58.716 --> 0:05:01.596 two virus. This is just one protein from the virus 0:05:01.676 --> 0:05:04.876 that you will make. Therefore, the signs and symptoms that 0:05:04.916 --> 0:05:08.396 you develop will not resemble those of SARS cob two infection. 0:05:09.476 --> 0:05:12.356 So one of the best things about an RNA vaccine, 0:05:12.396 --> 0:05:15.796 if indeed it works, is that it avoids some of 0:05:15.836 --> 0:05:20.076 the potential downsides of more traditional vaccination. That's correct. Yes, 0:05:20.756 --> 0:05:22.876 Sometimes it's been said in the media and by the 0:05:22.916 --> 0:05:26.116 companies that it's easier to produce large numbers of doses 0:05:26.396 --> 0:05:29.276 of an mRNA vaccine than it is to produce large 0:05:29.316 --> 0:05:33.716 numbers of doses of a traditional killed or attenuated virus vaccine. 0:05:33.876 --> 0:05:35.716 Is that so, And if it is so, why is 0:05:35.716 --> 0:05:38.076 it so? I think there's a couple advantages for these 0:05:38.116 --> 0:05:41.876 genetic approaches. The so called genetic plug and play approaches 0:05:42.396 --> 0:05:45.836 are fast because they're very easy to construct. You just 0:05:45.916 --> 0:05:48.196 take the gene and in the case of mRNA, you 0:05:48.236 --> 0:05:49.676 give the gene, or in the case of some of 0:05:49.676 --> 0:05:53.116 these other so called viral vectors, you just insert the 0:05:53.156 --> 0:05:55.676 gene into that viral vector. So it's really very fast 0:05:55.716 --> 0:05:58.436 to be able to construct it, and then it's very 0:05:58.436 --> 0:06:02.596 easy to scale up rapidly. So MESSERNA, it's essentially synthetic. 0:06:02.716 --> 0:06:05.356 You're just manufacturing it, so it can be scaled up 0:06:05.396 --> 0:06:07.356 very quickly. I mean, I think Visor said that they 0:06:07.356 --> 0:06:10.276 would have fifty million doses by the end of twenty twenty, 0:06:10.276 --> 0:06:12.516 that they would have one point three billion doses in 0:06:12.556 --> 0:06:15.996 the year twenty twenty one. You mentioned the viral vector 0:06:16.076 --> 0:06:20.036 vaccines also sometimes called trojan horse vaccines. The Astroxenica approach, 0:06:20.076 --> 0:06:23.356 the Oxford approach is one of those. Could you describe 0:06:23.396 --> 0:06:27.276 how that works in relationship to the mRNA approach, right, 0:06:27.276 --> 0:06:30.196 So it's a little different. So the so called replication 0:06:30.356 --> 0:06:34.476 defective adnovirus vectors, which is the approach that's being used 0:06:34.476 --> 0:06:37.276 by Johnson Johnson, the approach that's being used by Astroxenica, 0:06:37.316 --> 0:06:39.956 the approach is being used by Russia. The approach is 0:06:39.996 --> 0:06:42.996 being used by Chin in part is the adnovirus is 0:06:42.996 --> 0:06:45.556 a human virus that can cause a variety of diseases. 0:06:45.796 --> 0:06:48.716 But by engineering the virus so that it's replication defective, 0:06:48.756 --> 0:06:50.876 that means that it cannot reproduce itself, that means that 0:06:50.956 --> 0:06:53.996 it cannot cause disease. But it's also genetically engineered so 0:06:54.036 --> 0:06:56.956 it has the gene that codes for the spike protein. 0:06:57.396 --> 0:07:01.836 So then you inoculate this replication defective viral vector into 0:07:01.876 --> 0:07:04.516 the person. It's taken up into muscle cells, and then 0:07:04.596 --> 0:07:08.996 that replication of vectivirus enters the cell nucleus, where then 0:07:09.236 --> 0:07:12.756 that gene that codes for the spike protein is transcribed 0:07:12.916 --> 0:07:16.596 into messenger rna, and then the messenger rna then enters 0:07:16.596 --> 0:07:19.476 the cytoplasm and then makes the protein, and then you 0:07:19.556 --> 0:07:21.276 make the protein. So it's sort of like a step 0:07:21.476 --> 0:07:24.596 back from the messenger RNA strategy, but essentially it's the 0:07:24.596 --> 0:07:28.316 same strategy. It's ultimately getting the cell to make sours 0:07:28.356 --> 0:07:31.796 covie to spike protein. And the reason that it's sometimes 0:07:31.796 --> 0:07:35.676 called the trojan horse vaccination approach is that the adnovirus 0:07:36.236 --> 0:07:39.556 is another virus that does in fact, in effect the cell, 0:07:39.676 --> 0:07:42.516 though not with the possibility of replication. And once it's 0:07:42.596 --> 0:07:46.396 in there, it delivers the genetic code for the spike 0:07:46.436 --> 0:07:49.356 protein exactly right, and then the human body makes the 0:07:49.356 --> 0:07:51.676 spike protein and then develops the antibodies to it, and 0:07:51.716 --> 0:07:53.636 we're off to the races, as it were, off to 0:07:53.676 --> 0:07:59.276 the races. Are those viral vector vaccines just as easy 0:07:59.356 --> 0:08:03.156 to produce in large numbers of doses as the mRNA 0:08:03.236 --> 0:08:06.116 vaccine is. Well, the mRNA is synthetic at some level, 0:08:06.196 --> 0:08:08.156 so it's in that sense easier to make, but it 0:08:08.156 --> 0:08:10.076 can be rapidly killed up. And there's a lot of 0:08:10.156 --> 0:08:13.676 experience actually with replication effective add and ofvirus vectors, which 0:08:13.756 --> 0:08:15.236 was used actually as one of the e bowl of 0:08:15.316 --> 0:08:18.436 vaccines by Johnson and Johnson, the so called replication effective 0:08:18.436 --> 0:08:22.196 ad ofvirus twenty six, So millions of doses were administered 0:08:22.276 --> 0:08:25.556 in West Africa associated with that outbreak. Plus, interestingly, I 0:08:25.596 --> 0:08:28.156 think many people don't realize this that product who had 0:08:28.156 --> 0:08:31.396 to be maintained on dry ice and it was successfully 0:08:31.396 --> 0:08:33.956 maintained on dry ice in West Africa, because that's going 0:08:33.996 --> 0:08:36.196 to be also the story with the Fiser vaccine. So 0:08:36.436 --> 0:08:38.196 we'll see how this plays out, but there is at 0:08:38.276 --> 0:08:41.916 least some experience, some commercial experience with this approach. I'm 0:08:41.956 --> 0:08:44.076 glad you raised the temperature issue, which seems like it's 0:08:44.076 --> 0:08:46.836 going to be an important one going forward. The Fiser 0:08:46.876 --> 0:08:49.476 folks are saying that their vaccine needs to be kept 0:08:49.516 --> 0:08:52.956 at negative seventy degrees centigrade, which is around ninety four 0:08:53.116 --> 0:08:57.356 degrees below zero fahrenheit. Why does it have to be 0:08:57.436 --> 0:08:59.436 kept at that cold temperature? So? People who work with 0:08:59.476 --> 0:09:02.836 messenge drying in a laboratories usually stored in liquid nitrogen, 0:09:02.876 --> 0:09:05.676 which is like minus seventy to minus eighty degrees centigrade 0:09:06.516 --> 0:09:09.596 in order to be able to make sure that that 0:09:09.836 --> 0:09:12.796 molecule doesn't break down at least the fives are construct. 0:09:13.356 --> 0:09:16.156 You have to ship it and store it at minus seventy, 0:09:16.156 --> 0:09:18.356 which means that for the people who are taking care 0:09:18.396 --> 0:09:21.596 of it, they have to constantly replenish the dry ice, 0:09:21.676 --> 0:09:23.516 which is a lot to ask. And it gets worse 0:09:23.556 --> 0:09:25.716 than that. Then what happens is when you've thought it 0:09:25.756 --> 0:09:28.676 out and you put it in the refrigerator, that concentrated 0:09:28.716 --> 0:09:31.996 form of Messenger RNA can only stay in the refrigerator 0:09:32.036 --> 0:09:34.516 for twenty four hours. After twenty four hours you have 0:09:34.556 --> 0:09:36.876 to throw it out. Also, if you reconstitute it and 0:09:36.916 --> 0:09:40.076 it's just reconstituted with just a normal as salt water solution, 0:09:40.836 --> 0:09:44.156 after you reconstitute it, you have six hours to give it. 0:09:44.356 --> 0:09:46.396 So that's a lot to ask and I think when 0:09:46.436 --> 0:09:49.156 you do these trials, it's forty four thousand person trial, 0:09:49.556 --> 0:09:51.636 you can be sure that the company was very good 0:09:51.676 --> 0:09:54.516 about making that these study centers that were doing these 0:09:54.556 --> 0:09:57.396 trials knew exactly how to do it, and we're good 0:09:57.396 --> 0:09:59.596 at doing it. When a thing gets out into the 0:09:59.596 --> 0:10:01.996 real world, you worry that people are going to be 0:10:02.036 --> 0:10:05.436 as good at making sure they kept this ultra cold 0:10:05.516 --> 0:10:08.316 chain going as we did into trials, and that the 0:10:08.356 --> 0:10:11.076 efficacy may be a little less in a real world center. 0:10:11.116 --> 0:10:15.196 Because messenger RNA breaks down very quickly. It decentegrates very quickly, 0:10:15.436 --> 0:10:17.196 and although that would not be an issue, I think 0:10:17.236 --> 0:10:19.716 in terms of safety, it would definitely be an issue 0:10:19.716 --> 0:10:23.236 in terms of potency. Why does it break down so quickly? 0:10:23.276 --> 0:10:27.556 If in the human body, mRNA is tremendously necessary, and 0:10:27.596 --> 0:10:31.276 of course the human body is not negative seventy degrees centigrade, right, 0:10:31.476 --> 0:10:33.516 it does break down quickly in the human body, but 0:10:33.516 --> 0:10:36.836 you're constantly making messenger RNA and it's constantly breaking down. 0:10:36.996 --> 0:10:38.996 I mean, one thing, it's interesting just from a nerdy 0:10:39.076 --> 0:10:43.116 virologious standpoint, when you're infected with this virus, you usually 0:10:43.156 --> 0:10:47.556 shed infectious virus for about a week, meaning live virus 0:10:47.596 --> 0:10:50.356 for about a week, but you can be PCR positive 0:10:50.396 --> 0:10:52.836 for three months. Which interesting about that is when you're 0:10:52.876 --> 0:10:56.676 PCR positive, what that means is is that the virus 0:10:56.796 --> 0:10:59.036 gene is being detected in the back of your throw, 0:10:59.076 --> 0:11:01.476 so it's not the live virus necessarily, it's just the 0:11:01.556 --> 0:11:04.916 virus genome. Well, if messenger RNA breaks down so quickly, 0:11:04.916 --> 0:11:07.716 and it does, why is it that you're positive for 0:11:07.756 --> 0:11:10.596 three months after you're no longer making effect as virus. 0:11:10.676 --> 0:11:13.396 I mean, shouldn't the mRNA breakdown very quickly? And the 0:11:13.396 --> 0:11:16.036 answer as it does. So the only explanation for this 0:11:16.236 --> 0:11:19.196 is that the virus continues to make messenger rna, continues 0:11:19.236 --> 0:11:22.236 to make its genome, but doesn't make whole virus particles, 0:11:22.276 --> 0:11:24.436 which would be the first virus at least that I 0:11:24.476 --> 0:11:26.596 know about, has ever done something like that. It's just 0:11:26.636 --> 0:11:30.516 a very strange virus, this bad coronavirus. Can you think 0:11:30.556 --> 0:11:35.116 of any adaptive advantage genetically for an organism to continue 0:11:35.116 --> 0:11:37.836 to make its genome, maybe if it's not making the 0:11:37.836 --> 0:11:40.116 thing that enables it to spread in the population. That 0:11:40.156 --> 0:11:43.236 doesn't sound super efficient from a sort of classic evolutionary 0:11:43.276 --> 0:11:46.076 advantage standpoint. I know, I can't think of a reason, 0:11:46.156 --> 0:11:47.796 but you know what, I'm going to assume the virus 0:11:47.836 --> 0:11:49.836 is smarter than I am, and it's doing it for 0:11:49.836 --> 0:11:52.236 a reason, because why would it expand the energy that's 0:11:52.276 --> 0:11:55.996 needed to make message RNA unless there was some advantage 0:11:55.996 --> 0:12:02.596 to its survivability. Fascinating of the viral vector vaccines, the 0:12:02.596 --> 0:12:06.076 ones that Johnson and Johnson and Astra Zeneca are producing, 0:12:06.956 --> 0:12:10.116 will those also have to be kept at a comparable 0:12:10.236 --> 0:12:12.276 level of coldness. You mentioned that the vaccine that was 0:12:12.356 --> 0:12:14.716 used in Africa was stored on dry eye, so that's 0:12:14.716 --> 0:12:17.596 at the same kinds of low temperatures. My understanding is 0:12:17.756 --> 0:12:20.636 it's they'll be either kept at freezer or refrigerator temperatures, 0:12:20.636 --> 0:12:22.596 so they're not going to nearly require the kind of 0:12:23.036 --> 0:12:24.676 issues that are going to be required at least with 0:12:24.716 --> 0:12:27.236 the Fiser vaccine. Which interesting is that the modernist vaccine 0:12:27.276 --> 0:12:29.796 is also an mr anda vaccine, but it doesn't have 0:12:29.796 --> 0:12:31.876 to be shipped in stored at minus seventy to Minusa. 0:12:31.876 --> 0:12:34.036 It can be shipped in stored at minus twenty degrees centigrade, 0:12:34.036 --> 0:12:37.516 which is basically freezer temperature. They're both mr Anda vaccines. 0:12:37.516 --> 0:12:41.116 The gene sequence that determines the so called receptor binding 0:12:41.156 --> 0:12:44.716 domain on the Saurus CoV two spy protein is identical, 0:12:45.156 --> 0:12:47.836 but they are different. I mean, Fiser's vaccine is given 0:12:47.876 --> 0:12:51.676 at thirty micrograms per dose in two successive doses. Madernas 0:12:51.716 --> 0:12:54.596 is a hundred micrograms and two successive doses, And they 0:12:54.636 --> 0:12:57.196 don't have the same so called ducleoside analog, so they're 0:12:57.236 --> 0:13:00.916 not the same molecule. Obviously, there's there's stability differences, physical 0:13:00.996 --> 0:13:03.556 chemical differences between those two products, and I'm not sure 0:13:03.556 --> 0:13:06.316 exactly why, because obviously I'm sure if Fizer could ship 0:13:06.396 --> 0:13:08.516 in store at freezer temperature, which is much more doable, 0:13:08.756 --> 0:13:12.076 they would, so will that potentially turn out to be 0:13:12.116 --> 0:13:16.916 a determinative factor for governments that are making specific orders 0:13:16.956 --> 0:13:19.836 or for healthcare systems that are making specific orders. I mean, 0:13:19.876 --> 0:13:22.956 I'm sitting in I don't know, the Massachusetts Department of 0:13:23.276 --> 0:13:25.236 Health and Human Services, and I'm trying to figure out 0:13:25.276 --> 0:13:27.836 which one should I buy? Would that be ir relevant 0:13:27.836 --> 0:13:30.556 consideration for me? I'd rather buy the one, for example, 0:13:31.076 --> 0:13:34.276 that can be shipped at a slightly higher temperature or 0:13:34.276 --> 0:13:36.996 stored at us slightly higher temperature. You would think that 0:13:37.076 --> 0:13:39.916 the degree of ease, the degree to which administration and 0:13:40.036 --> 0:13:42.836 storage is idiot proof, it would be attractive what is 0:13:43.036 --> 0:13:45.676 currently required for the Fiser vaccine, which is, you know 0:13:45.716 --> 0:13:48.076 that you can't keep in the refrigerator from more than 0:13:48.116 --> 0:13:50.196 a day once we constuted, can't be kept for more 0:13:50.236 --> 0:13:52.916 than six hours, that you constantly have to replace with 0:13:52.996 --> 0:13:55.356 dry ice. I can't imagine how that is going to 0:13:55.436 --> 0:13:58.316 be done in a large retail pharmacy. I can't. I 0:13:58.316 --> 0:14:01.916 can't imagine how it's going to be done at our hospital, frankly, so, 0:14:01.916 --> 0:14:03.956 so then how would it be done? One way would 0:14:03.996 --> 0:14:06.876 be to have a series of centers that are distributed 0:14:06.876 --> 0:14:09.396 throughout a city that are like a testing center sept 0:14:09.436 --> 0:14:12.756 here that are specifically devoted to giving the vaccine. That 0:14:12.796 --> 0:14:14.196 would be one way to do it, and that may 0:14:14.236 --> 0:14:15.676 be the way it's going to be done. So yes, 0:14:15.716 --> 0:14:19.156 I think you're exactly right. How operationally or we get 0:14:19.156 --> 0:14:21.476 a vaccine that has these kinds of requirements out there. 0:14:23.036 --> 0:14:25.556 When you just described that you're not even sure your hospital, 0:14:25.596 --> 0:14:27.676 which is one of the best hospitals in the country 0:14:27.676 --> 0:14:29.996 and indeed in the world, could do it, that actually 0:14:30.036 --> 0:14:33.996 makes me wonder about viability altogether. I mean, you describe 0:14:34.036 --> 0:14:36.436 setting up these centers in different cities. That might be 0:14:36.476 --> 0:14:39.196 all well and good in big cities that have lots 0:14:39.196 --> 0:14:41.516 of resources, but it sounds like it would be hard 0:14:41.556 --> 0:14:43.516 to do in lots of parts of the United States, 0:14:43.596 --> 0:14:46.596 and definitely very hard to do in lots of parts 0:14:46.636 --> 0:14:48.676 of the world where such centers don't exist, and would 0:14:48.676 --> 0:14:51.036 then have to be built from scratch. From the way 0:14:51.036 --> 0:14:53.476 you formulated it there, I almost thought you were hinting 0:14:54.156 --> 0:14:57.556 that unless there is no other choice, the Fiser approach 0:14:57.636 --> 0:14:59.836 doesn't sound like it's going to be doable at scale. 0:15:00.836 --> 0:15:03.276 I think it's doable, and I think it's doable at scale. 0:15:03.436 --> 0:15:05.436 I just think it's going to require an enormous effort, 0:15:05.476 --> 0:15:07.996 which means an enormous expenditure as well as time. Yes, 0:15:08.076 --> 0:15:10.396 I think that's right, And understandings in the United States 0:15:10.516 --> 0:15:13.396 has contracted to by one hundred million doses of the 0:15:13.396 --> 0:15:17.396 Fiser vaccine, which means that they could vaccinate fifty million people. 0:15:17.436 --> 0:15:19.916 Now that the number of people that have been considered 0:15:19.956 --> 0:15:24.196 sort of first tier responders meaning essential workers like healthcare workers, 0:15:24.196 --> 0:15:28.036 people in transportation, law enforcement, etc. People over sixty five, 0:15:28.076 --> 0:15:30.676 people who have certain high risk medical conditions, added up 0:15:30.676 --> 0:15:33.996 to about one hundred and fifty million American adults, which 0:15:34.036 --> 0:15:38.036 is roughly half the adult population. This vaccine to be 0:15:38.036 --> 0:15:41.436 given exclusively at least for that hundred million, doses to 0:15:41.516 --> 0:15:44.116 the United States would be about a third of that. 0:15:44.236 --> 0:15:46.396 So the only way we're going to vaccinate the American 0:15:46.396 --> 0:15:48.516 population is if there's more than one vaccine. That's going 0:15:48.516 --> 0:16:01.716 to have to be true. We'll be right back. When 0:16:01.756 --> 0:16:04.596 I try to picture a center, a newly created center 0:16:04.636 --> 0:16:07.676 that becomes the vaccination center in a city, I guess 0:16:08.236 --> 0:16:09.916 we're down at getting into the nitty gritty, But I 0:16:09.916 --> 0:16:12.236 guess you have to set up appointments for people. You 0:16:12.236 --> 0:16:15.436 can have fifty million people lining up and waiting for vaccines, 0:16:15.436 --> 0:16:17.596 among other things, they would probably be too proximate to 0:16:17.596 --> 0:16:20.236 one another and that might spread the virus, right, and 0:16:20.396 --> 0:16:23.076 you have to identify whether or not these people really 0:16:23.076 --> 0:16:26.076 are the first tier for whom the vaccine is recommended. 0:16:26.076 --> 0:16:27.236 Because I think there are a lot of people who 0:16:27.276 --> 0:16:29.116 were going to get it who are not necessarily in 0:16:29.156 --> 0:16:31.956 that first tier group. So how do you identify who 0:16:31.956 --> 0:16:33.516 they are? How do you make sure they come back 0:16:33.556 --> 0:16:35.996 twenty one or twenty eight days letter depending on the vaccine, 0:16:36.036 --> 0:16:38.196 so to make sure they got their second dose. If 0:16:38.196 --> 0:16:39.916 you look at shing ricks, which is probably the best 0:16:39.916 --> 0:16:42.556 equivalent for this, which is an adult vaccine that's given 0:16:42.556 --> 0:16:45.676 in two doses roughly separated by a month, what percentage 0:16:45.716 --> 0:16:47.716 of people come back for that second dose. The answer 0:16:47.756 --> 0:16:50.116 is it's pretty high. It's about eighty five percent or 0:16:50.156 --> 0:16:52.036 so ninety percent. But still, you know, one out of 0:16:52.036 --> 0:16:54.316 ten or more people don't come back for that second 0:16:54.356 --> 0:16:56.796 dose because, first of all, the first dose of a 0:16:56.836 --> 0:16:59.836 shingles vaccine does cause side effect, as these vaccines will 0:17:00.036 --> 0:17:03.076 for different reasons. Mess Darna is an adgement. By adgement, 0:17:03.156 --> 0:17:05.636 I mean it stimulates the immune system so that you 0:17:05.636 --> 0:17:08.396 can give a lesser quantity of the active ingredient. And 0:17:08.436 --> 0:17:10.276 so you may get a first US and think, yeah, hey, 0:17:10.316 --> 0:17:12.956 this wasn't fun. I had fever, including high fever, I 0:17:13.036 --> 0:17:16.476 had headaches, chills, muscle eggs. I'm not signing up for that. Seconds, 0:17:16.556 --> 0:17:18.716 which really is the shingle story. I mean, it's certainly 0:17:18.836 --> 0:17:21.356 nothing compared to what the benefit is, which is preventing 0:17:21.356 --> 0:17:24.436 a disease that could kill you. So it's certainly worth it. 0:17:24.476 --> 0:17:26.436 But you know, for some people, they may think, you know, 0:17:26.596 --> 0:17:28.636 I'm young and healthy, I'm probably not going to die 0:17:28.636 --> 0:17:30.356 from this, so I really have to go back for 0:17:30.436 --> 0:17:34.876 that second dose. This wasn't much fun. The fact that 0:17:35.156 --> 0:17:38.596 mRNA it can be used as an adjument, namely something 0:17:38.596 --> 0:17:41.596 that stimulates your immune system, does that mean that a 0:17:41.716 --> 0:17:44.836 high percentage of the population who takes the vaccine will 0:17:44.876 --> 0:17:48.516 have those kinds of quasi flu leg symptoms in response 0:17:48.556 --> 0:17:50.956 to taking the vaccine. Yes, I think that's right. I 0:17:50.996 --> 0:17:53.356 think probably as much as half of people will have fever, 0:17:53.396 --> 0:17:56.596 including high fever, and then the symptoms associated with fever, headache, chills, 0:17:56.676 --> 0:17:58.996 muscle as I think that's likely. And how long do 0:17:59.036 --> 0:18:02.316 those symptoms typically last When you've administered just an agement 0:18:02.516 --> 0:18:05.356 a day or two. I mean, it'll go away again. 0:18:05.396 --> 0:18:08.556 So people will know they don't have COVID because they've 0:18:08.596 --> 0:18:10.316 just taken the vaccine, but they may be a little 0:18:10.316 --> 0:18:12.556 nervous about it. Well, the same thing actually applies for 0:18:12.636 --> 0:18:15.396 the vaccine trials. In theory, the participant doesn't know whether 0:18:15.396 --> 0:18:18.356 they're getting vaccine or placebo. But because the mRNA vaccines, 0:18:18.356 --> 0:18:21.516 and actually also true for the replication effect of adenovirus 0:18:21.556 --> 0:18:23.916 vaccines for a different reason, that too had a fairly 0:18:23.996 --> 0:18:26.516 high side effect profile. So if you didn't have side effects, 0:18:26.516 --> 0:18:28.396 you probably did have a placebo, and if you did 0:18:28.476 --> 0:18:30.916 have side effects, you probably did have the vaccine. So 0:18:31.156 --> 0:18:34.556 most people probably do know which they got. Interesting. Interesting. 0:18:34.636 --> 0:18:37.556 The second question I wanted to ask about that scenario 0:18:37.876 --> 0:18:40.196 is if one hundred and fifty million people aren't being 0:18:40.236 --> 0:18:43.476 described as first responders, and as you say, that's half 0:18:43.516 --> 0:18:46.556 of the US adult population, that on some level that 0:18:46.676 --> 0:18:50.196 first responder categorization isn't that meaningful, and it's going to 0:18:50.276 --> 0:18:52.316 have to be more narrowed down, especially if let's say 0:18:52.316 --> 0:18:54.076 we have fifteen million doses to begin with, and even 0:18:54.076 --> 0:18:55.676 among that there's the question of the order in which 0:18:55.676 --> 0:18:58.396 it will be given. Do you have a view about 0:18:58.436 --> 0:19:01.636 what would be plausible ways to narrow it down beyond that, 0:19:02.116 --> 0:19:04.636 or do you think that the governments involved are just 0:19:04.676 --> 0:19:08.036 going to duck the issue because it's so difficult to 0:19:08.116 --> 0:19:11.116 do allocation processes like this in a way that seems 0:19:11.156 --> 0:19:14.476 fair to people. I think you're exactly right. I think 0:19:14.476 --> 0:19:16.436 it is going to be difficult to do that, But 0:19:16.476 --> 0:19:18.116 I don't think they're going to duck the issue. I 0:19:18.156 --> 0:19:20.676 think both the Advisor Community for Communization Practice to the 0:19:20.716 --> 0:19:23.276 CDC and the National Category Medicine, which have been charged 0:19:23.316 --> 0:19:26.716 with trying to figure out exactly how these tiers are 0:19:26.716 --> 0:19:28.716 going to work out who's in the top top tier, 0:19:28.756 --> 0:19:31.636 who's just below that top tier, they won't duck it. 0:19:31.836 --> 0:19:33.396 The question is how it then is going to play 0:19:33.396 --> 0:19:35.836 out in the real world when the rubber meets the road, 0:19:36.356 --> 0:19:39.156 and we'll see I'm sure that the healthcare workers will 0:19:39.196 --> 0:19:41.316 be right up at the top, as will people who 0:19:41.316 --> 0:19:43.396 are older. For in terms of people who are over 0:19:43.436 --> 0:19:45.596 sixty five, we do need data to prove that the 0:19:45.676 --> 0:19:49.316 vaccine is effective in that age group. Hopefully we'll have 0:19:49.436 --> 0:19:51.916 enough people in these fisor trials, and we're during the trials, 0:19:51.956 --> 0:19:53.516 which are going to be the first ones to go 0:19:53.596 --> 0:19:56.036 through the FDA, we'll have enough data to be able 0:19:56.076 --> 0:19:58.556 to make that statement. Because although you know, obviously you 0:19:58.636 --> 0:20:00.796 want to make sure that both genders weekly represented, you 0:20:00.796 --> 0:20:02.916 want to make sure that there's an adequate representation of 0:20:03.036 --> 0:20:05.316 racial and ethnic minorities. There's no reason to believe that 0:20:05.356 --> 0:20:08.276 there would be really differences in the ability to respond 0:20:08.516 --> 0:20:10.756 with the accept for someone older and people who have 0:20:10.836 --> 0:20:14.636 various medical conditions, like you know, say obesity or diabetes. 0:20:14.756 --> 0:20:17.516 So that needs to be clear or as we do this. 0:20:18.596 --> 0:20:21.036 I thought of that specifically because I heard an interview 0:20:21.076 --> 0:20:24.076