WEBVTT - The Future Without Herd Immunity 0:00:15.356 --> 0:00:23.676 Pushkin from Pushkin Industries. This is deep background to show 0:00:23.676 --> 0:00:26.916 where we explore the stories behind the stories in the news. 0:00:27.236 --> 0:00:31.596 I'm Noah Feldman. For more than a year we've been 0:00:31.636 --> 0:00:36.516 hearing about the idea of herd immunity. In recent weeks, though, 0:00:36.556 --> 0:00:38.996 it's become very clear that the United States is not 0:00:39.076 --> 0:00:42.796 in the foreseeable future going to reach the threshold for 0:00:43.356 --> 0:00:47.396 herd immunity. There are a range of reasons and causes 0:00:47.436 --> 0:00:51.596 for this, and they go from vaccine hesitancy, to the 0:00:51.596 --> 0:00:56.556 contagiousness of new variants, and beyond to the underlying science. 0:00:57.836 --> 0:01:00.836 As a consequence, we're all trying to figure out what 0:01:00.996 --> 0:01:06.276 this means for what happens next. Will COVID become a manageable, 0:01:06.476 --> 0:01:10.196 self contained disease not unlike the common coal, Will it 0:01:10.276 --> 0:01:13.516 alternatively develop new variants that require us to go back 0:01:13.516 --> 0:01:17.116 to the drawing board and develop new vaccines, or will 0:01:17.156 --> 0:01:20.596 it be something in between. To help us understand these 0:01:20.636 --> 0:01:25.356 pressing questions, we're joined by doctor Mark Lipsitch Our go 0:01:25.596 --> 0:01:29.596 to COVID expert here on the program and indeed throughout 0:01:29.636 --> 0:01:33.836 the country. Mark is a professor of epidemiology at the 0:01:33.836 --> 0:01:37.556 Harvard Shan School of public Health. He's affiliated both with 0:01:37.556 --> 0:01:40.516 the Epidemiology Department and with the Department of Immunology and 0:01:40.556 --> 0:01:45.196 Infectious Disease. He runs the Center for Communicable Disease Dynamics 0:01:45.316 --> 0:01:48.956 at Harvard. Regular listeners of the podcast will know that 0:01:48.996 --> 0:01:51.756 Mark was one of the first voices anywhere in the 0:01:51.876 --> 0:01:54.636 United States or indeed in the world, drawing attention to 0:01:54.676 --> 0:01:58.596 the future trajectory of COVID nineteen. He joined us as 0:01:58.596 --> 0:02:00.876 early as February twenty twenty to tell us where the 0:02:00.916 --> 0:02:03.396 disease was going to go, and he's managed to join 0:02:03.516 --> 0:02:07.196 us intermittently ever since, taking time out of his extraordinarily 0:02:07.236 --> 0:02:10.796 busy schedule to set us right about where COVID is, 0:02:11.156 --> 0:02:19.636 where it's been, and where it's going. Mark, thank you 0:02:19.956 --> 0:02:24.836 as always for joining us. In general, I've tried to 0:02:24.956 --> 0:02:27.916 keep you as a guest, reserved for those moments when 0:02:27.956 --> 0:02:31.436 something really important seems to be shifting in the trajectory 0:02:31.596 --> 0:02:35.516 of COVID nineteen and news reports suggest that maybe we're 0:02:35.556 --> 0:02:38.076 getting there at this moment as well, and that that's 0:02:38.076 --> 0:02:41.516 something has to do with our acknowledgement finally that herd 0:02:41.556 --> 0:02:44.276 immunity may not be coming our way in the United 0:02:44.316 --> 0:02:46.476 States and the feseable future. It's something you have been 0:02:46.796 --> 0:02:49.996 warning about really almost from the start. So I want 0:02:49.996 --> 0:02:52.716 to start by just asking you to remind us, all 0:02:52.836 --> 0:02:56.836 for definitional purposes, of what herd immunity is defined in 0:02:56.956 --> 0:03:02.556 terms of our zero the replication rate of the virus. Sure, 0:03:02.756 --> 0:03:05.356 I think what you're asking is about the herd immunity threshold, 0:03:05.356 --> 0:03:07.196 and I'll come back to that distinction in a minute, 0:03:07.196 --> 0:03:10.636 because I think it's actually helpful to talk about it, 0:03:10.916 --> 0:03:14.156 But because the herd immunity threshold is to find as 0:03:14.196 --> 0:03:18.396 that level of immunity in the population from whatever means, 0:03:19.116 --> 0:03:23.996 usually infection or prior infection or vaccination or a combination, 0:03:24.836 --> 0:03:28.876 that it can't spread widely because there are so many 0:03:28.996 --> 0:03:32.316 immune people that chains of transmission don't sustain themselves and 0:03:32.396 --> 0:03:35.156 they fizzle out before the virus can spread too far. 0:03:36.876 --> 0:03:41.116 That is quantified by the basic reproductive rate or basic 0:03:41.156 --> 0:03:45.036 reproductive number are zero are not, which is the number 0:03:45.076 --> 0:03:50.076 of secondary cases that each case creates, and when everyone 0:03:50.116 --> 0:03:52.876 is susceptible, and when you do a little bit of 0:03:52.876 --> 0:03:56.556 algebra with that expression and try to find a level 0:03:56.556 --> 0:04:00.356 of immunity where instead of infecting, say three or four 0:04:00.396 --> 0:04:03.796 other people, the average case infects less than one other person, 0:04:03.956 --> 0:04:05.796 meaning the number of cases is going to go down 0:04:05.916 --> 0:04:08.556 over time. If you do the math, you end up 0:04:08.636 --> 0:04:12.996 getting the proportion that have to be immune is one 0:04:13.396 --> 0:04:17.276 the reciprocal of that number our zero one one over 0:04:17.316 --> 0:04:21.716 our zero. And so, to give some examples, if our 0:04:21.796 --> 0:04:24.436 zero is three, then that's two thirds. If our zero 0:04:24.556 --> 0:04:30.356 is four, that's three quarters. You've been saying ever since 0:04:30.356 --> 0:04:33.476 people started talking about the possibility of herd immunity being 0:04:33.516 --> 0:04:38.196 created partly through the spread of vaccines, that it would 0:04:38.196 --> 0:04:40.596 be optimistic. I think that's the word you used to 0:04:40.716 --> 0:04:44.836 actually imagine we could get there. As I understand some 0:04:44.876 --> 0:04:47.316 public statements that you've made recently, including the New York Times, 0:04:47.356 --> 0:04:50.116 you're now willing to shift a little bit from it's 0:04:50.156 --> 0:04:53.556 unlikely that we'll get there, too. It seems extraordinarily improbable 0:04:53.916 --> 0:04:55.876 that we're going to get there in the foreseeable future 0:04:56.436 --> 0:04:59.196 in the US, at least not through vaccinations as opposed 0:04:59.196 --> 0:05:05.796 to vaccinations plus natural infections. What has shifted your empirical observation. 0:05:05.796 --> 0:05:07.996 I don't think your theory has changed, but what has 0:05:08.436 --> 0:05:13.396 caused your perical observation to evolve to that point? Well, 0:05:13.476 --> 0:05:16.476 I think I do want to now mention the concept 0:05:16.516 --> 0:05:19.396 that hurt immunity and that threshold are slightly different. The 0:05:19.436 --> 0:05:22.196 threshold is the point where there is so much hurt 0:05:22.236 --> 0:05:25.996 immunity that we don't have ongoing transmission when we return 0:05:26.036 --> 0:05:30.236 to normal behavior. Herd immunity is a quantity, it's between 0:05:30.356 --> 0:05:33.236 zero and one, and we are getting more and more 0:05:33.276 --> 0:05:35.596 of it, So we are getting hurt some hurt immunity. 0:05:35.996 --> 0:05:38.756 But my statements have been about whether we're going to 0:05:38.956 --> 0:05:42.236 reach a level of immunity that means that we can 0:05:42.436 --> 0:05:47.196 expect zero or nearly zero transmission despite pre pandemic types 0:05:47.236 --> 0:05:50.076 of behavior. So, first of all, thanks for that clarification, 0:05:50.116 --> 0:05:53.356 because I and I think most other non scientists have 0:05:53.436 --> 0:05:56.596 been using the term herd immunity when what we should 0:05:56.596 --> 0:06:00.316 have been saying is the threshold of enough hurt immunity. 0:06:00.396 --> 0:06:03.236 So you could say, well, right, it's like the blueness 0:06:03.276 --> 0:06:05.036 of the blue thing. It could be very faintly blue 0:06:05.036 --> 0:06:06.796 and it would still be blue. But the question is 0:06:06.796 --> 0:06:08.396 how blued you need it to be for whatever your 0:06:08.436 --> 0:06:14.756 purpose is. Right, Okay, that's important. That's important for I mean, 0:06:15.356 --> 0:06:19.356 everybody is, including scientists, are sometimes sloppy about using her 0:06:19.436 --> 0:06:22.076 immunity is shorthand for the threshold. The reason I try 0:06:22.076 --> 0:06:25.196 to be very careful about it is that herd immunity 0:06:25.396 --> 0:06:27.956 is a good thing. Even a little bit is good, 0:06:28.076 --> 0:06:30.556 and a little more is a little better. And being 0:06:30.596 --> 0:06:33.116 below the threshold does not mean it's not doing any work. 0:06:33.196 --> 0:06:35.796 It is doing a lot of work. So that's actually 0:06:35.796 --> 0:06:38.476 some of the good news is that we are building 0:06:38.556 --> 0:06:41.156 up a lot of herd immunity. And the reason to 0:06:41.236 --> 0:06:45.516 answer now your question, the reason why I think it's 0:06:45.556 --> 0:06:49.396 extremely unlikely that we will get to the threshold in 0:06:49.436 --> 0:06:53.796 the United States is a few things. One is, when 0:06:53.796 --> 0:06:56.916 we started out, we had no data on whether these 0:06:56.996 --> 0:07:03.156 vaccines were protective against infection and a transmission, and that's 0:07:03.196 --> 0:07:06.956 the part of vaccine effectiveness that matters to her immunity. 0:07:07.036 --> 0:07:10.356 If everybody gets a technis shot, that doesn't protect the 0:07:10.356 --> 0:07:12.916 next person from getting tetanus because it doesn't do anything 0:07:12.916 --> 0:07:16.556 to transmission of the bacteria which comes from the soil. 0:07:17.476 --> 0:07:20.716 If the vaccine isn't stopping transmission, then but it's just 0:07:20.716 --> 0:07:24.036 stopping disease, it's not doing anything for her immunity. These 0:07:24.116 --> 0:07:27.596 vaccines do a lot for her immunity. Initially, it was 0:07:27.676 --> 0:07:30.996 unclear how much the first number I think that was 0:07:31.116 --> 0:07:34.356 meaningful that came out with sixty one percent, but that 0:07:34.436 --> 0:07:37.556 was from one dose and probably an underestimate for technical 0:07:37.596 --> 0:07:40.836 reasons that aren't that interesting for the Maderna vaccine, And 0:07:40.956 --> 0:07:44.396 now the numbers have come out through various sources of evidence. 0:07:44.396 --> 0:07:47.636 It's still uncertain, but it seems like it's probably somewhere 0:07:48.116 --> 0:07:51.276 between about sixty and ninety percent, probably seventy and nine 0:07:51.436 --> 0:07:57.636 protective against the process of transmission. So that's really good news, 0:07:58.116 --> 0:08:03.836 but it's not one hundred percent. And that distinction matters 0:08:03.956 --> 0:08:06.956 because to get to the herd immunity threshold, we have 0:08:06.996 --> 0:08:10.556 to cut transmission to one minus one over our zero, 0:08:11.276 --> 0:08:15.196 not just vaccinate that number of people. So the more 0:08:15.836 --> 0:08:18.316 the closer to one hundred percent effect of the vaccine is, 0:08:19.036 --> 0:08:20.956 the more we can interchange how many people have been 0:08:20.996 --> 0:08:23.836 vaccinated and how many people are totally immune. But we 0:08:23.916 --> 0:08:26.596 can't totally do that yet. It's because we have to 0:08:26.676 --> 0:08:28.636 multiply one by the other. Right, the question is not 0:08:29.156 --> 0:08:31.636 how many people have the vaccine, and it's not how 0:08:31.716 --> 0:08:33.876 much does the vaccine do, it's how much does the 0:08:33.956 --> 0:08:35.756 vaccine do for the number of people who have been 0:08:35.796 --> 0:08:39.956 vaccinated exactly. Yeah, okay, so we now understand that number, 0:08:40.036 --> 0:08:44.876 and though it's surprisingly good seventy nine, it's still not 0:08:44.996 --> 0:08:47.036 going to get us necessarily where we need to go 0:08:47.196 --> 0:08:49.756 when you consider it as a percentage of all of 0:08:49.756 --> 0:08:51.836 the people who've been vaccinated, which is the part that's 0:08:51.876 --> 0:08:55.356 not so high. Right. So the other bit of good 0:08:55.396 --> 0:08:58.396 news that makes it easier to get close to the 0:08:58.396 --> 0:09:01.676 threshold is that children really don't seem to be as 0:09:01.716 --> 0:09:05.596 important for transmission, and so that one one over our 0:09:05.716 --> 0:09:09.916 zero is an average. And as you learn more about 0:09:09.916 --> 0:09:12.556 the population, if you leave out some of the people 0:09:12.676 --> 0:09:16.276 from vaccination who are less important to transmission, that matters 0:09:16.356 --> 0:09:19.036 less than leaving out people who are more important to transmission. 0:09:19.076 --> 0:09:21.076 So that probably buys us a little bit of margin. 0:09:21.876 --> 0:09:24.396 How far did those numbers go mark on kids not 0:09:24.476 --> 0:09:26.996 being involved in transmission? And the reason this is relevant 0:09:27.076 --> 0:09:29.676 is one of the conversations that I've heard repeated a 0:09:29.716 --> 0:09:32.316 lot among all kinds of people is people say, well, 0:09:32.316 --> 0:09:35.276 I'm vaccinated, but my kids aren't vaccinated, and so I'm 0:09:35.316 --> 0:09:37.716 worried that there is some possibility that I might transmit 0:09:37.756 --> 0:09:39.636 to them, or that they might transmit to me, and 0:09:39.676 --> 0:09:41.996 even though they wouldn't get that sick, most probably they 0:09:41.996 --> 0:09:44.436 would nevertheless transmit it. And so if the number of 0:09:45.156 --> 0:09:47.716 kids not transmitting is relatively high, then that worry is 0:09:47.796 --> 0:09:51.436 much less salient. It seems to increase with age, So 0:09:51.556 --> 0:09:54.796 a fifteen year old is probably effectively an adult from 0:09:54.836 --> 0:09:59.156 sars Kovi two's perspective, roughly speaking, and a five year 0:09:59.156 --> 0:10:03.116 old is definitely considerably less I'd say that's the sort 0:10:03.156 --> 0:10:06.476 of rough picture. Okay, So those are the bits of 0:10:06.516 --> 0:10:10.596 good news. Mostly, the bits of bad news that make 0:10:10.676 --> 0:10:14.516 it unlikely that, say, the United States will quickly get 0:10:14.516 --> 0:10:17.716 to the herd immunity threshold are First, that variants are 0:10:17.756 --> 0:10:22.996 more contagious than the original strain of sars Kobe two. 0:10:23.636 --> 0:10:27.796 So everyone agreed pretty much that the original strain had 0:10:27.836 --> 0:10:30.476 a reproductive number of about two and a half or three. 0:10:30.556 --> 0:10:33.516 I think that might have been too simple, and maybe 0:10:33.516 --> 0:10:35.916 it's higher in some places, but let's say for the 0:10:35.916 --> 0:10:37.676 sake of argument, it was two and a half or three. 0:10:38.836 --> 0:10:41.516 The B one one seven variant that's now very common 0:10:41.596 --> 0:10:44.516 in many parts of the world is thought to be 0:10:44.516 --> 0:10:48.436 about fifty percent more contagious, more transmissible, so that pushes 0:10:48.476 --> 0:10:51.836 it up to maybe four and a half, and so 0:10:51.876 --> 0:10:55.636 that pushes the herd immunity threshold close to eighty percent. 0:10:57.956 --> 0:11:01.956 So that means that say we need say it's seventy 0:11:01.956 --> 0:11:04.516 five percent, say we need to immunize seventy five percent 0:11:04.556 --> 0:11:07.756 of the population, and say that the vaccine is eighty 0:11:07.796 --> 0:11:12.276 percent of transmission, then we need to get very close 0:11:12.356 --> 0:11:15.716 to whatever seventy five divided by eighty is, so very 0:11:15.716 --> 0:11:19.156 close to one hundred percent coverage in the population in 0:11:19.276 --> 0:11:24.476 order to reach that threshold. And given the combination of 0:11:24.476 --> 0:11:28.116 hesitancy poor access, which I think are two sides of 0:11:28.156 --> 0:11:33.476 the same coin, and so far not vaccinating children under sixteen, 0:11:33.556 --> 0:11:36.396 soon it will probably be under twelve, I think it's 0:11:36.476 --> 0:11:41.556 just very hard to imagine getting to that level. So 0:11:41.596 --> 0:11:45.436 now let's turn to what this means in practical terms. 0:11:45.996 --> 0:11:49.956 There are a few different dimensions. Let's start by thinking 0:11:49.996 --> 0:11:52.756 about modeling, which is one of the things that you 0:11:52.836 --> 0:11:55.036 do for a living and that you've done so skillfully 0:11:55.196 --> 0:11:59.836 in this entire epidemic process. When you think about what 0:11:59.916 --> 0:12:06.796 models might look plausible for how the current COVID virus 0:12:07.036 --> 0:12:10.876 is going to proceed. Circumstances where we're not at the 0:12:10.916 --> 0:12:14.636 threshold of herd immunity. What's the modeling space, as it were, 0:12:14.716 --> 0:12:20.876 What are the possibilities that you see as most plausible. Yeah, 0:12:20.996 --> 0:12:25.556 I think the most plausible scenario, not the only plausible one, 0:12:25.556 --> 0:12:27.716 but really the most plausible one is one that was 0:12:27.876 --> 0:12:32.036 described in science in a paper by Rustamantia and Jenny 0:12:32.116 --> 0:12:37.516 Levine and Autar Bjornstad. And what they do is essentially 0:12:37.556 --> 0:12:43.396 make an analogy to other coronaviruses. So the most important 0:12:43.436 --> 0:12:47.036 difference probably between this coronavirus and other ones is that 0:12:47.236 --> 0:12:50.476 everyone in the world has been infected with the other 0:12:50.516 --> 0:12:55.476 coronaviruses many times by the time they're say a teenager, 0:12:56.116 --> 0:12:59.156 and so people get infected over and over and it 0:12:59.236 --> 0:13:02.116 just circulates. They just circulate. And those are mostly they're 0:13:02.156 --> 0:13:03.956 not all of the common cold viruses, but they are 0:13:03.996 --> 0:13:06.476 within the family of the common cold viruses. They are 0:13:07.076 --> 0:13:13.076 justifiably obscure except virologists because they don't make people very sick. 0:13:14.116 --> 0:13:18.116 And so I think a very likely outcome is that 0:13:18.156 --> 0:13:21.236 this one behaves similarly, and that what vaccines are going 0:13:21.236 --> 0:13:23.916 to do for us is to get us over the 0:13:23.996 --> 0:13:27.196 hump of the period in history, namely the one we're 0:13:27.196 --> 0:13:30.436 living through where there are a lot of people who 0:13:31.116 --> 0:13:34.716 would get very sick from a first exposure to this virus, 0:13:34.796 --> 0:13:38.676 and everybody's getting first exposures because it's a new virus, 0:13:39.196 --> 0:13:43.036 and therefore that's a bad combination. So if the vaccines 0:13:43.196 --> 0:13:46.356 can be used to put us in a position where 0:13:46.396 --> 0:13:49.676 nobody is getting or a few people are getting exposed 0:13:49.716 --> 0:13:52.276 for the first time when they are also old or 0:13:52.316 --> 0:13:56.716 have comorbid conditions, then the vaccines will have prevented a 0:13:56.716 --> 0:14:01.036 lot of illness and death. And then it's quite possible 0:14:01.116 --> 0:14:04.756 that the residual circulation of the virus among the people 0:14:04.756 --> 0:14:07.836 who aren't vaccinated, or among the people in whom the 0:14:07.876 --> 0:14:12.876 vaccine immunity slowly wanes, is going to give us longer 0:14:12.996 --> 0:14:17.756 term protection against severe disease, so that five years from now, 0:14:17.836 --> 0:14:21.636 you and I and our children and our parents will 0:14:21.636 --> 0:14:24.676 have probably been infected by the coronavirus if we don't 0:14:24.796 --> 0:14:27.996 continue to vaccinate very heavily for the next five years, 0:14:28.876 --> 0:14:32.436 but it won't bother us because we will have all 0:14:32.476 --> 0:14:35.956 been vaccinated once and or had it before at an 0:14:35.956 --> 0:14:39.836 age when we were not likely to get very sick, 0:14:40.476 --> 0:14:43.396 and so it will behave much like the other coronaviruses. 0:14:44.036 --> 0:14:46.436 So the good news part of that is that at 0:14:46.476 --> 0:14:51.116 least over time, that describes a kind of normalization where 0:14:51.236 --> 0:14:54.036 childhood infection is protective in a lot of good and 0:14:54.116 --> 0:14:56.516 healthy ways. I assume the downside of that is that 0:14:56.556 --> 0:15:00.076 among those who are not vaccinated and who are more vulnerable, 0:15:00.636 --> 0:15:03.396 a substantial number of people who have not been vaccinated. 0:15:03.436 --> 0:15:06.276 Among that class of people could get very sick and 0:15:06.396 --> 0:15:10.436 even die in the next let's say five who would 0:15:10.436 --> 0:15:14.436 not if they were vaccinated. Right, So the public health 0:15:14.796 --> 0:15:16.876 goal if that scenario is going to play out, is 0:15:16.916 --> 0:15:19.996 to vaccinate as many of the people known to be 0:15:20.036 --> 0:15:23.916 at high risk as possible, and probably also as many 0:15:23.996 --> 0:15:27.436 of the other people as possible, in order to slow 0:15:27.476 --> 0:15:32.076 down transmission and just give people's immune systems a chance 0:15:32.076 --> 0:15:35.676 to catch up. If that scenario plays out, then the 0:15:35.796 --> 0:15:39.076 vaccines are sort of a bridge to a more peaceful 0:15:39.116 --> 0:15:42.076 future rather than something we have to do all the time. 0:15:43.476 --> 0:15:47.556 So that's the vaccine as bridge scenario. And it's not 0:15:47.676 --> 0:15:50.036 so bad relative to the other possibilities, and you think 0:15:50.076 --> 0:15:52.556 it's the most probable, So that's good news. Talk to 0:15:52.636 --> 0:15:56.236 us about some of the other possibilities. Well, the other 0:15:56.276 --> 0:16:01.156 possibilities would be that immunity to severe disease from the 0:16:01.236 --> 0:16:06.196 vaccine and or from natural infection is not long lasting, 0:16:06.596 --> 0:16:12.516 either because the immunefectors wan over time, or because the 0:16:12.596 --> 0:16:16.716 virus changes and is not as strongly affected by the immunity, 0:16:16.836 --> 0:16:20.636 or both, And so then it's a sort of more 0:16:20.676 --> 0:16:24.396 ongoing war because we have to keep trying to protect 0:16:24.476 --> 0:16:28.236 people from infection, not only from their first infection, but 0:16:28.356 --> 0:16:33.876 from their second, third, fourth infections. And is possible. I 0:16:33.916 --> 0:16:38.996 think infection immunity very likely will wane, But the question 0:16:39.116 --> 0:16:42.716 is whether there is this long term, relatively long term 0:16:42.716 --> 0:16:45.956 immunity that gets you from infection to infection and then 0:16:45.956 --> 0:16:51.796 gets boosted again against getting really sick. So that's one 0:16:51.836 --> 0:16:54.436 of the two subpossibilies that you just describe, that infection 0:16:54.476 --> 0:16:58.196 immunity itself WANs, whether from natural infection or from the vaccine, 0:16:58.196 --> 0:17:01.276 and as you say, whether that's a disaster or not 0:17:01.356 --> 0:17:04.596 really depends on whether the virus is circulating in enough 0:17:04.676 --> 0:17:08.276 quantity that you can get a natural booster from being exposed. 0:17:09.356 --> 0:17:12.876 Then there's the possibility that you mentioned that there might 0:17:12.916 --> 0:17:17.836 actually be an evolutionary process in which the virus evolves 0:17:17.916 --> 0:17:21.596 to the point where it is vaccine resistant. And I 0:17:21.596 --> 0:17:24.356 guess what I want to ask you about is you've 0:17:24.396 --> 0:17:28.916 done plenty of modeling of other viruses that have evolved 0:17:28.916 --> 0:17:31.516 to be vaccine resistant, presumably, and there are lots of 0:17:31.516 --> 0:17:35.276 bacteria where this has happened over time where there's pretty 0:17:35.276 --> 0:17:38.276 good data I think on trying to figure out that, 0:17:38.356 --> 0:17:41.236 and so there must be familiar and available models to 0:17:41.276 --> 0:17:44.476 you when you think about vaccine resistance. Is there any 0:17:44.516 --> 0:17:47.516 way to think intelligently about the probability of something like 0:17:47.556 --> 0:17:52.356 that happening? Yeah, I mean flu certainly is the sort 0:17:52.396 --> 0:17:55.116 of classic example of a viral infection that changes over 0:17:55.156 --> 0:17:59.036 time to resist our natural immunity, and at the same 0:17:59.076 --> 0:18:03.596 time it happens to also escape from existing vaccines, and 0:18:03.636 --> 0:18:06.876 that's why we keep changing the flu vaccine. So I 0:18:06.916 --> 0:18:13.196 think that's the example or the analog. The viruses are 0:18:13.236 --> 0:18:17.396 different and they evolve differently, and I'm not sure how 0:18:17.396 --> 0:18:20.316 to put a probability a sort of how far the virus, 0:18:20.476 --> 0:18:24.156 this virus can go in escaping our immunity. It's like 0:18:24.196 --> 0:18:26.076 we've chased it down an alley, and the question is 0:18:26.076 --> 0:18:27.756 at the end of that alley, is there a brick wall, 0:18:27.756 --> 0:18:30.596 and it's stuck and we've got it. It's escaped as 0:18:30.596 --> 0:18:32.516 far as it can escape, and now there's nowhere more 0:18:32.556 --> 0:18:34.436 for it to go, or is there a big vista 0:18:34.476 --> 0:18:38.996 of other things for it to do? And I don't 0:18:39.516 --> 0:18:42.276 I don't know any way to put probabilities on that. 0:18:42.556 --> 0:18:46.316 I think the best way to know it probably would 0:18:46.316 --> 0:18:48.556 be to try to do it in the lab and 0:18:48.636 --> 0:18:51.476 see where it goes from the variance we've already seen, 0:18:53.036 --> 0:18:55.196 which is itself a somewhat dangerous thing to do, but 0:18:55.276 --> 0:19:00.436 probably a very valuable one. That's a fascinating topic, which 0:19:00.436 --> 0:19:01.796 I would like to come to in just a second, 0:19:01.836 --> 0:19:04.916 but before we do, I'm sort of surprised to hear 0:19:04.956 --> 0:19:07.636 you say that there isn't a kind of ability to 0:19:07.716 --> 0:19:10.716 make a prediction about probability of evolution, especially in light 0:19:10.756 --> 0:19:14.476 of the fact that we've now observed the virus evolving 0:19:14.516 --> 0:19:18.396 pretty quickly with respect to the variants that are out there. 0:19:18.436 --> 0:19:19.796 I mean, is there no I guess there isn't a 0:19:19.916 --> 0:19:24.236 really way to extrapolate from the virus's capacity to evolve, 0:19:24.876 --> 0:19:28.916 to evolve these new variants that are more capable of 0:19:28.916 --> 0:19:32.436 infection than the kind before. To extrapolate from that to 0:19:32.796 --> 0:19:34.756 whether it would be able to evolve in ways that 0:19:34.796 --> 0:19:38.796 would escape the vaccine, Well, I think there are a 0:19:38.796 --> 0:19:42.196 few things. One is, it can mutate. I mean it's 0:19:42.356 --> 0:19:45.356 generating mutations all the time, and the existing variants are 0:19:45.396 --> 0:19:49.436 generating new variants that are more different from the original 0:19:50.356 --> 0:19:53.716 strain than the say B one one seven itself. So 0:19:53.876 --> 0:19:56.676 B one one seven is making new versions of itself 0:19:56.676 --> 0:19:59.796 that are further mutated. So that's not in doubt. That's 0:19:59.836 --> 0:20:03.796 just RNA viruses do that. The question is what will 0:20:03.836 --> 0:20:08.036 the impact be on escaping our immune responses, and even 0:20:08.076 --> 0:20:12.116 for the existing variants, that remains a little bit unclear. 0:20:12.196 --> 0:20:15.996 It is very clear that they escape neutralizing antibodies to 0:20:16.076 --> 0:20:18.956 varying degrees depending on the variant you're talking about. But 0:20:19.116 --> 0:20:22.316 whether that means that they totally escape our ability to 0:20:22.356 --> 0:20:27.956 control them. That's mostly unobserved and still being documented. So 0:20:29.276 --> 0:20:31.836 they can change, that's not in doubt. But whether they 0:20:31.836 --> 0:20:35.876 can change in ways that really get around to a 0:20:35.996 --> 0:20:39.796 large degree, our ability to fight them off with our 0:20:39.836 --> 0:20:42.916 antibodies and other forms of immunity, I think is still 0:20:42.956 --> 0:20:46.156 an open question. Even for the existing to maybe one 0:20:46.196 --> 0:20:49.356 three five one the South African variant or the Brazilian 0:20:49.396 --> 0:20:52.116 variant or the Indian variant. So that's a question. It's 0:20:52.116 --> 0:20:54.036 not whether they can evolve, it's whether how far can 0:20:54.076 --> 0:20:59.476 they go in their biological properties, And that's something that 0:20:59.636 --> 0:21:02.916 you can't really answer, mostly because evolution is not a 0:21:02.956 --> 0:21:05.876 perfectly modelable process, right, I mean, it has contingent features, 0:21:05.996 --> 0:21:09.676 and you know there aren't necessarily absolute is that will 0:21:09.716 --> 0:21:13.516 tell you in relation to both the underlying biology and 0:21:13.516 --> 0:21:16.556 then the way it interacts with the world outside what's 0:21:16.596 --> 0:21:18.436 going to happen. If it were, we could do a 0:21:18.476 --> 0:21:21.156 lot more predictive work on evolution than we actually are 0:21:21.196 --> 0:21:24.396 able to do. Yeah. Yeah, I mean there are a 0:21:24.476 --> 0:21:27.516 number of us, including our group with bacteria, trying to 0:21:27.556 --> 0:21:30.396 chip away at this problem. But this is a major 0:21:30.876 --> 0:21:34.556 hard problem in biology, and we aren't there yet. We 0:21:34.596 --> 0:21:36.876 don't know what the space of possibilities is and how 0:21:36.876 --> 0:21:40.356 it relates to the sequence. Talk to me about what 0:21:40.516 --> 0:21:42.676 in the real world it would look like in this 0:21:42.716 --> 0:21:45.836 scenario where let's call it the flu like scenario. If 0:21:45.876 --> 0:21:48.756 we started with the vaccines as a bridge, this is 0:21:48.796 --> 0:21:50.956 the flu like scenario where we have to go back 0:21:51.436 --> 0:21:55.036 and try to get a new vaccine each time a 0:21:55.156 --> 0:22:00.196 dangerous new variant emerges. Why do we do as poorly 0:22:00.236 --> 0:22:02.956 as we do with respect to the flu vaccine, which 0:22:03.196 --> 0:22:05.876 I guess only prevents about forty to sixty percent of 0:22:05.916 --> 0:22:11.436 the flu each time it's redvised. Yeah, it's a good question. 0:22:11.596 --> 0:22:14.556 I think that in itself is a scientific discussion that 0:22:14.996 --> 0:22:18.196 isn't totally resolved. Why the flu vaccines have been so 0:22:18.236 --> 0:22:22.556 hard to make as good as say, these existing coronavirus vaccines. 0:22:23.356 --> 0:22:27.156 Partly it's about predicting which sequence to use, but even 0:22:27.196 --> 0:22:30.076 when it's well matched, it's not always very good. So 0:22:30.116 --> 0:22:33.356 I think there's some reason for optimism here that the 0:22:33.476 --> 0:22:36.516 first guests at what to do about a coronavirus vaccine 0:22:36.516 --> 0:22:39.916 turned out to be as much as ninety five percent effective, 0:22:39.996 --> 0:22:44.396 and that's much better than flu vaccines. So it may 0:22:44.436 --> 0:22:48.796 be that coronaviruses are easier. But this coronavirus may continue 0:22:48.836 --> 0:22:53.476 to change, And then again, the question is whether it 0:22:53.556 --> 0:22:56.756 changes in a way that evads our infection immunity, which 0:22:56.756 --> 0:23:02.356 would mean that we have to consider trying to control it, 0:23:02.516 --> 0:23:07.596 or whether it evades our severe disease immunity, which would 0:23:07.636 --> 0:23:10.516 be a much bigger deal. And what I mean by 0:23:10.556 --> 0:23:13.916 that is if we didn't have flu vaccines, as most 0:23:13.956 --> 0:23:17.716 of the world doesn't use flu vaccines, there are people, 0:23:17.916 --> 0:23:20.636 many people who die because they don't get flu vaccines, 0:23:21.196 --> 0:23:24.556 but it is not the same kind of global catastrophe 0:23:24.716 --> 0:23:29.876 as this has been. And that's because existing immunity to flu, 0:23:30.196 --> 0:23:33.476 even though the flu viruses are changing, is still protecting 0:23:33.476 --> 0:23:36.436 people to a large degree against getting very sick and dying. 0:23:37.556 --> 0:23:41.116 So the sort of flu analogy is a worse scenario, 0:23:41.236 --> 0:23:43.556 and we probably would try to make better vaccines that 0:23:43.716 --> 0:23:46.476 keep up with the new strains, but it's still not 0:23:47.076 --> 0:23:49.756 a new pandemic every year. It's in the realm of 0:23:50.756 --> 0:23:55.476 public health problem rather than public health catastrophe. We'll be 0:23:55.556 --> 0:24:09.116 right back mark. When you see the virus running maybe 0:24:09.196 --> 0:24:11.876 checked is the wrong word, but running hard and fast 0:24:12.116 --> 0:24:14.396 through a population, as seems to be happening right now 0:24:14.436 --> 0:24:18.876 in India, Apart from the understandable concern about the human 0:24:18.916 --> 0:24:23.636 suffering that that's going to entail, do you think to yourself, oh, boy, 0:24:23.676 --> 0:24:27.596 that raises the probability of new variance emerging that could 0:24:27.596 --> 0:24:32.076 be ultimately vaccine resistant, or do you think, rather, look, 0:24:32.156 --> 0:24:34.916 this is what the virus was always going to do. 0:24:35.076 --> 0:24:38.636 If not restrained and people are catching it, and so 0:24:38.716 --> 0:24:41.036 there's no particular reason to think that it would need 0:24:41.116 --> 0:24:45.196