1 00:00:15,396 --> 00:00:33,676 Speaker 1: Pushkin Pushkin from Pushkin Industries. This is Deep Background, the 2 00:00:33,716 --> 00:00:36,916 Speaker 1: show where we explore the stories behind the stories in 3 00:00:36,956 --> 00:00:41,796 Speaker 1: the news. I'm Noah Feldman. Before we start today, I 4 00:00:41,836 --> 00:00:43,516 Speaker 1: want to let you know that this is the last 5 00:00:43,556 --> 00:00:47,796 Speaker 1: episode in our season about power. After this, we're going 6 00:00:47,796 --> 00:00:50,716 Speaker 1: on a hiatus for the next few months to work 7 00:00:50,796 --> 00:00:54,116 Speaker 1: on our next season. If you have thoughts or suggestions, 8 00:00:54,516 --> 00:00:57,076 Speaker 1: please let me know. You can find me on Twitter 9 00:00:57,396 --> 00:01:00,476 Speaker 1: at Noah R. Feldman, or you can reach me on 10 00:01:00,516 --> 00:01:04,876 Speaker 1: my website Noah Dashfeldman dot com, where I also have 11 00:01:05,116 --> 00:01:07,436 Speaker 1: a newsletter which you can use so that we can 12 00:01:07,516 --> 00:01:11,036 Speaker 1: keep in touch while I'm off the air. It's been 13 00:01:11,076 --> 00:01:13,516 Speaker 1: a joy to explore behind the headlines with you all 14 00:01:13,596 --> 00:01:15,916 Speaker 1: these last two seasons, and I want to take a 15 00:01:15,996 --> 00:01:19,556 Speaker 1: moment to thank you for joining us on this journey 16 00:01:19,796 --> 00:01:24,436 Speaker 1: over the years. Okay, on with the show. For our 17 00:01:24,516 --> 00:01:27,436 Speaker 1: last episode of the season, we're returning once more to 18 00:01:27,516 --> 00:01:31,756 Speaker 1: the biggest story of them all, the global pandemic. Joining 19 00:01:31,836 --> 00:01:35,276 Speaker 1: us once again on just about the exact second anniversary 20 00:01:35,556 --> 00:01:38,956 Speaker 1: of his first time on the show, we have Mark Lipsich, 21 00:01:38,996 --> 00:01:43,556 Speaker 1: the brilliant and influential epidemiologist from Harvard University's School of 22 00:01:43,636 --> 00:01:47,196 Speaker 1: Public Health. Mark is a professor of epidemiology and he 23 00:01:47,276 --> 00:01:51,396 Speaker 1: directs the Center for Communicable Disease Dynamics. It's no exaggeration 24 00:01:51,476 --> 00:01:54,796 Speaker 1: to say that Mark has been the go to person 25 00:01:55,116 --> 00:01:58,916 Speaker 1: for interpreting the trajectory of the COVID nineteen pandemic and 26 00:01:59,076 --> 00:02:06,076 Speaker 1: indeed for trying to make sense of its future. Mark, 27 00:02:06,116 --> 00:02:09,116 Speaker 1: thank you so much for joining me. It's almost exactly 28 00:02:09,276 --> 00:02:12,276 Speaker 1: two years since we first had a conversation in the 29 00:02:12,356 --> 00:02:15,396 Speaker 1: very early days of realization of what was having with COVID, 30 00:02:15,396 --> 00:02:18,476 Speaker 1: and we've checked in periodically since. And I would like 31 00:02:18,556 --> 00:02:21,396 Speaker 1: nothing better than for this to be a valedictory conversation 32 00:02:21,436 --> 00:02:23,436 Speaker 1: on the topic, so that next time we could talk 33 00:02:23,436 --> 00:02:26,356 Speaker 1: about some other aspect of disease dynamics. But somehow it 34 00:02:26,396 --> 00:02:29,676 Speaker 1: won't quite go away. So how many more times are 35 00:02:29,716 --> 00:02:31,316 Speaker 1: you and I are going to do this? I mean, 36 00:02:31,396 --> 00:02:33,676 Speaker 1: but put another way, how many more letters of the 37 00:02:33,716 --> 00:02:35,876 Speaker 1: Greek alphabet are we going to need to learn? Is 38 00:02:35,956 --> 00:02:40,436 Speaker 1: this is the variant process, one that is probabilistically likely 39 00:02:40,556 --> 00:02:44,516 Speaker 1: to just come back again and again and again. Well, 40 00:02:44,636 --> 00:02:49,436 Speaker 1: until we see a protracted period without new variants, we 41 00:02:49,556 --> 00:02:52,916 Speaker 1: have to assume they will keep coming. What their characteristics 42 00:02:52,916 --> 00:02:56,916 Speaker 1: will be we can make some speculations about but those 43 00:02:56,956 --> 00:03:02,756 Speaker 1: speculations would not have probably included omicron in the form 44 00:03:02,836 --> 00:03:05,716 Speaker 1: that it had, so we should be humble about our 45 00:03:05,756 --> 00:03:08,996 Speaker 1: speculations as well. I mean, I think when you have 46 00:03:09,676 --> 00:03:13,196 Speaker 1: tens to hundreds of millions of people infected in any 47 00:03:13,236 --> 00:03:17,116 Speaker 1: given a short period of time around the globe with 48 00:03:17,276 --> 00:03:21,156 Speaker 1: a virus, there is an opportunity for natural selection and 49 00:03:21,916 --> 00:03:26,716 Speaker 1: genetic drift to play their tricks and for new variants 50 00:03:26,756 --> 00:03:32,076 Speaker 1: to evolve, and our immune systems impose selective pressure. Our 51 00:03:32,116 --> 00:03:36,836 Speaker 1: transmission behavior impose a selective pressure. So the ingredients are there. 52 00:03:37,156 --> 00:03:41,836 Speaker 1: We all knew sort of intellectually that variants were a possibility. 53 00:03:41,916 --> 00:03:45,436 Speaker 1: There was some hope that maybe the evolutionary rates were 54 00:03:45,436 --> 00:03:49,396 Speaker 1: a little bit lower in coronaviruses, but that has not 55 00:03:49,516 --> 00:03:51,756 Speaker 1: turned up to be true. And in fact, the big 56 00:03:51,796 --> 00:03:56,476 Speaker 1: puzzle in some of my friends minds right now is 57 00:03:56,956 --> 00:03:59,796 Speaker 1: why is omicron so different from from the last one. 58 00:03:59,876 --> 00:04:04,476 Speaker 1: So I think we're going to be at this COVID 59 00:04:04,556 --> 00:04:09,756 Speaker 1: game for a long time and the real question what 60 00:04:09,956 --> 00:04:13,676 Speaker 1: the impact of that on health is and what the 61 00:04:13,716 --> 00:04:16,756 Speaker 1: properties of these variants are, which is I think the 62 00:04:16,796 --> 00:04:19,836 Speaker 1: hardest thing to predict other than likely being more and 63 00:04:19,876 --> 00:04:24,516 Speaker 1: more transmissible, and the easier thing to predict but still 64 00:04:24,556 --> 00:04:28,036 Speaker 1: not certain, is what is the state of us in 65 00:04:28,116 --> 00:04:32,276 Speaker 1: terms of our immunity and the level to which vaccine 66 00:04:32,516 --> 00:04:38,116 Speaker 1: and prior infection confer on us lasting immunity. I would 67 00:04:38,116 --> 00:04:41,556 Speaker 1: love to learn more in our conversation Mark about what 68 00:04:41,676 --> 00:04:45,316 Speaker 1: are the kinds of logics that you and your colleagues 69 00:04:45,396 --> 00:04:48,756 Speaker 1: use when trying to talk about what those properties might be, 70 00:04:48,996 --> 00:04:52,836 Speaker 1: understanding that they're not perfectly predictable. So you mentioned transmissibility, 71 00:04:52,876 --> 00:04:56,196 Speaker 1: that seems like the obvious one. What are other criteria 72 00:04:56,356 --> 00:05:03,596 Speaker 1: of fitness that you usually ascribe to viruses that would 73 00:05:03,716 --> 00:05:06,316 Speaker 1: lead one to make any kind of speculations? And it 74 00:05:06,476 --> 00:05:07,956 Speaker 1: might be interesting just to hear some examples of what 75 00:05:07,996 --> 00:05:12,996 Speaker 1: you expected to happen how omicron differs from those. Yeah. Well, 76 00:05:13,076 --> 00:05:19,196 Speaker 1: so transmission for the virus is sort of, roughly speaking, 77 00:05:19,756 --> 00:05:24,316 Speaker 1: a two part job. It has to find new naive hosts, 78 00:05:24,476 --> 00:05:27,636 Speaker 1: and as those become less and less common because more 79 00:05:27,676 --> 00:05:31,196 Speaker 1: people are immune from prior infection or vaccination or both, 80 00:05:31,556 --> 00:05:36,676 Speaker 1: it also needs to transmit to immune hosts. So one 81 00:05:36,716 --> 00:05:41,796 Speaker 1: sort of generalization is that initially the selection is for 82 00:05:41,956 --> 00:05:45,836 Speaker 1: more transmissibility. When almost everyone as naive, and as more 83 00:05:45,876 --> 00:05:49,636 Speaker 1: people are immune, it's always good to be more transmissible. 84 00:05:49,676 --> 00:05:51,916 Speaker 1: But there's more and more of a premium on being 85 00:05:51,916 --> 00:05:59,236 Speaker 1: able to escape immunity, particularly for infection and transmission, Meaning 86 00:05:59,556 --> 00:06:03,996 Speaker 1: there's not direct selection to escape immunity against severe outcomes 87 00:06:04,476 --> 00:06:07,596 Speaker 1: that may happen as a side effect of selection for 88 00:06:08,156 --> 00:06:12,116 Speaker 1: immune escape. That's not the primary goal of the virus. 89 00:06:12,836 --> 00:06:15,476 Speaker 1: So I mean market for one quick second, I mean 90 00:06:15,956 --> 00:06:19,076 Speaker 1: it's never the primary goal of a virus to make 91 00:06:19,116 --> 00:06:21,876 Speaker 1: you very sick. It's just that the virus will do 92 00:06:21,916 --> 00:06:24,556 Speaker 1: whatever it takes to make more of the virus, and 93 00:06:24,596 --> 00:06:26,756 Speaker 1: if it happens to be then making you very sick, 94 00:06:26,836 --> 00:06:30,876 Speaker 1: does that the virus will do that at least in 95 00:06:30,916 --> 00:06:32,516 Speaker 1: so far as it doesn't kill you and therefore make 96 00:06:32,556 --> 00:06:35,156 Speaker 1: it harder to spread to more people. Right, That's right, 97 00:06:35,196 --> 00:06:39,276 Speaker 1: And that's why everybody's watching very carefully to see whether 98 00:06:39,396 --> 00:06:44,556 Speaker 1: the immune escape of omicron, for example, is to one 99 00:06:44,596 --> 00:06:50,196 Speaker 1: extent it also escapes the immunity to severe disease that 100 00:06:50,316 --> 00:06:53,356 Speaker 1: people have, and it's less but to some extent it 101 00:06:53,396 --> 00:06:57,516 Speaker 1: does escape even that level that type of immunity. Okay, 102 00:06:57,556 --> 00:06:59,356 Speaker 1: so sorry interrupted, but go go ahead back to what 103 00:06:59,436 --> 00:07:03,636 Speaker 1: you're saying. So as you say, the virus wants to 104 00:07:03,676 --> 00:07:06,436 Speaker 1: make more copies of itself once in an evolutionary sense, 105 00:07:06,436 --> 00:07:08,996 Speaker 1: to make more copies of itself. There's been a long 106 00:07:09,196 --> 00:07:14,836 Speaker 1: standing discussion in the evolutionary biology community and parallel, mostly 107 00:07:15,036 --> 00:07:19,996 Speaker 1: separate discussion in the medical and public health community about 108 00:07:20,156 --> 00:07:23,956 Speaker 1: what that does to the severity of viruses. And in fact, 109 00:07:24,036 --> 00:07:27,116 Speaker 1: that was what I wrote my PhD thesis on long 110 00:07:27,156 --> 00:07:31,876 Speaker 1: time ago, was making models of that interaction between the 111 00:07:31,916 --> 00:07:35,796 Speaker 1: severity of the infection and the direct targets of selection, 112 00:07:35,836 --> 00:07:39,716 Speaker 1: which are more transmission. So in the old days, people said, 113 00:07:40,556 --> 00:07:44,636 Speaker 1: in a sort of hand wavy way, without much quantitative reasoning, 114 00:07:44,716 --> 00:07:47,076 Speaker 1: that if you kill somebody that you in fact then 115 00:07:47,116 --> 00:07:51,276 Speaker 1: you can't spread if you're a virus, And so viruses 116 00:07:51,916 --> 00:07:57,276 Speaker 1: try to become over evolutionary time, less harmful to their hosts, 117 00:07:57,276 --> 00:07:59,916 Speaker 1: and at the same time the hosts become immune. It 118 00:07:59,996 --> 00:08:05,356 Speaker 1: was then, on sort of conceptual grounds, noted that that's 119 00:08:05,396 --> 00:08:08,876 Speaker 1: true up to a point. But if a virus is 120 00:08:08,876 --> 00:08:11,436 Speaker 1: trying to grow in a host and does so so 121 00:08:11,516 --> 00:08:13,876 Speaker 1: weakly that it doesn't make more copies of itself, that's 122 00:08:13,916 --> 00:08:17,356 Speaker 1: the other extreme. So killing the host is too much growth, 123 00:08:17,356 --> 00:08:21,036 Speaker 1: and not even making many copies of itself to transmit 124 00:08:21,636 --> 00:08:25,036 Speaker 1: is the other extreme. And so the notion of that 125 00:08:25,316 --> 00:08:28,636 Speaker 1: viruses evolved to an intermediate level of virulence to their 126 00:08:28,676 --> 00:08:32,916 Speaker 1: host was sort of what many models predict, and then 127 00:08:33,356 --> 00:08:37,436 Speaker 1: factors that can modulate that include how it's transmitted and 128 00:08:38,036 --> 00:08:41,316 Speaker 1: the relationship between how many copies of itself it makes 129 00:08:41,756 --> 00:08:46,436 Speaker 1: and the transmission rate. So the old idea they always 130 00:08:46,476 --> 00:08:50,556 Speaker 1: try to become more mild is not widely held by 131 00:08:50,596 --> 00:08:52,596 Speaker 1: people who know what they're talking about, but is widely 132 00:08:52,636 --> 00:08:57,396 Speaker 1: held by the general public. Right, yeah, So is it 133 00:08:57,436 --> 00:09:01,556 Speaker 1: correct even to say that, as a probabilistic matter, of 134 00:09:01,596 --> 00:09:04,476 Speaker 1: the viruses we know about, they are more likely to 135 00:09:04,676 --> 00:09:08,996 Speaker 1: evolve to being less harmful over time, or is even 136 00:09:09,196 --> 00:09:11,956 Speaker 1: that which I've sometimes heard as a fallback statement, Is 137 00:09:11,996 --> 00:09:16,756 Speaker 1: even that not empirically observably true. I don't know if 138 00:09:16,796 --> 00:09:21,836 Speaker 1: we have enough of the history of viral virulence to 139 00:09:21,916 --> 00:09:25,356 Speaker 1: look back at and watch. The most famous experiment was 140 00:09:25,396 --> 00:09:29,556 Speaker 1: the release of mixomatosis, a disease of rabbits caused by 141 00:09:29,716 --> 00:09:32,916 Speaker 1: maxomavirus in Australia, which was done as an effort to 142 00:09:33,116 --> 00:09:37,796 Speaker 1: kill off the Australian pest rabbit population, and indeed that 143 00:09:37,956 --> 00:09:42,236 Speaker 1: started out as an exceedingly virulent virus and did evolve 144 00:09:42,316 --> 00:09:45,716 Speaker 1: to become less harmful beautiful. Experiments done by Frank Fenner, 145 00:09:46,196 --> 00:09:50,716 Speaker 1: who was better known for a smallpox eradication, he showed 146 00:09:50,916 --> 00:09:54,236 Speaker 1: very conclusively that it did become milder. It didn't become mild, 147 00:09:54,276 --> 00:09:59,156 Speaker 1: it became milder, and the counterbalancing problem was that if 148 00:09:59,156 --> 00:10:01,916 Speaker 1: it became very, very mild, it just couldn't grow in 149 00:10:01,956 --> 00:10:07,476 Speaker 1: the rabbits. So that's probably the best documented example of 150 00:10:08,356 --> 00:10:12,356 Speaker 1: watching evolution in practice, because rabbits and that virus both 151 00:10:12,876 --> 00:10:15,476 Speaker 1: reproduce quickly, so you had a lot of generations each year. 152 00:10:16,276 --> 00:10:19,636 Speaker 1: There is also a sort of mechanistic consideration that seems 153 00:10:19,636 --> 00:10:22,876 Speaker 1: to be true in flu viruses and might be true 154 00:10:22,916 --> 00:10:28,396 Speaker 1: also for omicron, which is that replicating deep in the 155 00:10:28,516 --> 00:10:34,316 Speaker 1: lungs is a different property from replicating further up the 156 00:10:34,316 --> 00:10:38,636 Speaker 1: respiratory tract. Replicating deep in the respiratory tract down in 157 00:10:38,676 --> 00:10:42,116 Speaker 1: the lungs is more likely to cause severe disease, and 158 00:10:42,236 --> 00:10:45,156 Speaker 1: replicating up at the top of the respiratory tract is 159 00:10:45,196 --> 00:10:47,996 Speaker 1: more likely to spread. So to the extent that that's 160 00:10:47,996 --> 00:10:52,876 Speaker 1: a tradeoff. There might be some selection for transmission that 161 00:10:52,996 --> 00:10:56,596 Speaker 1: is indirectly selection for mildness. But you can imagine a 162 00:10:56,596 --> 00:10:59,356 Speaker 1: situation where that's not true. Is it fair to say? Then? 163 00:10:59,396 --> 00:11:01,676 Speaker 1: So I'm trying to get what one should say around 164 00:11:01,756 --> 00:11:04,276 Speaker 1: educated people. Somebody says, well, you know, the great thing 165 00:11:04,276 --> 00:11:07,436 Speaker 1: about omicron is that it shows you that, like all viruses, 166 00:11:07,476 --> 00:11:09,836 Speaker 1: this is getting more mild. I mean, the first thing 167 00:11:09,836 --> 00:11:13,236 Speaker 1: to say is that's an old view and it's not 168 00:11:13,436 --> 00:11:17,236 Speaker 1: on conceptual grounds. Is not necessarily true. And then there 169 00:11:17,276 --> 00:11:21,716 Speaker 1: are certainly counterexamples of viruses that have not evolved to 170 00:11:21,876 --> 00:11:26,436 Speaker 1: be substantially less virulent. Are there any that come to mind? 171 00:11:26,476 --> 00:11:28,956 Speaker 1: What happened with smallpox? By the way, which you mentioned, 172 00:11:29,076 --> 00:11:31,876 Speaker 1: my layman senses that smallpox was still pretty virulent up 173 00:11:31,916 --> 00:11:34,556 Speaker 1: to the time when it was eliminated. Yeah, that's right. 174 00:11:34,716 --> 00:11:38,276 Speaker 1: What's difficult is that proving a negative is hard, and 175 00:11:38,876 --> 00:11:43,716 Speaker 1: we didn't see the initial emergence of most viruses when 176 00:11:43,756 --> 00:11:46,916 Speaker 1: they became human pathogens or pathogens of whatever organisms they 177 00:11:46,956 --> 00:11:50,396 Speaker 1: In fact, that's why Maxsoma introduced into Australia was such 178 00:11:50,396 --> 00:11:53,356 Speaker 1: a great example. You could watch the whole time course. 179 00:11:53,916 --> 00:12:00,116 Speaker 1: But I think it's hard to settle the history, especially 180 00:12:00,156 --> 00:12:02,996 Speaker 1: because we usually also can't separate the changes in the 181 00:12:03,036 --> 00:12:05,916 Speaker 1: host from the changes in the virus. In other words, 182 00:12:05,996 --> 00:12:08,596 Speaker 1: as we become more immune, even the same virus will 183 00:12:08,636 --> 00:12:12,076 Speaker 1: cause less severe disease. Mark we want to warn readers 184 00:12:12,236 --> 00:12:15,356 Speaker 1: not to generalize for the mixed homa case to thinking 185 00:12:15,396 --> 00:12:17,956 Speaker 1: that's true of all viruses. Tell me again so that 186 00:12:18,036 --> 00:12:22,596 Speaker 1: I understand it. The conceptual reason that we cannot assume 187 00:12:22,716 --> 00:12:25,556 Speaker 1: the way people did in the old days through hand waving. 188 00:12:25,596 --> 00:12:29,996 Speaker 1: As you said that overtime virulence would necessarily be reduced. 189 00:12:29,996 --> 00:12:36,676 Speaker 1: In this kind of Dayton picture, virulence is selected along 190 00:12:36,676 --> 00:12:41,036 Speaker 1: with transmissibility to maximize transmissibility. And so when there is 191 00:12:41,036 --> 00:12:45,516 Speaker 1: a trade off between making more copies of the virus 192 00:12:45,676 --> 00:12:51,316 Speaker 1: and harming the host, the virus will choose making more 193 00:12:51,356 --> 00:12:55,356 Speaker 1: copies of itself. When there's a reinforcement between making more 194 00:12:55,356 --> 00:12:58,156 Speaker 1: copies of itself and harming the host, the virus will 195 00:12:58,196 --> 00:13:01,476 Speaker 1: choose making more copies of itself. So what it does 196 00:13:01,516 --> 00:13:03,596 Speaker 1: to us, as you said at the beginning, it doesn't 197 00:13:03,596 --> 00:13:08,396 Speaker 1: really care. It's trying to maximize its own function. It 198 00:13:08,556 --> 00:13:13,236 Speaker 1: is true, I think where there have been observations of evolution. 199 00:13:13,956 --> 00:13:16,836 Speaker 1: The virulence has gone down in several examples, and I 200 00:13:16,876 --> 00:13:19,836 Speaker 1: can't think of an example where it started mild and 201 00:13:19,916 --> 00:13:23,756 Speaker 1: became more virulent that we can really document, but that 202 00:13:23,796 --> 00:13:26,276 Speaker 1: would be hard to see. If it did happen, we 203 00:13:26,356 --> 00:13:28,836 Speaker 1: might just see when it jumped out. So I think 204 00:13:28,916 --> 00:13:31,236 Speaker 1: the thing to say is that there are some examples 205 00:13:31,276 --> 00:13:34,276 Speaker 1: where viruses have become more mild, and there are some 206 00:13:35,356 --> 00:13:40,916 Speaker 1: reasons why that might happen, But more mild and completely 207 00:13:40,956 --> 00:13:44,636 Speaker 1: harmless are very different things, and that really the part 208 00:13:44,636 --> 00:13:48,636 Speaker 1: that we can control is our immunity. We can control 209 00:13:48,716 --> 00:13:52,476 Speaker 1: to some extent, and that is almost always a beneficial 210 00:13:53,356 --> 00:13:56,876 Speaker 1: thing in terms of virulence of the virus. So that's 211 00:13:56,916 --> 00:13:59,476 Speaker 1: the part where at least we can do something about it. 212 00:14:00,316 --> 00:14:03,116 Speaker 1: You mentioned that one thing that variance want to do 213 00:14:03,236 --> 00:14:05,356 Speaker 1: is of course they want to find new naive hosts, 214 00:14:05,356 --> 00:14:07,756 Speaker 1: but over time that gets harder and harder, and so 215 00:14:07,876 --> 00:14:10,516 Speaker 1: then they want to be able to get around sound immunity. 216 00:14:11,076 --> 00:14:16,076 Speaker 1: Omicron seems to be pretty good at getting around immunity. 217 00:14:16,356 --> 00:14:18,556 Speaker 1: Is there a sense a clear sense now of how 218 00:14:18,596 --> 00:14:22,116 Speaker 1: it does so? And if so, is that a strategy 219 00:14:22,116 --> 00:14:27,516 Speaker 1: that is likely to be replicated in future variants. Yeah, 220 00:14:27,556 --> 00:14:29,836 Speaker 1: I mean, I think what's striking about omicron is that 221 00:14:29,916 --> 00:14:33,396 Speaker 1: it not only has some mutations in its spike protein, 222 00:14:33,756 --> 00:14:36,836 Speaker 1: which is a major target of antibodies, but it has 223 00:14:36,836 --> 00:14:39,316 Speaker 1: a lot of mutations, more than it should given the 224 00:14:39,316 --> 00:14:42,156 Speaker 1: amount of time that's passed if it were a typical 225 00:14:42,836 --> 00:14:48,236 Speaker 1: virus out there. So I think the mechanism is still 226 00:14:48,276 --> 00:14:52,356 Speaker 1: being understood in detail. But pridly speaking, the shape of 227 00:14:52,356 --> 00:14:55,596 Speaker 1: its protein is different from the shape that the antibodies 228 00:14:55,636 --> 00:14:59,356 Speaker 1: recognized which we're generated to previous variants, and so those 229 00:14:59,396 --> 00:15:02,756 Speaker 1: antibodies don't bind as well, they don't neutralize as well, 230 00:15:03,076 --> 00:15:06,716 Speaker 1: and therefore don't work as well. Any sense, people must 231 00:15:06,756 --> 00:15:08,756 Speaker 1: be theorizing about this. You must be theorizing about this 232 00:15:09,116 --> 00:15:12,076 Speaker 1: out why the jump seems to be as big as 233 00:15:12,076 --> 00:15:16,076 Speaker 1: it is from earlier variants. Yeah, the evolution was faster 234 00:15:16,196 --> 00:15:23,316 Speaker 1: than is typical in typical humans, and so the two 235 00:15:23,596 --> 00:15:27,716 Speaker 1: leading hypotheses are it happened in a not typical human, 236 00:15:27,996 --> 00:15:31,116 Speaker 1: meaning a human who perhaps had an immune system that 237 00:15:31,276 --> 00:15:36,316 Speaker 1: was just good enough to exert selection but not good 238 00:15:36,396 --> 00:15:41,076 Speaker 1: enough to end the infection. Part of why evolution doesn't 239 00:15:41,076 --> 00:15:44,516 Speaker 1: happen too much during a typical infection is that there's 240 00:15:44,516 --> 00:15:46,516 Speaker 1: a lot of selection to escape it, but not much 241 00:15:46,556 --> 00:15:50,636 Speaker 1: time before the virus is gone, and dead viruses don't mutate, 242 00:15:51,116 --> 00:15:54,516 Speaker 1: so once you clear an infection, it doesn't have the 243 00:15:54,596 --> 00:15:58,956 Speaker 1: chance to evolve further. Immuno Compromised people in various forms 244 00:15:59,196 --> 00:16:03,956 Speaker 1: often have much longer infections. If they're deeply immunocompromised, then 245 00:16:03,956 --> 00:16:07,156 Speaker 1: they they may not exert much selection on the virus, 246 00:16:07,156 --> 00:16:09,556 Speaker 1: and they may not survive for very long because they 247 00:16:09,596 --> 00:16:11,876 Speaker 1: won't be able to control the virus. But if they 248 00:16:11,876 --> 00:16:14,956 Speaker 1: are then this is just speculation. I mean compromised in 249 00:16:14,996 --> 00:16:17,956 Speaker 1: some particular way that allows the virus to persist, but 250 00:16:18,156 --> 00:16:23,196 Speaker 1: maintains that selection pressure that could accelerate. The other class 251 00:16:23,196 --> 00:16:27,076 Speaker 1: of explanations is that, as we've seen, the Saris Kobe 252 00:16:27,156 --> 00:16:30,196 Speaker 1: two can infect other mammals. For example, there was a 253 00:16:30,196 --> 00:16:33,316 Speaker 1: lot of interest in the white tailed deer being infected. 254 00:16:33,356 --> 00:16:37,636 Speaker 1: They were minks in Denmark that were infected earlier in 255 00:16:37,676 --> 00:16:42,076 Speaker 1: the pandemic. So entering a new host species is often 256 00:16:42,156 --> 00:16:45,636 Speaker 1: a trigger for accelerated evolution because the virus has a 257 00:16:45,676 --> 00:16:48,796 Speaker 1: lot of new problems to solve to get good at 258 00:16:48,796 --> 00:16:53,996 Speaker 1: infecting that host and So those are the two major 259 00:16:54,076 --> 00:16:58,556 Speaker 1: hypotheses that people have thought about. We'll be right back. 260 00:17:08,756 --> 00:17:12,436 Speaker 1: Mark word that one hears more and more is COVID 261 00:17:12,476 --> 00:17:14,396 Speaker 1: is on its way to being endemic. Sometimes you hear 262 00:17:14,436 --> 00:17:18,196 Speaker 1: people getting fancy and talking about a state of endemicity. 263 00:17:18,356 --> 00:17:21,876 Speaker 1: My question is, first of all, what's the working definition 264 00:17:22,116 --> 00:17:25,636 Speaker 1: that epidemiologists use for that? So what does endemic actually 265 00:17:25,716 --> 00:17:29,276 Speaker 1: mean to an epidemiologist? And the second is in practice, 266 00:17:29,596 --> 00:17:31,516 Speaker 1: what does that mean if and when we are there? 267 00:17:33,036 --> 00:17:36,596 Speaker 1: I think we're The dirty laundry of the epidemiology community 268 00:17:36,636 --> 00:17:40,436 Speaker 1: continues to be aired, and different people use these words differently, 269 00:17:40,676 --> 00:17:43,836 Speaker 1: but I think the core idea of endemicity is that 270 00:17:43,916 --> 00:17:48,236 Speaker 1: an infection is present at some level, almost constantly in 271 00:17:48,316 --> 00:17:52,836 Speaker 1: a population, and it may go through say seasonal swings, 272 00:17:53,356 --> 00:17:57,596 Speaker 1: and sometimes you call that seasonal upturn an epidemic, and 273 00:17:57,676 --> 00:18:01,276 Speaker 1: sometimes people call averaging over the whole year to be 274 00:18:01,476 --> 00:18:05,396 Speaker 1: endemic an endemic state. But it's a situation in which 275 00:18:06,196 --> 00:18:11,356 Speaker 1: most people, by the time they reach some reasonably young age, 276 00:18:11,796 --> 00:18:15,476 Speaker 1: have been exposed to the infection. That's an important characteristic, 277 00:18:15,596 --> 00:18:22,156 Speaker 1: and where the swings are either very small, as with 278 00:18:22,436 --> 00:18:25,716 Speaker 1: some infections that are just sort of pretty similar all 279 00:18:25,796 --> 00:18:30,516 Speaker 1: year round, like some respiratory bacterial infections that are a 280 00:18:30,516 --> 00:18:33,756 Speaker 1: little bit seasonal but basically kind of always there at 281 00:18:33,796 --> 00:18:38,436 Speaker 1: similar levels, or they're predictable swings that are every winter 282 00:18:38,636 --> 00:18:41,756 Speaker 1: or every summer or something like that. So it has 283 00:18:41,796 --> 00:18:47,036 Speaker 1: aspects of predictability of most people having prior exposure. And 284 00:18:47,116 --> 00:18:49,556 Speaker 1: therefore the reason why it's sort of a comforting word 285 00:18:49,796 --> 00:18:54,076 Speaker 1: is that the two things that have really been miserable 286 00:18:54,236 --> 00:18:58,396 Speaker 1: about sarskovi two have been the very large and unpredictable 287 00:18:58,436 --> 00:19:01,516 Speaker 1: swings in the number of people infected, and the fact 288 00:19:01,516 --> 00:19:04,196 Speaker 1: that it's preying on a population of us that is 289 00:19:04,236 --> 00:19:08,036 Speaker 1: mostly naive to it and therefore at greater risk of 290 00:19:08,116 --> 00:19:12,116 Speaker 1: having bad outcomes then we will be when we've all 291 00:19:12,476 --> 00:19:17,676 Speaker 1: had the infection and or vaccination. The upshot that if 292 00:19:17,716 --> 00:19:20,916 Speaker 1: I understand you correctly, is that even though endemic and 293 00:19:20,956 --> 00:19:24,396 Speaker 1: epidemic are obviously etymologically related in terms of their relationship 294 00:19:24,476 --> 00:19:27,596 Speaker 1: to the public, they're not in any very very sharp 295 00:19:27,836 --> 00:19:31,876 Speaker 1: relationship to each other. Because something can be endemic and 296 00:19:31,956 --> 00:19:36,716 Speaker 1: yet there can be epidemics that are seasonal. Is that right? 297 00:19:36,756 --> 00:19:38,396 Speaker 1: So that those two and yet or you can have 298 00:19:38,436 --> 00:19:40,676 Speaker 1: an epidemic that is not endemic, or you can sending 299 00:19:40,676 --> 00:19:42,476 Speaker 1: it is endemic and is not epidemics. So it seems 300 00:19:42,476 --> 00:19:44,876 Speaker 1: to have almost all the possible logical relationships. But I 301 00:19:44,916 --> 00:19:49,956 Speaker 1: think I think the more helpful contrast probably is pandemic 302 00:19:50,036 --> 00:19:54,916 Speaker 1: versus endemic. So the signal features of pandemics, although these 303 00:19:54,956 --> 00:19:58,196 Speaker 1: are also revised as we as we have more of them, 304 00:19:58,236 --> 00:20:01,076 Speaker 1: because they're each one is special. But the signal features 305 00:20:01,076 --> 00:20:06,636 Speaker 1: of pandemics are a very naive population that is experiencing 306 00:20:06,676 --> 00:20:13,556 Speaker 1: something for the first time, and being very widespread and 307 00:20:13,876 --> 00:20:16,716 Speaker 1: having large swings and incidents and prevalence because of those 308 00:20:16,756 --> 00:20:21,076 Speaker 1: two things. Yeah, so that's super helpful. I mean, that's 309 00:20:21,076 --> 00:20:23,436 Speaker 1: super helpful because one can sort of think a pandemic 310 00:20:23,676 --> 00:20:26,596 Speaker 1: nobody has it at first, then lots of people get 311 00:20:26,636 --> 00:20:29,916 Speaker 1: it in bunches, and that's the pandemic endemic. Everybody's been 312 00:20:29,916 --> 00:20:31,476 Speaker 1: exposed to it from the time that they were pretty 313 00:20:31,516 --> 00:20:34,356 Speaker 1: small children, but it's still out there in the population. 314 00:20:34,436 --> 00:20:38,156 Speaker 1: That seems to be very, very helpful. The thing that 315 00:20:38,316 --> 00:20:42,476 Speaker 1: is a bit confusing to me at least is if 316 00:20:42,516 --> 00:20:45,716 Speaker 1: we think about the relationships, say of omicron, to the 317 00:20:45,756 --> 00:20:50,636 Speaker 1: earlier versions of COVID, it seems like even though in 318 00:20:50,716 --> 00:20:53,076 Speaker 1: principle we should be moving to a place where almost 319 00:20:53,076 --> 00:20:57,196 Speaker 1: everybody has been exposed or vaccinated one of the two 320 00:20:58,236 --> 00:21:01,636 Speaker 1: that lots of people who were previously exposed to those 321 00:21:01,636 --> 00:21:05,036 Speaker 1: other things or were vaccinated are getting o macron because 322 00:21:05,076 --> 00:21:10,036 Speaker 1: of its capacity to evade immunity. And if that's the case, 323 00:21:10,156 --> 00:21:11,916 Speaker 1: do you guys start thinking of it as though it 324 00:21:11,916 --> 00:21:15,356 Speaker 1: were a separate disease and so therefore it doesn't really 325 00:21:15,396 --> 00:21:18,676 Speaker 1: matter if let's say it becomes endemic. Let's say omicron 326 00:21:18,756 --> 00:21:21,316 Speaker 1: becomes endemic, but something a new variant comes along that 327 00:21:21,356 --> 00:21:25,676 Speaker 1: evades immunity, then aren't people sort of a naive population 328 00:21:25,716 --> 00:21:30,996 Speaker 1: again with respect to that new variant if they're evading immunity, Yeah, 329 00:21:31,036 --> 00:21:35,716 Speaker 1: that is the big question. The reason why omicron has 330 00:21:35,796 --> 00:21:39,396 Speaker 1: been bad but not worse than it was is that 331 00:21:40,276 --> 00:21:45,636 Speaker 1: the combination of somewhat lower severity and growing amounts of 332 00:21:45,676 --> 00:21:49,316 Speaker 1: population immunity to severe disease, which still to a large 333 00:21:49,356 --> 00:21:53,556 Speaker 1: degree though not perfectly hold against omicron, has meant that 334 00:21:54,396 --> 00:21:58,236 Speaker 1: there are enormous numbers of cases, but not correspondingly many 335 00:21:58,716 --> 00:22:02,916 Speaker 1: deaths and hospitalizations. And that's a kind of new thing. 336 00:22:03,036 --> 00:22:07,196 Speaker 1: We haven't had a flu experience that's quite like that, 337 00:22:07,756 --> 00:22:10,356 Speaker 1: and we haven't had a far as Kobe two experience. 338 00:22:10,436 --> 00:22:13,476 Speaker 1: It's quite like that. So this is a new combination 339 00:22:13,556 --> 00:22:18,556 Speaker 1: of properties to deal with. One way that I find 340 00:22:18,556 --> 00:22:22,516 Speaker 1: it helpful to think about what's ahead in the next 341 00:22:22,556 --> 00:22:29,596 Speaker 1: few years is that, as you say, the bad option 342 00:22:29,836 --> 00:22:34,436 Speaker 1: will be if new variants continued to come and they 343 00:22:34,956 --> 00:22:40,556 Speaker 1: really are either so good at escaping immunity and transmitting 344 00:22:41,156 --> 00:22:45,116 Speaker 1: that the cases go shooting up, as they have with Omicron, 345 00:22:46,356 --> 00:22:50,036 Speaker 1: or they are really good at escaping our immunity to 346 00:22:50,116 --> 00:22:53,756 Speaker 1: severe disease, which was not that high at the beginning 347 00:22:53,796 --> 00:22:57,516 Speaker 1: of Omicron, should be higher after Omicron, we hope. But 348 00:22:57,596 --> 00:22:59,996 Speaker 1: if they're good at escaping our immunity to severe disease, 349 00:23:00,036 --> 00:23:02,996 Speaker 1: then even modest numbers of cases could be a problem, 350 00:23:03,716 --> 00:23:07,316 Speaker 1: and that would be like almost like a new flu pandemic. 351 00:23:07,356 --> 00:23:11,476 Speaker 1: It would be an evolutionary jump that is highly consequential 352 00:23:11,556 --> 00:23:14,676 Speaker 1: and is what we used to talk about with flu pandemics. Right. 353 00:23:14,676 --> 00:23:16,636 Speaker 1: It's the reason that the flu vaccine, it's a good 354 00:23:16,676 --> 00:23:18,276 Speaker 1: thing to get it, but it doesn't guarantee that you 355 00:23:18,276 --> 00:23:20,716 Speaker 1: won't get the flu, right because the variants comes so fast. Right, 356 00:23:22,076 --> 00:23:25,036 Speaker 1: partly and partly because they just aren't fully protective even 357 00:23:25,236 --> 00:23:27,436 Speaker 1: against what they're supposed to talk and nearly as good 358 00:23:27,436 --> 00:23:29,916 Speaker 1: as these these vaccines that I say, I kind of 359 00:23:29,916 --> 00:23:33,716 Speaker 1: categorize like the two possible futures are that we have 360 00:23:33,836 --> 00:23:37,116 Speaker 1: changes like the usual changes between years of flu, or 361 00:23:37,156 --> 00:23:39,956 Speaker 1: we have changes like new flu pandemics that just are 362 00:23:40,036 --> 00:23:44,596 Speaker 1: more frequent, And those are the two broad categories that 363 00:23:44,676 --> 00:23:47,476 Speaker 1: we really really hope the first happens, but we have 364 00:23:47,516 --> 00:23:51,156 Speaker 1: to consider the possibility in the second. Mark I'm trying 365 00:23:51,156 --> 00:23:54,756 Speaker 1: to figure out what the right kinds of policy responses 366 00:23:54,756 --> 00:23:57,316 Speaker 1: are at this moment, partly in order to get sense 367 00:23:57,356 --> 00:23:58,996 Speaker 1: of what they're going to look like going forward if 368 00:23:58,996 --> 00:24:02,756 Speaker 1: we have more variants. So, for example, at our mutual employer, 369 00:24:02,916 --> 00:24:05,956 Speaker 1: Harvard University, on the one hand, we have classes at 370 00:24:06,036 --> 00:24:08,876 Speaker 1: least at the law school in person, but we are 371 00:24:08,916 --> 00:24:11,036 Speaker 1: all told not just to wear masks, but to wear 372 00:24:11,116 --> 00:24:14,196 Speaker 1: a ninety five masks and possibly to wear two masks. 373 00:24:14,236 --> 00:24:17,316 Speaker 1: And there seems to be a heightening of concern about 374 00:24:17,516 --> 00:24:20,876 Speaker 1: transmission because I guess of the great transmissibility of omicron. 375 00:24:21,356 --> 00:24:23,756 Speaker 1: On the other hand, we're in person, which we weren't 376 00:24:23,796 --> 00:24:27,916 Speaker 1: obviously at an earlier stage, and What's more, everyone is 377 00:24:27,956 --> 00:24:32,676 Speaker 1: mandatorily vaccinated and boostered, So what's the policy logic if 378 00:24:32,716 --> 00:24:37,556 Speaker 1: you can reconstruct it behind that kind of heightened prevention 379 00:24:37,716 --> 00:24:43,836 Speaker 1: coupled with diving right in and having classes. Well, another 380 00:24:43,876 --> 00:24:46,356 Speaker 1: part of it, at least at our school public health, 381 00:24:46,636 --> 00:24:51,236 Speaker 1: is that contact tracing is basically now left to the individual. 382 00:24:51,276 --> 00:24:56,836 Speaker 1: There's no centralized contact tracing. So putting that together with 383 00:24:57,076 --> 00:25:03,396 Speaker 1: what you just described, my interpretation is that people are 384 00:25:03,436 --> 00:25:08,676 Speaker 1: trying to do the things that are efficient and relatively 385 00:25:08,756 --> 00:25:16,356 Speaker 1: low impact that reduced transmission, while reallocating resources from very 386 00:25:16,436 --> 00:25:22,116 Speaker 1: very costly in terms of time efforts like contact tracing, 387 00:25:22,756 --> 00:25:26,556 Speaker 1: and trying to return to doing as much of what 388 00:25:26,596 --> 00:25:29,236 Speaker 1: we're supposed to be doing as a university as possible. 389 00:25:30,156 --> 00:25:34,316 Speaker 1: So that's my interpretation. And an environment where let's say 390 00:25:34,356 --> 00:25:37,876 Speaker 1: almost everybody or everybody has been vaccinated and boosted, then 391 00:25:38,316 --> 00:25:41,636 Speaker 1: the goal would be try to avoid too many people 392 00:25:41,676 --> 00:25:44,196 Speaker 1: getting omicron so that they have to miss class and 393 00:25:44,356 --> 00:25:48,676 Speaker 1: stay home and give more people omicron, but nevertheless still 394 00:25:48,676 --> 00:25:51,516 Speaker 1: try to push forward with as much normalcy as can 395 00:25:51,556 --> 00:25:54,396 Speaker 1: be mustered under these circumstances. And I guess the question 396 00:25:54,476 --> 00:25:56,796 Speaker 1: that leads me to is and It's not that I 397 00:25:56,836 --> 00:25:58,476 Speaker 1: think either has the answer to it, but I want 398 00:25:58,476 --> 00:26:01,916 Speaker 1: to talk about it. Is this the new normal? Right? 399 00:26:01,996 --> 00:26:04,356 Speaker 1: I mean, is there any reason if people can bear 400 00:26:04,476 --> 00:26:06,476 Speaker 1: going to class in masks or teaching in masks? Will 401 00:26:06,476 --> 00:26:08,356 Speaker 1: there be a policy argument to you me going forward 402 00:26:08,396 --> 00:26:12,516 Speaker 1: that even if as the omicron surge continues to decline, 403 00:26:12,556 --> 00:26:15,316 Speaker 1: as it's doing in Massachusetts, we should just stick with 404 00:26:15,356 --> 00:26:20,396 Speaker 1: this because it's a good preventive measure. To get people 405 00:26:20,436 --> 00:26:22,436 Speaker 1: to comply with something like that, there would have to 406 00:26:22,476 --> 00:26:27,476 Speaker 1: be a continuing real threat of severe outcomes in large 407 00:26:27,556 --> 00:26:32,636 Speaker 1: numbers in the populations doing those behaviors, and or of 408 00:26:33,036 --> 00:26:37,516 Speaker 1: overwhelming healthcare, which are closely related, of course, although not 409 00:26:37,916 --> 00:26:41,676 Speaker 1: perfectly correlated. Because the burden on hospitals from omeocron has 410 00:26:41,676 --> 00:26:46,676 Speaker 1: been enormous, the severity has been less, and that's because 411 00:26:46,716 --> 00:26:48,436 Speaker 1: so many people were getting it at the same time. 412 00:26:49,116 --> 00:26:53,556 Speaker 1: So I can't imagine that in a few years we 413 00:26:53,636 --> 00:26:57,396 Speaker 1: will all be wearing masks for our daily life. I 414 00:26:57,436 --> 00:27:01,236 Speaker 1: don't expect it, because I think, in my mind, the 415 00:27:01,316 --> 00:27:06,716 Speaker 1: most likely scenario is that our immunity to severe disease 416 00:27:06,756 --> 00:27:12,956 Speaker 1: continues to get ampleified by probably continued vaccination, and also 417 00:27:13,356 --> 00:27:18,516 Speaker 1: continued circulation of the virus, and that this becomes a 418 00:27:18,556 --> 00:27:22,236 Speaker 1: vaccine preventable disease, at least for the severe manifestations, and 419 00:27:22,316 --> 00:27:26,956 Speaker 1: therefore we will start to dial back these control measures 420 00:27:26,956 --> 00:27:29,596 Speaker 1: as they are dialing back. In fact, in many parts 421 00:27:29,596 --> 00:27:32,716 Speaker 1: of the country already well in some parts of the country, 422 00:27:32,756 --> 00:27:35,756 Speaker 1: they never really dialed up, right, They were dialed back 423 00:27:35,796 --> 00:27:38,436 Speaker 1: from the very beginning, and they never stopped. I have 424 00:27:38,476 --> 00:27:41,476 Speaker 1: a good friend in Oklahoma who this is long ago 425 00:27:41,516 --> 00:27:43,676 Speaker 1: in this process. I asked him something about a public 426 00:27:43,756 --> 00:27:45,436 Speaker 1: lecture and I said, he mentioned public and I said, 427 00:27:45,436 --> 00:27:47,236 Speaker 1: there's going to be a public lecture, and he just 428 00:27:47,356 --> 00:27:51,116 Speaker 1: laughed and he said, we have never stopped doing these things, 429 00:27:51,116 --> 00:27:53,036 Speaker 1: he said, And by the way, my wife and I 430 00:27:53,076 --> 00:27:56,396 Speaker 1: and all of our kids have had COVID, so's there's 431 00:27:56,436 --> 00:28:00,116 Speaker 1: clearly a lot of local variation around the country. Yeah, 432 00:28:00,156 --> 00:28:04,316 Speaker 1: But I mean, I think it's important to consider all 433 00:28:04,356 --> 00:28:08,276 Speaker 1: the ways things could go bad, and it's really hard 434 00:28:08,316 --> 00:28:11,076 Speaker 1: to do that at the saint and actually really put 435 00:28:11,156 --> 00:28:14,916 Speaker 1: policy energy towards preparing for those and at the same 436 00:28:14,956 --> 00:28:18,916 Speaker 1: time to have I think a reasonable level of optimism, 437 00:28:19,396 --> 00:28:22,636 Speaker 1: like a realistic level of optimism that those things might 438 00:28:22,676 --> 00:28:25,596 Speaker 1: well not happen, and we probably will not be wearing 439 00:28:25,636 --> 00:28:28,556 Speaker 1: masks and a few hears, I think, and maybe even 440 00:28:28,796 --> 00:28:31,796 Speaker 1: much sooner than that. So I mean, I think it's 441 00:28:31,836 --> 00:28:37,276 Speaker 1: even possible that in say April, the amount of omicron 442 00:28:37,316 --> 00:28:41,316 Speaker 1: immunity will be so great that will have a long 443 00:28:41,636 --> 00:28:45,476 Speaker 1: rest from this. But it's also possible that we will 444 00:28:45,836 --> 00:28:50,356 Speaker 1: have a new variant that creates bigger problems. Last question 445 00:28:50,436 --> 00:28:54,236 Speaker 1: mark one of the optimistic thoughts. I don't want to 446 00:28:54,236 --> 00:28:58,076 Speaker 1: say fantasies, but hopes that when sometimes hears about response 447 00:28:58,116 --> 00:29:01,596 Speaker 1: to potential future variance, is one vaccine to rule them all, 448 00:29:01,636 --> 00:29:05,116 Speaker 1: like some sort of a vaccine that is sufficiently protean 449 00:29:05,196 --> 00:29:09,396 Speaker 1: and powerful that all it'll affect almost all coronaviruses, maybe 450 00:29:09,396 --> 00:29:13,196 Speaker 1: all coronaviruses, such that you know, whatever these variants may be, 451 00:29:13,316 --> 00:29:15,956 Speaker 1: they will probably be coronaviruses, and then we'll fall under 452 00:29:15,996 --> 00:29:21,116 Speaker 1: that rubric. I guess what I'm wondering is, from the 453 00:29:21,156 --> 00:29:24,396 Speaker 1: standpoint of epidemiology, do you have any thoughts on what 454 00:29:24,436 --> 00:29:27,396 Speaker 1: are the probabilities of such a thing being possible? Are 455 00:29:27,436 --> 00:29:31,676 Speaker 1: there other instances or areas where we've had effective vaccines 456 00:29:31,716 --> 00:29:35,476 Speaker 1: that cover like a broad range of phenomena under some 457 00:29:35,556 --> 00:29:41,276 Speaker 1: rubric like say coronavirus. Yeah, there have been. And the 458 00:29:41,356 --> 00:29:46,116 Speaker 1: approach so far that has been the most effective with 459 00:29:46,196 --> 00:29:49,076 Speaker 1: the vaccine that I used to study before COVID, which 460 00:29:49,156 --> 00:29:52,436 Speaker 1: was the new Mecoco vaccine, and with the polio vaccine 461 00:29:52,876 --> 00:29:56,916 Speaker 1: and with the flu vaccine is to just try to 462 00:29:56,996 --> 00:30:01,756 Speaker 1: vaccinate people against everything that's around at once, and then 463 00:30:02,316 --> 00:30:07,636 Speaker 1: with flu to change it over time. So those precedents exist, 464 00:30:08,596 --> 00:30:12,276 Speaker 1: but other than flu, those are for things where there's 465 00:30:12,316 --> 00:30:14,796 Speaker 1: a lot of variation and you need coverage of a 466 00:30:14,796 --> 00:30:18,116 Speaker 1: whole bunch of different variants, but you have a list 467 00:30:18,116 --> 00:30:20,676 Speaker 1: of them. It's not a changing list. It's just the list, 468 00:30:21,356 --> 00:30:23,876 Speaker 1: or maybe a new one's discovered periodically, but it's kind 469 00:30:23,916 --> 00:30:27,436 Speaker 1: of a fixed list, especially if they're ones that are worst. 470 00:30:27,916 --> 00:30:32,476 Speaker 1: So that approach is well worn. There is a very 471 00:30:32,516 --> 00:30:36,196 Speaker 1: strong effort right now underway in many quarters to create 472 00:30:37,276 --> 00:30:40,836 Speaker 1: paying coronavirus vaccines. There will be different approaches of trying 473 00:30:40,876 --> 00:30:44,436 Speaker 1: to put in a mix of different types, or of 474 00:30:44,436 --> 00:30:46,596 Speaker 1: trying to find parts of the virus that are more 475 00:30:46,596 --> 00:30:52,756 Speaker 1: conserved where immunity will be effective. And there's reason to 476 00:30:52,836 --> 00:30:56,316 Speaker 1: be optimistic, but it still has to be proven. So 477 00:30:56,356 --> 00:30:59,356 Speaker 1: I think it's a very worthwhile effort and we have 478 00:30:59,396 --> 00:31:02,676 Speaker 1: to see if it works. Mark, thank you so much 479 00:31:02,716 --> 00:31:06,036 Speaker 1: again for your insights. And I would say that I 480 00:31:06,076 --> 00:31:08,596 Speaker 1: look forward to more conversations, and that would be true 481 00:31:08,636 --> 00:31:12,196 Speaker 1: about this substance of the conversations, because a conversation with 482 00:31:12,236 --> 00:31:15,156 Speaker 1: you is always illuminating. I hope we don't need too many, Moore, 483 00:31:15,316 --> 00:31:17,636 Speaker 1: but my guess is we will be checking in in 484 00:31:17,676 --> 00:31:20,116 Speaker 1: one form or another. Thank you so much for your time, 485 00:31:20,916 --> 00:31:24,836 Speaker 1: look forward to talking about something else. Sometimes we'll be 486 00:31:24,916 --> 00:31:37,596 Speaker 1: right back. As always, when talking to Mark Lipsitch, there 487 00:31:37,636 --> 00:31:42,876 Speaker 1: are clear takeaways. First, as a probabilistic matter, it is 488 00:31:42,916 --> 00:31:48,076 Speaker 1: overwhelmingly likely that variants are going to keep coming, possibly 489 00:31:48,156 --> 00:31:51,756 Speaker 1: for a long time. The reason for that, Mark explains 490 00:31:52,116 --> 00:31:56,156 Speaker 1: is that there is virus out there in the population, 491 00:31:56,516 --> 00:31:59,196 Speaker 1: and while virus is out there among a large number 492 00:31:59,236 --> 00:32:02,316 Speaker 1: of people, the probability that evolution will continue to do 493 00:32:02,356 --> 00:32:07,156 Speaker 1: its work and develop new variants remains. Next, Mark points 494 00:32:07,156 --> 00:32:10,956 Speaker 1: out that omicron has been a surprise in various respects, 495 00:32:11,276 --> 00:32:15,116 Speaker 1: most particularly in how different it is than the variance 496 00:32:15,236 --> 00:32:19,156 Speaker 1: that came before it, thereby suggesting that for various possible 497 00:32:19,196 --> 00:32:22,116 Speaker 1: reasons that we're not yet sure of the evolutionary process 498 00:32:22,196 --> 00:32:26,596 Speaker 1: is happening faster than we previously expect it. Third, and 499 00:32:26,676 --> 00:32:29,876 Speaker 1: this is to my mind very important, we should not 500 00:32:30,116 --> 00:32:35,116 Speaker 1: accept the viewpoint which we sometimes here expressed by non experts, 501 00:32:35,156 --> 00:32:40,396 Speaker 1: that all viruses necessarily evolve in the direction of becoming 502 00:32:40,716 --> 00:32:45,356 Speaker 1: less virulent. In fact, the virus will do whatever it 503 00:32:45,436 --> 00:32:50,116 Speaker 1: takes to replicate itself, seen in evolutionary metaphorical terms, and 504 00:32:50,196 --> 00:32:52,276 Speaker 1: that means that if it turns out that the virus 505 00:32:52,316 --> 00:32:55,276 Speaker 1: can spread more effectively while being less virulent, it will 506 00:32:55,316 --> 00:32:57,956 Speaker 1: do so. But if the virus needs to be more 507 00:32:58,156 --> 00:33:01,356 Speaker 1: virulent in order to spread more effectively, it will do 508 00:33:01,436 --> 00:33:05,996 Speaker 1: that too. Consequently, we cannot generalize and assume that we 509 00:33:06,036 --> 00:33:09,716 Speaker 1: are on the way to things automatically gradually getting better 510 00:33:09,836 --> 00:33:15,076 Speaker 1: via omicron Fourth, we are certainly approaching some quality that 511 00:33:15,116 --> 00:33:18,316 Speaker 1: could be called endemicity, or a state of being endemic 512 00:33:18,636 --> 00:33:23,516 Speaker 1: for COVID nineteen, defined to mean that almost everybody in 513 00:33:23,556 --> 00:33:27,916 Speaker 1: the population will have been exposed to the disease, often 514 00:33:28,036 --> 00:33:32,236 Speaker 1: relatively early in life. However, and this is the big however, 515 00:33:32,796 --> 00:33:35,916 Speaker 1: whether that matters in the long run in terms of 516 00:33:35,956 --> 00:33:39,196 Speaker 1: making it less likely that people get very sick depends 517 00:33:39,676 --> 00:33:45,596 Speaker 1: entirely on how good future variants are at avoiding immunity. 518 00:33:45,676 --> 00:33:48,796 Speaker 1: If people get sick when young and retain immunity, then 519 00:33:48,956 --> 00:33:51,596 Speaker 1: that is a good result in terms of the effects 520 00:33:51,596 --> 00:33:55,436 Speaker 1: of endemicity. But if future variants on the virus can 521 00:33:55,556 --> 00:33:59,636 Speaker 1: still infect people who have nevertheless been exposed, the serious 522 00:33:59,716 --> 00:34:03,436 Speaker 1: and indeed severe problems associated with the healthcare system and 523 00:34:03,556 --> 00:34:08,116 Speaker 1: COVID nineteen could in principle continue even when the disease 524 00:34:08,516 --> 00:34:13,676 Speaker 1: is endemic last and very much not least. Mark says 525 00:34:13,756 --> 00:34:17,756 Speaker 1: that the possibility of a vaccine that would effectively block 526 00:34:17,956 --> 00:34:21,636 Speaker 1: future variance by virtue of it being general enough to 527 00:34:21,796 --> 00:34:25,836 Speaker 1: prevent all forms of the coronavirus from spreading or alternatively 528 00:34:26,076 --> 00:34:28,716 Speaker 1: from getting the people who get them very sick, is 529 00:34:28,796 --> 00:34:32,556 Speaker 1: worth pursuing. Whether it will succeed or not, of course, 530 00:34:32,796 --> 00:34:36,036 Speaker 1: remains an unknown and not something on which it's possible 531 00:34:36,156 --> 00:34:40,156 Speaker 1: to put a probabilistic numerical judgment. At the human level, 532 00:34:40,276 --> 00:34:43,396 Speaker 1: Mark says he thinks it's very unlikely that in a 533 00:34:43,436 --> 00:34:45,676 Speaker 1: couple of years or even sooner than that will all 534 00:34:45,716 --> 00:34:49,516 Speaker 1: still be walking around wearing masks. That, for one leaves 535 00:34:49,516 --> 00:34:53,836 Speaker 1: me some reason to continue to be hopeful. Ultimately, and 536 00:34:53,876 --> 00:34:57,276 Speaker 1: this is me talking, not Mark. The power of this 537 00:34:57,796 --> 00:35:01,556 Speaker 1: virus has been to shape the way we in the 538 00:35:01,596 --> 00:35:06,316 Speaker 1: world respond to it in a broad set of complicated 539 00:35:06,356 --> 00:35:11,556 Speaker 1: ways that themselves deploy our own conception of social power. 540 00:35:12,756 --> 00:35:17,236 Speaker 1: Disease has power, Humans have power in responding to disease. 541 00:35:17,996 --> 00:35:20,636 Speaker 1: All of it involves us in a set of complex 542 00:35:20,756 --> 00:35:24,756 Speaker 1: trade offs and choices. The difference between us and evolution 543 00:35:25,156 --> 00:35:28,676 Speaker 1: is that evolution is making those choices blindly, with no 544 00:35:28,676 --> 00:35:31,516 Speaker 1: normative vision of how it wants to be or how 545 00:35:31,556 --> 00:35:34,756 Speaker 1: the world should be arranged. We as humans are in 546 00:35:34,756 --> 00:35:39,476 Speaker 1: a different position. Our judgments can be thoughtful, strategic, and 547 00:35:39,676 --> 00:35:44,236 Speaker 1: ethically inclined, and with any luck, they will continue to be. 548 00:35:46,916 --> 00:35:49,516 Speaker 1: As I mentioned at the beginning of the show, we 549 00:35:49,676 --> 00:35:52,236 Speaker 1: hear a deep background are going to take a hiatus 550 00:35:52,236 --> 00:35:55,316 Speaker 1: for a few months as we work on our next season. 551 00:35:56,156 --> 00:35:58,956 Speaker 1: We'll miss you, but I very much hope to hear 552 00:35:58,996 --> 00:36:01,996 Speaker 1: your voices through reaching me on Twitter at Noah are 553 00:36:02,036 --> 00:36:06,116 Speaker 1: Feldman or perhaps even more efficiently, on my website at 554 00:36:06,156 --> 00:36:11,796 Speaker 1: Noah Dashfeldman dot com. Until the next time I speak 555 00:36:11,796 --> 00:36:17,556 Speaker 1: to you, breathe deep, think deep thoughts, and, if at 556 00:36:17,596 --> 00:36:21,156 Speaker 1: all possible, under the circumstances of our world, try to 557 00:36:21,236 --> 00:36:25,076 Speaker 1: have a little fun. Deep Background is brought to you 558 00:36:25,156 --> 00:36:28,876 Speaker 1: by Pushkin Industries. Our producer is mo La Board, our 559 00:36:28,916 --> 00:36:32,756 Speaker 1: engineer is Ben Taliday, and our showrunner is Sophie Crane mckibbon. 560 00:36:33,476 --> 00:36:37,636 Speaker 1: Editorial support from noahm Osband. Theme music by Luis Guerra 561 00:36:38,316 --> 00:36:42,436 Speaker 1: at Pushkin. Thanks to Mia Lobell, Julia Barton, Lydia, Jean Coott, 562 00:36:42,716 --> 00:36:47,676 Speaker 1: Heather Faine, Carlie mcgliori, Maggie Taylor, Eric Sandler, and Jacob Weisberg. 563 00:36:48,276 --> 00:36:50,636 Speaker 1: You can find me on Twitter at Noah R. Feldman. 564 00:36:51,116 --> 00:36:53,476 Speaker 1: I also write a column for Bloomberg Opinion, which you 565 00:36:53,516 --> 00:36:57,356 Speaker 1: can find at Bloomberg dot com slash Feldman. To discover 566 00:36:57,436 --> 00:37:01,516 Speaker 1: Bloomberg's original slate of podcasts, go to Bloomberg dot com 567 00:37:01,556 --> 00:37:04,836 Speaker 1: slash podcasts, and if you liked what you heard today, 568 00:37:05,236 --> 00:37:08,356 Speaker 1: please write a review or tell a friend. This is 569 00:37:08,396 --> 00:37:09,116 Speaker 1: Deep Background.