A Very Bumpy Ride, Part 1

A Very Bumpy Ride, Part 1

Life in the Time of COVID
Larry Brilliant, MD [11.26.20]

[EDITOR'S NOTE: At the beginning of the COVID-19 outbreak, I called on Larry Brilliant, a leading epidemiologist and pandemic expert with unique experience and expertise, to ask him to talk about how we could begin to think about COVID-19 and what was in store for us. Now, eight months later, in this Thanksgiving Day talk, he provides an update from the field. —JB]

We need to have a strong WHO, a strong United Nations, a strong global alliance for vaccines and immunizations (GAVI), a strong Global Fund, and all these different organelles that make it possible for us to deal with global threats. I would extend it a little bit out of my lane to say we need desperately to deal with climate change, nuclear proliferation, drought, and famine. But in the area that I know, we can't stop a pandemic without having global collaboration. We have failed to learn the lessons of Taiwan, Vietnam, Singapore, Korea, New Zealand, Iceland—the countries that have done really well—because we don't have a strong way to take the best lessons from the success stories in dealing with this pandemic and globalizing them. This is because we deal with disinformation, and because we hold up the Swedish example even though it wasn't a good example of how to deal with the pandemic, and because we don't have a love of science in the leadership of the world, and because we don't talk to each other in the way that we need to.

Epidemiologist and pandemic expert LARRY BRILLIANT, MD, is on the advisory board for Ending Pandemics. He is also on the board of the Skoll Foundation and was the founding executive director of Google's non-profit organization. Dr. Brilliant lived in India for more than a decade while working as a United Nations medical officer, where, in 1971, he helped run the successful World Health Organization (WHO) smallpox eradication program in South Asia. He also worked for the WHO polio eradication effort and chaired the National Bio-Surveillance Advisory Subcommittee, created by President George W. Bush. He has won the TED Prize, TIME 100, and many honorary doctorates and is the author of Sometimes Brilliant: The Impossible Adventures of a Spiritual Seeker and Visionary Physician Who Helped Conquer the Worst Disease in History. Larry Brilliant, MD, Edge Bio Page 

THE REALITY CLUB: Jennifer JacquetFrancesca Vidotto, Daniel Kahneman, Lee Smolin, Nick Bostrom, Jesse Dylan, John BrockmanCarlo Rovelli, Jacob Burda

A Very Bumpy Ride, Part 1: Life in the Time of COVID

Larry Brilliant: I'm going to talk about the pandemic and where we are at this moment in time, but it is Thanksgiving, and I'm reminded that it was actually 400 years ago that the pilgrims supposedly came to the United States, in 1620. I started thinking, why don't we celebrate that? If it had been an event filled with glory, we'd be celebrating 400 years, and we would all have known that. I just didn't think about it until I saw something come across some data feed. And I think it's because there's a lot of shame, and should be a lot of shame, associated with the appropriation of natural resources and the genocide of many of the tribes. I just thought it'd be wrong to not begin with that.

I got interested in that because somewhere along the way, during what we call the French and Indian Wars, the first act of bioterrorism on American soil was created. It led to the naming of Amherst College and Amherst city after Lord Jeffrey Amhurst, who wrote a notorious letter instructing his generals and the people who fought with him (mostly British) to take scabs from people who were dying of smallpox, pulverize them, impregnate blankets with these scabs, and then give them as gifts to Native Americans. Small villages in New England to this day have annexes of the historical cemeteries that are called "pox acres," where Native Americans who were murdered by the first act of bioterrorism in the United States are buried.

In keeping with that theme, and in keeping with my promise to John that I would start off with light-hearted amusement, I thought I would begin with that, before coming to the pandemic, though it's also not exactly lighthearted amusement.

So where are we with COVID? This is the worst pandemic in our lifetime. It's the worst pandemic certainly in 100 years, probably the worst in the history of the United States. (It's hard to figure out if smallpox was a pandemic at that time or just a really bad endemic disease.) Today, we are encroaching 200,000 cases a day in the United States and well over half a million cases a day globally.

I was on a call yesterday morning with an informal group of senior WHO advisors. Every other Wednesday morning we go around the globe and get a report on how it is in Singapore, in Russia, India, Latin America, the United States, and China. It's really a tale of two cities. East Asia is feeling extremely uncomfortable because they haven't had a case in days. Vietnam went 100 days without a case, Taiwan went 200 days without a case, Singapore today is over a month without a single case of COVID. And so they look at us in the United States, Germany (which is having an explosion right now), in the UK (which is just beginning to dip after a huge peak), and they basically say, what the fuck is wrong with you people? They don't understand. They don't understand how we could have blown it as badly as we have. And we have indeed blown it really badly.

In the United States, we will pass 90,000 COVID patients in hospitals. We don't have any more hospital beds in parts of the United States. I grew up in Detroit, Michigan. One of the hospitals I trained at in medical school was in Detroit, and it's still around. In May and June, at the peak then in Detroit, there were refrigerated trucks that had to drive up to the morgue of the hospital and collect the dead bodies because there was no more room in the morgue. I'm sorry to say that, and we'll have a lot to talk about of all the things we're grateful for, but I'm not grateful for the fact that the next month or two will be filled with images of refrigerated trucks because the morgues and hospitals will not be adequate to hold all the bodies in the United States killed by COVID-19.

We really messed it up badly. So much of this was unnecessary. I tried to think of literary images for this group, and right now Sisyphus would be a good one—trying to keep that rock from falling on our heads. Maybe Tantalus, the poor fellow who kept on reaching for the grapes—the victory that eluded him. This idea of a Dickensian moment of the best of times and the worst of times is also a useful image. It's the worst of times, clearly, because this is not the peak of the epidemic; this is Everest base camp. We're going to Everest before the vaccine arrives. It's clearly the worst of times so far, in the pandemic, in the world.

Every day in the United States, we set a new record of the number of cases and number of deaths. So, it's the worst of times as far as the pandemic is concerned. But it's the best of times for science because just as a virus moves at exponential speed, so has science. Just take a moment to think about that.

MIT keeps track of all the peer-reviewed articles on COVID. It's exceeded 60,000-80,000 articles, and many of them are really good. Lots of them are really good, maybe not all of them. We have 146 vaccines that are in some form of trial, and we have three that have passed the milestone of being put into the arms of tens of thousands of people with relatively minor side effects. The mRNA vaccine from Moderna and Pfizer have had modest side effects. We're not sure about AstraZeneca. There are some issues that we could talk about. Although it's undoubtedly a good vaccine with efficacy, we don't know exactly how much.

How quickly we've gone. For those of you who don't know, the previous world speed record in getting a vaccine was the mumps vaccine—four years. We had the smallpox vaccine for 200 plus years before we had vaccine programs on a global scale. We had the polio vaccine for 70 years before we had vaccine campaigns as we do now. We're going to have a vaccine campaign in two months. We're going to go from the appearance of this novel virus to a global vaccine campaign in 14 months.

And what about the speed of monoclonal antibodies? We're barely into a world that can understand what a monoclonal antibody is and we will have two, at least, and many more following, treatments that appear to work, if given in the right way at the right time.

Let me put our use of diagnostic testing into perspective—tests that everybody is maligning, including Trump, who is saying the only reason for high case counts is because more testing is being done. These tests, historically, are used to confirm diagnostic hypotheses. A patient comes in to see me as a physician, and I think maybe they might have diabetes so I do a glucose test, or an A1C test, or some kind of lab test to confirm a hypothesis. We are now using these tests to make the Democratic Convention safe and to get Hollywood productions back. New Zealand and Taiwan are using these tests to exclude people from coming, in a good way exclude, (maybe the only time I could ever use the word "exclude" in a good meaning). We're using these tests in a totally different way, and whether they're PCR tests, antigen tests, CRISPR tests, or LAMP tests, there is such an explosion of these tests that we now don't even have enough space to store all the antigen tests, let alone find the right exact way of using them. A good $5 at-home test for COVID-19 is really right around the corner, a couple of months. Vaccines, treatments, testing, the science behind it is breathtaking. And the speed at which it has accelerated is unprecedented; it is equal to the challenge of the problem of a novel pathogen that jumped from a zoonotic host into humans.

We're not going to be able to do a classical eradication program even with all of that, because the virus appears to infect not just bats, not just civet cats, but mink, cats, and non-human primates. And while we're not sure if that is a two-way infection—that humans can infect minks, minks can infect other minks, then infect cats, and then infect humans—it's enough of an asterisk that the programs we will be mounting globally, which will be the largest vaccine campaigns in history if you take into account the space of time in which they'll be done.

We have to vaccinate somewhere between 5 and 7 billion people, most of them with two doses of the vaccine, many of them with annual boosters. And we have to do it right now, with two vaccines that are ill-suited for that, Moderna and Pfizer, because they require refrigeration at -80, -100 degrees. That's why there's a lot of interest in the AstraZeneca vaccine, because if it could only be one dose and didn't require more than modest refrigeration, it could be the global vaccine we need. None of the vaccines that we currently have will be perfect, but like everything in science, we will grow, increase, improve iteratively, and we will get there.

It's the best of times for the science; it's the worst of times for the history of the disease, looking at the epidemic curve and the death rate. The reason it became the worst of times is because of several components. One, we are living in an age of pandemics. Every year, two, or three, or four zoonotic viruses jump from animals to humans. Some percentage of those are innocuous, but a high percentage of them are bad. Somebody is going to write a poem or a song that's going to get all these names into one song like that element song. They're going to say, "Zika, Ebola, West Nile, Lassa fever, and Marburg, H1N1, H5N1, H7N9, swine flu, and bird flu," you don't want me to keep going. Those are all the zoonotic diseases, including HIV/AIDS, that didn't, in an important way, exist in humans four decades ago, three decades ago, and one decade ago in many cases. But there are going to be more, and it's going to grow.

Ironically, in the 1960s, the Surgeon General United States said that we ended the age of infectious disease. This is a growth period for infectious disease doctors, unfortunately—virologists and epidemiologists. We're going to have more of these diseases because there are more human beings, humans have entered into animal territory, we're cutting down rainforests, we're eating more bushmeat and exotic animals, and we have transportation that can take what used to be an isolated event occurring somewhere in a forest and bring it into Manhattan in under 16 hours from almost any place in the world.

We need to grasp the lessons we've learned in watching science travel at an exponential speed. In this pandemic, unfortunately, we will have occasion to use those lessons going forward in the future. That leaves me with what I think is the most optimistic of the best of times/worst of times framing of this, and that is Ron Klain—Ebola czar and now chief of staff of President-elect Biden—and the scientists who are now replacing the political operatives who ran what was supposed to have been a taskforce. We're in the problem that we're in because of these long-term secular trends of animals and humans living in each other's territory and viruses jumping from animals to humans. But we're also in the short-term secular trend of nationalism.

I'm not a historian, but I love history. In my view, something happened after the Second World War, when the concentration camps came under scrutiny and we watched the skeletons emerge; we watched the firebombing of Dresden; we saw the mushroom clouds over Hiroshima and Nagasaki; we witnessed the awesome power of technology in the midst of war, and hatred, and anger; we saw the brutality, the ugliness, and the horror of the fascist regimes. There was no singular event like one of John's or Steffi's magical events, but it seemed as if humanity whispered to each other, Let's never do that again. We've looked over the precipice and seen the gates of hell, let's not do that again. We created all these institutions to bind us together in order to deal with the centrifugal forces, and to make them centripetal. We created the United Nations, Bretton Woods, the World Bank, FAO, UNESCO, UNICEF, NATO (there was also a SATO in those days), and the alphabet soup of all these agencies and organizations. We created all these alliances and partnerships and global communities to bring us back together and to stop these things that were pulling us apart.

Katinka and John's whole universe is another example of the kind of sisterhood and brotherhood of global intellectualism, global economy. Over the past few years, it hasn't worked for everybody. Putin, Erdogan, Bolsonaro, Trump, Brexit—these are all symptoms of the centrifugal forces pulling us apart.

That's not my lane. That's not something that I know a lot about. But as an epidemiologist, it's the worst thing that could happen to us. We need to have a strong WHO, a strong United Nations, a strong global alliance for vaccines and immunizations (GAVI), a strong Global Fund, and all these different organelles that make it possible for us to deal with global threats. I would extend it a little bit out of my lane to say we need desperately to deal with climate change, nuclear proliferation, drought, and famine. But in the area that I know, we can't stop a pandemic without having global collaboration. We have failed to learn the lessons of Taiwan, Vietnam, Singapore, Korea, New Zealand, Iceland—the countries that have done really well—because we don't have a strong way to take the best lessons from the success stories in dealing with this pandemic and globalizing them. This is because we deal with disinformation, and because we hold up the Swedish example even though it wasn't a good example of how to deal with the pandemic, and because we don't have a love of science in the leadership of the world, and it's because we don't talk to each other in the way that we need to.

That's my way of tying together the peril of the moment. That doesn't end with Trump's defeat, although it's certainly better. It doesn't end until nationalism and the forces that pull us apart are seen for the danger that they pose to the world we want to live in. I only offer the pandemic as one exemplar. God help us when we deal, as we must, with climate change in a world that's being torn apart by nationalism.

I'm optimistic compared to three weeks ago, just before the election. I don't know about you guys, but I don't wake up with the same sense of dread every morning that I did. At the first WHO meeting I attended after the election, I almost cried as we went around the Zoom world, listening to people talking about how they were doing on the pandemic—not a single country failed to say to the Americans on the call, "Welcome back. We've really missed you."


Jennifer Jacquet: Thank you, Larry. I really liked in your first talk when you said we shouldn't be thinking about this as a peak. You said it's a wave, and it was more like a tsunami, and now we're in the third wave. It feels like that messaging replaced the peak idea because there were many to follow. I know that some of the early mistaken messaging around surfaces and germs have been replaced with Michael Osterholm's "don't swap air." I'm curious about this East-West divide you mentioned from the WHO call. That doesn't seem to be true, given the New Zealand and Iceland examples. I worry that some of this is getting attributed: "Well, the Eastern countries are going to do so much better than the Western." But we have these cases of Western countries that have gotten COVID under control. And you mentioned that. I'm curious how that narrative is playing out in your world.

LB: All the Western countries that have done well are run by women. Being islands helps, but Germany, not an island, was also an early great example of a success story run by a woman. Now, it's having a big problem. It isn't the countries so much that should be the exemplars, although it is resident in that country; it's what they did. There are so many ways to defeat this virus. You don't all have to do the same thing. In Vietnam, they weren't very fast in dealing with it, but they were incredibly meticulous—they would do contact tracing of 100% of contacts. They would find every single contact of every case and either quarantine them, or in some other way remove them from the density of susceptibles.

The success in Taiwan is almost entirely due to speed. They would respond so quickly to any new case that even though they may have been less careful than the Vietnamese system in isolating and quarantining, they were so fast. That speed is what made it work. Iceland benefited from a long history of genetic information and a great database. They were data driven. In New Zealand, they used exclusionary methods to keep the virus from coming in. Singapore had two very different cultures. The regular Singapore, which has a kind of built-in self-policing, where individual volunteers appointed themselves to go up and down the street, and if they saw somebody without a mask, they would report them. They also had guest workers who lived in cramped quarters, very hard and unsanitary conditions, and the epidemic kept on increasing among the poorest and most vulnerable in the guest quarters, leading back into Singapore proper until they understood that. They then did something that we've not been able to do, which is they decided to improve free housing, give free food, and free quarters for anybody who was sick with COVID, which seems obvious, but nobody else does that the way they did in order to stop the disease. There's 100 different ways to defeat the virus. We just need to do the best practices that others have already innovated.

I'm reminded of the polio program, and the guinea worm program, and the smallpox program, which started off in every case with flawed hypotheses. In no case did those programs begin with the plan that they ended with. But because they had a porous kind of governing structure, where any good idea would immediately be tested and then socialized and spread everywhere—that's the way a big program like that on a global basis works.

We've gotten so many great ideas and innovations; they happen to, yes, come mostly from East Asia right now, but not exclusively. They happen to come from countries that are run by women, though not exclusively. But we don't have a structure that does as good a job of gathering those great ideas and socializing them, and then having the political will to follow them. You're absolutely right, it shouldn't be East-West. The virus “hates” everybody equally, if you can anthropomorphize the virus that way. You're absolutely right to not make it into an East-West thing.

Francesca Vidotto: I have two questions about the future, even though I don't want to put you in the position of trying to make guesses because it's a situation that is dynamical and is difficult to make previsions. One is, in the short term, how much will our life change? To what extent are we not going to come back to the old way of life we had before? What precautions do we have to take in the future for our survival? The second question is more related to what you were saying about nationalism always being fueled by capitalism. There is currently a lot of reflection in society about using this particular moment as an opportunity to change for the better. On one hand, science can be used to cover totalitarian moves, like to control more people and possibly to turn our society into a more controlled one using the virus as an excuse, possibly. On the other hand, there is always also a lot of discussion in making society more democratic, freer, and changing our way of life in more ecological and more sustainable ways. How do you feel about this?

LB: I don't know the answer to your question at all. There's something about this notion of freedom, as in "we can do whatever we want," or individualism—some combination of individualism and Ayn Randian notions of freedom. They don't go very well when you're dealing with threats that are a loss of public goods or market failures. The structures to deal with climate change don't exist inside of capitalism or any individual enterprise. The same thing is true for vaccines, which are a public good, but it's not really in any anybody's individual interest to be the first to take the risk of trying vaccines, or even to fund the research on them.

We don't have the organizational capacity to deal with a class of problems that modernity has brought us, into which this pandemic, climate change, and maybe some of the droughts we've had fall. I do worry about adding to this already uneasy relationship between freedom, individualism, and global welfare massive disinformation and social media that can disseminate that disinformation so quickly, and the politicization of calamity. We've just not dealt with it. I worry about that. The only alternative I see is strengthening, not world government per se, but strengthening a globalism that the world seems to be reacting against. I want more globalism, more sharing of information, and ideas, and best practices. I don't know how else we deal with that category of threats into which climate change and pandemics are two of "n," where we could debate what "n" is and how many there are.

The earlier question was something like what does normality look like? And how do we get back to normal? I don't know. I get asked that question so many times that I think people think I should know. Some of the things that have occurred because of this pandemic, one of which is what we're doing right now, will have long legs. It's hard for me to believe that the life I led before, where I would get on a plane and fly 16 hours for a two-hour meeting, stay one night and fly back, seems less likely to happen now. When I watch the exodus out of the cities, into leafy suburbs instead of the increasing squalor of a place like San Francisco—which I love but is hardly at her best moment these days—it's hard for me to believe the repopulation of the cities, after a pandemic, will occur as quickly as it might have if there hadn't been the opportunity for some set of workers to work from home.

There are some big societal things that seem to have occurred during the pandemic that are likely to have legs. Some that won't. I spent a bit of time advising the travel industry or trying to advise the travel industry. It's hard to imagine that industry will be as it was before for quite some time. But having said that, it is remarkable how quickly a change we thought was taking forever to come—how quickly it arrives when it does arrive. There are some famous quotations on that. Once we have adequate vaccines, if they are effective as we hope they are, and if they have as few side effects as we hope, and if they don't become politicized, things will get back to normal.

We lived in a normal world before with a lot of yellow fever. I don't know if anybody on this call has felt your world destroyed by yellow fever, but it's a terrible disease. It's worse than COVID. And it does exist in the communities that are hit by it, they're ravaged by it and, and yet we have a good vaccine. So, with a good vaccine, and a yellow card, or a digital version of the old yellow card, we got back to life dealing with yellow fever, even with malaria, even with HIV/AIDS.

We live with terrible diseases, worse than COVID in many ways, and still deal with them. Until smallpox was eradicated, we lived with it being almost everywhere, and most of us didn't even know it. In 1967, the Summer of Love, 2.5 million people died of smallpox. Yet we had the Woodstocks and the Summer of Loves in the middle of pandemics like that because we have vaccines, which will transform the fear, the vulnerability, the sucking out of all the oxygen from the conversation that COVID and Trump both seem to do. COVID will not occupy all of our emotional intelligence or emotional time. That'll be the biggest change that I can see.

And then these others are knock-on effects. I hope that one of the changes will be a reversal of this trend of centrifugal forces in the world, and maybe through technology to begin exploring our commonalities a lot more than we have before. I use best practices as an exemplar of what the benefits are of recognizing that we're really all in this together. And I just want to mention one more thing about the anti-vaccine movement and the politicization of vaccines. It's not just Andrew Wakefield, it's not just the Lancet's error in publishing a bogus piece of science that was funded by a bunch of lawyers, it's not just the conflation of vaccines and autism, which is not true but is certainly a meme. It's not just that. There's something else that's happened to the anti-vaxx movement in the United States.

For those of you who are not in the United States, you may not know about an event that took place in the state of Michigan, where a group of pro-Trump, anti-lockdown militias who were dressed all in military garb with machine guns took over the state capitol and then threatened to kidnap the governor of the state of Michigan. The pictures of this armed militia in the middle of Lansing, the state capitol of one of our major states, is indelibly etched in my brain. To think that that was a protest against the governor's attempt to try to put in place measures to stop COVID, which is really what was the beginning of that, and then Trump fanned the flames, telling people to liberate Michigan. That was how it got started. All of the logistics for that, the money for that, was funded by the anti-vaxx movement. What is the relationship between a mostly out-of-state militia going into a state capitol, threatening to take over, and the anti-vaxx movement? Well, the anti-vaxx movement has an infrastructure, which was energized by those two group's movements in the United States. Those two groups came together, and they are now cemented together in many ways.

I worry about the anti-vaxx movement and the politicization of it. That won't merely be a misunderstanding about a relationship to other diseases—it's a political movement. And it's a strong political movement. I do worry about that.

Daniel Kahneman: Can you say more about the infrastructure of the anti-vaccine movement? This is an organized movement?

LB: It has a lot of the accoutrements of a political campaign. There are films such as Vaxxed, newsletters, the combination of legitimate, honest concern about how we have packed so many different childhood vaccines into such a short period of time in the earliest days of a kid's life—a real honest and legitimate concern—coupled with a kind of selfishness, I guess. I don't know exactly how to describe it. A "why should my child have a 1% increased risk in order to give society a 50% increased opportunity of health?"—that kind of selfishness that's not uniquely American, but we seem to have perfected it.

I live in Marin County, which is one of the epicenters of the anti-vaxx movement, so I'm more sensitive to the more benign parts of it. But I don't think Michigan feels like the anti-vaxx movement was benign at all because of how it was organized. What the relationship is between armed militias and the anti-vaxx movement is part of a dark underground of right wing, and not even right wing—I think the wings are gone (there's no way of accounting for this in classical economic, right wing/left wing kind of terms)—but the dark web is part of the organizing areas for this. We're going to find out a lot more about it in the coming months, as more and more COVID vaccines become available.

There's good news, too. Somebody said that we should celebrate our public health victories more than we do. In the United States, we've now reached almost 80% of Americans who routinely wear masks. If that were any other public health intervention and 80% of people used it, we'd be celebrating and dancing in the street, but somehow we're lamenting the 20% instead of celebrating the 80%. In a similar way, I want to celebrate the fact that we've reached 55% or 60% of Americans who now say they will take the COVID vaccine when that was 40% or 42% only three months ago. That's a pretty high number given a vaccine that didn't exist for a disease that didn't exist a year ago. And I think it'll increase.

Maybe this will be pressure against the anti-vaxx movement, or maybe this will be a catalyst for the anti-vaxx movement to become more aggressive. I don't know. I hear all the time that there are people who profit off the anti-vaxx movement, but I don't know who they are, and I don't quite understand it. It's not like it's the Koch brothers who make all their money from fossil fuels, so naturally they're fighting against fossil fuels. I'm sure there's somebody else who knows a lot more than I do about where the economics lie. The political commonality between the ultra-right in the United States and the Freedom Movement—"I am free to not take a vaccine," "I'm free to not wear a mask"—I understand the superficial similarity between those things. They're not very deep and profound, but I don't know more than that.

Lee Smolin: When the vaccines are introduced, we understand that there will be not very much compared to the demand, and the numbers of vaccine available will grow. Therefore, does the strategy with which the initial doses of vaccine available are distributed matter a lot to the course of the epidemic?

LB: What a great question. In my mind, there are two offsetting dynamisms here. The equitable distribution of vaccine, fair, just, is going to the people who need it the most. A wonderful group of people at the National Academy of Sciences, a committee called the Equitable Use of Vaccine committee, was chaired by Bill Foege and Helene Gayle. Helene had been the head of care, and Bill was the head of CDC and the head of the Carter Center, and a saint. He's one of the patron saints of public health. These are wonderful people. They made a great committee, a lot of chairmans of the Department of Epidemiology and Ethics were in that committee. They have published their report, available for anybody to see, where they have recommended a cadence in which the first group of people to get the scarce vaccine—call it the first tranche—will be first responders and people working in hospitals in the healthcare field. That is both out of fairness to these people who've risked their lives and out of the practical consideration that if they're sick we won't be able to advance the program as much. The second group will be those who are most vulnerable and dying from the disease. That has some subcomponents in it, some of which are demographic groups, age groups, people living in nursing homes, pre-existing conditions. And then that cadence goes on and on. That's an ethically driven calendaring, or prioritization of vaccine distribution.

It is not the same thing as what we will be able to do once that initial demand has been met. I'm waiting for a boutique nuance bit of science to come forward, which is called PEP (post-exposure prophylaxis). I'm waiting to see if any of the 146 vaccines provide post-exposure prophylaxis, which simply means that if you vaccinate somebody who's already been exposed and the virus is cooking and will become either a real disease or will become a spreader, you can still vaccinate them and abort the disease or abort the spreading. We've had vaccines that had that characteristic in the past, but they are few. If we have a vaccine that has that characteristic, it will then allow us to do the most rational thing of all, which is to find every case and vaccinate the people around them. We call that ring vaccination or selective epidemiological control. Ironically, the father of that field is Bill Foege, who also chaired the Equitable Use committee. We don't yet have a vaccine like that, that we know for sure. Although, with 146 lotto coins, we can be optimistic about it. If we get that, then these plans may diverge.

The WHO is having a big problem because they've only got enough money for 1.2 billion doses of the vaccine in this COVAX agreement, one of these other global consortiums that Trump pulled out of and Biden has said he will rejoin. That's 600 million people who can be vaccinated, which is less than 10% of the world. But more importantly, WHO, SEPI  GAVI—these global health agencies are the ones who are nominally taking it as their job to provide vaccines for the countries that can't afford it themselves. So 1.2 million doses is only enough for 600 million people and there are billions more who can’t afford the vaccine. That's a big problem.

There'll be plenty of vaccines for the developed world. The US has pre-production purchase agreements for well over a billion doses, which is more than enough for Americans. England has plenty purchased. India is going to turn out to be the largest producer of vaccine and has made a commitment that half of all the vaccine that the Serum Institute of India, in Pune, India, will be able to manufacture. The Chinese, the Russians, well, we don't know very much about their vaccines. Over a million people have been vaccinated in China already. There'll be a profusion of vaccines with different characteristics that will be very difficult for all of us to figure out which one is the best and which one is the safest. As I said earlier, sometimes it takes forever for something to happen and then it happens all at once. We'll see a profusion of good vaccines.

Lee Smolin: What if one could show that the most efficient strategy was not the ethical one?

LB: We can. The most efficient strategy is the one that we did in smallpox, and has recently been done in Ebola, which is to find every case and vaccinate everybody who's susceptible. Maybe efficient is the wrong word—effective, that's the most effective strategy.

Nick Bostrom: I wonder if the main concern is that, ultimately, not enough people will choose to get vaccinated to achieve herd immunity. If there are a lot of people with anti-vaxxer sentiments, even if they're not all the way there, maybe you could run an argument that the better approach would be to start with health care workers, but then rather than going immediately to, say, the most vulnerable people, you start with social elites so that it becomes seen as a desirable thing. People see these rich and famous people getting their hands on the vaccine early and everybody will want it, they'll see it as a good thing. Then, as soon as there are more doses, everybody will want to have their own families vaccinated. Whereas if you start with the elderly, maybe it's seen as this thing that weak people do. Perhaps if you are strong, a "real man," who's healthy and young, you don't want to be associated with that.

LB: Yes. Tesla started off with a James Bond roadster to make electric cars sexy. I understand. Let's talk about herd immunity for a second. There's something funny about the way in which COVID has spread through the population in that it is lumpy. It doesn't spread the way a normal respiratory disease spreads. Whether you're talking about R0 or R instantaneous, R community effects—all these mathematical models that we've had—it's still 20% of people who are sick spread 80% of the disease. Those 20% are, as Nick said, probably highly networked individuals. Therefore, the first group of people to get the disease, because they have a lot of network connections, were probably the first group of people to spread the disease.

The argument goes that lumpiness means that traditional notions of herd immunity have some challenges to them. There's a lot of truth in that. There's even more challenge to the notion of herd immunity, and let's separate out two kinds of herd immunity. Historically, epidemiologists talk about herd immunity, meaning, what percent of people need to be vaccinated to stop the disease. And there's a formula, which is herd immunity must be greater than 1 minus 1 over R0.

Thus, if the virus is spreading at a speed where 1 gives rise to 3, and that's your replication value, R, then 1 minus 1/3 is 2/3. You have to vaccinate 2/3 of the people. That's herd immunity in that sense. A lot of people have been using herd immunity to mean what percent of people need to get the disease. That's not really an authentic historical use of herd immunity. In part we don't know how long, and we can't control how long people are immune; we're not sure about the inoculum.

But, Nick, you don't need to get to herd immunity to stop this effing disease. We never got to herd immunity with smallpox. And in some places where 95% of people were vaccinated, they had huge epidemics of smallpox. Likewise, with polio. The idea is that there are so many asymptomatic people that those rules don't apply—in polio, 999 out of every 1,000 people who get polio are asymptomatic, so it's not that. If we can find every case of COVID, and there's a good argument for the number in the United States being 3 million people (it's probably 2 to 10 million), but 3 million is the number right now we're using that are infectious. That means that 327 million are not infectious right now. If we could find those 3 million and vaccinate everybody that they are face-to-face exchanging air with and vaccinate them with a 90% effective vaccine, the disease stops.

Of course, if you add to that, you find everybody, you vaccinate them, and you isolate them, then even if the vaccine fails, you can still stop the disease. But that's augmented by what I said earlier, which is this post-exposure prophylaxis. If you vaccinate someone after they're exposed and it doesn't do any good, then you have all these other problems. But I agree with you.

Lee Smolin: My concern was that if you could show that there are strategies which are not the ethical strategies that give you, say, five to ten times more effectiveness, that is each dose of the vaccine is worth five or ten times where it would be, who would make that decision?

LB: I don't know who would make that decision. It would be different, I presume, in different countries in different places. It is ironic that the history of that ring vaccination strategy, which was based on the most ethical decision making process that I know of in vaccines, because Bill Foege was a missionary doctor in Nigeria during the Igbo War, and he had a very small amount of vaccine and a very big epidemic. He had to make a decision as to what was the most ethical distribution. At the time, it was the richest and the most powerful people in Nigeria asking him to vaccinate them. He thought that the most ethical thing to do was to give it to the people who are most at risk of getting the disease next, the same as the strategy of vaccinating a ring around everybody who is infected. And so his strategy and his paper, which is called "Selective Epidemiological Control" was based on his own ethical struggle to make that decision.

It's not an easy thing to sell. It's counterintuitive that you don't vaccinate the most highly networked individuals who are creating more clusters, super-spreader events, or the richest people in the world who are making the most demands, or the poorest. Instead, you vaccinate the people who are the most susceptible in the moment, and you remove them from the density of susceptibles. I don't want to get too wonky, but the single biggest driver of an epidemic is the density of susceptibles. The single biggest driver of a forest fire are the susceptible trees around it. That's not to say it's the cause of the forest fire, but the driver of it. If there are no other trees around and you have a big flaming eucalyptus tree, it's not going to make any difference because there are no other structures to burn. It's the same thing with an epidemic.

Jesse Dylan: We've had such a short period of time that we've created these vaccines. Before we started, we would have never thought that you could necessarily do it this quickly. What does that mean for the future of medicine and the things that are going to be possible as a result of this? And then my other question is, we say "vaccine," but if you have certain comorbidities, what's the selection process for which vaccine I'm going to take? Or you're going to take? It seems like there's a lot of varieties, how are we going to go through a process for people just to select a vaccine? There's two on the market now, but I mean, there are 150 coming.

LB: The two mRNA vaccines that are first out of the chute, Moderna and Pfizer, offer a vaccine that is less likely to have bad side effects because they're not actually infecting you with a modified vaccine or an attenuated vaccine. They're just giving you a little bit of code that programs your immune system through the messenger RNA. To me, that's the most exciting of the many different kinds of vaccinology that have been pressed into service by the pandemic.

The opportunity of using messenger RNA to do other things is really exciting. Some of the science that comes out of this has the potential of being valuable not just for vaccines, but for treatments, and not just for infectious diseases, but for chronic diseases as well. I'm really excited about that. Although, none of us know anything about whether these vaccines are indeed safe. And let me just take a moment on that.

We use the term "efficacy signal—a shitty term—which means, does the placebo-controlled trial that you're doing with your vaccine in this case show an efficacy signal? Does it show effectiveness? Let's just take the one study that did 30,000 people and fit them into two groups. Fifteen thousand got placebos, which is salt water in the same kind of injection, same color package, and then 15,000 got the vaccine. They're allowed to go out into the world and get infected if they do or not infected. It's not a challenge study, so you don't vaccinate them and then give them the disease. In this study with 30,000 people, about 90 some odd people got infected, and of the people who got infected, more than 90% had not been vaccinated. You convert that into what is your risk of getting the disease if you've been infected, and your risk is nine times less than the other group. So it's 90% effective. That's the efficacy signal that we got from both Moderna and Pfizer, roughly.

Now, what's the safety of it? Well, you can't do the same thing with safety. Literally, these vaccines have been in trial for three months. We only know what side effects occur three months after you're vaccinated. And while it is true that the majority of side effects take place within a couple of months of being vaccinated, that is not true for the worst side effects, which may not happen for a year or five years.

Some of you may remember in 1976-77 when we had a swine flu scare, and CDC vaccinated millions of people with an H1N1 vaccine that was rapidly created. Only after millions of people were vaccinated did we discover that quite a few people got Guillain-Barré syndrome, and that program had to be pulled back. The real side effects of a vaccine that occur later, we can't know until later. These trials can give you an efficacy signal quickly, but they can't give you a safety signal quickly. There's no way to truncate that time, and because absence of evidence is not evidence of absence, we can't prove that there's an absence of side effects right now. So that's something to think about.

John Brockman: I have a question for Jesse. In terms of communication strategies and the divisions of the country, I'm sure this is something you've thought about, how do you present a vaccination program? What thoughts do you have?

Jesse Dylan: It's too early to say. I worked for President Obama, and we'd done a lot of design research on people's attitudes and feelings about Obama, and then Trump came in and all of that had to be redone. The feelings that people had were completely different when Trump was president. I've worked on Warp Speed, and I've worked at NIH on a bunch of different things, so I'm hopeful that when the government changes again, people will be more tolerant. Larry was talking about frontline workers. At the current time, only 60% of frontline workers are willing to take the vaccine. Larry, what is this cognitive dissonance that people have about it? And what are the repercussions? Let's just say half the country doesn't get vaccinated, what are the long-term repercussions of that for all of us?

LB: They're both better and worse than we think. The question that we are being asked is an abstract question: "Would you take the vaccine?" It's not, "Your mother has just died in a nursing home, would you take the vaccine?" If the strategy of ring vaccination or selective targeting of vaccine around clusters or outbreaks is used, then the question shifts from the abstract Will you take a vaccine?" to "Hell, I've just lost somebody I love or I know people who are dying all around me, will you take the vaccine?" That will change the calculus. Every human being makes an individual cost-benefit decision, and your data set is different.

Jesse Dylan: I had somebody in my family years ago who had polio. That's always been in my mind since I was a little kid. Do people not remember what polio was like in this country? That because they don't see it now, they think, I'm not going to get vaccinated against polio? And then we get a resurgence of something that is so horrible.

LB: Jesse, I think in a way you are answering your own question. You have in your memory bank, and in your life's experience, the experience of polio. That's less and less every year. There are less than a few dozen cases of polio in the world today. The lived experience of polio, which is indeed the major contributor for people's motivation to invest in a polio vaccine, do the trials for polio vaccine efficacy, and take the vaccine themselves, that diminishes. The lived experience for COVID, even though we've had just shy of 15 million cases in the United States and just shy of 70 million cases in the world, that's a very small percentage of the population.

It's still true that more people have not had a family member or friend be hospitalized for COVID then have. That will change if the vaccine focus is on cluster control, outbreak control. And we can't do that yet. With 200,000 cases a day going on 250,000 in the United States, how on earth can you see where the clusters are? And what county health officer can investigate an outbreak and do contact tracing? I mentioned earlier that Vietnam success was based on 100% contact tracing. A comparable figure in the United States is probably 5%. So how can we control a disease when we can't even see where the clusters are or the outbreaks are and find all the contacts?

Lee Smolin: I think we should think harder about that question.

Jesse Dylan: Yes. And what role does the federal government play in all of that?

LB: In another period of time, in an age with more rainbows and unicorns, I would have answered, well, CDC does it. It's going to take a little while to repair the damage done to CDC's reputation. That's the source of authentic scientific information, historically. On those international calls I mentioned earlier, when everyone around the world says, "Welcome back. We missed you, America," they're really saying, "We missed you, CDC. We missed your love of science and expertise and leadership in the field of epidemic control."

It's the US, and it's these phenomenal scientists at CDC that have always led our campaigns against infectious disease and epidemics. They're still there, for the most part. Many of them have retired and left and tried to get out of this circular firing squad that the Trump administration brought to CDC. But many of them are still there, and many of them will be called back. A lot of them will be called out of retirement to come back, I'm sure. But that's where it'll come from.

It is not just a political talking point to lament the fact that we don't have a national strategy. What Trump did, in retrospect, by saying, "Ventilators, not my problem; governors, buy them. Testing, not my problem" was have 50 states compete with each other for masks, drive up the costs, and make for scarcity. It isn't just the material scarcity that occurs when 50 states compete with each other, it's the intellectual scarcity. To this day, the Trump administration's national strategy was "not here, not me, not real." That's all going to change under the new administration. That would have changed under any new administration, and it will be particularly true under this administration.

John Brockman: Question for Danny Kahneman. A while ago, you spoke about the difficulty people have with the idea of exponentials, and all that is coming home to roost now. In your field, are people thinking about how to communicate these issues that most people are not equipped to even think about? In terms of the last six months, are you and your colleagues thinking about this kind of thing?

Daniel Kahneman: I don't think I have much progress to report on that. Educating people to think about exponentials is not going to be easy, and I don't think it's at all feasible. It really is a matter of the policymakers. I don't think it's the public that needs to be educated. There needs to be a national strategy. There needs to be more respect for facts. That's where the problems are. I don't think that the problem is the psychology of thinking about exponentials, which is not going to be fixed easily.

LB: Danny, I just want to say that the first time John put you and me in contact I asked you what you thought was the biggest problem we would have in dealing with COVID. You said that we'd be able to do a lockdown once, but once you've done that and you open it up, you'll never be able to get people to close down a second time. And by God were you right and prescient. That has turned out to be one of the biggest problems that we faced.

Daniel Kahneman: That was really predictable and almost built in, because once you impose it again, people are conscious of unfairness and they are conscious of being affected more than other people are, whereas the initial lockdown was acceptable to everybody. But you really get fragmentation. In truth, we're seeing that everywhere.

I was going to ask you, Larry, about Germany, because one of the things that has been very striking to me is that we had a success story and it doesn't seem to hold. Now, if the success story isn't holding, what is it? What is happening? Is it because Germany is not isolated? Or because you really need to achieve a certain degree of eradication, which they did in Singapore and other places, before you can really open up and relax?

LB: The success in Germany is due to two major factors. One is you have a scientist and an engineer as your prime minister, who has been interested in pandemics and sponsored all of the G8 and G7 resolutions on pandemics for the past 10 years, way before COVID. You have the perfect leader at the perfect time. The second thing is that Germany had planned ahead with a national insurance plan and excess hospital capacity. As a consequence, they never had the surge problems that we had elsewhere in the world where we ran out of capacity. There's a lot of other reasons, too. But you're right.

Daniel Kahneman: My question is about their difficulties now, not about their initial success. Their success was understandable. But why is it so hard to retain? Why have they been successful in the East and apparently not in Europe, not in Israel, where you achieve some initial successes and then it rebounds? What do we know about the rebounding?

LB: As I said earlier, it's not just the East; it's Iceland and New Zealand, which are not necessarily it, but it's definitely those individual countries that have each succeeded by a combination of practices that we would think of as best practices culled from global experience. Germany was the first to make a test kit, and actually it was a German scientist who made it and gave it to WHO. Germany had a real leadership position early on.

There's some kind of regression towards the mean going on in Europe, in general. It's not Germany alone that has had a spike; it's Spain and France, horribly, and England until just about a week ago. So I can't answer your question. I don't know the answer. It may be that, as you say, you never got it down to a low enough number that outbreak control alone could offset the continuing importation of cases from outside the country, which is what fuels that. It wasn't just community spread. It was a constant reigniting of new forest fires that led to the larger conflagration that we're seeing right now.

Lee Smolin: Is it that the Europeans just said, as July looked better and better, "The hell with it. We're going to have a regular August going everywhere as we always do, no masks, no social distancing"?

LB: No one knows the answer to those questions. My best guess is that the school semester that begins in the autumn will be a normal-ish school semester, that kids will be going back to a few camps during the summer. And that wealthy, elite, well connected individuals in wealthy countries will show islands of normalcy—normalcy being no COVID. The world will begin to look a little bit like Swiss cheese, where the holes are COVID-free zones and the yellow meaty part of the cheese is the rest of the world until those holes coalesce, and then counties are free, states are free, countries are free, and then they'll erect borders. Then there'll be bubbles that are made between countries that are free.

Recently, an interesting experiment between Hong Kong and Singapore to create a bubble of travel fell apart. But there are such experiments going on between Australia and New Zealand. That'll grow from the holes in the Swiss cheese to the rest of the world. We will eventually kick this disease into the dustbin of history, but it won't be without going through hell in the next couple of months. We have some logistical issues with taking vaccine production up to scale. And the better vaccines, Moderna and Pfizer, will be the hardest to get to scale. Vaccines like the AstraZeneca will be easier to get to scale because it can be made in huge factories in India. It's a vaccine made in a way that other vaccines have been made before, not novel in every way, like the mRNA vaccines are. But it'll take the world being free. I'll say what everybody knows, if there's COVID anywhere, there's COVID everywhere, until we have these islands of freedom.

Carlo Rovelli: Let me distinguish two things. One is the foolishness that we have seen both in some government and political forces, in a lot of people ignoring scientific facts, who are willing to believe things which are not true, and so on. I see that very clearly, and it's obvious the damage done by this. But let's try to forget that for a moment.

Suppose people were not foolish. Suppose people were reasonable. Is the problem of defending ourselves from this pandemic just a technical problem or not? I have the impression that some societies have found themselves in a choice between saving more lives and making more people poor. Things are far more complicated than that, obviously. If the choice is between having more people die and having more parts of the population that become poor, that's a political choice, not a technical choice. I'm in favor of saving people, know that. I would be happy to live in Taiwan or in Vietnam, going through political choices that I share and am happy with. But I do understand the arguments of those who say, "Wait a minute, okay if some old people die, or some people die if in exchange, we can avoid the impoverishment of society." And then the problem becomes political, not technical. So, the question I'm asking is—let's agree for now the foolishness of ignoring scientific facts—beyond that, is there also an issue in this pandemic that is political, not technical?

LB: Of course. But that's a distinction without a difference. Historians will look at the Swedish experiment, which is encapsulation in one form, and they'll look at it as one of the great tragedies because you can't get there that way. You can't get to economic growth without solving the problem of a pandemic. History shows that, in every pandemic, in every place. There are two differences here. There's geographic spread. This is really a pandemic. The plague of Athens didn't go much beyond Athens. You have to look at, can I isolate my entire country and isolate it from the effect of a pandemics all around me? Islands can do that better than the countries that are contiguous with landmasses or have open borders. The other is time. So, it's geography and time.

Once you have a vaccine, or vaccines, in sufficient quantity, and tests in sufficient quantity, and treatments in sufficient quantity, which we're going to have in a matter of months, this argument disappears. In fact, it is a lack of confidence that there would ever be a vaccine or ever be a therapeutic that does give some strength to the question you're raising. Because if you think that there will never be a vaccine or a therapeutic, and that this state of a pandemic is permanent, then of course the choice between economic well-being and death rates become much more cogent. But once you have those, as Tony Fauci says, once the cavalry arrives, in terms of prophylactic preventative measures and cure, then they're the same thing. If you don't bet on there being a vaccine or treatment, you might make that choice, but I don't think it's a real choice. It's a false choice. And certainly, in retrospect, it will look like that.

Jacob Burda: Just going back for a moment to the German perspective, we have a country where we can trace a much higher amount than in the US right now, in terms of cases and outbreaks and where they're coming from. Would you advise those countries who have tracing capabilities like this to advance a strategy of vaccination which is more in line with identifying current people infected and people that they've been exposed to? Because from what I'm understanding, in the German discourse right now, that's never been discussed fully. And that's not really something that they're looking at, when it's been very interesting hearing you today. That sounds like an incredibly appealing alternative, particularly if they have a pretty good handle on outbreaks and on tracing.

LB: A really great question. It depends on what vaccines pass the hurdle of being effective and whether they have this post-exposure prophylactic characteristic or not. For example, if you have to get two doses one month apart, and then an annual booster dose, the idea of using vaccines as part of outbreak containment becomes a little less valuable than one dose, where you'd never have to find the same people again and no annual dose is needed.

This idea of the hammer and the dance, this innovative way of looking at how you deal with shutdowns and closing the economy for a short period of time, and then dancing with all these non-pharmaceutical interventions like masks, social distancing, hand washing, and outbreak containment—that becomes more important in this context.

Warren Buffett said, "Until the tide goes out, you can't see who's swimming naked." Until the tide goes out of the epidemic, you can't see where the rocks are, the outbreaks, the clams. You can't see anything. It's covered by a tide. You can't do outbreak investigation, you can't do testing tracing in isolation. If Germany can do that, as certainly Taiwan, Vietnam, Korea, and New Zealand can do that now, then the idea of the hammer has done its job. Now you can do a different dance because you have a vaccine. Then it would be absolutely appropriate to take a look and see if ring vaccination or targeted vaccines would work. You could start off by just doing testing tracing and quarantine and vaccination until you have a vaccine that could carry more of the burden itself. But absolutely, you've made this investment to gain control of the epidemic, you might as well now profit from that investment that you've made.

Lee Smolin: Does any epidemiologist think about whether you could understand this well enough to predict where the outbreaks will be, to predict who will get infected yet? Not exactly, but probabilistically?

LB: Yes, there are a number of people—Dylan George, who used to be at BARDA and he's now at In-Q-Tel, has been trying to launch a global weather service that predicts where the pandemic will go next.

There are a lot of people at MIT who are working on stochastic processes and predictive models. Jeff Shaman at Columbia University has done a really good job on that. I think Sam Scarpino at Northeastern has done quite a bit of that using mobility. In fact, he's published extensively on the Wuhan outbreak, using only mobile phone, digital vapor trails to predict where the outbreak would have gone. He then looked at real data and saw a congruence in what happened with following mobile phone digital vapor trails.

Until there is a reduction in the ocean, the tide, the huge amount of disease, it's not going to help you very much. But it's extremely valuable once that ambien viral load goes down a little bit. But let me say it a different way. If we have 250,000 cases a day, or 200,000 cases a day, and the average infectivity is, let's say, five days (that's not right, but let's say that), so there are a million people who are sources of the disease right now. You have to contact trace 50 people for each of them. That's 50 million people you have to find, and locate the right person, and then you can predict where it's going to go next. It's just overwhelming. We can't do that in the United States right now. You can do it in Germany, apparently, you can do it elsewhere.

Lee Smolin: The information is in there. Information is in the phones.

LB: Yes, the information is in the phone. It's also in funny things like in what Sam Scarpino just published. He found that there were super-spreader events that included particular churches that had particular practices, particularly restaurants that had particular seating patterns, particular attractions that created the opportunity for super-spreader events. He's one of the people who investigated this outbreak in Maine. Yes, it's entirely possible to do a probabilistic prediction pattern. As the load of the epidemic becomes less, Germany perhaps could do it right now.