Making Sense - Sam Harris - Special Episode： Engineering the Apocalypse

00:00:00.000 Imagine we're in another pandemic, and the disease has been deliberately engineered to be more

00:00:05.560 contagious and way more lethal than COVID-19. That's right, it's a man-made pandemic. And the

00:00:11.620 virus is so deadly, it kills roughly half the people it infects. So if you and your spouse

00:00:16.700 catch it, at least one of you will probably die. And maybe you both will. Likewise, any other duo,

00:00:23.100 you and your best friend, you and your kid, the president and vice president,

00:00:27.120 and an uncontrollable outbreak is underway. Next, imagine this outbreak sweeping through

00:00:33.380 a power plant. Do the lights stay on? With half the staff dead or dying and the other half thinking

00:00:39.260 they're next? And if the power goes out, how do we reach the internet? And with no internet,

00:00:45.520 how do we find out, well, practically anything that we need to know to navigate this unprecedented

00:00:50.580 existential threat? Now imagine you're a frontline worker at the power plant for caring for the sick.

00:00:57.120 Or delivering food. People are getting wiped out at 50 to 100 times the rate of COVID.

00:01:03.140 It's a coin toss as to whether you'll survive if you get sick. Do you report to work? Or do you

00:01:08.580 hunker down with your loved ones at home? Until you all get really hungry? Supply chains disintegrate

00:01:14.920 in situations like this. The grocery stores that actually open sell out, not just out of toilet paper.

00:01:20.740 And they don't get restocked. And pretty much everything else disintegrates too. For all of

00:01:26.660 its horror, COVID hasn't shut down the power, the water, law enforcement, or the flow of information.

00:01:33.700 But something this lethal could just shut them all down. And while you may be more imaginative than I

00:01:39.220 am, I just can't picture civilization surviving an encounter with something this deadly. And the problem

00:01:45.900 is we're on a collision course with some version of this scenario. Hi, I'm Rob Reed, and I've been

00:01:53.100 worried about artificially modified viruses for a few years now. My background is that I'm a long-time

00:01:58.260 tech entrepreneur who went on to become a writer. I write science fiction for Random House, and I'm

00:02:02.800 also a science writer and science podcaster. A while back, I wrote four articles for Medium about

00:02:07.960 artificial pandemics and other subjects. That led to an episode on my own podcast, which is called

00:02:13.060 the After On podcast, and mostly considers fairly deep scientific issues in ways that non-experts

00:02:18.900 can follow. That particular episode was a conversation with the thinker and entrepreneur

00:02:23.560 Naval Ravikant, and it led directly to a talk that I gave on the TED conference's main stage about a

00:02:28.760 year and a half ago. I'll be integrating some of that earlier work here, and then building on it in

00:02:33.640 this short series. In the course of it, I believe I'll persuade you that an engineered pandemic will

00:02:39.100 almost inevitably happen eventually, unless we take some very serious preventive steps.

00:02:44.380 And I'll tell you exactly what those steps are. We'll also talk about the science and techniques

00:02:49.100 that are at play here, about the sorts of people who might actually want to inflict a pandemic on

00:02:53.680 the world, and what drives them. But first, a big spoiler. It may not sound like one, but I'm an

00:03:01.140 incurable optimist. I wouldn't be telling you all this if I wasn't convinced this story can have a happy

00:03:06.060 ending. And more than anything, this series is about navigating our way toward one.

00:03:12.080 I'll start out with this strange claim that we actually got rather lucky with COVID. Not in an

00:03:17.260 absolute sense, obviously. This is clearly the most horrifying year humanity's endured in quite some

00:03:22.320 time. But compared to what might have happened, in terms of sheer deadliness. Now, I say this with

00:03:28.280 a caveat that it's hard to know exactly how deadly COVID is, in percentage terms. We can't just use

00:03:33.740 simple ratios of deaths to officially reported cases, because huge numbers of cases never get

00:03:39.200 diagnosed. Many people who catch COVID never get symptoms, for one thing. And for those who do get

00:03:44.760 sick, testing capacity is notoriously inadequate. So countless cases go undetected. But adjusting for

00:03:51.220 all this murkiness, the World Health Organization estimates that between a half a percent and one percent

00:03:56.780 of infected people die. And in many age groups, it's a tiny fraction of one percent.

00:04:01.520 And I'm saying we got lucky because there is no biological reason why the death rate

00:04:06.740 had to be this low. I mean, take SARS. It killed about 10% of the people it infected. That's an

00:04:14.220 order of magnitude worse than COVID. And we were lucky with SARS, too, in that people got so obviously

00:04:20.600 sick so fast, patients were easy to identify in quarantine before they spread the disease very far.

00:04:26.400 So fewer than a thousand people died of it. But if SARS had been like COVID, and spread like mad when

00:04:32.920 people were still asymptomatic, or thought they just had a cold, we'd be living in a very different

00:04:38.200 and badly diminished world right now. And SARS is a kitten compared to Middle East Respiratory Syndrome,

00:04:44.400 or MERS, which kills over a third of its victims. So we're incredibly lucky MERS just doesn't happen to be

00:04:51.220 very contagious. And then MERS is mild compared to H5N1 flu, which kills about 60% of the people who

00:04:59.060 catch it, making it even deadlier than Ebola. So thank God it's insanely hard to catch. How insanely

00:05:06.300 hard? Well, the World Health Organization tallied every instance of H5N1 over a decade and came up

00:05:12.260 with just 630 cases and 375 deaths. To put that scale in perspective, lightning kills about 60,000

00:05:20.900 people in a typical decade. So H5N1 is barely contagious at all. In its natural form, that is.

00:05:28.920 But unfortunately, there's an artificial form of H5N1 as well. It exists because several years ago,

00:05:35.200 some scientists started poking at the virus in hopes of understanding just how dangerous it could be.

00:05:39.960 Since it was plenty deadly, but barely transmissible, they set out to create a contagious 0.75

00:05:45.480 form of it. And you heard me right. They deliberately produced an artificial version of this

00:05:50.560 ghastly virus with a terrifyingly high potential to spread easily between people. This incident is

00:05:56.980 the basis of the grim pandemic scenario I opened with. A contagious, modified form of H5N1 killing half

00:06:04.360 the people it infects. The researchers made this monster by manipulating its genes via passing the

00:06:11.660 virus between several generations of ferrets, ferrets being common stand-ins for humans and virus

00:06:17.060 research. Eventually, they had a strain that could pass from ferret to ferret without any contact

00:06:21.980 through the air. The head of the Dutch team, Ron Fouchier, candidly admitted that his creation was

00:06:27.320 quote, probably one of the most dangerous viruses you can make. Over in the U.S., the National Science

00:06:34.380 Advisory Board for Biosecurity didn't disagree. In a press statement, it said that the modified

00:06:39.880 virus's release could result in quote, an unimaginable catastrophe for which the world is inadequately

00:06:46.080 prepared. Coming from an organization that's not known for drama, the words unimaginable catastrophe

00:06:52.360 are bone-chilling. If that's not scary enough for you, I'll add that this work wasn't done in the

00:06:58.660 world's most secure labs. Literally. Because both the Wisconsin and Holland facilities were certified

00:07:04.300 biosafety level 3, which is a big notch below the top rating of biosafety level 4. This isn't very

00:07:11.380 reassuring, given the history of deadly substances erupting from profoundly secure labs. Think of the

00:07:17.720 anthrax attacks of 2001, when the lethal spores found their way from a U.S. Army lab to the offices

00:07:24.540 of the Senate Majority Leader. Or consider that the last person killed by smallpox caught it because a

00:07:30.380 British lab let the bug escape after decades of globally coordinated efforts had eradicated it from

00:07:36.500 the entire planet. Or consider Britain's 2007 foot-and-mouth disease outbreak, which began with a leak from

00:07:43.680 a biosafety level 4 lab. Incidents like these make it blindingly clear that any pathogen can

00:07:50.620 potentially escape from any lab, because humans are fallible. And so are labs of any biosafety level.

00:07:58.800 Knowing these facts, what kind of person brings into existence a pandemic-ready bug that could be a

00:08:04.520 hundred times deadlier than COVID, that could kill a majority of the people it infects, and perhaps be

00:08:10.680 wildly contagious. In this case, not evil people. These were virologists who thought their research

00:08:17.240 would help us face subsequent natural mutations in H5N1. But they were shooting dice with our future.

00:08:23.260 And given their equipment and sophistication, they didn't need to ask any outsider's permission

00:08:27.780 to do that. They may have run things by an internal review board of some kind, but they only needed

00:08:33.820 outside permission to publish their results once they were done. And they did encounter some speed bumps

00:08:38.940 on that front. But no regulator, no judge, no outside body of neutral citizens was in a position

00:08:45.820 to say, don't you dare take that gamble, however small it may be, on humanity's future. To say,

00:08:52.880 your judgment alone does not give you clearance to perhaps bet millions of lives on your assistant

00:08:59.180 never screwing up, or on your lab not being just a little bit imperfect. I call this sort of thing

00:09:05.640 privatizing the apocalypse. By this I mean that at the dawn of the Cold War, playing chicken with

00:09:11.340 doomsday went from being something no one could do, because it was impossible with pre-atomic weapons,

00:09:16.660 to something that two people could do. Kennedy and Khrushchev, Nixon and Brezhnev, Reagan and Gorbachev,

00:09:23.840 etc. This transition traumatized generations. But the leaders represented giant countries with hundreds of

00:09:31.340 millions of citizens, which made the act of risking annihilation a perverse form of public good.

00:09:39.620 This approximate situation is still with us, and there's obviously plenty to dislike about that.

00:09:44.940 But at least we've only needed to keep a fairly low number of decision makers in line.

00:09:49.260 People who spend years looking after a nation's well-being, who have major international obligations

00:09:54.200 they hopefully take somewhat seriously, and who are subject to certain checks, balances, and fail-safes.

00:09:59.900 None of that's true for an autonomous researcher running a lab, who decides to make an apocalyptic

00:10:05.360 pathogen in the general name of science. Even if the odds of it escaping are small, the decision to

00:10:11.780 play chicken with doomsday has effectively been privatized. Which is plenty scary when the folks

00:10:17.160 who get to toss the dice in these situations are very few and far between, and are generally,

00:10:22.420 you know, good guys, white cowboy hats. But as we'll soon discuss, the casino's about to throw the

00:10:28.600 doors wide open. Not because anyone thinks that's a good idea. Very few people have even considered

00:10:34.440 this issue, which is a big part of the problem. But rather because relentless advances in technology

00:10:40.320 are about to make these kinds of gambles, and these kinds of potentially genocidal powers,

00:10:46.580 very widely available to far more people than we can keep an eye on, and to people we can't keep in

00:10:52.160 line by threatening with wrist slaps, like delaying publication of their research papers. In the next

00:10:57.780 section of this podcast, we'll talk about the terrifying proliferation of doomsday powers,

00:11:02.440 and who might abuse them, and why. But for now, consider the landscape this is happening in.

00:11:09.000 COVID is our dress rehearsal for handling something much worse. And in lots of places,

00:11:14.060 certainly including the United States, it's been one of the most disastrous dress rehearsals in the

00:11:18.680 history of theater. It's like half the actors forgot all their lines. A quarter got bizarrely

00:11:24.660 doctored scripts, which have them saying and doing the opposite of what they're supposed to do.

00:11:29.580 The lights have caught fire, half the costumes didn't show up, and disease is spreading throughout

00:11:34.440 the cast. To step out of the dress rehearsal analogy, I'm referring to things like the ongoing

00:11:39.620 disaster connected to adequate COVID testing and timely results, our early lack of PPE,

00:11:45.780 are all but non-existent contact tracing, the lethal politicization of slowing infection

00:11:51.960 via masks, etc. In an October editorial, the normally sober and understated New England Journal

00:11:58.400 of Medicine frankly stated that, quote, the magnitude of this failure is astonishing.

00:12:04.380 And remember, this is just a dress rehearsal. Opening night is coming. Which means that as we do

00:12:09.720 the post-mortem on this botched rehearsal, it's vital that we start planning maniacally for the next

00:12:15.200 pandemic. That we start thinking obsessively about all the cannonballs we've had the great fortune

00:12:21.060 to partially dodge lately. That we consider the next set of cannonballs which are inevitably on their

00:12:26.520 way. And that we humbly acknowledge that no one's luck lasts forever. For one thing, the rate of

00:12:33.540 diseases jumping over from animals to the human population is rising dramatically as we encroach ever

00:12:39.040 more on natural habitats. So nature is taking potshots at us with increasing frequency. As for artificial

00:12:45.420 viruses, there's no reason they'll hit us at nature's relatively leisurely recent pace of one major scare

00:12:51.760 every five to ten years, because the cadence will be determined by the people behind them.

00:12:56.800 All this means that humanity's future depends on keeping our guard up if and when we put COVID-19 into

00:13:02.960 the grave. And I mean way up, preparing for absolute worst-case scenarios. Natural pandemics are random

00:13:10.680 case scenarios, because evolution is driven by blind chance. But nothing will be random about a virus

00:13:16.720 designed by a malicious and murderous party. Unfortunately, we don't have a great track record

00:13:22.140 for keeping our guard up after a major disease scare has passed. Despite all the close calls of recent years,

00:13:28.000 civilian biosecurity funding fell by 27 percent between 2015 and 2019, according to The Economist

00:13:35.140 magazine. Meanwhile, governments haven't exactly inspired the private sector to carry the ball. 0.82

00:13:41.200 The Economist also tells us that after the swine flu pandemic petered out, European and American

00:13:46.160 governments reneged on contracts with vaccine makers, leaving them hundreds of millions of dollars in

00:13:51.600 the hole. Speaking to The New York Times, virologist Peter Daszak summed up the situation saying,

00:13:56.920 quote, the problem isn't that prevention was impossible. It was very possible. But we didn't

00:14:02.500 do it. Governments thought it was too expensive. Pharmaceutical companies operate for profit. 0.79

00:14:08.300 In light of this, we should consider the finale of one of the most popular TED Talks of all time,

00:14:12.960 in which Bill Gates warns against the dangers of complacency. He wraps up by saying,

00:14:17.880 if anything good can result from the current outbreak, quote, it's that it can serve as an early

00:14:22.420 warning, a wake-up call to get ready. If we start now, we can be ready for the next epidemic.

00:14:28.560 Unfortunately, Gates didn't get his wish. Because as many of you probably know, he wasn't talking

00:14:33.360 about COVID, but Ebola. That talk was recorded over five years ago. And of course, we were far,

00:14:39.960 far from ready for the coronavirus outbreak that followed it. Now, as I said up front, there are many

00:14:45.260 steps we can take to dramatically increase our resilience against pandemics, both natural and

00:14:49.800 unnatural. And although we have a history of hitting the snooze bar hard enough to scatter

00:14:54.720 alarm clock fragments into the next county, the wake-up call we're getting from COVID is uniquely

00:14:59.960 thunderous. In response to it, I say we take inspiration from the ways our own bodies fight

00:15:05.080 off infections and build a global immune system to identify and destroy deadly new diseases on a

00:15:10.820 planetary basis. This system can be agile and adaptive, just like the ones in our bloodstreams.

00:15:16.780 We'll talk about the components such a system might have, and the fascinating science and

00:15:21.320 technologies underpinning each of them. And I think you'll agree that if we finally heed

00:15:25.700 the warnings nature has been sending, and resending, and re-resending to us, we can navigate this

00:15:32.340 danger. Bottom line, if you take only one thing away from this series, I want you to understand

00:15:37.800 that a catastrophic pandemic is heading our way. But it's not too late to prevent its arrival,

00:15:43.120 if we can push our policymakers to rally to this challenge.

00:15:49.100 Okay, Rob, that was terrifying. So before we jump into the topic of pandemics, engineered and

00:15:58.680 perhaps natural, let's just get a little bit of your background here. How did you come to be

00:16:04.260 interested in this? And I know you have a generic interest in science as a science fiction writer,

00:16:10.040 but how did you come to be worried about this particular topic of the catastrophic risk posed by

00:16:18.680 an intentionally engineered pandemic?

00:16:22.780 Well, I guess the earliest thread of that actually goes all the way back to when you and I

00:16:27.560 overlapped briefly as Stanford undergrads. At the time, I was studying a ton of Arabic and

00:16:33.120 Middle Eastern history. And after graduating, I went to Cairo on a Fulbright fellowship,

00:16:37.260 where I spent a year doing research on the secular opposition, people who were pushing for a non-religious,

00:16:43.920 non-dictatorial government, a faction whose political heirs ultimately, to a great extent,

00:16:49.100 led Egypt's Arab Spring Revolt, although they didn't actually gain any power from that long story.

00:16:55.120 And one person that I spent a lot of time with back then was a guy named Farag Foda,

00:16:59.500 who was Egypt's most prominent secularist at the time. And the fundamentalists hated him because he

00:17:05.900 was vocal, he was for a non-religious government, and he was really brave. And really tragically,

00:17:11.660 not long after my year in Cairo wrapped up, Farag was assassinated. And that kicked off a ghastly wave

00:17:18.340 of terrorism that Egypt endured throughout the 90s and, you know, beyond. And it was a really big shift

00:17:24.900 because there'd been almost no terrorism in Egypt for years prior to that. And really, as a direct

00:17:30.420 result of that, I got, you know, very focused on terrorism as an issue. And that's a focus that

00:17:37.980 persists to this day. Fast forward, you know, significantly, I founded a company that created

00:17:45.440 the Rhapsody Music Service, which some of your listeners might be familiar with. And although that's

00:17:50.460 unrelated, just give a quick side note, Rhapsody, for those who don't know it, it's pretty fair to

00:17:55.540 say it was the first Spotify. After I sold that, I really became sort of a two-fisted person. I'm a

00:18:02.000 tech investor with some of my time, but I'm also kind of a media creative type of person. And I've

00:18:08.980 written a few books, a couple of which are science fiction novels for Random House. And when I was

00:18:13.340 writing the second science fiction novel, a book called After On, I delved into a whole bunch of the

00:18:19.340 technologies that we'll be talking today, particularly synthetic biology. There was a subplot in the

00:18:23.740 story that was connected to a symbioterror attack. And when the book came out, I decided to do what I

00:18:30.160 thought would be a very limited podcast series, just going deeper into the science of the various

00:18:37.040 things that were in this science fiction novel. And then that podcast ended up taking on a life of

00:18:42.300 its own. And I've now done over 50 episodes, quite a few with leading lights in synthetic biology. So

00:18:47.940 that's really where the other thread came in. Yeah. Well, one thing that one gets from your

00:18:54.220 discussion thus far is that it really can't be a matter of relying on there being no one willing

00:19:02.340 to do this sort of thing. You know, there's a level of incredulity psychologically that one has to cut

00:19:09.540 through here when you think about, well, who is going to want to unleash a catastrophic pandemic

00:19:16.220 upon the whole world. For some reason, it takes some convincing for people to acknowledge that

00:19:23.360 not only will there always be someone who will, there will always be many people who will aspire to

00:19:32.680 do that sort of thing. And many, you know, you know, 10 is many, but there are probably hundreds,

00:19:38.760 if not thousands in any generation who would be willing to do such a thing. And therefore,

00:19:46.300 it just can't be a matter of messaging successfully to these people, changing their minds, preventing

00:19:52.520 the wrong memes from lodging in their brains. The memes are already there. And therefore, we have to

00:19:59.780 fundamentally make acquiring the technology so difficult as to dial down the probability that this

00:20:06.540 will ever happen. So as things stand now, we're on a collision course with the democratizing of this

00:20:14.380 kind of technology. Where should we start here to absorb this initial lesson?

00:20:19.480 The first thing to think about is what kinds of things can we do to make the near future tools that,

00:20:27.780 let's say, a less sophisticated person, somebody who's not a top mind in synthetic biology,

00:20:32.480 might be able to turn to in 10, 15, 20 years. Tools that we'll be able to do things that the

00:20:38.640 entire project of synthetic biology can't possibly do today. And what we need to do is to really

00:20:47.040 exercise our imaginations about what tools like that could possibly do in a short period of time.

00:20:55.820 Because I would argue that there is a very different level of moral responsibility

00:21:01.460 on inventors and scientists and regulators. When we're starting to develop and handle

00:21:08.000 a potentially catastrophic exponential technology, exponential being that this is something that can

00:21:15.140 go in radically unexpected places in a short number of years, than when we're handling a normal

00:21:22.340 dangerous technology. So to use a somewhat silly example, whoever the medieval Chinese 1.00

00:21:28.840 blacksmith was who first invented a firearm, we don't blame that person for mass shootings.

00:21:36.780 Mass shootings approached us at an incredibly slow speed over centuries, meaning it was on us to dodge

00:21:43.420 those literal bullets or not. And we could have done things to make mass shootings difficult and rare,

00:21:48.020 like keeping guns out of private hands. Now, I don't want to dive into a Second Amendment discussion

00:21:54.020 because that could last for hours. I'll just say that whatever your position on gun rights,

00:21:57.940 we can agree that society had ample time to decide whether or not mass shootings are a reasonable price

00:22:04.420 to pay for today's policy. This situation did not sneak up on us at an exponential pace. But it's very

00:22:10.620 different when something's improving a thousandfold in a few years. Because while it's impossible for

00:22:16.720 anyone to definitively predict where that trajectory is going to lead, the people closest to the

00:22:22.280 technology have a much better shot at it than the rest of us, which puts a particular moral weight on

00:22:27.840 them to ask what rapid changes could end up ambushing a society that just doesn't see them coming.

00:22:34.640 So one example of this, the U.S. Department of Health and Human Services includes in its huge grip

00:22:42.180 the CDC, the FDA, the National Institutes of Health, and clearly has all the intellectual and technical

00:22:49.300 firepower it needs to be profoundly informed about synthetic biology. But it was the HHS of all entities

00:22:57.360 that posted the 1918 flu genome to the internet in 2005. When smart people like Ray Kurzweil, who's

00:23:07.120 basically the godfather of exponential thinking, who really came out stridently against doing that,

00:23:12.820 could have easily told them that this information might be catastrophically weaponized within a couple

00:23:18.360 of decades. And we can't keep having failures like that. Which means private sector leaders need to use

00:23:25.140 their imaginations a lot, and academics a lot, about worst-case scenarios, be very transparent about them,

00:23:31.040 and self-regulate more than any industry in history. And meanwhile, governments have to be

00:23:36.920 unbelievably smart about synbio, synthetic biology, and they have to monitor the industry relentlessly.

00:23:42.700 And they have to regulate dangerous practices on a coordinated international level. And I'm a

00:23:48.880 generally very free market-oriented person, so I don't say any of this lightly. But this sort of thing

00:23:54.400 is just necessary when we have a wildly promising exponential technology that we want to nurture and benefit

00:24:00.220 from, but which also has a cataclysmic downside. And the funny thing is that we don't really have a

00:24:07.300 good precedent or analogy that we can turn to to guide us. This wasn't the case with digital technology,

00:24:15.040 another exponential technology. Whatever we think of super AI risk today, computing posed no innate

00:24:21.180 existential risk for its first 50-plus years. It could surprise and delight us with astounding,

00:24:27.320 unforeseen developments for years in a row, no real downside. So we just don't have a good historic

00:24:33.040 map to turn to for guidance here. You and I are recording this during hopefully the waning days of

00:24:41.260 the COVID-19 pandemic. Let's hope. We're in this frustrating, uncanny valley of knowing that vaccine

00:24:50.400 is everywhere sitting on shelves and it's being administered at a shockingly leisurely pace.

00:24:59.700 California was just declared the worst state in the nation with respect to the velocity of its

00:25:06.700 vaccination program. Good grief.

00:25:09.300 How we achieve that is anybody's guess. But, you know, many of us have drawn the lesson

00:25:15.240 here that we have experienced a comparatively benign pandemic. I mean, it almost couldn't be more

00:25:24.720 benign. You know, it's worse than flu and then perhaps tenfold worse than flu. But it is still

00:25:32.840 killing at most one percent of people infected and disproportionately elderly people. So the impact

00:25:42.140 of something tenfold more lethal or more is really difficult to picture or rather it's easy to picture

00:25:50.920 how catastrophic that would be because I'm not alone in thinking that, you know, this is a dress

00:25:57.100 rehearsal we've experienced for something quite a bit worse. And we have just manifestly failed this

00:26:06.200 dress rehearsal. Our response to COVID has been abysmal. And it's been abysmal even though the

00:26:15.320 scientific response has been amazing. The public health response has been as inept as you could have 0.95

00:26:22.320 ever feared. But the research response, the molecular biology response, the vaccine production

00:26:28.980 response has been amazing. I mean, the Moderna vaccine was created apparently before there was a

00:26:35.440 single death in the U.S. from COVID. It's astounding that we have the juxtaposition of that kind of

00:26:41.600 technical competence and the utter mismanagement of a public health response. And, you know, as we know

00:26:50.240 and need not get sidetracked by, there's been a layer of political controversy and chaos that in part

00:26:57.720 explains how bad we are at this, but not entirely. We're a society that can't figure out how to produce

00:27:05.120 masks at scale, it seems, or Q-tips. So we have supply chain problems. It's been a colossal embarrassment

00:27:14.080 and an excruciatingly consequential one given the body count. And again, this is about as easygoing

00:27:22.980 a pandemic as we could have hoped for. So what lesson do you draw from this given that what would

00:27:30.260 be engineered, you know, would very likely be quite a bit worse. And as we know, and as you've discussed,

00:27:37.720 and we'll discuss further in this series, there are natural variants of diseases that we're already

00:27:44.800 worried about, which are quite a bit worse than COVID. And it's just by sheer luck that they haven't

00:27:52.260 spread more efficiently than they have. So we know that almost everything on the menu is worse than

00:27:59.680 COVID. And yet this has unmasked our near total inability to respond quickly to a challenge like this.

00:28:05.900 To summarize all that, frankly, the private sector has covered itself in glory. And in many countries,

00:28:12.980 certainly, including the United States, the public sector has covered itself in shame. And we need to

00:28:18.120 do much, much better than that. You mentioned order of magnitude. I actually think that's exactly the

00:28:23.580 right way to think about hypothetical future diseases, because, you know, movements of 25-50%

00:28:30.740 on different metrics are kind of hard to model out. But let's think about order of magnitude

00:28:35.440 along two metrics, deadliness and transmissibility, which is to say transmissibility, how contagious

00:28:41.000 the disease is. Because particularly if there's an artificial pandemic, we can rely on the malevolent

00:28:46.940 designers of that to dial things up significantly beyond where COVID is. And we also can't rely on

00:28:53.240 nature, as you rightly pointed out, to keep things dialed down to where they are with COVID. So let's

00:28:58.740 start with deadliness. As I mentioned in the recording, the World Health Organization puts COVID's

00:29:03.900 case fatality rate somewhere between half a percent and 1%. So that could be dialed up by

00:29:09.140 up to two orders of magnitude. One order of magnitude, and it's 5% to 10%. Two orders of

00:29:14.120 magnitude, and it's 50% to 100%. And as you noted, these are not unheard of numbers. SARS kills about

00:29:20.340 10% of the people it infects. H5N1 flu over 50%. So there is no biological reason why the next pandemic,

00:29:26.980 even if it's natural, necessarily has to top out at 1% fatality. And if it's artificial, we can

00:29:31.660 rely on it topping out higher. As for transmissibility, the big number, of course,

00:29:37.400 is R-naught, which is how many people the average sick person infects. And without public health

00:29:43.320 measures, COVID's R-naught is 2-ish or 3-ish, something like that. Estimates vary. To get a

00:29:49.160 sense of what it would be like if the R-naught was much higher, think of the measles, whose R-naught can

00:29:55.660 hit, I think, the 15 to 20 range. An example, if you get into an elevator a minute or two after

00:30:01.040 someone with COVID leaves it, almost all the aerosolized particles will fall into the ground,

00:30:06.580 and you'll be extremely unlikely to catch COVID. But if you're unvaccinated for measles, and a sick

00:30:12.380 person leaves an elevator two hours before you show up, you could very easily catch the measles. So

00:30:19.240 imagine a one order of magnitude disease and transmissibility. Think of something as deadly

00:30:24.540 as COVID. It currently is, but as contagious as the measles. The result of that situation would be

00:30:30.300 that virtually everyone would catch it in very short order, and we'd have an unbelievably hard

00:30:36.840 landing into herd immunity. I think that would be absolutely ghastly. The death rate would go north

00:30:43.780 of what COVID is because hospitals would be overwhelmed, but I'm pretty confident civilization

00:30:47.760 would survive. As for the death rate going up by one order of magnitude, 5 to 10 percent,

00:30:54.540 I'm still confident society would march on, but a bit less so. Not because of what it would do to

00:30:59.700 people who were lucky enough to seclude at home. They could probably still dodge the virus, but what

00:31:05.100 it could do to supply chains. Like if there's a 5 to 10 percent chance of death, do meat packers show up

00:31:10.800 at work or grocery store workers? And if you start having food supply outages, even small anecdotal ones,

00:31:17.480 just imagine the pandemonium of hoarding that would ensue and the road warrior-like scenes that

00:31:24.420 would unfold in stores. And we could barely handle a toilet paper shortage, which itself was kind of

00:31:30.060 like the GameStop run-up. I mean, it was a reflection of crowd psychology, not of an actual supply chain

00:31:35.460 breakdown. Still, I don't think that's a civilization-canceling scenario either, but it'd be

00:31:40.980 way more dangerous than what we're facing now. Now, those are two one order of magnitude diseases

00:31:47.760 beyond COVID. As for two orders of magnitude, all bets are off. I mean, I don't know if anyone shows up

00:31:53.560 to work if there's a 50 to 100 percent fatality rate, or if there's an order of magnitude jump in fatality

00:32:00.160 combined with one in transmissibility. And in that sort of scenario, I start worrying about staffing the

00:32:05.540 electrical grid. Because if the power goes out for a sustained period over a national grid, or God

00:32:10.320 forbid, a global footprint, civilization teeters very, very quickly. So if there ever is a wide

00:32:17.560 outbreak, and I'll come back to those words, wide outbreak in a moment, of a two order of magnitude

00:32:21.760 disease, the only way society could possibly survive would be with very meticulous contingency plans

00:32:28.080 that are drilled at local and national levels, and very, very careful to keep power, food, and law

00:32:34.040 enforcement flowing. Plans which I'm sure we don't currently have. Now, a much-

00:32:39.060 It was right behind the Q-tip plan and the mask plan.

00:32:43.460 Exactly. Once the Q-tip plan was contingency plan, the survive a doomsday apocalyptic disease plan.

00:32:50.280 Now, a much better alternative to ever facing a wide outbreak scenario would be to have an incredibly

00:32:55.920 robust global immune system response to quash the disease the instant it shows up on a radically

00:33:02.920 improved global surveillance network, which we're going to talk about a lot later in the series. So

00:33:08.260 in any event, somewhere between one to two orders of magnitude distributed between deadliness and

00:33:13.800 transmissibility, I do think civilization teeters. And there's no way we could survive a wide

00:33:20.320 outbreak much more than one order of magnitude without a radically improved public health game.

00:33:26.300 Hmm. There's a couple of threads I want to pick up on here. One is this distinction between natural and

00:33:32.880 synthetic pandemics. You focus on the synthetic possibility, but really everything you say

00:33:40.540 is just as relevant to anything nature might cook up for us.

00:33:45.980 I absolutely agree.

00:33:46.840 And also, I think the boundary there is a little blurry because even in the case of natural pandemics,

00:33:54.380 you're still talking about human behavior. I mean, anyone who's putting a bat on top of a pangolin

00:34:00.120 and calling it lunch is teasing out these xenoviruses from the womb of nature. And that's

00:34:08.180 one vector by which they get into our population. So we have to figure out how to modify human behavior

00:34:14.680 across the board so as to reduce the likelihood of this kind of thing happening. And we already know

00:34:19.840 that there are natural viruses and other pathogens that have very high lethality, and

00:34:27.500 a single mutation could make them super transmissible in ways that they're not currently. And we know that

00:34:35.260 nature is running that experiment continuously. This is the Darwinian principle by which things change.

00:34:42.940 But there is one human behavior that I think we do want to shine a light on and very likely

00:34:50.540 block. And that is related to the experimentation on H5N1 that you discuss. And this is what often

00:34:59.540 goes by the name of gain-of-function research, where biologists, in studying how a pathogen might

00:35:08.280 behave, can actually modify its genome such that it acquires a different rate of transmissibility,

00:35:16.680 say, right? So something that was not yet transmissible human to human becomes so. And it's easy to see how

00:35:24.320 well-intentioned people might think it wise to do such research, assuming they have extraordinary

00:35:35.720 confidence that they're not going to accidentally leak one of these pathogens out of their labs.

00:35:42.140 But we know so much about how difficult it is to be perfectly careful in an ongoing way that

00:35:49.080 after a few minutes of reflection, some of this research seems patently insane. What's your current

00:35:56.500 view on the H5N1 research that you began speaking about?

00:36:00.300 Well, so you made an important point, which is that gain-of-function research is done by

00:36:06.160 well-meaning people. It's done with the public health agenda. These aren't mad scientists. They're

00:36:10.080 trying to probe at the worst things that could conceivably happen so we can better prepare for

00:36:14.300 them. And the whole debate that the scientific community has had, and to a lesser degree, society

00:36:20.020 writ large, is actually geared off of precisely this H5N1 research that we've been discussing.

00:36:26.540 There was, and to some degree, remains some confusion about the virulence and transmissibility

00:36:32.420 of the H5N1-modified viruses that were created. Some have questioned the consistency of the

00:36:38.840 statements at least one of the researchers made. And also, the transmissibility that the research

00:36:43.620 achieved was in ferrets. So we really have no idea how these viruses would behave in humans. Of course,

00:36:49.520 they didn't infect humans. They could have been way worse than the ferret results. They could have

00:36:53.660 been a dud. We don't know. So for this reason, I use the H5N1 incident both as a scary and 0.90

00:37:00.020 thought-provoking historic fact—I mean, this happened, and holy shit—but also as a bit of

00:37:05.460 a metaphor, like a touchstone for conversation. And that what we can say is that a virus of unknown

00:37:12.820 but potentially catastrophic power resulted from gain-of-function work in 2011 using the technology

00:37:19.760 that time. And to assess what that means for our security, now we need to consider the speed with

00:37:26.600 which the tools and techniques of synthetic biology have been improving since 2011 and the degree to

00:37:32.020 which they've been spreading. And we'll get into much more detail on that in a later section, but

00:37:36.800 short answer is these tools are improving with unbelievable speed. And just as rapidly, they're

00:37:42.580 spreading to very large, widespread levels in academic biology and beyond. So the original H5N1 0.67

00:37:50.840 gain-of-function research was the roughest of prototypes for what's possible now for a much,

00:37:56.520 much larger group of people, which makes any clouded understanding of the human transmissibility of

00:38:02.620 those original viruses kind of immaterial. Anyway, to get back to what happened, in 2014,

00:38:07.440 2015, there was a series of blunders that the U.S. government committed in relation to some scary

00:38:14.720 pathogens. In one incident, some live anthrax spores were mailed from one lab to another. In another

00:38:20.700 one, really crazy, live smallpox virus was discovered in a forgotten FDA storage facility. And as a result of

00:38:30.480 these and some other things, concern ramped up about deadly pathogens. And one result of this

00:38:36.180 was a pause on government funding of gain-of-function research. Emphasis on pause and government

00:38:43.580 funding. So gain-of-function wasn't banned by any means. This just meant the U.S. government itself

00:38:48.940 wouldn't fund any of it. And both of those projects had some U.S. government funding. As for private

00:38:53.660 research, there was, I think the words were, request for a voluntary moratorium on gain-of-function.

00:38:59.880 So nothing like a ban and certainly nothing like enforcement. Then after three years of, you know,

00:39:06.960 careful thought, I'm sure, the government put together some ethical frameworks and other things.

00:39:12.320 Government funding for gain-of-function was resumed. I think that was 2017. And then in 2019,

00:39:18.440 funding for the exact two H5N1 research projects that we've been discussing resumed. So now it's all

00:39:24.600 systems go for gain-of-function as far as the U.S. government's concerned. And as for whether it

00:39:30.320 should actually be practiced, I've given this a huge amount of thought and I fully appreciate

00:39:33.880 the conceptual value of anticipating the worst bugs that might arise naturally by developing them

00:39:40.440 artificially first. But I still, despite that, do not believe gain-of-function research should be

00:39:46.560 carried out at all. The first reason is that it is enormously possible that nature will never get

00:39:53.280 around to creating the ghastly things that we invent with our gain-of-function research. I mean,

00:39:58.920 no highly contagious form of H5N1 has ever managed to evolve across however many centuries.

00:40:05.640 So widespread gain-of-function research will inevitably bring god-awful pathogens into existence

00:40:13.040 that would never have existed otherwise. And why do that? But an even better reason to never do any

00:40:19.700 gain-of-function research is, as you pointed out, no laboratory of any level of security

00:40:25.040 can be wholly immune from leakages and accidents. And history shows this very, very clearly. And if

00:40:31.340 you'd like, I could run through a few quick and rather unfortunately chilling examples that illustrate

00:40:36.240 that. The first one that I often draw attention to was a smallpox leak that occurred back in 1978. And

00:40:45.580 the timing is relevant because just one year before that, smallpox had been eradicated from the entire

00:40:51.120 world after a heroic 10-year effort. And right before that eradication effort, 2 million people a year

00:40:58.260 were dying from smallpox still in the late 60s after hundreds of millions had been killed in the first

00:41:03.980 half of the century. Yeah, it was something like 500 million people died in the 20th century from smallpox.

00:41:08.660 Crazy, crazy numbers. And so we can imagine the level of care and attention that must have been

00:41:14.380 lavished on every remaining sample of smallpox one year after the eradication. But nonetheless,

00:41:21.460 smallpox managed to escape from a British lab. It infected two people and killed one of them. So 0.86

00:41:26.180 the last person in history to die of smallpox died as a result of a lab leakage. And as for biosafety

00:41:34.020 level four labs, which is the very, very highest level of biosafety by an international set of

00:41:39.380 standards. And biosafety level four is extremely rare. There aren't a lot of them in the world.

00:41:45.180 So this is the pinnacle. We can look at a foot and mouth disease outbreak in, or leakage rather,

00:41:50.860 in Britain once again back in 2007. And again, this timing is relevant because just a few years before that,

00:41:58.620 Britain's cattle industry had suffered a crippling foot and mouth outbreak. So high alert,

00:42:03.780 foot and mouth in the UK. But despite that, the virus literally leaked out of this BSL-4 lab

00:42:11.160 into the surrounding groundwater. And then two weeks after that lab resumed work,

00:42:17.000 it happened again. So we're at the pinnacle of biosafety in a country that's been blighted by this

00:42:22.820 disease recently, and we have this leak. And in light of that, do we really want to do gain-of-function

00:42:27.860 research into pathogens that might imperil civilization itself? And by the way, many very

00:42:35.200 level-headed people believe that COVID itself might have leaked out of a biosafety level four lab,

00:42:39.940 the Wuhan Institute of Virology. Now, I haven't dug deep enough into that to fully form my own point

00:42:45.480 of view on whether that would have been a leak or not. But it's definitely not just the realm of the

00:42:51.160 tinfoil hat crowd. And then the last example, which is relevant for an additional set of reasons,

00:42:56.820 as if it's not grim enough, is the anthrax attack of 2001, which killed five people.

00:43:02.580 This was a week after 9-11, and envelopes containing anthrax spores showed up at some

00:43:07.920 media outlets, as well as the offices of a couple senators, including the Senate Majority Leader,

00:43:12.500 Tom Daschle. And as it happens, I was in Daschle's office that week, so this one's kind

00:43:17.220 of seared into my memory. And it turns out that those spores came out of a high-security U.S. Army

00:43:24.360 biodefense lab, probably at Fort Detrick in Maryland, although some people think it might

00:43:29.540 have been another Army lab. Now, there's always going to be a swirl of mystery and conspiracy

00:43:34.600 theory around this one, because the FBI's main suspect actually killed himself before any

00:43:40.700 indictments or trials. But regardless of who took the spores out of the lab,

00:43:45.420 it's hard to imagine a country at a higher level of alert than the U.S. after 9-11, one week after

00:43:52.220 9-11. And it's hard to imagine a significantly more security-minded and security-capable organization

00:43:59.160 than the U.S. military. And yet, even in those circumstances, anthrax made its way from the heart

00:44:05.680 of the military-industrial complex into the office of the Senate Majority Leader. Again, well, proving two

00:44:11.580 things. One, any facility can leak. But also showing us that safety measures, which are meant to prevent

00:44:17.600 accidents, are all but helpless against a malicious insider, because that's not the disaster scenario

00:44:24.200 they're designed around. And, you know, the odds of there being an unhinged insider go up as you

00:44:31.240 increase the number of places working with disastrous pathogens. The consequences go up as the pathogens

00:44:38.100 become exponentially more terrifying than anthrax or even COVID, which again leads us to question,

00:44:44.900 why in the world would we ever do gain-of-function research?

00:44:49.320 Yeah. Yeah. Well, there's another variable here which you discuss throughout the series,

00:44:54.320 the prospect that this technology will become increasingly democratized. And you'll have,

00:45:00.400 you know, high school students performing experiments that now the most sophisticated laboratories would

00:45:05.900 struggle to perform because there's some desktop piece of technology 5, 10, 15 years from now that it

00:45:14.640 embeds so much knowledge that you don't even have to be a person in the field of, in this case, biology

00:45:23.120 to do biological experiments that no team is currently, or few teams are currently capable of.

00:45:30.280 You know, it's very easy to see how the consequences of this meddling will get away from you. And the idea

00:45:37.080 that we are poised to spread the tech around to the level of high school students is fairly terrifying.

00:45:45.300 But at the same time, there is something that's undeniably cool about high school students discovering

00:45:52.400 things like synthetic biology and doing really cool things with it. And so, a little bit of a sidetrack,

00:45:57.480 the most vivid evidence of synbio technology in high schools, to me, is something called the iGEM

00:46:04.560 competition. And iGEM is sort of an annual synbio jamboree for students, which spun out of MIT a while

00:46:11.420 back. And each year, thousands of students grouped into several hundred teams compete in creating sort

00:46:18.260 of little synbio marvels. And those teams come out of grad schools, they come out of colleges, and they do

00:46:23.520 come out of high schools. I recently eyeballed the list of last year's teams, and I'd say about a quarter

00:46:29.060 of them came out of high schools. And the high school projects I read about included a virus testing

00:46:33.940 system that delivers PCR-like technology at home, which is not easy to do. Another was a field kit you could

00:46:41.480 take out of the woods to test wild mushrooms for toxicology. So, pretty sophisticated stuff coming out of

00:46:48.360 today's high schools. And I do think iGEM is a great thing, as I mentioned. And I don't think that we have

00:46:53.900 to worry at this instant about a rogue high school kid doing something catastrophic, you know, with

00:46:59.440 synbio today. But we do have to appreciate that this is the endpoint of the academic transmission

00:47:05.240 channel, and it's wide open. So, things that are only possible for today's top synbio professors

00:47:11.100 will rapidly diffuse to smart grad students, and then to smart undergrads, and then to smart high school 0.68

00:47:16.500 kids, and eventually to dumb eighth graders, right? And we obviously can't put a biosafety level four

00:47:21.360 protection, you know, protocol into every high school. So, we either have to stop the diffusion

00:47:28.040 of this technology, which I think would be tragic and also completely impossible, or we have to start

00:47:33.620 building safeguards that selectively prevent dangerous practices down the line, which is tricky

00:47:40.080 because our intuitions reliably defeat us when exponential change is involved. I mean, there's

00:47:46.380 a famous question of whether it's better to have a million dollars or a penny that doubles every day

00:47:50.820 for a month. And our intuitions scream, take the million bucks, but it turns out the penny is a much

00:47:55.140 better deal. And I believe we have this miswiring because our ancestors simply never encountered

00:48:03.020 exponential processes when they were living on the savannah, and they were evolving on the savannah.

00:48:07.960 They had to solve all kinds of de facto Newtonian physics problems when they went hunting, when they

00:48:14.360 fled predators, when they were cracking things open. So, that kind of mathematical intuition is very

00:48:19.200 hardwired into us, but not exponential processes. So, therefore, we have things like HHS naively posting

00:48:26.740 the Spanish flu genome to the world. And rather than laugh at that, we need to be unbelievably concerned

00:48:32.980 about what information and methodologies we're putting out in the world today to,

00:48:37.020 spoiler alert, a little smidgen from section two of the recording, the awesomeness of this,

00:48:43.980 the speed of this advance in SynBio to me is best captured in looking back at the Human Genome Project,

00:48:50.780 which lasted 13 years and cost about $3 billion and ended in 2003, so not in ancient history,

00:48:57.040 at which point the team had basically read out a single human genome. And today, you can have

00:49:04.660 your genome read not for $3 billion, but for $300. And 2003 wasn't that long ago. It's a 10 million

00:49:13.220 to one price drop. Yeah. I mean, that's flabbergasting. Yeah. And so, that is the kind of pace of change that we

00:49:21.440 are simply unaccustomed to dealing with, that our ancestors were utterly unaccustomed to dealing with,

00:49:27.700 that defeats our intuitions. And so, I go back to the point I made earlier, that those who are 1.00

00:49:33.240 deep in the process of creating this technology have a much, much higher moral weight on them

00:49:38.360 to try to forecast the things that might otherwise blindside a society that doesn't see it coming.

00:49:44.480 And there really needs to be a symphony of coordination between academia,

00:49:50.000 a self-regulating private industry, and really, really smart public health people

00:49:54.720 to prevent catastrophic unforeseen circumstances. Okay. Well, it will not surprise you to know that

00:50:00.680 you have not yet made me an optimist, Rob. But happily, you've got further installments in this

00:50:06.340 series to try. Absolutely. There's more to come, and much more optimistic ones to come.

00:50:14.480 We've talked about the apocalyptic nature of artificial pandemics. Now, let's consider the

00:50:19.280 reasons someone could possibly have for unleashing one. Doing this would almost certainly doom the

00:50:24.200 unleasher. If he doesn't die of his own awful disease, he ends up in a post-apocalyptic hellscape. 0.51

00:50:30.400 That doesn't sound like a great incentive structure, so it's fair to question whether anyone

00:50:35.000 would ever actually do such a thing. A doctrine called mutual assured destruction comes to mind.

00:50:40.560 It got us through the Cold War, and basically said that since a nuclear slugfest would annihilate

00:50:46.140 everyone, neither side would start one. The policy had some terrifying holes in it. But you gotta

00:50:53.000 admit, here we still are. Meanwhile, a vial filled with an obliterating contagion has its own

00:50:58.600 mad deterrence built into it. So if we could trust the Soviets with thousands of nukes, and it turns out 0.88

00:51:04.760 we could, who couldn't we trust with that vial? When I've explored this issue in writing or in talks

00:51:11.200 or interviews, I've come to gravitate toward a handful of examples that really helped frame it.

00:51:16.260 On the question of whether anyone would ever unleash a doomsday virus, I often think of the Las Vegas

00:51:21.420 shooter who murdered 58 concertgoers in 2017. For starters, unlike the Soviet Union, he was committed 0.78

00:51:29.440 to self-annihilation, making him undeterrable by nature. Given that, would he have preferred to

00:51:35.500 unleash something a hundred times worse than COVID if he somehow had that capability? Obviously, we don't

00:51:42.480 know if he would have done that. But we sure can't say he wouldn't have. After all, this guy, like

00:51:48.800 countless other mass shooters, had no proven boundaries when it came to inflicting death

00:51:53.100 and untold suffering on as many strangers as possible. And there's really no reason to think

00:51:58.800 he even grazed the outer limits of the horror he would have liked to inflict. So we can't say he

00:52:05.140 didn't want to topple civilization. We can only say he didn't get to. Now, this guy was no rocket

00:52:13.860 scientist, nor was he a world-class biologist. In 2017, that meant he didn't get to have a vial full

00:52:20.640 of deadly man-made viruses. So we don't know what he would have done with one. But here's the thing.

00:52:26.660 I bet he didn't know squat about ballistics either. And that he couldn't have designed a

00:52:31.000 semi-automatic weapon any more than he could have hoisted himself to Mars. But he did get to have a

00:52:37.160 private arsenal. Which illuminates a critical point. Even if it takes geniuses to create a technology,

00:52:44.120 and more geniuses to translate it into functional tools, it may only take a sick lunkhead to operate 1.00

00:52:50.580 those tools. Now, the frontiers of biology are generating extraordinary tools. And for now, 0.55

00:52:56.960 they're both created and operated by brilliant people. But there's no reason why this has to be

00:53:01.680 the case forever. In fact, the tools and techniques in question are set to spread far and wide. Which

00:53:08.480 we'll discuss in a bit. But for now, the key point I always make when discussing this topic is that when

00:53:14.400 suicidal mass murderers really go all in, technology is the force multiplier.

00:53:20.780 For a low-tech example of this, I often cite a series of school attacks that occurred in China

00:53:24.840 several years ago. There was a rash of 10 of them. Just like in the U.S., they were carried out with

00:53:30.440 the deadliest things you could find in the local stores. But since this was China, that wasn't 1.00

00:53:35.740 semi-automatic rifles. But things like knives and hammers and cleavers. Just like the Vegas shooter,

00:53:42.580 the 10 attackers in China pushed their technology to its murderous limits. But all of them combined

00:53:48.100 killed less than half as many victims as the Vegas shooter alone. To slide to the other end of the tech

00:53:54.280 spectrum, consider the German wings pilot who decided to end it all in 2015. He wasn't armed with a knife

00:54:00.360 or a machine gun, but with an Airbus 320. Which he drove into a mountainside, killing everyone on

00:54:06.460 board. A lot more than twice as many people as the Vegas shooter, who himself killed more than any

00:54:11.840 other mass shooter in history. So again, in the hands of suicidal mass murderers, technology is the

00:54:18.520 force multiplier. With this in mind, let's return to the problem of artificial superbugs.

00:54:24.020 Here, the question isn't whether someone can make a bug that could potentially kill at the scale of a

00:54:30.080 world war. That one was already answered twice when those two teams made H5N1 flu contagious almost a 0.90

00:54:37.120 decade ago. So the real question now is how many people can create something diabolical? Because as

00:54:44.400 the group of people who can grows, our ability to monitor and deter them vanishes. To frame this,

00:54:51.180 let's reconsider that situation in the Cold War, when just two heads of state held annihilating

00:54:56.020 powers. The world ultimately spent trillions of dollars to monitor them and to deter them from

00:55:01.880 hitting the red button. Early warning systems, diplomacy, vast militaries maintaining the balance

00:55:07.760 of power, missile stockpiles so huge they could destroy the enemy even if he struck first, etc. All this

00:55:15.260 to deter just two people from doing the unthinkable. But what if we had to keep the chieftains of

00:55:20.620 30 nuclear arsenals in line? Or a thousand? There wouldn't be enough money or resources in the

00:55:26.380 world to fund all that deterrence. So we're lucky that two is such a low number. We're also lucky that

00:55:33.040 the heads of the superpowers were mostly serious, stable people who spent decades soberly making their

00:55:38.800 way to the top. Now we could probably say similar things about a very different duo. The two had

00:55:45.280 researchers who created the contagious form of H5N1. They were brilliant biologists, the heads of labs.

00:55:51.820 They had decent budgets, excellent equipment, and spent years cultivating their minds until they could

00:55:56.960 do things that no scientist had done before. A decade ago, when they did their thing, the cadre of

00:56:03.000 people who could create genocidal pathogens was a pretty elite club with really high admission

00:56:08.060 standards. Ones that would tend to weed out loopy, erratic people. But what if that club grows? And

00:56:14.700 the hurdles to joining it plummet? Again, try to imagine an analogous world with thousands of

00:56:20.560 sovereign nuclear powers. It's a very unstable picture. Now on the biology front, we're way past

00:56:26.760 the point when just two-ish people in the world could groom a bug as deadly as the contagious form of

00:56:31.540 H5N1. The reason is a new branch of science called synthetic biology, I'll call it SynBio from now on for

00:56:39.340 short, is what's known as an exponential technology. That means it gets more powerful and cheaper in

00:56:45.700 rapidly compounding ways. The output that cost $1,000 last year might cost $500 a day, $250 next year,

00:56:53.760 and before we know it, just pennies. When this goes on, things don't just get cheaper, but capabilities

00:57:00.580 spread. From nobody, to a handful of people, to masses of people. We've all personally lived through

00:57:08.140 this with computing, another exponential technology. 15 years ago, not even Bill Gates could casually

00:57:14.860 place video calls from his cell phone. But today, billions of people can. And I'm one of them. But that

00:57:21.920 sure doesn't mean I know more about computing than Bill Gates knew 15 years ago. This sort of thing happens

00:57:27.280 all the time with exponential technologies. Over just a few years, complete non-experts pick up

00:57:33.280 capabilities that were initially beyond the top people in the field. That's pretty cool when it's

00:57:38.220 video calls. Not so much when it's unleashing an artificial disease. To give a sense of how steep

00:57:44.400 the exponential curve is in biology, I always cite the Human Genome Project. It lasted 13 years and cost

00:57:51.480 about $3 billion. When it ended in 2003, the team had read and documented a single human genome.

00:57:59.180 Today, you can have your genome read for $300. That's a $10 million to one price drop in less

00:58:05.700 than 20 years. So the impossible is now affordable. And soon, it'll be practically free.

00:58:13.480 Of course, lots of things are still extremely hard in SynBio. For now, only a tiny handful of truly elite

00:58:19.540 scientists can generate viable replicating viruses from scratch, just from genetic code. And it's a

00:58:25.560 good thing that capability is so rare. Because the genomes of eradicated monsters like smallpox

00:58:31.700 and the flu that killed 50 million people right after the First World War are up on the internet

00:58:36.480 for anyone to download. And yes, that means smallpox can now be created from scratch by anyone with the

00:58:43.420 skills and motivation. Two researchers recently proved this point by synthesizing the closely related

00:58:49.100 horsepox virus, which is extinct and harmless, with a $100,000 budget and some mail-order DNA.

00:58:55.980 This definitively showed that highly specialized scientists can now cook up some smallpox.

00:59:01.400 But that elite monopoly won't last, because rare capabilities routinely become widespread

00:59:06.360 when exponential technologies are in play. Again, think of video calls.

00:59:11.540 The trailblazers on the edge of SynBio tend to be brilliant, career-minded,

00:59:14.920 and highly non-murderous. But as the trail gets worn down and the tools get simpler,

00:59:21.020 lower and lower levels of skill, expertise, and long-term dedication will be needed.

00:59:26.620 And at some point, probably fairly soon, freshman pre-med students will have homework assignments

00:59:32.100 that the entire field of SynBio couldn't complete today. With this in mind, let's go back to that

00:59:39.280 grim subject of suicidal mass murderers. The ones who hit those Chinese schools had simple tools and

00:59:44.860 killed a couple dozen people between them. The guy who killed a lot more people than that in Vegas

00:59:49.360 had guns, which, much smarter people than him, designed to slaughter humans. The German wings pilot 1.00

00:59:56.040 had a plane designed by people much smarter than him, and so on. Each killer hit the limits of his

01:00:01.280 technology, but there's no reason to think they hit the limits of their ambitions. None of them was in a

01:00:06.700 position to die while launching a pandemic. But once again, that doesn't mean none of them would

01:00:11.220 have, given the chance. It just means none of them got to. So how rare are these sorts of people?

01:00:18.560 These days, the U.S. alone averages over one mass shooting per day, according to the Gun Violence

01:00:23.120 Archive. A big proportion of the perpetrators are suicidal. And a big fraction of that subgroup,

01:00:29.300 like the Vegas shooter, take every random stranger they can with them. We need to worry about this group

01:00:34.400 as massively deadly technologies become widespread. Because again, their death tolls reveal the limits

01:00:40.240 of their technology, not the limits of their bloodlust. And no doubt, some people in this

01:00:45.120 category have no upper limits. Each year, this group is replenished as hundreds of people throughout

01:00:51.380 the world go on a final, deadly spree. Think of those killers as being in a circle, on a Venn diagram.

01:00:57.980 It's very small and stable in size, but it's extremely significant. In a neighboring circle are

01:01:04.220 those who could trigger the deaths of millions of us if they really wanted to. That circle is even

01:01:09.760 smaller. It's barely a speck, but it's growing. It used to include just a few heads of state,

01:01:16.120 as we discussed. Then in 2011, assuming their creation was in fact contagious between humans,

01:01:21.940 those H5N1 biologists entered it. And these days, quite a few more scientists are surely in that circle. 0.60

01:01:28.100 Because in biology, the heroically difficult feats of 10 years ago are just a hell of a lot easier

01:01:34.220 now. The enabling technology is simply moving so fast. For instance, the world's most celebrated

01:01:40.040 and prominent gene editing tool, which is called CRISPR, didn't even exist when the H5N1 flu was

01:01:45.860 modified. And today, CRISPR is taught in high schools. And post-CRISPR tools, which are even more

01:01:52.360 powerful, are now cropping up and are also proliferating. So again, we have two circles

01:01:57.820 in our Venn diagram. One contains the people who are going to snap this year and kill as many people 0.74

01:02:02.720 as they can. And the other contains those who could kill millions of us, or more, if they really 0.94

01:02:09.000 wanted to. That second circle is set to grow with insane speed due to the proliferation of ever more

01:02:15.320 powerful symbiotools and techniques. Which means unless something changes, those circles are going to

01:02:21.120 collide and intersect. And the world will be home to someone who wants to kill us all, and is capable

01:02:28.220 of producing or obtaining an annihilating pathogen. The deadliness of that pathogen could have absolutely

01:02:35.460 no precedent. Because for all its faults, a bug like the coronavirus has nothing against us. Technically,

01:02:43.860 viruses aren't even alive. And many deadly ones actually become less deadly over time. Because killing

01:02:50.200 off all your hosts is no way to win the game of evolution. So natural viruses will never go out

01:02:56.000 of their way to maximally harm us. They just don't have ways to go out of. That wouldn't be true of

01:03:01.900 someone who sits down to design a deadly virus. For instance, one thing that makes COVID dangerous is

01:03:07.700 that some people are contagious without any symptoms. That period's thought to last a few days.

01:03:12.100 So why not extend it to a month? The coronavirus won't take that on as a personal goal, but a designer

01:03:18.540 might. A designer might also make something a hundred times deadlier than COVID, like a contagious form of

01:03:24.400 H5N1 flu. Now, this wouldn't be easy, but ease is a function of tools and skill. And we know the raw tools of

01:03:32.340 DNA synthesis and editing are improving at breakneck speeds. As this continues, some profoundly skilled people

01:03:38.560 with perfectly benign motives will probably design some profoundly deadly things. They might be

01:03:44.640 virologists pushing biology's outer limits. Graduate students doing thesis projects. Militaries exploring

01:03:51.660 what their enemies might cook up. Counter-terrorism units doing the same thing. I expect that almost all

01:03:57.460 the people playing this game will be white hat operators, precisely because of the brilliance and 0.94

01:04:02.000 resources it'll require at first. But that doesn't mean their work can't be dangerous. For starters,

01:04:07.640 we've already talked about how many deadly bugs have found their way out of secure labs. And they

01:04:12.720 could also escape in non-physical ways. Because although good guy scientists may make critters in 0.99

01:04:18.860 petri dishes, they'll really be creating tiny data files. The H5N1 genome is just that, a packet of

01:04:25.920 information with just 10,000 letters in it. That's nothing. A transcript of this recording would have way more

01:04:32.860 letters than that. And data networks get hacked constantly. And when they do, the significant

01:04:38.820 files go missing, then get copied, and copied, and copied. Just ask any music label, movie studio,

01:04:46.140 or Fortune 500 company that let hackers get the intimate details of millions of customers.

01:04:51.000 Like, ask Equifax. Now, when the first deadly genome gets swiped and spread all over the dark

01:04:57.240 web, technology may not be advanced enough for bad guys who are not elite scientists to do much with

01:05:03.540 it. But the internet never forgets. And a decade or two later, the technology to synthesize genomes

01:05:10.040 could be a million times more powerful, and in a million labs. You see, injecting the time variable

01:05:16.140 between the brilliant good guy who does the hard work and a later bad guy who abuses that work is

01:05:22.440 really destabilizing. Because while the bad guy may not be brilliant at all, a couple decades could

01:05:27.660 give him access to vastly more powerful tools that make up for that. Again, think of the Vegas shooter,

01:05:33.000 who was no ballistics expert, but who stood on the shoulders of generations of them. Or think of

01:05:37.780 whoever posted the genetic recipes of smallpox in the 1918 flu to the internet. They couldn't possibly

01:05:44.580 have been thinking exponentially. Which means they either couldn't imagine a near future in which

01:05:49.920 platoons of people could resurrect those diseases, or they didn't bother trying. With this in mind,

01:05:55.880 please dial up your inner science fiction writer for a moment. Let's imagine it's the intermediate

01:06:00.380 future, a few decades out, and every high school biolab has a benchtop DNA synthesizer. These already

01:06:07.020 exist, as we'll soon discuss, but definitely not in high schools, because they're way too expensive.

01:06:11.420 However, like the personal computers of the 1970s, they'll get much cheaper and better. And it's

01:06:17.720 hard to imagine their descendants won't end up in high schools. Now let's imagine this high school

01:06:22.160 printer can crank out a complete error-corrected virus genome if you input its genetic code. You

01:06:28.260 can't do this with today's DNA printers. They can only produce batches of about 2,000 error-corrected

01:06:33.820 letters of DNA, whereas viruses typically run in the low tens of thousands to hundreds of thousands

01:06:39.440 of letters. But history's shown that 10 to 100x improvements are fairly short walks in exponentially

01:06:45.820 compounding technologies like SynBio. Recall the 10 millionx improvement in reading DNA in the 18

01:06:52.000 years since the Human Genome Project. Next, let's imagine that modern tools make the complex process

01:06:57.460 of translating a genome into a viable replicating virus easy enough for smart high school kids to

01:07:03.140 master. Now everything I've described so far is so plausible, it verges on inevitable given enough

01:07:09.480 time. If not in this decade, then a bit further out. And yet I've described an all but impossible

01:07:15.140 world. Because remember, those genetic blueprints of smallpox and the 1918 flu are already floating

01:07:21.940 around the internet. And God only knows what other blueprints will eventually join them. In our scenario,

01:07:27.960 any smart but disturbed high school through postdoc student, along with millions of people working in

01:07:33.580 life sciences, could start an outbreak. That world just can't exist, or at least not for long. So we

01:07:41.440 need to do whatever it takes to avoid ending up on a glide path that leads to it. When I think of this

01:07:47.080 kind of intermediate future, suicidally murderous individuals worry me because the world produces so

01:07:52.600 many of them. Groups with those motives are much rarer. But they're inherently scary too, because

01:07:58.280 groups can be way more capable and formidable than individuals. And some groups do have bizarre urges

01:08:04.160 to sweep the earth of humanity. There's plenty of doomsday cults out there. And at some point,

01:08:09.540 one of them will get bored and decide to speed things along. Japan's Aum Shinrikyu cult did this.

01:08:15.080 It gathered over a thousand members, including several biologists. And it meant to bring about the end of

01:08:20.320 the world. But the tools to do that just weren't around in 1995. So it made its big move with a

01:08:26.100 sarin gas attack in the Tokyo subway. When the next Aum Shinrikyu comes along, I doubt they'll limit 0.97

01:08:31.480 their arsenals to deadly gases. Meanwhile, environmental or maybe animal rights extremists

01:08:37.380 could decide that humanity doesn't deserve a future. Or consider the strange philosophy of

01:08:42.580 antinatalism, which argues that human lives are so unpleasant, the ethical thing is to minimize the

01:08:48.320 number of humans living them. For now, the people who think this way just try to avoid having

01:08:52.900 children. But who knows where that could lead? The crazy motives we can imagine driving someone

01:08:58.160 to launch a doomsday pandemic are terrifyingly broad. And that's not counting the ones we can't

01:09:04.140 imagine. Meanwhile, the ways for dangerous, well-intentioned work to leak out are boundless.

01:09:10.600 Okay, that's the bad news. But luckily, there is a way out of this. That's the whole premise of this

01:09:16.880 series. But before we get to the right way out, let's briefly discuss the wrong way out. Which

01:09:22.520 would be a technology ban. Because we can't stop Sinbio from advancing. And we'd be fools to try.

01:09:29.140 If a worldwide ban is enacted, could we really trust China and Russia to respect it?

01:09:33.880 Would they trust us? Could anyone trust North Korea? Unlike nuclear programs, which require 0.95

01:09:40.200 vast industrial complexes and therefore can be monitored, biology can be practiced almost invisibly.

01:09:47.180 So swear off of Sinbio, and you're giving some rival a Sinbio monopoly. Again, think of North Korea. 0.97

01:09:53.380 This is a really bad idea. Much more importantly, we shouldn't want to stop Sinbio in its tracks,

01:09:59.440 because its promise is almost boundless. It's already starting to revolutionize medicine,

01:10:04.500 and is set to save untold millions of lives. It holds extraordinary promise for the environment,

01:10:09.660 in the form of crops that need less pesticides, biodegradable plastics, and perhaps even biofuels

01:10:15.340 secreted by engineered microbes. And it has some sci-fi wonders up its sleeve. Like clean meat that's

01:10:21.380 molecularly identical to the real stuff, but is produced without animals, so there's no suffering

01:10:26.180 in factory farms, and greenhouse gases are sharply cut. Yet another giant reason to forego a Sinbio tech ban

01:10:33.120 is that our greatest allies will be people trained in this field. And while a tiny handful of such people

01:10:38.620 almost inevitably go rogue, as training proliferates ever more broadly, the ratio of allies to enemies

01:10:44.660 will be staggeringly high in our favor. I mean, think about it. The bar to being a good guy is that

01:10:50.580 you're opposed to wiping out humanity. That's about as low as a bar gets. So the more Sinbio experts the

01:10:57.060 world creates, the safer we'll be on a certain level. So how do we put the good guys to work in

01:11:02.440 protecting us? In the next part of this series, we'll talk about the right way out of this predicament.

01:11:09.020 Okay, I'm back with Rob Reed. That was section two. Rob, you have raised this terrifying memory of

01:11:16.800 what smallpox did to the world, and the prospect that it could be resurrected. What's your thinking there?

01:11:24.500 Well, I'd say the thing that unfortunately gives us confidence that some people out there could

01:11:30.120 resurrect smallpox today, if they put their minds to it, is that someone recently created the harmless

01:11:36.000 but closely related horsepox virus from scratch. And they're very closely related. So if you can create one,

01:11:41.800 you can absolutely create the other. And in fact, the researcher behind that indicated in one of his

01:11:46.400 interviews that part of the reason why he did this horsepox work was to force the world to confront 0.67

01:11:51.760 the possibility that smallpox could be resurrected. And so how many people could also create these viruses

01:11:59.000 in addition to this researcher whose name was David Evans today? And, you know, in asking that,

01:12:04.220 I think there's two things to note. The first is that the horsepox work was done in 2016. So this was

01:12:09.520 almost five years ago. Using the tools of its day and all kinds of syn-bio tools have improved

01:12:14.600 dramatically since then. And secondly, it was done by a very talented team, which kind of constricts the

01:12:20.380 group of people who could do this. Because at the time, it was actually the largest virus that had ever

01:12:24.980 been assembled from scratch. So that was not a small thing to do. So who did this? Like I said,

01:12:29.640 his name is David Evans. And he's a virologist at the University of Alberta. And when he's described

01:12:36.140 his work publicly, both in a paper that he put out there and in interviews, he's basically said two

01:12:41.680 things. And I'm, of course, paraphrasing here. One is that for good or for ill, the world's full of

01:12:47.140 talented scientists who, like him, can stitch together disparate bits of widely published

01:12:53.060 knowledge to create things that don't have ready-made recipes on the internet. But he also

01:12:59.180 said, you know, so that's the bad news, but he also said that doing what he did would require,

01:13:04.200 you know, advanced scientific training, a very specialized lab, and a fair amount of inside

01:13:08.840 knowledge. All of which I'm sure was entirely true in 2016, and all of which I'm equally sure is

01:13:15.760 less true today. Now, I can't reliably place David Evans in the, I don't know, global constellation

01:13:22.160 of virologists. But for what it's worth, and take it with a grain of salt, I found what looks like a

01:13:27.680 bottomless list of the world's most influential virologists online, based on AI rankings, which

01:13:33.740 presumably includes things like academic citations and whatnot. And he wasn't listed in the top 500.

01:13:39.880 So take that with a big grain of salt. But it doesn't seem like he's the top virologist in the world.

01:13:44.360 So if we triangulate from all that, I would say that conjuring up the horsepox virus, and therefore

01:13:51.460 smallpox, would probably be hard, but doable for a high-powered academic virologist who's really

01:13:58.040 determined to do it. And my gut sense tells me that's probably hundreds of people in that category.

01:14:04.260 So not thousands, but not mere dozens. But that's a really high number when you think of the terrifying

01:14:10.280 power each of those people could potentially wield if they went off the rails. I mean, we are, in a very

01:14:15.920 real sense, counting on all of those people to never go Columbine.

01:14:19.480 The analogy to guns is not reassuring, because guns do not have this exponential

01:14:26.480 quality to them, right? I mean, you only kill as many people as you shoot. It's not like you unleash

01:14:32.320 rounds of ammunition onto the world and they keep spreading and killing people. And we know where

01:14:39.520 the trend lines for all of this technology, really any technology, tend to go, which is to embed the

01:14:46.600 highly specialized knowledge that was required to create the tech in the tech itself, such that

01:14:52.760 a person without any real knowledge can use it and leverage all of that power to whatever end. And so,

01:15:03.700 you know, as you pointed out, you don't have to be a master of engineering of any kind or ballistics to

01:15:09.460 own the most powerful firearm available and use it. And someday you won't have to be a virologist

01:15:19.260 to engineer a virus if we don't manage to contain this technology.

01:15:25.720 Yeah. And a really scary thing you kind of touched on is just the open-endedness of a

01:15:31.960 symbio attack. I mean, every terrorist attack we've experienced so far has had inherent limits to it.

01:15:38.340 You know, there's only so many people on an airplane. There's only so many people in a

01:15:41.940 building that's being attacked or, you know, there's only so many victims one person can shoot

01:15:46.360 before the cops show up. But COVID makes it abundantly clear how open-ended a disease's

01:15:52.440 damage can be. We're a year into this thing. We still have no idea what the final bill is going to

01:15:57.440 come to. And what's also scary is to think about what would a dud of a symbio attack look like? I mean,

01:16:06.000 let's say someone who's really smart and really determined, who has completely mastered the best

01:16:12.000 biological tools that'll be available, I don't know, let's say 20 years from now. What if that

01:16:16.260 person sets out to cancel humanity and falls 99.9% short of that goal? I mean, that's 8 million dead.

01:16:24.280 And just imagine how the U.S. would react to an attack that kills on that scale proportionately in the

01:16:31.440 U.S. I mean, just think of how we reacted to 9-11, which killed fewer people than COVID currently

01:16:36.960 kills on a bad day. I mean, two wars costing trillions of dollars, civil liberty ramifications.

01:16:43.240 You know, the scary thing is that not only can we not afford to suffer a successful symbiotic attack,

01:16:49.160 but we probably can't afford to experience a failed one.

01:16:52.600 Yeah. Well, again, the analogy from COVID is depressing because this is just about as benign

01:17:00.100 as you could imagine while being worse than the ambient level of contagion that's already there.

01:17:08.100 You know, I mean, it's like if this were any more benign, we would barely notice it, right?

01:17:14.500 Right.

01:17:14.680 And it has brought global civilization to something like a standstill. We don't know what the ultimate

01:17:22.260 bill will be from this, but we know it is certainly more than a million dead globally and trillions of

01:17:30.900 dollars. And again, this is just, you know, if it were any more like flu, it would be the flu.

01:17:37.140 And so it's, yeah, just anything that would be properly weaponized with an intent to kill as many

01:17:43.680 people as possible. You have to imagine, you know, this is the dud scenario, you know, and it's still,

01:17:50.880 you know, scarcely tolerable. So, you know, we're talking about, by definition, people who would

01:17:59.360 intend to harm vast numbers of people by doing something in this space. The prospect that this

01:18:07.140 can happen by accident is something we've touched on, and that's also terrifying. But here we're talking

01:18:12.720 about the most malicious case. Who are we imagining would do such a thing?

01:18:19.700 Well, it's an interesting question, and it's obviously a really important one. And what I

01:18:24.500 personally go back and forth about is, is the risk greater from lone wolf individuals, or is the risk

01:18:32.700 ultimately greater from groups of individuals, from organized groups? And on the one hand, groups are

01:18:39.200 obviously way more dangerous on a one-to-one basis. Like if we compare a single group to a single

01:18:44.500 individual with an identical goal, because obviously, unlike the individual, the group of

01:18:49.380 five people, let's say, can be five places at once. It can pool expertise that might be hard to find in

01:18:55.500 a single person. It can pool resources. There are just countless advantages. But the thing is, it's not

01:19:01.320 really a one-to-one comparison. Because lone wolf operators are just way more common when it comes

01:19:08.120 to suicide attacks. Even if we include suicide bombings, which are the works of groups, in those

01:19:14.720 statistics, lone wolf suicide attacks are way more common. I mean, we had more than one mass shooting

01:19:19.720 per day in the U.S. last year, many of which were suicide attacks, and almost all of which were lone

01:19:26.220 wolf operations. I mean, things like Columbine, where you have multiple shooters coordinating are

01:19:31.000 incredibly rare. So I worry about groups because of their capabilities. But I worry about lone wolves

01:19:37.540 because of just sheer numbers. And it's also hard to find groups in history that have been committed

01:19:44.400 to total annihilation. I mean, the only one I can think of is Oma Shinrikyu. And I mean, I bet even 1.00

01:19:49.900 ISIS's leaders would have been horrified on their worst day by a plan to exterminate humanity.

01:19:56.120 That kind of nihilism is just much easier to imagine in an unhinged individual than an organized

01:20:01.540 group. But that said, groups aren't really historically known for focusing on trying to

01:20:08.080 do things that are utterly impossible on a technological basis, which has been the case

01:20:13.320 with total annihilation up until now, thank God. And there are schools of thought that might just be

01:20:19.780 a few deranged steps away from considering that. Like, should we be worried about what the outer

01:20:25.840 fringes of the environmental movement, or maybe the animal rights movement might do, let's say,

01:20:31.020 10 years from now, if they think they can create an off switch for humanity, or maybe a particularly

01:20:37.100 unhinged group of antinatalists?

01:20:40.840 Yeah, I would divide this more or less, as you have, into two possibilities. One is ideological,

01:20:48.260 and that is more or less what you would need to have a group do anything like this. There has to

01:20:53.660 be a belief system, some kind of doctrine that makes sense of this kind of apocalyptic,

01:20:59.720 genocidal behavior and suicidal behavior, unless you've also vaccinated yourself against this pathogen,

01:21:07.780 which is, I suppose, also a possibility, although then we're imagining very competent people doing this.

01:21:13.840 Right. So, but in the case of a lone wolf, I guess it could be ideological. You know, one person can

01:21:21.340 have a rationale for what they're doing that may seem consistent to them, and they may be alone in

01:21:27.880 doing it, but there's so many more ways for people to just snap, and it doesn't even have to make sense,

01:21:36.480 right? And they're equipped with this technology, they are far more dangerous than a school shooter,

01:21:43.020 right? You know, he may have some internal story as to why he's doing what he's doing, but

01:21:47.320 it doesn't need to be of the sort that we saw with someone like the Unabomber, who, you know, 1.00

01:21:53.540 published a disconcertingly coherent manifesto, and that was, he was a group of one, essentially.

01:22:03.800 They really are very different problems, even though they're terminating in the same way. I mean,

01:22:11.220 I know this from the space of just having to deal with crazy ideologues and crazy people

01:22:17.800 more than I would want, you know, and so you can have people who bend their attention toward you

01:22:23.700 based on their ideology that disagrees with you, and they criticize you and attack you, and in the

01:22:31.060 worst case, pose a security problem. But then there are just crazy people who think you're sending

01:22:37.040 the messages, right? And that's a completely different problem to think about and to try

01:22:43.940 to mitigate. And when you're talking about truly democratizing this tech and putting it in the

01:22:51.200 hands of people who could be starkly delusional, yeah, we clearly have to find some way of closing

01:22:59.660 the door to this. Yeah, and it's interesting to think of that starkly delusional side of it. I

01:23:06.260 mean, kind of one chilling example, if you remember the guy who shot up the movie theater in Colorado,

01:23:12.120 there was a Batman premiere dressed as a Joker. He was like a, you know, a PhD candidate, I want to say,

01:23:18.280 in some biological science with an NIH grant. So that level of delusion can actually penetrate

01:23:26.220 into fairly high academic circles. And then as the technology proliferates into ever lower circles,

01:23:32.960 you know, that high bar matters less and less. And I never really thought of this before,

01:23:37.760 but I guess an interesting question to ask ourselves, I just have no idea, is what percentage

01:23:42.940 of that daily mass shooter population in the U.S., for example, is actually schizophrenic or in some

01:23:51.500 ways deeply delusional. I mean, we should know that as a society. I mean, I think, you know,

01:23:57.640 if we kind of follow the logic of all this, we start realizing that suicidal mass murder could

01:24:04.280 absolutely begin to pose a national security risk. And if we look at it through that lens,

01:24:10.880 we should probably be treating every mass shooting kind of the way we treat, you know, the crash of an

01:24:16.680 airliner with an incredibly serious effort to figure out exactly what went wrong and what are the aspects

01:24:23.800 of this case that, you know, might've provided warning signs and really get a real epidemiology

01:24:29.460 of this phenomenon. And I don't know that we're not doing that, but I don't believe that we're doing

01:24:34.920 that. And it's something that we really understand a lot better. Yeah. That airline crash you referenced,

01:24:40.900 the German wings flight, where a pilot, it seems all but certain, intentionally crashed the plane.

01:24:48.460 I mean, that's one of those cases where this is a sort of murder-suicide that most people have never

01:24:54.540 even thought about, right? It's just one of the most horrific things you can imagine. But it's,

01:25:00.560 you can see how, it's a very odd case where you could see someone being, you know, I would imagine,

01:25:08.300 in this case, suicidally depressed, someone in that condition might be capable of doing something

01:25:14.720 like that. And it, you got to think it presents psychologically as different than arming yourself

01:25:22.960 and showing up at a school and shooting people. It's a different act. It is in fact a more murderous

01:25:30.360 one, but it is a more abstract one in some ways from the, you would imagine from the point of view of

01:25:37.780 the pilot. The pilot's experience is, he's just committing suicide, right? And obviously he knows

01:25:45.480 he's got a couple hundred people on the plane with him who he's going to kill. But you could imagine 0.59

01:25:50.660 that there's some state of the human mind where all of those deaths are really an afterthought.

01:25:58.260 And there's no kind of, you know, murderous rage needed to motivate the instantaneous murder of

01:26:07.160 hundreds of people. Whereas there would be, if you're going to start, you know, killing people

01:26:11.960 with, with a club, you know, out in the world or shooting them, you know, one by one. And, 0.99

01:26:18.660 or at least it does strike me as the method of creating harm really does select for a different

01:26:26.680 population of people who would be capable of causing that harm.

01:26:31.220 Yeah. There'd be a squeamishness that the pilot wouldn't have to overcome.

01:26:35.180 Yeah.

01:26:35.660 That, you know, somebody who's actually, yeah, getting into the gritty business of killing people

01:26:40.640 would have to overcome.

01:26:42.680 Yeah. There's no, I mean, the moment you've bought into, you know, you want to commit suicide anyway,

01:26:48.020 right? And, you know, for whatever reason, you're happy to kill a lot of people in the process. 0.98

01:26:53.800 But after that, there's no, it's all hypothetical. There's no up close and personal

01:26:58.120 encounters. There's no conflict. There's just a plunge out of the sky with you at the controls.

01:27:04.560 And this is, this is analogous to different actions in times of war, right? It's just,

01:27:09.640 it takes a different kind of person to just drop a bomb from 30,000 feet, knowing all the while that

01:27:15.360 beneath that bomb, there are hundreds or even thousands of people who are dying. That's different

01:27:20.820 than, you know, trench warfare or, you know, any other sort of conflict that produces death.

01:27:27.560 I mean, this is the example I give somewhere. I think it's in my first book, The End of Faith.

01:27:31.420 I mean, when you find out that your grandfather flew bombing missions over Dresden in World War II,

01:27:38.380 that's one thing. If you hear that he killed a woman and her kids with a shovel, that's another

01:27:43.860 thing. The visceral reaction to that difference is an appraisal of just how different a person you

01:27:50.620 would need to be to do those two things. And yet we know he would have killed many more people flying

01:27:56.120 a bombing run over Dresden than he would have killed with a shovel. These differences matter

01:28:00.800 when they interact with technological innovations, because, you know, we are now in a world where

01:28:09.340 you could kill a lot of people with what never seems like anything more than an idea. It is a kind

01:28:17.780 of an abstraction even when you're going through the steps required to weaponize a virus. I mean,

01:28:26.560 because on some level you're not sure what's going to happen, right? You're just going to release this

01:28:31.120 thing into the wild and let's see what happens. It's all hypothetical until it isn't, right? And it's

01:28:38.220 I don't know. I can see this kind of possibility interacting with mentally unwell people of 1.00

01:28:47.120 various sorts, where the bar to initiating this kind of thing is quite a bit lower than other acts

01:28:56.360 of violence that would not nearly be as harmful. Yeah, because most of that process of engineering

01:29:03.440 this thing and even unleashing it would involve gazing in a computer screen, dabbling with lab

01:29:10.140 equipment, you know, and the level, the bar to being able to brutalize somebody with a shovel

01:29:15.120 is one thing. It's lower, I'm sure, when it comes to, you know, killing somebody as a sniper in war

01:29:21.980 from 500 yards. It's yet another thing dropping a bomb. And, you know, designing and releasing a

01:29:28.620 pathogen might even be more abstracted than that. You can imagine people just deciding to do things

01:29:34.920 that pose, you know, incredible downside risk, but it's still, you're never quite sure, right? So

01:29:42.660 it's like you could decide, well, I want to get a lot of people sick to make a point. You know,

01:29:49.820 there is this prospect that this could get completely out of hand and, you know, kill millions,

01:29:55.200 you know, but that's not my intent, but what the hell, right? It's like, there's just,

01:30:00.680 it's the exponential part here that just makes this so scary because, you know, you keep rolling

01:30:07.880 dice of these sorts. And again, you know, what we have with COVID seems like a best case scenario.

01:30:16.760 Yeah, and you could even get somebody, I just thought of a grim scenario I hadn't thought of before,

01:30:21.500 you can even get somebody with a messianic complex who decides, oh, I'm going to release

01:30:26.200 a minor pathogen to warn the world about this stuff. You know, warning shot here, and that could

01:30:31.780 get out of control. I mean, there's all kinds of motivations that people could have on this.

01:30:37.040 Well, whenever you have a destructive technology of this sort that can be unleashed by a single

01:30:44.100 person, that variable alone is enormous. I mean, just the fact that it takes perhaps a dozen fairly

01:30:53.040 technical people to produce anything like a crude nuclear bomb. The difficulty factor for one

01:31:00.680 even super competent person is just too high. I mean, there's just too much engineering to do.

01:31:06.620 There's just too many parts to get together. You know, moving the thing requires collaboration.

01:31:12.300 I mean, it's just, you need some people. And when you take that away, and you deliver into the hands

01:31:19.580 of any single person technology that is potentially even more destructive, it seems like it does change

01:31:27.040 the game significantly. And groups get busted. Groups get busted because they have to communicate

01:31:32.560 with each other. They get busted because somebody defects from them. They get busted because they have

01:31:37.940 a lot of surface area with the rest of the world. And somebody's going to try to impress his girlfriend

01:31:43.320 by blabbing about something. I mean, you look at the statistics, and I don't remember the exact

01:31:47.860 numbers, but the number of terrorist plots that have reportedly been foiled since 9-11.

01:31:55.220 And it's a pretty impressive number, and a very small number of plots that actually went forward.

01:32:01.520 But if you look at somebody like the Vegas shooter, Omar Mateen, who shot up the nightclub

01:32:06.400 in Orlando, you know, there's no coordination. There's no signal leakage. All the actions that

01:32:13.260 those people took, you know, that most mass shooters take in preparing for their crimes are perfectly

01:32:19.020 legal. You know, and so if it's one person, it's just almost, you know, undetectable.

01:32:24.680 And yeah, I guess, you know, I'm swinging around to being all the more concerned about lone wolves

01:32:31.680 more than groups as we talk about this.

01:32:35.520 Hmm. Okay, well, let's get back into it and listen to section three.

01:32:42.960 A while back, I said the way out of this is to build a global immune system to identify and destroy

01:32:48.280 deadly new diseases. And there's plenty of inspiration to take from our own bodies. Our immune system

01:32:54.640 are simply amazing. They fight off countless attackers each year without us even noticing.

01:33:00.260 And countless attackers are bugs the immune system has never encountered before. Yet it fends off

01:33:06.460 these completely unknown enemies because it's agile, adaptive, and multilayered. We need to build

01:33:12.580 something like this for humanity as a whole to fight off new threats, whether it's an artificial

01:33:17.580 disease or a natural one, on a worldwide basis early. The great news is we can do this.

01:33:24.640 If after putting COVID behind us, to whatever extent we're able, we maintain our focus on the

01:33:30.220 threat of new diseases much, much, much more intensely than we did after SARS, MERS, Zika,

01:33:36.440 et cetera. As we'll see, doing this properly will take big investments, which can be very tricky to

01:33:42.100 fund. But let's compare that to the cost of doing nothing. The Congressional Budget Office estimates that

01:33:47.840 COVID will cost the U.S. alone $7.9 trillion in economic activity, while former Harvard President

01:33:55.060 Lawrence Summers pegs the domestic cost at $16 trillion. Whichever estimate you use, it maps out to

01:34:01.840 tens of trillions of dollars worldwide from COVID, while an artificial bug could be vastly more deadly and

01:34:08.540 destructive. Indeed, as I said earlier, I'm not confident that civilization could even survive something like a

01:34:14.600 highly contagious version of H5N1 flu. I meanwhile can't imagine everything I'm about to discuss

01:34:20.740 combined, costing even one to two percent of the bill that COVID alone is sticking us with. And these

01:34:28.160 measures would come with a massive side benefit, in that they defend us from natural diseases as well

01:34:33.260 as artificial ones. That would include previously unknown enemies like COVID, or dreadful annual reruns like

01:34:40.200 the flu. Let's talk about the flu for a second. The White House Council of Economic Advisors estimates

01:34:46.360 that it costs the U.S. alone $361 billion a year in medical spending and lost productivity. This maps to

01:34:53.920 over a trillion dollars worldwide. And as we'll discuss in a bit, we might all but eradicate the flu if we get

01:35:00.280 just one thing off of my wish list. Not definitely, but we'd have a great shot at it, for less than one

01:35:06.780 percent of the flu's annual cost. Modern life sciences, absolutely including SynBio, are magical

01:35:13.860 arts, and we can and should enlist them against ancient enemies along with emerging ones. Now, as I

01:35:19.580 said, this immune system should be a global thing. But global initiatives can take years to gin up. 0.88

01:35:25.400 So we can and should get started, everywhere, at national levels. Although it would be best if we

01:35:30.440 eventually do things collaboratively and cover the globe. I've divided the immune system into five

01:35:36.340 components. The first is about making it much trickier for bad actors to hijack our SynBio

01:35:41.800 infrastructure and use it to churn out awful things. The second component is outbreak surveillance.

01:35:48.400 The earliest days of an outbreak can make all the difference between derailing a disease and letting

01:35:53.300 it go global. So we should monitor the biosphere for new outbreaks as carefully as we watch the skies for

01:35:59.040 enemy nukes. As we'll see, some really interesting science could help a lot with this, if it gets the

01:36:04.840 right funding and prioritization. The third component is about hardening society against

01:36:09.600 a SynBio attack or a natural pandemic. In military terminology, a hard target has some protection and

01:36:16.800 is tougher to destroy than a defenseless soft target. Like you could say the U.S. hardened its airports back

01:36:22.040 in the 70s when it first equipped them with metal detectors, then hardened them again after the 9-11

01:36:27.100 attacks by creating the TSA. Component number four is about conquering viruses. This is all about getting

01:36:33.520 ahead of the next viral outbreak with vaccines and medications that could just stop it in its

01:36:38.080 tracks. There's a huge amount that could be done here. But again, it's all about getting the right

01:36:43.380 funding from a society that tends to underinvest badly in these things. I call the last component

01:36:48.740 battle infrastructure. What do we need in place to fight the next novel disease after it's broken out,

01:36:54.780 to either stop it from becoming a pandemic or to dampen a pandemic that takes off despite all of our

01:37:00.180 other measures? At least one thing we'll discuss may sound like science fiction.

01:37:05.140 The immune system I'll describe will be a dual-purpose framework. While some parts of it

01:37:09.380 are specifically targeted at artificial diseases, some of it would also pay huge dividends and are

01:37:14.620 never-ending battle against natural ones. So even if no one ever attempts to create an artificial bug,

01:37:21.440 which I find almost impossible to imagine, it would still pay for itself probably hundreds of times

01:37:26.640 over in saving lives, suffering, and economic damage. Before we start, I should say this isn't

01:37:32.360 meant to be the last word in anything. It's instead a framework for thinking about how to respond to an

01:37:37.680 existential threat humanity faces, one that the COVID crisis has brought into much sharper focus

01:37:43.140 in the year and a half since I gave my TED Talk about these things. It's not meant to be comprehensive.

01:37:49.160 It can't be. For one thing, this podcast is meant to have a manageable duration. Also,

01:37:54.680 so much is changing in syn-bio and infectious disease research due to COVID that one writer

01:37:59.860 can't hope to have it all on his radar. There might be dozens of measures and promising technologies

01:38:05.320 worth slotting into each of my notional components. And if some form of this immune system does arise,

01:38:11.220 I certainly hope it'll be that deep and rich. So my hope in this is to start a conversation,

01:38:17.180 not to complete one. A conversation that could lead to a blueprint for an immune system more agile,

01:38:22.800 multi-layered, and adaptive than anyone can currently imagine.

01:38:27.240 So, on to component one, hardening the syn-bio infrastructure. A few minutes back,

01:38:32.980 I mentioned the TSA. Most of us have a friend who likes to say that if they wanted to hijack a plane,

01:38:39.100 it would be so easy because the TSA sucks. Next time that happens, ask your friend how many U.S.

01:38:45.860 hijackings there have been since the TSA got started and cockpit doors were hardened. The answer

01:38:51.220 is zero. Not because it's become impossible to hijack planes, but it's tricky enough that hardly

01:38:57.660 anyone bothers. So while we haven't made aviation invulnerable, because that is impossible, we've

01:39:04.180 made it much, much harder to disrupt. This is what we need to do with the act of creating deadly

01:39:09.300 artificial bugs. We can't make that completely impossible, but we can push it past the reach of

01:39:15.580 most people, including people acting on urges that will eventually pass. This matters a lot with

01:39:21.040 someone bent on suicidal mass destruction, because most suicide attempts, and many mass shootings,

01:39:27.240 are driven by transient phases of extreme rage or despair. An analysis of over 175 academic papers

01:39:34.540 showed that less than 4% of those who tried and failed to kill themselves later successfully did so.

01:39:40.440 Now, that's obviously 4% too many, but it shows that most suicidal phases are impermanent.

01:39:48.000 Hijacking, of all things, is an interesting parallel. Believe it or not, it was once possible 1.00

01:39:52.840 to hijack a plane almost on a passing whim. Between 1968 and 1972, there were 130 U.S. hijackings,

01:40:03.260 almost all of them by domestic perpetrators. Many of them were radicals who just kind of wanted

01:40:08.880 to go to Cuba. It got so bad, Cuba created a special dormitory for wayward American hijackers. 0.98

01:40:16.180 Alarmed citizens, meanwhile, swamped the FAA with anti-hijacking suggestions, like building 1.00

01:40:22.280 trapdoors outside of cockpits. Eventually, metal detectors and so forth dropped the ambient level

01:40:27.840 of hijackings from about 40 a year to almost zero. Now, we clearly can't live with dozens of

01:40:34.720 biological attacks per year, so we need to think carefully about hardening the products

01:40:39.420 and services that create synthetic DNA. Luckily, this process is already well underway.

01:40:45.600 Back in 2010, the U.S. Department of Health and Human Services issued guidance for securis

01:40:50.640 and biopractices. And by then, the industry had already founded the International Gene Synthesis

01:40:55.980 Consortium, or IGSC, which is all about biosecurity. Its member companies represent about 80% of the

01:41:03.320 world's gene synthesis capacity, although nobody's quite sure how accurate that estimate is.

01:41:09.300 The government's guidance asked the industry to screen its customers for bad actors and to look

01:41:13.900 out for orders of dangerous DNA sequences. So the IGSC created a regulated pathogen database.

01:41:20.680 Its members now follow special review processes for potentially dangerous requests and contacts the FBI

01:41:26.760 when appropriate. They also follow government watch lists of terrorists, people subject to export

01:41:32.400 controls and more. I discussed these issues with science policy expert Sarah Carter. She has

01:41:38.200 estimated that IGSC members spend an average of almost $15 for each synthetic DNA order that they

01:41:44.600 receive on biosecurity compliance, which is a very serious investment. So there's lots of great news

01:41:50.940 here. The bad news is that the government hasn't once updated its guidance. That's a 10-year lapse in

01:41:57.340 guiding one of the fastest moving industries in history. Plus, that ancient government guidance

01:42:02.460 is just that. Guidance. In other words, it's voluntary. And while it's impressive that the IGSC's

01:42:08.700 members produce maybe 80% of the world's synthetic DNA, is that really enough? I'll use an analogy that

01:42:15.580 many current and former American high school students will identify with. When I was growing up, my five-town

01:42:21.300 area, a couple hundred thousand people total, had exactly one liquor store that reliably sold beer

01:42:27.560 to teens. Every young beer enthusiast knew all about that store. And for a while, there may as well have

01:42:34.380 been no drinking age whatsoever. Now, there had to be 99% compliance with the liquor laws amongst liquor

01:42:41.480 stores in our area. But that hardly mattered. So I'd say when the fate of the world might literally hinge on

01:42:48.280 controlling deadly DNA, 80% self-directed compliance to voluntary guidance is nowhere near enough. That

01:42:56.820 other 20% in the hands of companies that are doing their own thing is just a gaping hole. And even for

01:43:03.560 its members, the IGSC is no real arbiter because it thoroughly lacks independence. Its chair works for an

01:43:10.020 IGSC member called Thermo Fisher. And the other folks who give it bits of their time also work for one

01:43:15.500 member company or another. So if you're wondering why the IGSC website has no phone number, it's

01:43:21.080 because they have no phone. Now, luckily, I wouldn't call this a pure Fox-watching-the-henhouse

01:43:27.440 scenario. Because SynBio executives have huge incentives to prevent SynBio attacks. As humans,

01:43:34.960 they'd suffer as much as the rest of us. And even a botched attack that hurts no one could lead to calls

01:43:40.160 to shut down their industry. That said, any company's prime directive is to make money.

01:43:45.920 And every IGSC representative has a day job and a company that has to make quarterly goals.

01:43:51.300 So it's not surprising that in a recent SynBio industry survey, Sarah Carter wrote that the people

01:43:56.800 she interviewed, quote, repeatedly emphasized that biosecurity considerations were not a priority for

01:44:03.160 the industry overall, with very little attention paid to the topic by investors and in industry venues.

01:44:09.000 Now, this isn't true everywhere. A thought leader in this field is Twist Bioscience,

01:44:14.340 a relatively large and publicly traded SynBio company and an IGSC member. A company representative

01:44:20.400 told me that Twist treats the consortium standards as a baseline starting point for their own biosecurity

01:44:26.220 measures. They have a small, full-time staff of PhDs who drill down on every DNA order that could

01:44:33.060 possibly be misused. And the list of sequences that trigger reviews goes far beyond the IGSC

01:44:38.980 regulated pathogen database. That said, not everyone has Twist's resources. And the cost of

01:44:46.000 synthetic DNA is dropping, while the cost of screening is increasing as databases of concerning

01:44:51.400 sequences grow larger and more complete. This means screening is heating up a growing share of

01:44:57.380 companies' margins, which increases the incentives to cut corners. And my contact at Twist said that some

01:45:03.500 companies are, in fact, opting out of the IGSC for profitability reasons, particularly internationally.

01:45:10.520 This worries him, and he's not alone. The World Economic Forum and a non-profit called the Nuclear

01:45:16.120 Threat Initiative have teamed up to address it. They've proposed a common screening platform that's robust,

01:45:22.600 open source, and given to all industry players for free or at a very low cost. In a 2020 white paper,

01:45:29.500 they wrote, quote, development of a common mechanism for screening pathogen and toxic DNA would reduce

01:45:35.500 the time and expertise required to adopt and implement synthetic DNA screening practices and thereby expand

01:45:42.740 those practices to a wider range of DNA providers. They hope to have this available this year. In their white

01:45:49.180 paper, they called for governments to require DNA screening practices through legislation or regulation.

01:45:54.940 And although I'm generally a very free market-oriented person, I fully agree. Governments worldwide should

01:46:01.660 collaborate on tough regulations to forbid the distribution of any synthetic DNA to anonymous

01:46:07.540 parties or known bad actors. As for dangerous DNA, it has its uses in research and other settings.

01:46:14.480 And there are gradations of danger which should be treated differently. But in general, it should only be

01:46:20.120 provided to highly trusted customers with excellent reasons for needing it. And as for pandemic-grade

01:46:26.380 DNA, it should never be synthesized or distributed, period. I'll add that there's no reason to ever

01:46:33.540 mutate living organisms in ways that could let them cause devastating pandemics. I'm looking at you,

01:46:39.920 H5N1 flu, and those who modified you in 2011. Not even if the head researcher has the most

01:46:46.140 angelic history and motives. Because no lab is 100% secure, as we've discussed. Plus, lab security is

01:46:53.600 about preventing accidental leaks, not deliberate ones. And it's always possible that some lab worker

01:47:00.100 will pass through an incredibly dark year and decide to cause the world enormous harm. This is evident in

01:47:07.080 the mass shootings that happen on a roughly daily basis in the U.S. alone. No social class or level of

01:47:13.760 education makes people immune to this. The regulators should be as brilliant as the people in the

01:47:19.400 industry they oversee. And they should coordinate globally. Yes, the U.S., China, Russia, and others

01:47:25.680 disagree on plenty. But they each have everything to lose from SinBio run amok. Finally, regulators need

01:47:32.820 to move as fast as the industry. No more 10-year lapses. For one example of what happens when regulators

01:47:39.820 fall asleep? That ancient U.S. government guidance didn't foresee the rise of benchtop DNA printers,

01:47:46.040 which could be the future of the industry. These generate DNA in users' labs, so they don't have to

01:47:52.380 order it from companies like Twist. This is significant because history is full of transitions from the

01:47:58.400 center to the edge. By this I mean capabilities that used to be provided by specialists migrate into the

01:48:05.420 hands of users themselves. For example, getting photographed used to require a technician with

01:48:11.640 pricey gear. To send text messages, people used to go to telegraph offices. Printing anything on paper

01:48:18.600 required professionals with special equipment. All these things can be done by users themselves now.

01:48:24.640 The list is endless. The move from the center to the edge is generally a wonderful and empowering trend.

01:48:30.540 But there have been regulatory tragedies. For instance, the explosion in child pornography has

01:48:36.900 been partly attributed to the fact that pictures are no longer printed in photo labs where developers

01:48:41.960 could spot something evil. At some point, benchtop DNA printers will be powerful enough to aid and

01:48:47.960 abet an apocalypse. Long before that, they all need to report any dangerous sequences that they're asked to

01:48:54.900 create, triggering level-headed review processes. Now luckily, this is already happening.

01:49:00.000 The most advanced product on the market is called the BioXP, and I spoke extensively with its creator,

01:49:06.300 Dan Gibson. The way it currently ingests and processes raw materials requires close communication

01:49:12.400 between its user and its manufacturer, a company called CodexDNA, which Dan co-founded. Codex is an

01:49:19.840 IGSC member, and it doesn't let its printers synthesize any DNA without a review. Over time, BioXPs will become

01:49:28.340 more autonomous in terms of the raw materials they process. But Dan says they'll continue to report

01:49:34.580 all print runs back to Codex so they can be reviewed like any order to an IGSC member. So far, so good.

01:49:41.880 But this won't be the status quo for long. For one thing, the current version of the BioXP is analogous

01:49:47.580 to the Apple II computer in 1977, which is to say that revolutionary as it is, its capabilities are

01:49:54.300 minuscule compared to what's coming. And with the passage of time, the limitations of the BioXP and its

01:50:00.440 errors will melt away. Limitations like its current inability to crank out a virus-length genome.

01:50:06.880 Another factor is that someday, there'll be cheap knockoffs of the BioXP's distant descendants,

01:50:12.920 and they'll be capable of things we can scarcely imagine. Because remember, a lone lab tech can now

01:50:19.280 sequence a human genome in a few hours, something that recently took the entire field of biology 13 years.

01:50:26.940 So we can count on the fact that someday, undergrads will be doing things the entire

01:50:31.920 field of SynBio can't possibly accomplish right now. And many of them could be using knockoff DNA

01:50:37.860 printers made by amoral companies that cut corners and ignore safety measures, unless they're sternly

01:50:44.920 required to follow them. By then, hundreds of thousands of people could have access to gear that

01:50:51.120 could cause a terrifying outbreak. And we cannot count on all of those people never having a

01:50:57.740 catastrophically dark day. So there needs to be an iron set of rules and an iron culture about keeping

01:51:04.580 dangerous DNA out of the wrong hands, and the most deadly DNA out of all hands. And the time to create

01:51:11.920 these universal rules is now, not a few months before distributed printers attain apocalyptic powers.

01:51:19.000 This may sound like a terrifyingly tall order, and I'm sure government skeptics are particularly aghast at the

01:51:26.020 need for brilliant and fast-moving regulators. But remember, in less than a century, we humans banished

01:51:32.600 diseases that had plagued us for millennia, made 200-ton chunks of metal fly, and transitioned from slide rules

01:51:39.740 to the internet. And I'm just talking about shaping an industry that's still in its infancy, and is leaning in the

01:51:45.920 right direction. We can put a very serious lid on this. Now, that won't make it completely impossible

01:51:52.820 for some disturbed person or group to make a profoundly lethal pathogen. Because like eradicating

01:51:58.880 all hijackings, that is impossible. Which is why our immune system has four more components.

01:52:06.900 So let's talk about the second component, early detection. Early detection is everything in epidemics,

01:52:12.840 especially when a new disease is stalking the earth, like COVID or any artificial pathogen that

01:52:18.020 could be unleashed in the future. That's because in the first days of an outbreak, cases tend to grow

01:52:22.900 exponentially. And we saw how profound exponential growth is when we discussed SynBio's speed of

01:52:28.860 improvement. COVID illustrates the cost of ignoring a novel disease's outbreak. A study published in

01:52:34.880 Nature estimates that if China had implemented lockdowns and other measures three weeks sooner,

01:52:39.820 the number of Chinese COVID cases could have been reduced by 95%. Had that happened, who knows if

01:52:46.920 the disease would have reached the rest of the world? And the tragic fact is, China squandered much more 0.59

01:52:52.380 early lead time than that, according to an investigation by the Wall Street Journal. The head of the country's

01:52:57.960 own Center for Disease Control and Prevention learned about the outbreak not from some advanced disease

01:53:03.580 monitoring system, but from reading the news online. And by then, there were dozens of suspected cases.

01:53:11.260 Why? Among other things, the journal reports that local hospitals didn't log cases in the China CDC's

01:53:17.100 real-time tracking system. Plus, local authorities wanted to hide bad news from Beijing.

01:53:22.900 National leaders later followed suit by hiding information from the rest of the world.

01:53:27.360 This is not meant as national finger-pointing, because my own country's CDC has a dismal COVID

01:53:33.200 history. I instead want to show how vital early detection will be if a deadly artificial pathogen

01:53:39.480 is ever unleashed. So how do you find the first signs of a pandemic? It's not like you can just

01:53:44.660 Google it. Or can you? One of the most fascinating COVID-related articles I've read was written by a data

01:53:50.680 scientist named Seth Stevens-Davidowitz for the New York Times in April of 2020. In it, he showed that

01:53:57.020 Google searches for the phrase, I can't smell, almost perfectly tracked the prevalence of COVID

01:54:02.360 across the 50 U.S. states. Loss of smell had only just been recognized as a COVID symptom at that

01:54:08.120 point. So the article's chart seemed almost magical to me. In a conversation, Seth told me that Google

01:54:14.200 is remarkably generous with their search data, and he didn't need any special access to write his piece.

01:54:19.680 In it, he boldly predicted that eye pain would emerge as a COVID symptom. This was not recognized as a

01:54:25.760 symptom at the time. But he'd seen searches for it spike by as much as 500% in countries like Italy,

01:54:32.280 Spain, and Iran, when they were in the throes of their COVID outbreaks. Sure enough, within a few 0.90

01:54:37.340 months, news articles were identifying eye pain as a COVID symptom. If you'd like to hear a lot more

01:54:42.500 about this, then I can squeeze in here. And many other topics Seth has explored using data science,

01:54:47.680 I interviewed him for my own podcast, which is called the After On Podcast. I'm posting that

01:54:52.640 interview simultaneously with Sam's posting of this episode, meaning that it should be available now.

01:54:58.800 So could searches be used to predict outbreaks? Work by Bill Lampost of the Computer Science

01:55:03.940 Department at University College London says yes. He and a team of researchers dug deep into search

01:55:09.840 traffic across several countries and compared it to reported COVID cases and deaths. They found that

01:55:15.420 search traffic pointed to national outbreaks an average of 16 days before case counts started to

01:55:21.380 spike. This could be an amazing tool for countries trying to get early warnings of outbreaks before

01:55:26.820 local doctors have even seen many patients. And in fact, Bill told me that Public Health England is now

01:55:32.640 using his COVID models, as well as a search-powered flu detector that his team has built. I'd like to see

01:55:38.880 this kind of work grow exponentially for our global immune system. Since we don't know what symptoms an

01:55:44.160 artificial pathogen or any new disease would trigger, we should continuously scan the search

01:55:49.780 sphere for every known symptom of every known disease. And yes, I know that sounds like an insanely

01:55:55.360 tall order, but big data is called big for a reason. Any symptom spike outside of a seasonal norm,

01:56:02.600 like the huge spike Seth saw in loss of smell searches in Italy, could be a signal. And if it's a cluster of

01:56:08.800 symptoms, it could be a strong signal, especially if that cluster shows up in more than one place at once.

01:56:14.680 Now, building this would present all kinds of interesting data science challenges. As Seth and I discuss in our

01:56:20.660 interview, the biggest one would probably be dealing with false positives. But Bill Lampos believes that such a

01:56:26.640 system is buildable. Better yet, he wrote to me, quote, a moderate scientific research budget can support the

01:56:33.540 development of a system like that. This translates to the very low millions of dollars to potentially get

01:56:39.780 way ahead of something that could cost us trillions or even cost us everything. Of course, there are many

01:56:47.100 offline places to search for emerging pandemics. One of the best, and certainly most obvious, is in the

01:56:53.180 bodies of sick people who turn up at doctor's offices. One day, artificial pathogens could strike

01:56:59.040 anywhere. But meanwhile, we can greatly expand our virus hunting expertise by relentlessly identifying

01:57:05.100 and neutralizing new natural diseases and hotspots where viruses commonly jump from animal hosts to

01:57:11.360 humans. Southern China is one such place, and parts of Africa are others. SARS, MERS, Ebola, and perhaps

01:57:18.780 COVID all jump from animals and are known as zoonotic viruses. Zoonotics are especially dangerous because

01:57:24.880 until the moment they jump, no human body has any immunity or experience in fighting them.

01:57:31.120 An amazing program that's just rolling out in West Africa called Sentinel could be a role model for the

01:57:36.900 developed world as well, as we gear up for a time in which new diseases could strike anywhere. One of its

01:57:43.240 co-leaders is Pardis Sabedi, who has appointments at both Harvard and the Broad Institute. The Broad is

01:57:48.900 basically a joint venture between Harvard and MIT and is worth knowing about because a huge proportion of the

01:57:54.680 world's best genetic science is coming out of there. Sentinel is called, quote, a pandemic preemption

01:58:00.180 system for the real-time detection of viral threats, and it's launching first in Nigeria. It will be a

01:58:06.360 multi-tiered system. Its creators believe that we are, quote, on the cusp of a new era. Ultrasensitive

01:58:12.540 genomic technologies have the unprecedented ability to detect virtually any pathogen, including those

01:58:18.980 circulating under the radar, and can be leveraged to create simple point-of-care diagnostics,

01:58:24.680 to be deployed anywhere. In parallel, powerful new information systems allow us to continuously

01:58:31.180 collect, integrate, and share viral surveillance data. By unifying these tools into a coherent

01:58:36.960 system, for the first time ever, we can detect and prevent pandemics on the ground before they

01:58:43.180 start. End quote. So basically, it's sci-fi-grade genomics meets cloud computing. And it sounds pretty

01:58:51.120 good, huh? Sentinel will be built around a three-tier system with simpler tools out in the field and more

01:58:56.600 powerful ones in regional and national centers, and data about every single infection flowing back

01:59:02.300 to a central system for tracking and analysis. If a patient has one of the area's top priority

01:59:08.320 diseases, Pardis expects that they'll be able to identify it within an hour and to identify any other

01:59:14.280 known human virus within a day. When I asked her how long it would take to create a test for a

01:59:19.360 previously unknown disease that they discover out in the field, she said, a day to build it and a week

01:59:25.120 to know that it works. Pardis absolutely believes we need something like Sentinel in the U.S. and

01:59:31.120 throughout the rest of the world, although her own focus is currently on West and Central Africa.

01:59:35.800 And she shares my concerns about biosecurity. So could we afford a worldwide Sentinel system?

01:59:41.620 I've seen the program's budget. And while it's confidential, I can say it's absolutely in the reach of any

01:59:47.160 developed country, and any less developed country with just a little bit of outside financial health.

01:59:52.540 In the U.S., adjusting for cost of living factors and population size, I estimate it would cost in

01:59:58.080 the low billions per year. This is a trifling sum just compared to what we lose to the flu every year,

02:00:04.100 let alone a pandemic like COVID. And it's negligible compared to what a truly nasty artificial pathogen

02:00:10.200 could cost us if it goes undetected for a few critical weeks. How else might we detect a new

02:00:16.220 pathogen? Well, how about plucking it right out of the air? A handful of researchers are now pioneering

02:00:22.200 bioaerosol science, including Mark Hernandez at the University of Colorado. One technology he's

02:00:28.440 excited about is called condensation particle capture, or CPC. This uses humidity to condense

02:00:35.080 incredibly tiny particles out of the air. It then concentrates them into a little vial from which

02:00:40.820 DNA and RNA can be sequenced. Next-generation CPC systems are small, roughly shoebox-sized. They're

02:00:47.900 also networkable and cheap, about $1,000 each. Someone needs to collect those little vials so CPC doesn't

02:00:55.020 provide instant results. But if the samples arrive at a robust enough lab, there's no limit to the number

02:01:00.700 of pathogens you could test for. Mark and I talked about a plausible future CPC system, which could

02:01:06.440 do analysis right inside the box with a miniature robotic lab. He believes that if the right R&D

02:01:12.180 resources are applied, this could be achieved in about five years, and the system might be about

02:01:17.180 the size of a ticket kiosk. These could be deployed at transit hubs and other places you'd want to

02:01:22.100 monitor particularly closely. There was actually an early U.S. government effort to do something like

02:01:27.580 this, called BioWatch. It arose in the wake of the anthrax attacks of 2001 and was deployed in dozens

02:01:34.080 of cities, targeting six pathogens. Although it got some terrible press, Mark says BioWatch wasn't bad

02:01:40.940 for its day, that it did pull genetic information out of the air and achieved its goals to some degree.

02:01:47.140 Another technology Mark is excited about has the fabulous name of spectrophotometric comb.

02:01:52.460 This is more physics than biology and uses lasers to characterize gases and the particles in them.

02:01:58.900 The proportions of gases we exhale change when we get sick, and tracking changes could be a fantastic

02:02:04.220 early warning tool. A group Mark works with has proposed an experiment looking at the breath of

02:02:09.620 mice infected with COVID to see how their exhalations change as they get ill. Unlike CPC, Mark could see

02:02:16.220 this technology one day plugging into a phone. Breathe into it daily, and it will get a baseline

02:02:21.880 understanding of what you exhale when you're healthy. Diverge from the norm, and it could mean

02:02:26.520 something's wrong. As the science gets smarter about what different shifts mean, better early warnings

02:02:31.800 could be delivered. And if millions or billions of people start to do this regularly to monitor their

02:02:37.520 personal health, the aggregate data could amount to an amazing early warning system.

02:02:42.060 Mark is one of over 100 contributors to a global microorganism survey called MediSub, run by

02:02:49.200 geneticist Chris Mason, a professor at Weill Cornell Medicine. Each year, researchers in 114 global

02:02:55.920 cities, plus an outpost in Antarctica, spend a day sampling an average of 50 local sites. Some sample

02:03:02.640 the air, like Mark Hernandez. Others sample wastewater. But most of them swab surfaces in places including

02:03:08.940 public transit systems, shopping malls, hospitals, and homes. You could think of this as a microorganism

02:03:14.860 census. But it could be converted into a massive disease surveillance network by doing swabbing and

02:03:21.140 analysis on a daily, rather than yearly basis. Chris Mason ballparks that a budget of about $3 billion

02:03:27.580 would enable this with extremely deep genetic sequencing, which would uncover even highly rare bugs in each

02:03:33.620 environment. Like everything discussed in this series, that's nothing compared to the annual cost of the

02:03:39.180 flu, let alone a devastating pandemic. And about half of that cost is for reading genes, costs which are

02:03:46.040 continuing to drop dramatically. Over time, this could let hundreds of additional cities join the survey for

02:03:51.800 the same budget. Or the budget could be increased to expand coverage, because after all, it is peanuts

02:03:57.780 compared to the stakes. Over time, investments in R&D could result in robotic systems to do the swabbing

02:04:04.120 automatically and do the genetic analysis right on the machine, potentially enabling far more sampling

02:04:09.840 or allowing more to be accomplished on the same budget. The bottom line is, disease surveillance is an

02:04:15.700 incredibly promising frontier for improvement, if we prioritize the right investments today.

02:04:21.560 Okay. Well, Rob, in thinking about how to solve this problem, we have to think about how to pay for

02:04:31.300 the solution. What is the role of money in this equation?

02:04:36.600 Well, I think there's two things to think about. How much is it going to take? And is society actually

02:04:41.600 going to be willing to make those investments, given that we know society basically hit the snooze bar

02:04:47.240 after SARS, after Zika, after a bunch of other things. This time around, there's definitely

02:04:54.180 promising signs. I do think that COVID's wake-up call is uniquely noisy. And the Biden administration

02:05:02.060 has, of course, drawn up a mega-billion-dollar pandemic budget. But with almost all the conversation,

02:05:08.680 understandably enough, focused on the immediate project of fighting COVID, it's a little hard to

02:05:14.280 tease out what permanent changes will be made to our pandemic readiness. But there are some really

02:05:19.840 good ideas starting to circulate. And also, the real test won't be what we're doing against pandemics

02:05:25.560 in 2022, but what we're doing in 2032, if we've been lucky enough to have a quiet decade. Like, do we

02:05:33.000 lose focus and let our capabilities atrophy after COVID's a distant memory? And for this reason, the right

02:05:41.140 way to look at this, and I think the only way to look at this, is through a national security lens,

02:05:46.100 in that we spend massive amounts on defense every year, even though the huge majority of our military

02:05:51.580 capacity isn't being used at any given moment, because we want to be prepared for an extreme

02:05:57.120 military emergency that's never happened before. And since pandemics are huge national security risks,

02:06:03.740 that's definitely how we need to budget for them. And viewing through this lens, I'd say, for example,

02:06:09.040 the odds of another pandemic happening vastly outweigh those of an all-out nuclear war happening,

02:06:16.200 right? And the U.S. currently spends about $35 billion a year, according to at least one report

02:06:22.620 that I saw, maintaining its nuclear arsenal, while the world as a whole spends about $70 billion a year.

02:06:29.100 Now, that kind of annual budget would fund every pandemic preparedness measure I'm going to mention

02:06:35.600 in this series many times over. So it's a highly precedented level of investment to make against

02:06:41.860 a major national security risk, and an investment that I think would do the trick of defending against

02:06:47.480 future pandemics if it's spent wisely, which of course governments don't always do, but they can

02:06:51.560 in a pinch, and this is a pinch. But it needs to be a relentless investment year in, year out, across

02:06:56.960 even pandemic-free decades. So again, the analogy has to be defense spending, which like an even bigger

02:07:03.240 example is counterterrorism, which the U.S. has spent trillions on since 9-11, including two world

02:07:07.960 wars. And all that shows we absolutely have the resources to fund almost any imaginable pandemic

02:07:14.500 immune system on a national or global level. It's just a matter of political will.

02:07:20.120 Yeah. And the point I would make here, which I think we've made at least a couple of times already,

02:07:25.000 is that everything we're saying about defending against a syn-bio attack applies to natural pandemics,

02:07:34.500 right? Absolutely.

02:07:35.440 Even if we manage to completely solve the problem we're mostly focused on here, you know, we manage to

02:07:41.740 keep the tools of syn-bio out of the hands of all the bad or crazy people that could ever want to

02:07:48.560 wield them. We still have this massive risk, which we know is never going away, that nature will

02:07:57.980 produce the next pandemic. That, you know, if it doesn't wipe us out, it still can be much worse

02:08:05.060 than COVID, you know, unimaginably worse than COVID in its effects on civilization if we can't

02:08:11.880 immediately deal with it. So every step we would take here to prevent bioterrorism,

02:08:18.560 we should be taking anyway to prevent the bioterrorism of mother nature. 0.94

02:08:24.020 Yeah, that's absolutely the right lens to look at it through. And every countermeasure we're going

02:08:28.520 to talk about, or pretty much every one, is equally applicable to natural pandemics.

02:08:33.300 Then on top of that, just look at the flu. Even if we never face another pandemic again, which is,

02:08:37.760 you know, awfully unlikely, the White House Council and Economic Advisors put the annual cost of the

02:08:43.480 flu in the U.S. alone at $361 billion a year. That's lost productivity as well as medical spending.

02:08:50.120 I mean, that maps out to a trillion dollars a year and hundreds of thousands of lives worldwide.

02:08:55.720 I mean, there's plenty of ways to recoup any investment that we make against these things.

02:08:59.940 Yeah. So how do members of the IGSC screen for dangerous DNA? How is any of this being monitored?

02:09:08.860 Well, the good news is it's actually a really interesting and ambitious precedent. And it's

02:09:15.920 a great place to start. We start thinking about hardening our syn-bio infrastructure against being

02:09:21.420 hijacked. So I'll start with a quick overview of the market for long error-corrected strands of DNA

02:09:28.100 and RNA. Those strands are mostly assembled by specialized companies. For customers who don't want to create

02:09:34.460 their own advanced DNA synthesis capability, which is almost everybody, because that's very expensive

02:09:39.280 to build. So it's kind of like how people used to get their photos developed at drugstores rather

02:09:43.900 than building home dark rooms, right? Now, the centralized DNA creators are almost shockingly

02:09:51.720 unregulated. There's just this voluntary guidance, which the government issued over 10 years ago to keep

02:09:57.880 dangerous DNA away from bad guys. Guidance which has never been updated. But luckily,

02:10:02.800 the industry itself doesn't want a Hindenburg moment, you know, like a catastrophic biosecurity

02:10:07.960 lapse, because that could lead to massive regulation or even the industry getting shut down,

02:10:12.740 which is why we have this self-regulating body called the IGSC, which doesn't really have its

02:10:17.880 own staff or resources, but its members jointly maintain a comprehensive database of pathogen genomes.

02:10:25.320 That's the main function of the IGSC, as far as I can tell. And the members screen all of their

02:10:30.780 orders against that list. It's pretty impressive. And every order is tagged either red, yellow, or green.

02:10:35.780 So if there's no meaningful overlap between the order and the genetic code of any known pathogen,

02:10:42.320 the order is marked green and it sails right through. That's about 95% of orders. But about 5%

02:10:48.620 of orders are yellow. And that means there is significant overlap with some stretch of DNA in a

02:10:52.940 pathogen. Those orders are very carefully reviewed for maybe an hour or two. And it usually turns out

02:10:58.580 that the overlap is with a benign stretch of DNA, like maybe it's a housekeeping gene or something

02:11:04.160 like that. But every so often, a yellow order becomes a red order, because the genetic code

02:11:11.280 that someone's requesting is directly connected to some kind of dangerous machinery in a pathogen.

02:11:17.560 And those orders take several hours to review. And sometimes they're ultimately approved,

02:11:22.060 sometimes they're amended. And in some cases, I understand they're actually reported to the FBI.

02:11:26.640 Now, the thing that's interesting is this review work is done by bioinformaticians, I mean, very often

02:11:32.480 PhDs. So it's a very thorough apparatus, and it's also very expensive. And the industry is doing this

02:11:39.560 on its own already. It's a hell of a start. But its expense is why some companies are just opting out of

02:11:46.680 the whole thing and don't join the IGSC at all, because none of this is required by law. And the IGSC has

02:11:53.420 the statistic that it represents 80% of total industry capacity. But that was really just an

02:12:00.500 educated guess that someone, and nobody can seem to remember who, made many years ago. And I'm

02:12:05.720 totally confident in saying that it's very outdated, because the IGSC has exactly one Chinese member.

02:12:12.260 And China's symbiocapacity is growing like mad, because it's a huge government priority.

02:12:17.020 So what should change? Well, the guidance on synbiosafety, first of all, has to stop being

02:12:23.200 voluntary. It has to stop being 10 years out of date. It definitely has to apply to 100% of the

02:12:29.320 industry. And it's got to be internationalized through careful cooperation with China and everyone

02:12:33.980 else. And that's a very tall order. But the great news is that the starting point that the IGSC has

02:12:41.340 coordinated can absolutely form the core of the first layer of our global immune system of hardening

02:12:48.340 up our synbioarchitecture. Because if it's universalized, it would, without question,

02:12:54.740 just hugely reduce the number of people who could do something awful with synthetic DNA. Because

02:12:59.660 working around universal restrictions would just require so much more planning, so much more stealth and

02:13:07.000 skill than simply ordering something from a rogue supplier that doesn't implement any protections.

02:13:12.900 So we have a great start. But it does need to be universal. And, you know, again, it has to be up

02:13:18.500 to date. 10-year lags don't cut it. But what is the mechanism that would enforce compliance

02:13:25.080 internationally here? I mean, certainly if you're talking about a rogue state, well, it's in the very

02:13:30.940 nature of being a rogue state that it is not compliant with international demands. Again, North Korea, 0.94

02:13:36.480 is a perfect example. But even state-level misbehavior aside, even within, you know, labs or individuals

02:13:45.800 within other countries, what leverage do we or any collective we have to make sure that this

02:13:54.560 compliance is truly international? Yeah, I mean, there's two dimensions of that. One, how do you get

02:14:00.760 IGSC-like regulations enforced by all countries that have sin bio, private sin bio industries? And

02:14:08.320 that is challenge number one, and it's an ample challenge. But there are, you know, I'm sure there

02:14:14.500 are many industries that have relatively universalized regulations throughout the world, in part because

02:14:19.260 that's in the interest of industry, to not have to comply with rules and countless jurisdictions that

02:14:24.440 might be different and so forth. But that's hard enough, and I don't want to minimize that. But,

02:14:28.660 you know, state actors are a whole nother wrinkle. I mean, because if we look to the Montreal Protocol

02:14:33.260 for reassurance, the hole in that analogy is that state actors themselves didn't have big chlorofluorocarbon

02:14:40.120 projects of their own. Those were industrial ingredients. They were coolants for air conditioners.

02:14:44.140 They were making foam packaging for McDonald's, that sort of thing. So in that case, governments were

02:14:51.360 regulating society, which they're perfectly happy to do. But sovereign governments get really grumpy

02:14:56.940 about restrictions on their own actions. And so it's not hard to imagine the Chinese state or the

02:15:02.180 U.S., for that matter, secretly developing governments and bio capabilities to stay ahead

02:15:06.440 of the rest of the world. So, you know, in addition to an internationally coordinated IGSC-like system

02:15:13.140 for keeping private industry safe, we definitely need something like the Nuclear Non-Proliferation Treaty

02:15:19.100 for Symbio Amongst Nations, which is a really tall order. And it's not something I have a ready-made

02:15:26.100 playbook for. But I will say that as we scale up all of our national protective layers, it's really

02:15:32.900 important not to neglect the international side of things. And this has to be a feat of very significant

02:15:39.220 and determined international diplomacy, without any question.

02:15:42.540 Hmm. So are there any lessons to draw from, you know, on this point of cooperation and its

02:15:51.200 enforcement internationally, from our experience with China and COVID? I mean, there's so many ways in

02:15:59.200 which cooperation almost happened and then failed, and then we're still trying to figure out to what

02:16:06.640 degree your rank deception is the story of what China has done here. What lessons do we draw from COVID? 0.67

02:16:16.440 Well, it's obviously not an encouraging example on so many levels. I mean, the denialism,

02:16:23.720 the suppression of people spreading the word about the outbreak, the fact that people in regions like

02:16:30.400 Wuhan are often afraid to report bad news up to Beijing. So there was stonewalling internally,

02:16:35.980 according to that very extensive research that I cited in the recorded material by the Wall Street

02:16:43.700 Journal. There was obviously stonewalling on an international level. But what we can hope for, 1.00

02:16:50.380 and I don't think this is a naive hope, is that a lot of people in a lot of countries are looking

02:16:55.580 at all the botched responses to COVID and saying never again. And they're saying it with the kind

02:17:01.320 of determination that carries over across years and across decades. And, you know, the kind of

02:17:08.660 encouraging thing in a weird way is that I think China's disease detection system might have actually

02:17:15.660 been up to the challenge of containing COVID, but for some tragically delayed responses, which Beijing

02:17:23.520 will presumably do everything possible to avoid in the future. And from that, my optimistic side says

02:17:28.800 the world may be closer than we think already to adequate warning and detection systems. And where I

02:17:34.560 get this from is a fascinating paper in the journal Nature, whose lead author is Shenji Lai, L-A-I,

02:17:43.060 at the University of Southampton. And it analyzes China's so-called non-pharmaceutical interventions

02:17:49.720 against COVID, which is a fancy term for quarantines, lockdowns.

02:17:54.280 It's a fancy term for welding people into their apartments.

02:17:57.000 Exactly. And masking and that kind of thing. The non-pharmaceutical interventions, NPIs.

02:18:02.320 And the paper's analysis goes into a lot of depth and says that these interventions

02:18:06.900 had been implemented a week earlier. China's COVID cases could have been cut by about two-thirds,

02:18:14.240 or cut by something like 85% if they were implemented two weeks earlier, or 95%.

02:18:19.720 If the lockdown and so forth happened three weeks earlier. So, you know, did China have three

02:18:24.520 weeks? And the answer is these interventions started, I think it was on the 23rd of January.

02:18:31.000 And as early as late December, this fairly heroic doctor that some people have probably heard of

02:18:36.780 named Li Wenliang first sent a message to some fellow doctors warning of a SARS-like outbreak in

02:18:42.760 Wuhan. So yeah, that's over three weeks of lead time. And since this was a lone doctor,

02:18:48.140 you know, basically successfully tuning into the pandemic, just from his narrow personal

02:18:53.040 experience, I think we can safely assume the local health authorities who would have had much

02:18:58.500 broader access to data had to be aware of something. Now, this is just terrible to even think about,

02:19:04.940 because a 95% drop in China's cases may well have prevented the global outbreak. But it's also,

02:19:11.720 it feels just really unlikely that a delay like that will happen again in a post-COVID world.

02:19:17.780 There's just going to be so much more urgency about any warning signs. And there's meanwhile,

02:19:22.560 a ton of things we can do to dial up the sensitivity of early warning systems throughout

02:19:28.440 the world, which we'll talk about. And all that together gives me real optimism about our ability

02:19:34.500 to detect and hopefully also snuff out potential pandemics, whether they're natural or artificial.

02:19:42.260 Is there any more that you've uncovered on the monitoring front or just how we can pay attention

02:19:47.580 to what's happening in the world? Because it's, again, this is the kind of thing that by its very

02:19:55.320 nature will emerge by stealth. You know, I mean, I guess some maniac could decide to take the Bond

02:20:03.560 villain approach to this, saying, you know, that if my demands are not met, I will be releasing the

02:20:08.840 doomsday virus on New Year's Eve. But generally speaking, we're just going to hear about people

02:20:14.700 getting sick somewhere. And we're not going to know what's going on, or for how long it's been going

02:20:20.620 on, unless we build some system by which we detect these things earlier and earlier.

02:20:27.740 Yeah, I mean, I would definitely like to draw attention back to that Nigerian system called

02:20:35.200 Sentinel, or it's being rolled out in Nigeria, called Sentinel that I talked about in the recording,

02:20:40.240 which, just to quickly review, is, I think they call it a pandemic prevention system using real-time

02:20:48.060 detection of viral threats or something like that. The expectation with Sentinel is that they'll be able

02:20:54.140 to empower community health workers to diagnose any of a region's most common viral infections or

02:21:03.000 highest priority viral infections, so probably the common ones along with rare, scary ones like

02:21:08.340 Ebola or whatever, within an hour. And to basically diagnose any known human virus within a day by pushing

02:21:18.020 things up the chain to a central organization. And, you know, my back of the envelope math on that,

02:21:24.920 as I mentioned in the recording, is that it would cost in the low billions to trot out something like

02:21:29.480 that, for instance, in the U.S. And, you know, you've got to ask yourself, on a certain level,

02:21:36.580 why in the hell haven't we done that? And part of the answer is that some of Sentinel's technology is

02:21:42.400 very new. And also the amount of genetic sequencing that it involves would have been impossibly

02:21:47.680 unaffordable just six or seven years ago. But the bigger reason is the American healthcare system

02:21:53.140 is just this baffling thicket of overlapping jurisdictions. I mean, some things are managed

02:21:57.940 by 50 different states. Other things are managed by 3,000 different counties. And at least for now,

02:22:04.200 a nationally coordinated system like Sentinel seems to be completely beyond us. I mean, just one example

02:22:08.680 from yesterday's New York Times, an editorial in yesterday's Times said that 20 million COVID

02:22:14.760 vaccines have essentially gone missing in the U.S., which is a huge number when 40 million vaccines

02:22:21.140 have actually been injected so far. And I think the intent of the editorial was that they've gone

02:22:24.880 missing from the standpoint of the federal government, which basically means the federal

02:22:28.480 government is pumping out the nation's scarcest and most precious resource into 3,000 counties in 50

02:22:34.680 states and losing all track of it. And we obviously need to do better than that.

02:22:38.680 And when it comes to disease surveillance, we need to do what Sentinel is bringing to Nigeria, 1.00

02:22:43.680 this real-time radar of viral infections. And obviously, counties can't build that. It needs

02:22:49.380 to be a national system. And I think it would have to hinge on radically expanding testing and diagnosis

02:22:56.240 of all respiratory infections. I mean, flu, rhinoviruses, you know, minor brushes with a common cold,

02:23:02.720 the whole shebang, which we don't currently even attempt. I mean, have you ever in your life

02:23:08.120 had a flu diagnostic? Like, has a doctor ever said, hey, you don't have the flu, you have a

02:23:12.880 rhinovirus? Or you have influenza A, not influenza B? I mean, basically, no one has ever experienced

02:23:18.080 that. Because people usually recover from these things, and collecting the data didn't seem

02:23:22.600 important. But this has got to change. Because the only way we're going to know if something new

02:23:26.740 and dangerous is emerging is if we track the full national inventory of viral infections as close

02:23:32.400 as we can. Which basically means, in my mind, a project warp speed for diagnostics, for testing,

02:23:38.320 not just COVID testing, obviously, but every respiratory infection we know of. And I understand

02:23:42.960 the Biden administration plans to invest a lot in tests. And I don't know how much of that is for the

02:23:48.420 current crisis and how much of that is ongoing. But we basically need a whole new category of

02:23:53.620 diagnostics, ones that can test for multiple diseases, and which are reliable, which are cheap

02:23:59.720 as hell. And above all, can be taken at home. Because we want to track these things much more

02:24:04.820 closely, but we don't want to trigger an avalanche of new doctor visits. We just don't have the capacity

02:24:09.240 for that. And most people wouldn't bother with a doctor visit for a mild infection anyway. So

02:24:14.760 these tests should be in every home, they should be free. And somehow the results should be automatically

02:24:21.100 logged with the national cloud. Like maybe you need to scan some kind of coded display on the test

02:24:28.140 with your phone to get the results. And all of this disease information needs to go into a real-time

02:24:35.220 integrated system that's inhaling lots of other data as well. I mean, something kind of like NORAD,

02:24:43.120 the super high-tech military command that scans the skies for nukes and enemy planes. Like a disease

02:24:49.040 tracking center that's staffed 24-7 by data scientists looking at data from all kinds of sources,

02:24:55.000 like all those diagnostic tests, also online data, search engine queries, and so forth like we talked

02:25:00.980 about. And hopefully we're smart enough to invest in a bioaerosol grid. And the technologies I talked

02:25:07.300 about for pulling viruses out of the air in public spaces, that data should also feed in continuously.

02:25:12.780 And hopefully we're also smart enough to build a hugely expanded version of Medisub, that academic

02:25:18.920 project which tests surfaces and wastewater and air samples for viruses in over 100 cities. That data

02:25:25.620 would feed into. And it should also be dialed into, obviously, the local public health systems. So if

02:25:32.060 there's an alarm signal somewhere, you can get boots on the ground and see what's happening. Now that's

02:25:37.180 quite a wish list, but we could build something like that. And it would be an amazing layer two for our

02:25:43.680 global immune system. Yeah, well, at least two parts to this that are distinct. There's the actual

02:25:51.000 diagnostic end of it, where you have to swab the door handle on a bank or the keypad on an ATM

02:26:01.340 or somebody's nose or get a saliva sample. And then you need to take all the friction out of the system

02:26:09.500 that allows those samples to be processed and analyzed. But then there's just this massive

02:26:15.760 information integration problem and, you know, prospective and retrospective search of the data

02:26:23.120 looking for patterns. And I got to think on that second piece, once again, the 20% time companies like

02:26:31.540 Google and Palantir and these other, you know, major tech corporations that have so much engineering

02:26:38.220 talent, that could profitably be spent there. And it's got to be shouldered as a responsibility by

02:26:47.980 every smart person who has something to contribute here. My fear is that we will solve COVID. The

02:26:56.300 vaccines will ultimately get distributed and they will work, you know, if not in the first volley,

02:27:02.860 maybe the second, right? We still have these variants now that could be outrunning some of the

02:27:07.760 vaccines. But you can imagine us putting this behind us fairly conclusively and then that ushering in a

02:27:17.620 kind of roaring 20s-like spirit of, okay, well, we've reset everything, you know, hallelujah, and that we

02:27:24.860 could lose the lesson that we really must draw from this, which is we can't let this happen again. Again,

02:27:32.320 this is a dress rehearsal that we have manifestly botched in almost every way, apart from the speed

02:27:39.460 with which we produced vaccines. And yeah, so I do worry that once we get out from under this,

02:27:47.400 we will lose the sense of urgency and just assume, okay, this sort of thing only happens once a century

02:27:52.640 anyway, so we can go back to sleep.

02:27:54.820 Yeah, I mean, and that's why, you know, I'll come back to the idea that this absolutely needs to be

02:28:01.200 viewed through a national security lens. And maybe just because it is so damn good at lobbying for

02:28:07.840 hundreds of billions of dollars every year, we kind of hold our nose and put it under the Department

02:28:12.120 of Defense because, you know, they sure know how to lobby for dollars. And it's got to be something

02:28:16.380 that is done relentlessly year in and year out, like we do with funding military capacities that

02:28:22.060 at almost any given moment are 99% unutilized. And we've become okay with that as a society because

02:28:28.960 we know that we sometimes might someday might need to draw on emergency capacity. But the other thing

02:28:35.500 is, you know, that the IT work, I mean, I'm just sort of glibly describing something like NORAD. I

02:28:41.740 assume NORAD works really well. I don't know. I've never been there. But what we do know is that

02:28:46.100 the IT contracting that the government has done for all kinds of things has at times been completely

02:28:53.500 catastrophically inept. And, you know, just look at the debacle of the vaccine rollout.

02:28:59.780 The New York Times editorial that I just mentioned about the 20 million vaccines that have gone

02:29:03.860 missing also mentions that the federal government gave Deloitte $44 million no-bid contract to develop

02:29:12.100 software for states and others to use during their vaccine rollouts. And the product is simply

02:29:19.620 catastrophic. You know, most, a lot of health departments have completely ceased to use it.

02:29:24.500 And we can't have that level of incompetence and that lack of seriousness invade or infest something

02:29:33.380 like this if we're really going to build a, you know, a radar screen for emerging pandemics. We can

02:29:38.900 absolutely do it. But I take much more heart from the kinds of things that companies like Palantir can

02:29:45.380 allegedly do than from the kinds of projects the federal government has overseen. I mean,

02:29:50.260 it's hard to imagine a more urgent task than getting vaccines distributed. But even that IT

02:29:55.940 project was colossally botched. So there just needs to be a completely different level of governance,

02:30:03.380 much, much higher standards. And again, just a radically higher level of seriousness as we

02:30:09.940 tackle this thing. And again, maybe this gets back to that 20 percent time notion, not that you would

02:30:14.740 want this natural detection grid to be staffed by part-timers, but maybe people who are intent on

02:30:21.700 careers in SynBio view things from, you know, kind of a linear standpoint and say, maybe I'll give,

02:30:27.700 you know, 20 percent of my career to doing work in the public interest. And so maybe we could have

02:30:33.140 some really, really top flight people from academia and private industry see to it these systems are

02:30:41.140 outstanding and work incredibly well.

02:30:43.140 Yeah. Yeah. And I'm sure there's a role for philanthropic organizations here to point

02:30:52.340 resources in the right direction and just lobby for this being a priority. Some of the most important

02:31:00.260 work that can be done here, I think, is just to make the case that we need to allocate the resources,

02:31:07.300 you know, at the government level. And this is the problem we've run into all these long years with

02:31:13.780 climate change. You know, we're still barely at the starting line because the war of words has been

02:31:22.180 so difficult to win. And we really need to figure this one out. Somehow I think this is less abstract

02:31:30.020 to most people than the risk of climate change is. But, you know, we're also living in a country where

02:31:36.260 it seems that, you know, at the time of this recording, something like half the country is

02:31:44.580 fairly carefree about the prospects of catching COVID and quite worried about getting vaccinated for

02:31:53.300 it. It's the absolute inverse of what you would think would be psychologically possible. So we obviously

02:32:00.820 do have a major messaging problem here, which also requires a commitment of resources. And that is,

02:32:08.740 in large part, the purpose of this podcast. So, Rob, let's listen to the fourth and final section of

02:32:16.020 your, by turns, fascinating and harrowing meditation on the future of SynBio and global pandemic.

02:32:25.220 This brings us to the third component of our immune system, which is hardening society against future

02:32:29.700 pandemics. So what can we do to toughen things up? Well, probably dozens of things. And as I said

02:32:36.420 earlier, this podcast can't be a comprehensive list of everything we could do. But I'd like to lay out a

02:32:41.860 couple of intriguing possibilities that might just be game changing. For now, they're both unproven.

02:32:47.460 But they're examples of the types of investments we should be making, in some cases, tiny ones,

02:32:52.500 to bulk up our arsenals. The first is a very particular ray of light, of ultraviolet or UV light.

02:33:00.180 As you may know, UV is invisible to human eyes. It's carved up into various bands and subbands,

02:33:05.860 just like radio. UVA and UVB light from the sun shine through our atmospheres and cause sunburns and

02:33:12.420 skin cancer. A higher frequency band called UVC light doesn't get through, but we can make it ourselves

02:33:18.420 down here with lamps. UVC has lots of energy, so much that it kills microorganisms by frying their DNA.

02:33:26.500 You may have seen it sterilizing things in hair salons. It's also used to sterilize operating

02:33:31.220 rooms and hospitals and buses in some countries, but only when those places are empty. Because again,

02:33:36.500 UV light is bad for us. Or at least most of it is. The UVC spectrum has its own little neighborhoods.

02:33:43.700 One of them is called far-UVC. And fascinating research shows that it may not damage human tissue

02:33:49.620 at all. David Brenner, a radiation physicist at Columbia, has done most of the groundbreaking work

02:33:55.700 here. In a July 2020 interview with Ted's David Biello, he explained that light around the 222 nanometer

02:34:02.500 wavelength just can't penetrate the dead cells that form the surface of our skin and our eyes. He's exposed

02:34:08.980 the skin and eyes of mice, as well as human skin to it, and there's no sign that it gets through that

02:34:14.340 outer layer to do any damage. But viruses and other bugs are much tinier than our cells, and this light

02:34:20.580 zaps them. David Brenner's experiments have shown that it kills off airborne thugs like influenza and

02:34:26.020 coronaviruses. He'd like for far-UVC lights to be in indoor spaces everywhere and to be switched on

02:34:31.700 safely in the presence of humans whenever outbreaks occur. He's calculated that 99.99% of the pathogens

02:34:39.620 in an enclosed room could be knocked out by these lights in just a few minutes. Now this wouldn't

02:34:44.740 sterilize diseases out of existence. After all, it takes seconds, not minutes, for a sick person to

02:34:50.500 sneeze on you in the subway. But it could bring the ambient level of pathogens way down and completely

02:34:56.100 sterilize surfaces. In other words, while it wouldn't make the built environment virus-proof,

02:35:01.380 it could harden it quite a bit. But there's a puzzle here. Dangerous UV wavelengths aren't all

02:35:07.060 that much longer than far-UVC. It's all measured in nanometers. So why can the bad UV penetrate our

02:35:13.460 skin when far-UVC can't? I talked to a Scottish physicist based in Australia named Charlie Ironside

02:35:20.100 who explained this. Different materials absorb and reflect different frequencies of light, and the

02:35:25.140 proteins in our cells happen to be highly absorbent right around that magic 222 nanometer wavelength.

02:35:32.100 And when light is absorbed, it decays away exponentially as it enters the material. So,

02:35:38.100 boom, our outer layers of dead cells are bulletproof, or at least very opaque, at 222.

02:35:45.060 To make far-UVC today, you need clunky tubes which are big, ugly, inefficient,

02:35:50.260 and generate way too much heat. Charlie has spent decades working with LEDs and has issued a call

02:35:55.860 to arms to the industry to make far-UVC LED products. If things work out, he thinks they

02:36:01.540 could even be integrated into smartphones, letting them act as germicidal wands. No more need for hand

02:36:08.020 sanitizer. But lots of research and development would need to be done. And as Physics World recently pointed

02:36:14.180 out, nothing's going to happen until safety is proven beyond a doubt. David Brunner's intriguing

02:36:19.700 experiments notwithstanding, this is yet to be done. If you're like me, you're wondering,

02:36:25.140 why in the world not? Safety studies would cost in the millions, in a world that's losing trillions

02:36:31.700 to a pandemic. A world which will, without question, face future pandemics. And this could be a game

02:36:38.740 changer. Or it could be a dud. But we'll only find out if we put it to the test. Our global immune

02:36:45.380 system has to fund research that could strengthen our pandemic readiness, especially when next steps

02:36:50.820 cost so little, and excellent research shows that the results could be transformative.

02:36:55.700 This brings us to the BCG vaccine. BCG prevents early childhood tuberculosis and has been given over 4

02:37:02.260 billion times since the 1920s, more than any other vaccine. It's so safe, it's given to over 120

02:37:09.060 million infants each year. And there have been signs that it fights many diseases beyond tuberculosis for

02:37:14.420 almost a century. Way back in 1927, a Swedish study found that BCG vaccinated children turned out to be

02:37:21.860 three times less likely to die from any cause. More recently, a 25-year study of over 150,000 kids in 33

02:37:30.660 countries showed the vaccine reduced lower respiratory tract infections by 40%. Then a very recent study in

02:37:37.380 Greece showed an 80% drop in respiratory infections amongst older adults who were given the vaccine,

02:37:43.540 as well as a 50% drop in all other forms of infection. And BCG's superpowers go far beyond this.

02:37:50.820 It's now a frontline treatment for bladder cancer. And there are promising signs that it might even help

02:37:55.860 to prevent cancer from arising in the first place, and possibly even prevent Alzheimer's.

02:38:03.300 BCG seems to work its magic by strengthening the innate immune system over the long term.

02:38:08.660 Think of this as being your body's first responders. It's the innate immune system that instantly kicks

02:38:13.780 in when something punctures your skin, or when you first get an infection. It's ready to fight

02:38:18.580 anything, unlike the adaptive immune system, which creates highly effective specialized responses to

02:38:23.780 specific enemies, but needs time to get started. So, could widespread BCG use help foil a pandemic?

02:38:30.980 Well, as early as March, people started noticing that countries with long-running BCG programs,

02:38:36.260 like Japan, generally had much lower COVID infection and death rates than countries with no BCG programs,

02:38:43.220 like the US. A rigorous study of this effect appeared in the July 28 edition of the Proceedings of the

02:38:49.460 National Academies of Sciences. To control for things like socioeconomics, population structure,

02:38:55.780 and urbanization, the researchers looked at a set of what they called socially similar European countries,

02:39:02.260 and they found that for every 10% increase in a BCG coverage index, COVID death rates dropped by 10.4%.

02:39:10.100 An intriguingly stark example was found in Germany. Back when the country was divided,

02:39:16.340 East Germany pursued a policy which has yielded far more BCG coverage in today's elderly adults,

02:39:22.660 who are of course the most vulnerable group to COVID. And today, the death rate from COVID is 290%

02:39:29.620 higher in Western Germany, the opposite of what we'd expect to see, given that Western Germany is the

02:39:35.540 far more prosperous region. Is all of this just a coincidence? Of course, it could be. Which means

02:39:42.180 this screams for multiple clinical trials. They should be run in places like the US, where almost

02:39:47.460 no one has ever had the vaccine. Researchers would then give one group of people BCG and another group

02:39:53.140 a placebo, and then compare COVID infection rates between the groups over time. Although some BCG COVID

02:39:59.540 trials are in fact underway, I'm still stunned by how hard it is to raise tiny research funds for such

02:40:05.140 obviously important work. As I was researching this, I got to know two scientists who were proposing some

02:40:10.820 exceptionally well-designed research into BCG's benefits for an extremely vulnerable population

02:40:16.260 to COVID. They're from one of the world's top and best known universities. But instead of running their

02:40:21.860 trial, they were hunting for a few million dollars in funding during a pandemic that's costing the US

02:40:27.300 $7 trillion, at least. Again, this is insane. Even though BCG, like far-UVC light, could admittedly

02:40:36.900 turn out to be a flop, we won't know until we fund the inexpensive research that tells us. You might

02:40:43.140 question why this research is still important, with so many COVID-specific vaccines entering the market.

02:40:48.740 The answer is that we have an entire planet to vaccinate, almost 8 billion people. Some of the new 0.99

02:40:54.500 vaccines are expensive, with limited production capacity, whereas BCG costs as little as 7 cents

02:41:00.100 a dose and is made by 22 different manufacturers throughout the world. And COVID aside, this could

02:41:06.340 be a game changer for future pandemics. BCG's greatest superpower seems to be fighting respiratory

02:41:12.180 infections of all types. And a huge percentage of pandemics, as well as novel diseases with the

02:41:17.700 potential to become pandemics, are respiratory in nature. SARS, MERS, COVID, flu, tuberculosis itself.

02:41:26.820 You get the picture. And God forbid we ever have an artificially modified H5N1 outbreak,

02:41:32.740 but if we do, boy will that be a respiratory nightmare. If a future pandemic could be greatly

02:41:38.580 softened by a precautionary BCG vaccination program, we'd be fools not to do the inexpensive

02:41:44.020 research to either prove or debunk BCG's efficacy. And again, if we do decide to vaccinate people,

02:41:50.740 BCG costs as little as 7 cents a dose. So giving the largest totally unvaccinated country, the US,

02:41:57.780 full coverage would cost peanuts. If you'd like to learn a lot more about the BCG vaccine,

02:42:02.820 tuberculosis and more, I interviewed a brilliant Harvard epidemiologist named Megan Murray for my own

02:42:08.420 podcast, which again is called the After On podcast. Her academic focus is tuberculosis,

02:42:14.100 and she knows tons about BCG and its potential. Our interview runs for well over an hour and goes

02:42:19.620 into much more depth than I can cover here. That episode may or may not be posted by the time

02:42:23.940 you're hearing this, but if it hasn't been posted, it's the next one in the queue. So you'll be able

02:42:29.220 to access it quite soon. The last method for hardening society that I'd like to highlight

02:42:34.420 doesn't hinge on cutting edge science, but on plain old public policy. It is to greatly increase

02:42:40.420 the social safety net that keeps people from sliding into states of extreme despair. Though it may be

02:42:45.540 hard to feel empathy for suicidal mass murderers, we have to accept that all of them arrive at profoundly

02:42:50.980 dark places that few of us can even imagine. These are not swift journeys, and all involve some form of

02:42:57.540 mental illness, be it extreme depression, uncontrolled rage, pathological narcissism, schizophrenia, or

02:43:05.140 something else. We need to study the case histories of everyone who snaps in this way, and greatly

02:43:10.820 increase our vigilance and generosity in detecting and treating the relevant conditions. Here in the U.S.,

02:43:16.500 a de facto policy of emptying asylums for the mentally ill back in the 80s has done us no favors.

02:43:22.260 More broadly speaking, every single one of us can be a white blood cell in this global immune

02:43:27.140 system by each doing what we can to ensure that no one goes unloved.

02:43:33.700 This brings us to the fourth component in our immune system, which is conquering viruses.

02:43:38.260 But before we talk about viruses, let's briefly discuss bacteria, which can be extremely dangerous.

02:43:44.580 They cause things like cholera and bubonic plague, which still bubble up in places with overwhelmed

02:43:49.140 healthcare systems. Plus, there's so-called superbugs, which resist all antibiotics. These killed about

02:43:55.380 700,000 people in 2016 and could be over 10 times as lethal by 2050, which means they could significantly

02:44:03.220 exceed the death toll of even COVID. We're desperately underinvesting in new antibiotics, and this urgently

02:44:09.700 needs to change. That said, almost every major epidemic since antibiotics were discovered has

02:44:15.940 been viral. Influenza, polio, mumps, yellow fever, measles, dengue, AIDS, SARS, MERS, COVID. And as for

02:44:25.380 true pandemics, only viruses cause them in the modern era. So why are viruses such tough customers?

02:44:33.140 Ironically, it's because there's not much to them. They lack the basic machinery of life and don't have

02:44:38.500 any cells, so they infiltrate our cells. That doesn't leave as many targets when we go after them,

02:44:44.180 because we don't want to wipe ourselves out along with a virus. Bacteria, on the other hand,

02:44:48.980 are cells, ones which are very different from ours. That gives us loads of targets when we fight them.

02:44:55.380 And many of our antibiotics are a broad spectrum, which means they can wipe out all kinds of bacteria,

02:45:01.380 sometimes too many. This makes it almost certain that the first deadly artificial pathogens will be

02:45:07.060 viruses. So does the second factor, which is that bacteria are radically more complex than viruses,

02:45:13.540 and are therefore much harder to engineer. Other deadly critters, like the parasites that cause malaria,

02:45:19.700 are more complicated still. Complexity also makes it almost certain that early man-made bugs will be

02:45:25.940 modifications of existing viruses, not completely artificial ones, because it's currently beyond

02:45:32.100 anyone's capacity to make complex, functioning viruses from scratch. So how should we face the

02:45:38.020 threat of artificially modified viruses, terrors like that contagious version of H5N1 flu, which has

02:45:44.340 already been created? Well, I'd say exactly how we should have been facing natural viruses for decades, steps

02:45:51.140 that probably could have stopped COVID in its tracks. There are two main sets of tools to consider. The first is

02:45:57.940 vaccines to prevent viruses from infecting us in the first place. The second is therapeutics,

02:46:03.620 a fancy word for medicines to help us fight viruses if we do get infected. The trick is that so far,

02:46:09.780 both sets of antiviral tools have been very narrowly targeted at very specific diseases,

02:46:15.140 rather than having the broad spectrum disease-fighting power of many antibiotics. So let's start by talking

02:46:21.300 about therapeutics. Here, Johns Hopkins Center for Health Security senior scholar Amesh Adalja sums things up,

02:46:28.820 writing, quote, the existing armamentarium, by the way, I love that word, of antiviral drugs is rapidly expanding and

02:46:36.580 now covers several viral families. However, very few existing antiviral agents have spectrums of activity that even

02:46:44.420 slightly measure up to the spectrum of penicillin, or sulfa, the first antibacterial agents discovered,

02:46:51.060 end quote. But it's not hopeless. In a conversation with me, Amesh pointed to several viral therapeutics

02:46:57.060 that hit multiple targets. One influenza treatment has proven effective against Ebola. Another medicine

02:47:03.060 fights members of four virus families, herpes, pox, adeno, and polyoma. And something called

02:47:09.300 ribavirin, which was name checked in the movie Contagion, can help treat hepatitis C and E,

02:47:15.460 influenza A and B, parainfluenza viruses, Crimean-Congo hemorrhagic fever, metanumovirus,

02:47:22.980 new and old world hemorrhagic arena virus, and SARS. Although it unfortunately has what Amesh calls

02:47:30.020 serious toxicity issues. So what do we do with all this? Amesh told me he'd like to see a serious

02:47:36.660 multi-year program to test every antiviral medicine that's ever been developed against

02:47:41.700 every dangerous viral family. Though reluctant to put a firm budget on this, he said it could cost

02:47:47.140 several billion dollars and take several years. Chump change in light of what we're up against.

02:47:52.260 And this would give us something crucial that we lack, a complete understanding of what our existing

02:47:57.060 weapons can already clobber. For now, we make these discovers haphazardly, or reactively, like when the

02:48:04.100 ebola medication remdesivir proved to have some effectiveness against COVID. There may be some

02:48:09.700 truly broad-spectrum wonders in our viral toolkit already that we just don't know about. So let's

02:48:15.780 figure this out. Amesh also calls for us to proactively develop new antivirals to cover full

02:48:21.780 viral families, like all coronaviruses. Pull that off and you've tackled SARS and MERS, as well as four

02:48:29.140 causes of the common cold, plus, above all, COVID. Just imagine where we'd be now if we'd launched a

02:48:36.180 successful campaign against the full coronavirus family right after the SARS crisis in 2003.

02:48:43.140 With a powerful anti-coronavirus treatment in our arsenal, COVID fatalities could have been a tiny

02:48:48.340 fraction of today's death tolls, and society and the economy could have been far less disrupted.

02:48:53.060 Amesh notes that it usually takes about a billion dollars to get a drug to market.

02:48:57.860 Big bucks. But small change compared to what's at stake. Even if you do this for every viral

02:49:03.220 family that sickens humans, of which there's just a couple dozen. Although there are a few viruses

02:49:09.140 that don't currently infect us that we should probably sharpen some weapons for. Remember those

02:49:14.260 zoonotic viruses? Something called the Global Virome Project keeps a wary eye on bugs that haven't

02:49:19.860 yet jumped to humans, but may one day do so. Like so much of what we're discussing,

02:49:25.300 all these antiviral measures would bring massive benefits against natural pathogens as well as

02:49:29.860 artificial ones. And strictly in light of the endless costs that natural diseases inflict on us,

02:49:36.100 we'd be crazy to skimp here. Also, there are things that could help bring the costs down,

02:49:41.460 like software-based modeling and screening of drugs against specific diseases,

02:49:45.940 a new field that's showing lots of promise and appears to be very cost effective.

02:49:50.340 Now, of course, the other side of the viral defense equation is vaccines. And here we'll start by

02:49:55.380 talking about the flu again, because lots of smart people have been calling for a universal flu vaccine

02:50:00.580 for years. By this, they mean a vaccine that works against all strains of the influenza virus.

02:50:06.420 So if you stamp out seasonal flu, you've protected people from rogue versions of H5N1 flu for free,

02:50:12.500 along with countless other variations. A universal flu vaccine would also hopefully be good for

02:50:17.940 multiple years, unlike the annual vaccines we currently get. There are lots of good reasons to

02:50:23.700 get blanket protection from influenza. As we've already seen with H5N1 flu, it can be hacked in

02:50:29.540 terrifying ways. It also kills three to 500,000 people worldwide each year and costs over a trillion

02:50:36.660 dollars in global economic activity. Plus, it mutates constantly, reinfecting people who recovered

02:50:42.820 from earlier strains. Those mutations can also trigger deadly pandemics, as happened in 1918 and

02:50:48.980 three times since. Finally, the current vaccine is just so inadequate. It's only 10 to 60 percent

02:50:55.780 effective depending on the year. And its manufacturing is largely based on 1940s technology. One of the top

02:51:02.900 people who has long called for a universal flu vaccine is Harvey Feinberg, a former dean of the

02:51:07.700 Harvard School of Public Health and a former president of the National Academy of Medicine.

02:51:12.740 He told me that he thinks it would cost just one to 200 million dollars to fund a fully

02:51:17.380 dedicated effort that would have, quote, a very good chance, end quote, of developing a universal flu

02:51:23.060 vaccine over about 10 years. You heard that right. Just 10 to 20 million dollars a year.

02:51:29.140 And he points off that even if he's off by an order of magnitude and it costs one to two billion

02:51:34.980 dollars total, it's a staggeringly good deal. Now, you could spend this money only to find out

02:51:40.740 that a universal flu vaccine is impossible with today's science. Harvey puts those odds at at least

02:51:45.860 25 percent, maybe in a stretch as high as 50. But if we take the worst possible numbers from all of his

02:51:53.540 ranges and figure it's two billion dollars to get just a 50-50 shot at saving the world a trillion

02:52:00.660 dollars and hundreds of thousands of lives each year, it's still the deal of the century.

02:52:07.380 And of course, there's no reason to stop with the flu. Harvey thinks similar programs against

02:52:12.020 other viral families would cost similar amounts and face similar odds. If given the budget, he'd start

02:52:17.780 with universal influenza and coronavirus vaccines. He thinks we'd learn enough from this to make later

02:52:23.060 efforts targeting other viral families faster and cheaper. So again, let's say we take the worst

02:52:28.740 possible number from Harvey's ranges and launch universal vaccine programs against all of the

02:52:34.420 couple dozen virus families that sicken humans. This one-time moonshot program would cost less than

02:52:41.060 five percent of what the flu alone costs the world every year and less than one percent of COVID's bill.

02:52:48.020 Even if artificial bugs are forever pure science fiction, this is an investment humanity cannot

02:52:53.620 afford not to make. And no, you wouldn't have to get all those shots, although you'd be wise to get

02:52:59.220 the influenza and corona ones. Instead, we'd stockpile these vaccines and have them ready in case something

02:53:04.820 is bad or worse than COVID emerges from one of those many viral families. And as with viral therapeutics,

02:53:11.380 just imagine if we'd had the foresight to launch a family-wide coronavirus vaccine program in response

02:53:17.540 to the SARS outbreak in 2003. Society literally could have been inoculated against COVID before it

02:53:24.420 even raised its head. On to our global immune system's final component, battle infrastructure.

02:53:32.260 So let's say the worst happens and an evil artificial bug, or something nasty and natural,

02:53:37.860 is on the loose. What do we need in our arsenal that we'll wish we had invested in today?

02:53:43.380 As a first step, Harvey Feinberg thinks we should adopt a national security mindset toward pandemics.

02:53:48.900 And I fully agree. These can be threats on the scale of a world war after all, which calls for a unified

02:53:54.900 command. And Harvey believes the head of it should carry, quote, the full power and authority of the

02:53:59.860 American president to mobilize every civilian and asset needed to win the war. That's the approximate

02:54:06.020 opposite of how the U.S. at least met COVID. One small example of dozens. The federal government

02:54:11.780 here triggered a bidding war between the 50 states for critical equipment and supplies

02:54:16.500 by refusing to coordinate purchasing and distribution. This turned the states into rivals rather than allies,

02:54:22.660 while prompting hoarding and backstabbing. In the words of the Wall Street Journal, quote,

02:54:27.380 some states turned against each other. One refused to give another contact information for lab supplies,

02:54:32.980 fearful of being outbid. Governors kept shipment details secret. Other governors dispatched state

02:54:39.060 police to airports to guard their cargo, end quote. A bigger example, the federal government left it to

02:54:45.140 each state to concoct its own defense and public health strategy against COVID. Of course, by definition,

02:54:51.300 states don't have national institutes of health or national centers for disease control. Thus badly

02:54:57.620 underpowered, states made their best guesses as to what might work, resulting in a stew of

02:55:02.100 conflicting policies and even quasi-border controls against citizens of other states. Could you imagine

02:55:07.940 approaching something 10 to 100 times deadlier than COVID with this sort of flailing? The virus would

02:55:14.660 finish us. Harvey also thinks voluntary quarantine should be more widely practiced and available on

02:55:20.740 demand. By this, he means offering temporary accommodations to people who have been exposed to

02:55:25.940 to protect the people they live with. This is important because close extended indoor contact

02:55:30.580 is the surest way to catch someone's infectious disease. Just consider how badly COVID spread in

02:55:35.380 nursing homes. Now, it may seem heartless to suggest that someone consider separating from their

02:55:40.740 housemates or family. But saying you should quarantine at home is an invitation to infect everyone there,

02:55:46.180 while only getting ad hoc homespun medical care, unless you happen to live with a doctor or a nurse.

02:55:51.940 Is that less heartless? Or more? Imagine someone's instead offered a free stay at a hotel that's been

02:55:58.420 shuttered by a pandemic. Harvey outlined a compelling pitch to me. You could stay somewhere other people

02:56:03.620 would pay hundreds of dollars a day to live in. You'll have room service because that enables social

02:56:08.420 distancing. You'll have 24-7 Zoom access to everyone you love via in-house broadband. Okay, you won't get

02:56:15.220 spa services, but you will protect your family for the next 10 to 15 days. Quarantine locations could have

02:56:21.380 trained personnel ready to manage mild infections much better than most people's housemates. And if

02:56:26.900 things turn ugly, someone under quarantine could be transferred smoothly and directly to a hospital.

02:56:32.020 We haven't seen much of this sort of thing outside of a few places like New York City,

02:56:36.180 perhaps partly because China adopted a very coercive approach to this with what they called fever

02:56:41.460 clinics, which gave the practice a bad name. It also takes forethought and perhaps some earmarked

02:56:46.900 funding to set up a more comfortable voluntary program. And COVID caught the world unawares.

02:56:52.100 But we have no excuse for letting the next pandemic sneak up on us. Especially if it's something much

02:56:57.220 deadlier and more contagious than COVID, a complete lack of quarantine could really sink us.

02:57:03.540 To all this, I'll add the dead obvious suggestion that personal protective equipment, ventilators,

02:57:08.340 and other defensive tools should be stockpiled to a degree that verges on absurdity. And that all

02:57:13.780 nations should try to establish highly local supply chains for this critical gear.

02:57:18.740 Also, this stockpiling should not be limited to governments. Just as all homes are mandated to

02:57:23.540 have smoke detectors, home stockpiles of N95 masks, hand sanitizer, and other essentials should be

02:57:30.180 mandated by law and perhaps paid for with government funds to ensure high compliance. I say this as

02:57:36.580 someone who tends to be highly anti-regulatory by nature. But if we get whacked by something much

02:57:42.340 worse than COVID, we cannot afford months of supply outages, hoarding, price gouging,

02:57:48.340 and counterfeit products on the personal protection market like we saw at the start of this pandemic.

02:57:54.100 And if you think all this sounds like a totalitarian imposition, recall that personal hygiene and PPE use

02:58:01.300 don't just affect the person practicing or not practicing them. They affect everyone, because

02:58:07.220 scofflaws and free riders infect the rest of us. So this isn't a matter of personal freedom, 0.99

02:58:12.340 like choosing to eat junk food. It's a matter of civic obligation, like refraining from drunk driving.

02:58:19.060 In this spirit, universal PPE stockpiles should be accompanied by a predefined set of rules and levels.

02:58:25.540 For instance, if a region goes to a certain infection level during an outbreak, universal mask wearing

02:58:30.500 in public becomes mandatory. Everyone knows the levels, everyone knows the rules, everyone has the

02:58:36.180 gear at home, and there are no excuses. Another relative novelty we should consider seeing more of

02:58:41.540 is challenge trials. These involve testing a vaccine by deliberately infecting healthy volunteers

02:58:46.660 with the disease it targets. Now I know that sounds insane, so let me explain the rationale,

02:58:52.420 using COVID as an example. Big COVID trials inject tens of thousands of people.

02:58:57.780 Half of them get the vaccine, half get completely inactive placebos. Then everyone waits until a 0.86

02:59:03.780 couple hundred people come down with the disease while going about their ordinary lives. If most or all

02:59:09.300 of the sick people turn out to have gotten the placebo, in other words, if the people who got the

02:59:13.860 vaccine don't get sick, then the vaccine's a winner. There are two issues with this approach. First,

02:59:20.820 it takes a long time to recruit tens of thousands of people to take an experimental injection. Second,

02:59:27.140 it can take months for enough people to get sick on their own to generate statistically significant

02:59:32.180 data. Which is normally fine, but what happens if thousands of people are dying each week? If your

02:59:38.740 vaccine works and you could have saved several months by running a challenge trial, tens of thousands

02:59:43.940 will die waiting for the results. Compare that to the number of test subjects who might die from

02:59:48.660 deliberate infection. In the case of a COVID challenge trial, that number may actually be zero.

02:59:54.820 The reason is you'd probably mostly allow young volunteers to enlist, people who are quite unlikely

03:00:00.500 to die from the disease. And instead of signing up tens of thousands of participants, you'd have just

03:00:05.940 a couple hundred. Why? Because you don't have to wait for a small percentage of a huge group to catch

03:00:11.460 the disease to get the couple hundred infectees it takes to determine efficacy. Because in challenge

03:00:16.900 trials, everyone's infected. And at least with COVID, if they're all healthy and mostly in their

03:00:21.860 twenties or thirties, the odds are decent that literally no one out of a couple hundred participants

03:00:26.580 will die. But what if one or two volunteers do die? Isn't that unconscionable? Well, compare that to the

03:00:33.300 tens of thousands of people who could end up not dying if your vaccine works. When are one or two

03:00:38.420 lives worth more than tens of thousands of lives? Well, when lawyers are involved, for one thing.

03:00:44.100 And that's one reason why we don't see challenge trials. Because the loved ones of someone who dies

03:00:48.580 in one might sue the trial manager, whereas the anonymous masses who die waiting for a vaccine

03:00:54.020 trial to run its course have no one to sue but Mother Nature. And she doesn't pay up. 1.00

03:00:59.060 Another reason is that doctors are deeply squeamish about imperiling anyone in their care. As they

03:01:04.500 should be, not only do our moral instincts scream this, but the Hippocratic Oath famously says,

03:01:10.420 first do no harm. The culture of medicine is built on that foundation, which of course is hugely admirable.

03:01:16.820 But it makes it hard to put the good of the many ahead of the good of the few,

03:01:20.260 if the few happen to be under your care and the many are countless strangers.

03:01:24.500 Now, an important moral dimension to consider about challenge trials is the mindset of the volunteers.

03:01:29.940 If they're fully informed of the dangers, as they absolutely must be, what are their motivations?

03:01:36.340 Well, if they're not being paid, they're probably signing up because they're willing to take a risk

03:01:41.620 to help fight something awful that threatens society. People joined the US military after the 9-11

03:01:46.980 attacks for somewhat similar reasons. Those volunteers put their lives on the line too. Many of them died.

03:01:53.380 And society didn't reject their offers of service, so should it reject people who volunteer for challenge

03:01:58.580 trials? These aren't hypothetical beings, by the way. Tens of thousands of people have volunteered

03:02:04.020 to participate in COVID challenge trials via an organization called One Day Sooner, and no one's

03:02:09.060 taken them up on that offer. I could fill a podcast twice as long as this one exploring the nuances

03:02:15.220 of challenge trials and their morality, but I'll leave it to you to decide where you come out on this

03:02:19.780 complex issue. And if you really want to dive into a rabbit hole, Google the term

03:02:24.180 trolley problem while you're thinking it through. Now, the one good thing about any future pandemic

03:02:30.500 is that it'll happen in the future, of course, giving Symbio's exponential momentum some growing room.

03:02:36.580 Which is great, because as I said early on, Symbio itself and the countless people who will one day

03:02:42.020 practice it at doctoral levels, high school levels, and everything between, are our best defense against

03:02:47.780 evil uses of biology. So I'll close on an appropriately optimistic note, describing one of the coolest

03:02:53.700 things I see in Symbio's midterm pipeline, which is teleporting vaccines. And yes, I mean that

03:03:00.580 metaphorically, but only just. To appreciate how valuable this could be, let's imagine an artificial

03:03:06.660 pathogen, or something natural and much more lethal than COVID, is on the loose. Having taken the various

03:03:12.820 precautions I discussed earlier, we have an effective vaccine that targets its viral family.

03:03:17.940 But it's incredibly deadly out there, and all supply chains are fragile or breaking.

03:03:23.460 It also takes months to manufacture hundreds of millions of vaccine doses using standard methods,

03:03:28.580 let alone billions of doses for the entire world. In this situation, you'd want the vaccine available

03:03:34.420 everywhere now, not in a few lucky places a few months from now.

03:03:38.980 You'd also want as few miles between you and your personal dose of that vaccine as possible.

03:03:45.300 So wouldn't it be great if vaccines could be printed right at the local pharmacy? Or better

03:03:50.100 yet, in your living room? Enter the BioXP, the DNA printer I talked about earlier. It will soon

03:03:56.580 be able to directly convert the four basic genetic letters, A, G, C, and T, into DNA or RNA strands,

03:04:03.940 giving it unlimited flexibility in what it can write, just as four-color inkjets can produce any

03:04:09.380 imaginable image. Its creator, Dan Gibson, actually invented it with vaccine production in mind,

03:04:15.940 particularly RNA vaccines, a new technology which is behind the wildly exciting vaccines

03:04:21.460 from Pfizer and Moderna. And here's where his teleporting term comes in. Imagine you have the

03:04:26.660 genetic code of a working vaccine at the center of your system, at the Centers for Disease Control in

03:04:31.460 Atlanta say. If you now print that genetic strand in thousands of pharmacies and doctor's offices,

03:04:37.620 you've basically teleported it throughout your network. Now, simply printing a strand of RNA

03:04:43.380 doesn't give you an RNA vaccine. There are several additional steps, often referred to as fill and

03:04:48.420 finish. Dan says the BioXP team is building these steps right into the machine. He believes fully

03:04:54.660 integrated systems should be operational at pharmacies and doctor's offices within three to five years.

03:04:59.300 As for consumer-friendly home systems, he puts those in the 10-plus-year time range,

03:05:04.740 which I'm sure sounds like science fiction. But most of what's happening in SynBio today would

03:05:09.300 have sounded like science fiction to the top people in the field when the Human Genome Project was wrapping

03:05:14.180 up just 17 years ago, as with most of what everyday folks do with computing today compared to the minimal

03:05:20.740 things that were possible on the world's most powerful computers just a few decades ago. That's the

03:05:26.660 thing about exponential technologies. They can deliver science fiction in short time frames.

03:05:31.620 Of course, they can also enable evil or disturbed people to wreak terrible devastation. But they can

03:05:37.140 enable the rest of us to prevent that devastation if we have the foresight to do it. As we come to the

03:05:43.060 end of this survey of what could go wrong with engineered pandemics, which is practically everything,

03:05:48.340 and what we can do to protect ourselves, there's lots of reasons for optimism. There are many steps we can

03:05:54.260 take to nip tomorrow's problems in the bud. Most of them have huge dual-use benefits in fighting the natural

03:06:00.020 diseases that clobber us constantly. And their costs are tiny compared to their benefits. To finish

03:06:06.260 making this case for optimism, let's style up your inner science fiction writer one more time.

03:06:10.900 Imagine it's 10 to 15 years from now. A smart person with a biology background and a crippling emotional

03:06:17.380 disease has decided to inflict a devastating pandemic on the world. He has access to a DNA printer with the

03:06:23.620 raw horsepower to crank out any viral genome, and tools we can scarcely imagine today which easily

03:06:29.380 translate printed genomes into replicating viruses. Worst of all, the dark web has given him the genetic code

03:06:35.620 of that contagious H5N1 flu, which those researchers created all those years ago. Only it's an upgraded

03:06:42.340 version which some darkly motivated biohackers have made wildly contagious, way more than COVID.

03:06:49.700 But luckily, our deeply disturbed protagonist lives in a world in which we have the foresight to defend

03:06:54.420 ourselves from his attack years before he even thought of launching it. Strong laws require all DNA printers,

03:07:00.580 not just 80% of them, to scan for deadly sequences before printing anything. So the only way to make

03:07:06.580 his virus is from scratch, using methods that only a few elite scientists ever bothered to learn,

03:07:13.060 many years ago before it became automated. That's a huge win right there. Because with that one step,

03:07:19.220 we've radically constrained the number of people who could do something awful. In other words, the population

03:07:25.060 of one circle in our Venn diagram, those who could kill millions, has plummeted, greatly reducing the

03:07:31.780 chances it ever intersects with the other circle, which contains the people who'd like to kill 0.97

03:07:37.060 millions. But let's say this person actually is an aging elite scientist who still knows the obsolete

03:07:43.700 methods of making viruses from scratch, and that he somehow infects a few people with his creation.

03:07:48.820 Now our early detection system kicks in. We're monitoring the air, wastewater, and surfaces in

03:07:55.060 hundreds of cities daily, with tools that are several generations beyond what we have today.

03:08:00.500 And everyone with a viral infection is diagnosed and logged the moment they show up at a clinic.

03:08:05.780 And many more are feeding in data from simple, rapid tests they take at home. So unlike with COVID,

03:08:11.540 the very first victims light up the global public health radar. If we're lucky and smart,

03:08:17.540 by then virtually all humans have had a universal flu vaccine anyway, which would stop an H5N1 outbreak

03:08:23.860 in its tracks, since it's in the influenza family. We've also made huge investments in therapeutics

03:08:30.100 for influenza, along with dozens of other viral families, which can help cure the unvaccinated 0.99

03:08:35.620 people who get sick. And if somewhere in the world there's a large unvaccinated geography,

03:08:40.740 and the epidemic gets momentum there, we can fall back on our unified command for fighting disease.

03:08:46.420 There's plenty of masks and ventilators, and no one's in a bidding war to access them.

03:08:50.980 And within hours of that local outbreak, vaccines are teleporting into its pharmacies and even some

03:08:56.100 living rooms, killing the outbreak in its crib. So that's my case for optimism. We do have time to

03:09:04.500 create our global immune system before this happens. It can be multilayered, and like our own immune

03:09:09.700 systems, agile and adaptive, with a diversity of tools to tackle whatever threat emerges.

03:09:15.300 The case for pessimism is that this immune system will not build itself. We've botched so much in the

03:09:21.620 face of COVID. And if we respond to COVID's hoped-for defeat in the same way we responded at the end of

03:09:26.980 SARS, the snooze bar could be the end of us. So for all my optimism, there's absolutely no room for

03:09:34.420 complacency. The new era in biology could put us in the best position we've ever occupied in relation

03:09:40.820 to disease, but only if we make the right investments and take the right precautions today.

03:09:46.580 Okay. Well, I'm back with Rob Reed. Rob, you finally brought us to something like a glimmer of

03:09:55.380 daylight here at the end. Let's talk about how we might yet survive. How would you characterize your

03:10:02.260 own outlook here at the moment? How optimistic are you?

03:10:05.220 I would say that I'm extremely optimistic for somebody who has really marinated as much as I have

03:10:12.900 in the twin dangers of suicidal mass murder and the relentless exponential advances in bio.

03:10:21.940 Not happy topics, and I've been marinating in them for much longer than I'd like to,

03:10:26.580 since even before the pandemic. But for somebody who has really grappled with those issues,

03:10:31.140 I got to say I'm wildly optimistic. Because the science and technology that's in the pipeline is just

03:10:37.460 so promising. And the dead obvious things that we fumbled during COVID should be incredibly fixable,

03:10:44.980 especially with a post-COVID mindset, which will give us, should give us, all the political will we

03:10:50.900 need to invest in fixing them. And so definitely optimistic. And I think it's important to highlight

03:10:57.780 that. Because the last thing you want to do in talking about this stuff is to bring people directly

03:11:03.220 from a state of denial to a state of despair. Because you don't do anything in either one of

03:11:07.700 those states. The first one, denial, you don't see a problem. And in despair, you think it's hopeless.

03:11:11.700 And in either case, you're equally motionless. And I think this is actually a problem that the

03:11:17.700 environmental movement had. I mean, I'll just pick on an inconvenient truth, which I thought was

03:11:22.580 absolutely brilliant. But I did think it had the tendency to put people on an express train from

03:11:29.140 denial to despair. And there's definitely no need to despair here. We can absolutely

03:11:35.300 harden our syn-bio infrastructure to make it really, really hard for any but the most

03:11:39.460 brilliant and determined people to do something lawful. That is doable. We can definitely invest

03:11:44.900 in pan-viral vaccines and therapeutics. I mean, the cost of investment is trivial compared to the

03:11:51.700 likely returns and all the rest of us. And in doing that, really make ourselves a hard target for

03:11:57.700 future pandemics, whether it's artificial or natural. So yeah, on the balanced, I think there's

03:12:03.700 just so much we can do that can be so helpful. Okay, so let's talk about some of the topics you

03:12:10.500 raised in this final chapter. Where are we with the FAR UVC light technology? So FAR UVC has had

03:12:18.980 unbelievably promising signs in the lab. But so far, it's been relatively small academic studies, and we need more.

03:12:27.700 I mean, the next step really is to do rigorous FDA quality tests that fully establish whether these

03:12:34.820 wavelengths annihilate pathogens, as we think they do, without damaging human health, which is obviously

03:12:40.660 unbelievably vital if we're going to contemplate exposing people to these lights for long periods

03:12:46.100 of time during flu season or in the case of a pandemic. The signs are really promising, but we do need to do more.

03:12:52.820 And if things really work out, unlike almost any of the other measures I'm talking about, this one could

03:12:58.260 be really expensive if we go all in. But we'd only go all in in an incremental manner, starting with that

03:13:03.780 relatively cheap step of proving this stuff out. And this could easily turn out to be a complete flop

03:13:11.300 for UVC light. But like I said in the recording, that's completely fine. Because while we're testing this,

03:13:16.340 we're also hopefully testing things like the BCG vaccine and dozens of other things. There's just

03:13:21.540 some incredible super weapons against pandemics almost inevitably in the tech and scientific

03:13:27.220 pipelines. We just need to turn over the rocks. So anyway, if FAR UVC light is everything we hope,

03:13:33.300 the next thing we'll need to do is figure out how to make LED lights that emit them. Because the current bulbs

03:13:39.300 are just huge, they're clunky, they're unbelievably expensive, and they throw off way too much heat

03:13:45.780 for use in public spaces, just way too much maintenance and everything else. Now getting

03:13:50.260 LEDs to emit FAR UVC light will take significant R&D work. I mean, the whole history of LEDs is one of the

03:13:58.500 industry turning its attention to new wavelengths of light and figuring out how to make them after some

03:14:04.260 heroic R&D efforts. And figuring out how to make blue LED light was actually particularly difficult.

03:14:10.340 And there's a really interesting story behind that, which we won't go into. But the LED industry is

03:14:15.140 good at this. And it basically is all about really precisely tuning the alloys of the LEDs,

03:14:22.340 semiconductors. But FAR UVC has already been demonstrated in an LED in the lab, I think in Japan.

03:14:28.740 So we know it's possible. It's a matter of, you know, bringing the science into technology.

03:14:33.060 And once the technology is dialed in, we would need to build a fab or a fabrication plant to build

03:14:39.860 the LED bulbs, which is probably a multi-billion dollar proposition. So like I said, not cheap,

03:14:46.100 but one that we would never take unless we had high confidence this was going to have a huge ROI for

03:14:50.500 society. Then once we're making the bulbs, the question becomes, how many bulbs and who pays for

03:14:56.100 them? So if these things actually work, we'd clearly want them in public transit. I mean, just imagine

03:15:00.980 how much safer a subway car would be if 99.99% of the pathogens in it are killed every few minutes,

03:15:08.260 which is what the science out of MIT shows is possible. And we'd also probably want to put them

03:15:13.460 in big public spaces. So basically, we'd have a lot of local governments buying bulbs, installing them,

03:15:18.660 maintaining them, et cetera. As for where you go beyond that, it's probably a bunch of private

03:15:23.860 decisions. You know, like stores and restaurants might install them if customers call for them or

03:15:29.140 want them. You know, maybe more to keep safe from flu and flu season than pandemics, you know, in

03:15:34.260 normal times. And maybe businesses will install them in offices also with flu in mind to cut down on sick

03:15:39.540 days, which would pay for an awful lot of bulbs. So the bottom line, if UVC becomes widespread,

03:15:46.020 it'll cost a lot, but it'll be a lot of justified and incremental investments made by people who are

03:15:51.780 thinking rationally. And, you know, the path to it, a real wide deployment, you know, feels like it

03:15:57.060 should be less than 10 years. It's not going to be right around the corner. There's a lot of work

03:16:01.300 to be done and building a fab takes time, but this is absolutely something in the intermediate future,

03:16:06.020 if it makes sense. Well, on the other end of the spectrum here, we have this BCG vaccine,

03:16:11.540 which I only just heard about during COVID. Describe what this is and why we can't get access to it,

03:16:19.780 even though it seems like an incredibly promising vaccine for a variety of reasons.

03:16:27.380 Well, what it is and why we can't get access to it here in the US are kind of the same answer,

03:16:32.500 which is that it's a tuberculosis vaccine. It's frontline for infant tuberculosis. So it's given,

03:16:38.900 you know, shortly after birth to a high majority of the babies who are born on earth in any given year,

03:16:45.460 but it's never been given in the United States because, well, it was developed in the 20s and

03:16:51.460 we definitely had a tuberculosis problem back then. So I can't really say why we never had it,

03:16:56.580 but the US, I think by the time universal BCG programs started kicking in, I think it was much

03:17:02.100 later than the 20s. It was invented in the 20s, but I think it's more like 50s, 60s, even 70s,

03:17:07.060 before countries began implementing universal vaccine programs. And by the 50s, you had the first

03:17:13.300 antibiotics and antibiotics can be quite effective against adult tuberculosis, also against infants.

03:17:19.540 And so I think there just wasn't a huge TB problem in the US by the time these vaccination programs

03:17:26.820 really started coming online. And there is this unbelievably promising data going all the way back

03:17:33.620 to the 1920s about BCG protecting against all kinds of things other than tuberculosis, above all,

03:17:40.980 respiratory infections and broad spectrum protection against respiratory infections,

03:17:46.100 the most recent study of which was quite recent. I think it was concluded just last year in Greece.

03:17:52.580 And in that case, they were basically taking older adults who were checking out of hospitals,

03:17:58.420 I think people 55 and up, and half of them got the BCG vaccine and half of them did not,

03:18:03.620 got a placebo. And the statistic was that 80% or those who got the vaccine had an 80% reduced incidence

03:18:12.900 of any kind of respiratory infection and a 50% reduced incidence of infections of all kinds. So there's

03:18:20.820 all this really intriguing data. And then of course, there was that unbelievable data that was in the

03:18:27.460 proceedings of the National Academy of Science that showed this huge inverse correlation between

03:18:33.140 national BCG vaccination rates and COVID cases. Now, the thing is, most of this data, not the Greek

03:18:39.860 study, but most of this data is what epidemiologists call ecological data, which means it's data about

03:18:46.100 groups of people rather than individual case studies. And also, it comes from observational studies

03:18:52.180 rather than hands-on work with injections and patients. So that inverse correlation amongst countries,

03:18:57.300 classic ecological data. But obviously, to get a vaccine approved for a specific disease, you have to

03:19:03.620 track cause and effect in individual subjects. In other words, you have to do a classic double-blind test with

03:19:09.700 control groups. And a full phase three trial for FDA approval is generally beyond the reach of academic

03:19:17.620 budgets. And the people who have been poking at BCG are mostly academics. Whereas pharma companies,

03:19:24.100 they're just not going to spend their limited capital on testing a seven cent vaccine that's in the public

03:19:29.620 domain. There's just no money in that. And I hope I'm not over pimping my podcast here. And if I am,

03:19:35.700 just tell me. But I'll be posting a really detailed interview with a Harvard epidemiologist named Megan

03:19:41.140 Murray about all this stuff, probably shortly after you post this conversation. And Megan actually is

03:19:47.300 hard at work on developing and trying to fund a phase three trial, despite being an academic and

03:19:53.300 this normally being a pharma thing. And we're counting on her to do this rather than Pfizer, because it's 0.93

03:20:01.060 a market failure. There's just no deep-pocketed players who are incented to do this research. And we

03:20:05.860 really need to fix this for two reasons. The most obvious one is that if BCG actually can protect

03:20:12.500 against COVID, and we don't know, but if it can, even if it's a long shot, figuring this out would

03:20:19.460 totally change the global vaccination timeline. Because there's 22 BCG manufacturers throughout

03:20:26.020 the world. And there are distribution channels for BCG into almost all the developing world with

03:20:31.620 armies of people who know how to store and administer the vaccine. And it's obviously just

03:20:36.580 morally urgent to speed up vaccinations in poorer countries. But it's also in the selfish interests

03:20:43.460 of rich countries that are about to get all the Pfizer and Moderna vaccines they need. Because every

03:20:48.980 person that COVID infects is another opportunity for it to mutate. And COVID is incredibly prone to

03:20:55.780 mutation, as we're seeing from these terrifying new strains, at least one of which is, you know,

03:21:01.140 the South African one is partly resistant to vaccines. And so if we take our guard down after,

03:21:07.220 you know, wealthy countries are vaccinated, if COVID keeps rampaging amongst billions of people,

03:21:12.900 we can pretty much count on a new strain emerging, which can steamroll through all of our hard-earned

03:21:19.780 defenses. And so we need a great phase three trial test of BCG against COVID, whether it's Megan's

03:21:25.220 or someone else's, even if it's a long shot. Because I mean, this would cost, this test would cost

03:21:30.820 tens of billions of dollars, not the billion plus we spent on each candidate for Project Warp Speed,

03:21:35.700 because there's no vaccine to be developed, it's just a test. And there are luckily some

03:21:40.420 huge philanthropists like Bill Gates, who have started investing in BCG with an eye toward COVID,

03:21:46.020 but we shouldn't sit around and wait for somebody to gift this to the world. It should just be an

03:21:52.180 immediate public investment. And, you know, the other reason to do this, to study BCG much more

03:21:58.420 deeply beyond COVID, is this apparent protection against respiratory diseases in general. Because,

03:22:06.260 you know, if that, you know, the initial trial in Greece, which is, you know, very promising, but

03:22:11.380 very initial, that pattern holds up. It could be a real game changer against the flu, against future

03:22:17.780 pandemics, which are almost sure to be respiratory in nature, against all kinds of things. But there's

03:22:22.420 a lot to be studied, like how frequently does BCG need to be given to have this effect? Does it work

03:22:26.580 in all age groups? Is it particularly effective against a certain class of respiratory infections,

03:22:31.140 and so forth? And, you know, again, we shouldn't be waiting for someone to gift this to the world,

03:22:37.060 particularly because an initial set of academic studies would cost very, very little.

03:22:40.740 Yeah, we have to become increasingly sensitive to market failures in this domain, in public health

03:22:48.820 generally, and, but, you know, across all of the fronts of where we're running something like

03:22:56.420 existential risk. I mean, we've been living with the problem of producing antibiotics in a market that

03:23:03.940 can't effectively incentivize it. You know, so we have antibiotics that are losing their power over

03:23:12.740 really, you know, every bug that concerns us, and we're meandering toward a time that will

03:23:21.860 be indistinguishable from the 1920s and 30s when we simply didn't have the drugs that could solve our

03:23:29.940 most basic infectious disease problems. And the reason is there's not enough money in it. You know,

03:23:37.540 you take a new antibiotic costs a billion dollars to produce, and you take it once for 10 days

03:23:47.860 in your life, and then that is if you're unlucky. You know, most people don't have to take them,

03:23:53.540 you know, any specific new antibiotic ever. Right.

03:23:57.460 And yet, if you need it, this is the one drug that's going to save your life. You know, it's,

03:24:03.060 so it's, we have to, and this is the role of government or major philanthropy. On some level,

03:24:09.380 we just have to say whether it makes any market sense in any rational time horizon for a business

03:24:18.020 person, we have to spend money on these things. Yeah, we've basically stood by as multiple

03:24:24.180 antibiotic companies have gone out of business in the U.S., and it just allowed this market failure

03:24:30.740 to propagate to the point that, you know, who's even developing new antibiotics? I can only think

03:24:35.860 of a couple of companies that are even in that business anymore. And we're not really talking,

03:24:39.460 we're talking more about viruses than bacteria, obviously, in this series, but that is an equally

03:24:44.180 glaring issue. And, you know, something that, you know, one estimate that I saw, you know,

03:24:50.820 superbugs could easily be killing millions of people per year within 10 years.

03:24:54.660 Yeah. So, what are the prospects of developing vaccines for whole classes of viruses? A universal

03:25:06.340 flu vaccine, a universal coronavirus vaccine, what have you uncovered on this front?

03:25:12.500 Well, this actually ties to what you were just saying about market failures,

03:25:17.780 because it seems, talking to some pretty informed people in this domain, that a universal flu vaccine

03:25:26.420 effort would probably have very good chances of succeeding, at least 50%, which is a shot worth

03:25:33.140 taking. And the budget that I was quoted was, you know, probably in the range of $200 million

03:25:40.580 over 10 years, with kind of an extreme, like, why don't we just for safety go up an order of

03:25:46.580 magnitude budget of $2 billion over 10 years? And you look at those numbers, and you remember that

03:25:54.180 the flu is costing the US alone $361 billion a year in lost productivity and medical spending.

03:26:00.740 And you, it's just flabbergasting. And I couldn't believe my ears when that budget estimate was

03:26:07.620 quoted to me, and it couldn't have come from a more informed person, who is Harvey Feinberg. He's

03:26:13.060 the former president of the National Academy of Medicine, and the former dean of the Harvard School

03:26:17.860 of Public Health. And more to the point, he's done a lot of work studying the potential for universal

03:26:23.940 flu vaccine, including at the Sabin Vaccine Institute. And so this is just another stunning

03:26:30.660 market failure. I mean, if you can spend, let's take the worst case scenario, $2 billion over 10

03:26:36.660 years for the chance of saving $361 billion a year, even if there's a 1% chance, you should take that.

03:26:43.300 And it's, you know, according to Harvey, it's probably more like a 50 to 75% chance.

03:26:47.060 And, you know, once again, to go back to what you were saying about antibiotics,

03:26:52.820 this is, you know, why this isn't happening? Well, pharma is not going to do this,

03:26:57.380 because it's a lousy business proposition to make a cheap vaccine that people might only use just once.

03:27:02.580 I mean, one of the models for universal flu vaccine is one and done in a lifetime. You'll

03:27:06.900 hopefully never need again. Or maybe it's even, even if it's annual every five years. I mean,

03:27:10.980 pharma companies just won't do this unless they're presented with non-market incentives.

03:27:14.900 And so there's that. But then obviously, this is also just a shocking failure of public policy,

03:27:21.540 because the ROI on this would be profound. Now, the optimistic way of looking at this,

03:27:26.980 which I prefer, is to say there's just so much low hanging fruit here. And Harvey Feinberg believes

03:27:34.100 that, you know, much as we could create a universal vaccine effort for influenza, we could do that against

03:27:40.500 any arbitrary number of viral families. And, and as I think I mentioned in the recording,

03:27:45.300 you know, he would suggest we start with influenza and coronavirus, get good at that,

03:27:49.220 and then start tackling more. And there's only a couple dozen viral families that actually infect

03:27:53.860 humans. And there's probably also a couple of other zoonotic diseases out there, viral families that

03:28:00.420 don't currently infect us that we want to be careful of. But even if you multiply this out by every

03:28:05.300 family we can think of, by $2 billion over 10 years, the numbers that come back are just minuscule,

03:28:14.020 just compared to, I mean, like I said earlier, compared to what we spend maintaining our nuclear arsenal

03:28:19.140 on an annual basis, just minuscule compared to anything that seems like a comparable. And, you know,

03:28:25.700 especially when we think of how quickly these COVID vaccines were created, just days in the case of

03:28:32.340 Moderna. So we're, we're obviously in a completely new age when it comes to vaccine science, which

03:28:39.300 screams for just ambitious new goals for vaccine science.

03:28:44.340 Yeah. And, and we've not only accelerated the time it takes to produce the vaccine itself, but we've,

03:28:51.860 we've accelerated the approval process. And it sounds like we could accelerate it even further if we

03:28:58.260 changed our cost benefit analysis and in how we do research. I mean, obviously we're doing research

03:29:03.700 now under duress with a global pandemic, crushing economies and killing hundreds of thousands of

03:29:10.260 people in even just in the United States. But what role would challenge trials play here? Because

03:29:18.500 this is something that many people first heard about in recent months under COVID, but they're

03:29:24.740 controversial. How do you think about this? Well, I think the right way to look at it, I mean,

03:29:30.740 it's ultimately an ethical question. So we can safely say that there's no quote unquote right answer,

03:29:37.300 you know, to this conundrum. But I do think that it helps a great deal to put concrete numbers

03:29:44.500 on the assets and liabilities in terms of human lives of the two approaches. So to just quickly review,

03:29:50.420 challenge trial would involve deliberately infecting a much smaller number of people

03:29:56.900 than you would have in a normal trial with COVID. The numbers are really, really stark. A normal COVID

03:30:02.500 trial, you're talking tens of thousands of volunteers. They get that huge number of people because they

03:30:08.660 need to wait until there's essentially maybe 200-ish people have come down with COVID from that vast

03:30:15.220 base of 30, 40, 50,000 people. And once 200-ish people have definitively tested for COVID, they can

03:30:23.060 basically take off the blinders and figure out which one of those, which of those people were in the

03:30:27.460 control arm of the trial, which of those people actually got the vaccine. And based on that, you can come up

03:30:32.500 with these exciting numbers like 95% effective. Now, if you're just doing a challenge trial and you know all

03:30:39.540 those people are going to be infected, instead of 50,000 people, you might just need 200 people or maybe a

03:30:44.180 little bit more, you know, just in case, you know, some data points bounce out for some reason.

03:30:49.460 So that really collapses the timeframe. And to compare a challenge trial with a normal trial,

03:30:58.020 let's imagine, I mean, I don't know exactly how long a challenge trial would take, but

03:31:02.020 recruiting 200 people would be harder on a per-person basis because you're asking them to submit to a hell of

03:31:06.980 a lot more than just an experimental vaccine. You're asking them to contract COVID. But as I said in the

03:31:11.300 recording, 20,000 people, I think it is, have already expressed a willingness to participate

03:31:16.580 in challenge trials through a group called One Day Sooner. So there's a ready body of people. Recruiting

03:31:22.580 presumably would not be anywhere near the challenge that it is with 50,000 volunteers.

03:31:27.380 And then in terms of the timeframe, you're infecting them on day one. So you're not waiting months and

03:31:32.500 months and months for people to contract things. I mean, it seems logical that this timeframe could

03:31:37.060 collapse into, you know, a very, very low number of months. Let's talk by comparison about the

03:31:44.020 AstraZeneca vaccine, because I was able to find, cobble together a detailed timeline on that.

03:31:49.380 Its last phase of trials started in the UK on May 28th. And they eventually recruited,

03:31:56.660 it was a smaller trial, 23,000 volunteers, mostly in the UK, but also in Brazil. Now,

03:32:03.540 there was some weirdness with this trial that people might remember. There was a pause to it

03:32:08.020 because of an adverse reaction in one of the volunteers, but that was only a six-day pause,

03:32:11.700 turns out. So it generally proceeded along its timeline. And the results of this trial were reported

03:32:18.900 out on November 23rd. So in other words, it ran for just under six months. And most of that time was

03:32:26.660 spent recruiting all those volunteers and then waiting for enough of them to test positive for the trial to

03:32:32.020 have a statistically significant result. Now, during that six-month period from May to November,

03:32:38.740 over a million people died of COVID worldwide. While what turned out to be an impressively effective

03:32:45.860 vaccine was slowly and methodically tested. And we can probably assume that other vaccine trials had

03:32:52.340 similar timelines. I just happen to know the dates with AstraZeneca. Now, a challenge trial obviously

03:32:58.100 wouldn't have been instantaneous, but it would shave months off that timeline, not weeks, during a time

03:33:02.900 when thousands of people are dying every day. But it would have involved deliberately infecting a

03:33:08.420 couple hundred people with COVID. While most of them would have presumably been younger volunteers,

03:33:12.500 so the fatality rate would have probably been extremely low, it's all too likely that one or more

03:33:17.700 of those people would have died. And it's also likely that very few of those 200 people would have

03:33:22.820 caught COVID on their own. So, you know, how do you balance the ethics out of that? I mean,

03:33:27.300 the numbers are enormous. Hundreds of thousands or a million people dying during the running of this

03:33:32.420 trial versus perhaps a tiny handful or even one or even no people dying in a challenge trial.

03:33:39.140 But it's very much like the trolley problem, isn't it?

03:33:41.860 Yeah, except with the variable of consent here, which I think is ethically decisive. So,

03:33:48.580 you know, there's just no argument against someone deciding to consent to a challenge trial

03:33:56.180 once they understand the risks they're running and the possible benefits. I mean, and as you say,

03:34:02.820 I mean, you know, it's surprising, but it is just a demonstrated fact that you can find people

03:34:09.380 eager to serve on this front and you can find people eager to take all kinds of risks that

03:34:15.540 that, you know, any individual listening to this might never entertain themselves.

03:34:22.420 Once there's a one-way ticket to Mars offered, you can be sure there are going to be thousands of

03:34:28.580 volunteers, you know, willing to die on Mars. You know, there's a spirit of wanting to advance the

03:34:35.860 human project and be part of something great. And in this case, again, there are relevant variables

03:34:44.660 here around just how widespread the illness is at each point when trials are being run. I mean,

03:34:52.500 that affects how long you have to wait around for people to catch the virus naturally.

03:34:57.780 Yeah, it totally affects it.

03:34:58.820 And it affects the perceived odds for anyone enrolling in a trial. You know, what are they,

03:35:05.540 how different is a challenge trial if this virus is burning so quickly through the population that

03:35:12.500 you seem guaranteed to get it anyway? But I do think consent is the master variable here ethically.

03:35:20.980 And yeah, we certainly should be talking about running challenge trials under circumstances

03:35:27.620 like this where we're having to respond to a pandemic that is burning out of control.

03:35:32.900 So it would be different if we're preemptively trying to design a, you know, a universal flu vaccine or

03:35:40.500 a universal coronavirus vaccine under conditions where we don't feel like we're currently losing

03:35:48.180 thousands of people a day to a pandemic. But it is very interesting. And it's amazing that so many

03:35:55.780 people volunteered. It's great.

03:35:57.060 Yeah. I mean, I guess it's kind of like the people who volunteered for the U.S. military after 9-11.

03:36:03.860 Yeah.

03:36:04.180 They were, you know, there was a big surge of signups and these people were certainly

03:36:08.180 signing up to risk their lives. And the government didn't tell them, no, we're not going to accept your

03:36:14.180 service. And in a sense, you know, because I don't, I don't think there was any serious conversation

03:36:19.460 about a challenge trial at all in this COVID period. Was there? I mean, I don't think there was.

03:36:23.940 I remember it being spoken about and obviously they, people volunteered, but I think most of

03:36:31.380 the conversation I heard about it was going on in the U.K.

03:36:34.820 Right.

03:36:35.220 And not in the U.S.

03:36:37.060 Yeah. I mean, and another thing to think about, which when it comes to this regulator saying,

03:36:42.900 no, you can't do that type of thing is, it's interesting that I guess both, well,

03:36:48.500 certainly the Russian vaccine and I believe the Chinese vaccine as well have started coming out.

03:36:53.700 There's starting to be some independent research that's signifying that these are actually reasonably

03:36:59.140 effective vaccines. And in both cases, the countries started administering the vaccines without

03:37:06.180 waiting for phase three data, which at the time was generally viewed as, or discussed as being

03:37:14.260 a particularly bad idea, at least in, I think I'd say the Western media. But as we're finding out that

03:37:21.700 these things actually work, you know, maybe that's another policy that policy makers should consider,

03:37:28.500 along with challenge trials, when future problems come up. Because, you know, imagine if,

03:37:34.740 and it's always easy to do something looking with the benefit of hindsight, but imagine if

03:37:38.980 the FDA said, okay, you know, Moderna has come up with this vaccine, it's going to go through rigorous

03:37:45.140 trials. It hasn't yet, but we're in an emergency time here. So any U.S. citizen who is courageous

03:37:52.420 enough to take the chance and is willing to sign, you know, a thick legal document saying that they're

03:37:59.380 not going to sue or anything is welcome to take this vaccine. And, you know, it's an experimental

03:38:05.140 vaccine. So there could be bad effects, probably unlikely, because they'd already, I think they'd

03:38:09.300 already done a safety trial before phase three, but, you know, may not work against COVID at all.

03:38:14.740 We could kind of imagine perhaps millions of people, I mean, I would have certainly entertained

03:38:18.420 that idea if there'd already been a safety trial on this thing. I mean, why not? And, you know,

03:38:23.300 if millions or tens of millions of people had been vaccinated with Moderna and Pfizer, Johnson and

03:38:28.260 Johnson and Johnson, whoever knows who knows what else, during the six months of trial times, we might

03:38:33.780 already be, you know, seeing the end of this thing already. Yeah, the safety stage is the most important

03:38:41.780 part from my point of view. I mean, whether it's effective or not is obviously important, but it's

03:38:47.860 the first do no harm principle, which I think everyone is rightly focused on, especially with a vaccine,

03:38:54.740 because you're not, you know, as has been pointed out many times before, this is a medication you're

03:39:00.340 giving to healthy people, by and large. This is not an intervention, you know, a new form of

03:39:07.140 chemotherapy when all other forms have failed you. So, you know, what do you have to lose? In this case,

03:39:13.460 you have a lot to lose if the vaccine is basically unsafe. And I guess the novelty of the current batch

03:39:23.060 was relevant here. I mean, the more we, the more work we do in this area and the more

03:39:28.100 any new vaccine has already been pre-characterized by similar vaccines in the past, you know, working

03:39:36.260 by a similar mechanism, perhaps the safety concerns get dialed down quicker.

03:39:42.260 Yeah, but particularly, and you're right, with the mRNA vaccines, this was a completely new type

03:39:49.060 of vaccine and safety testing was especially important. But now that we have seen that these

03:39:53.540 apparently are very safe vaccines, yeah, I do hope the policymakers take a different approach,

03:39:59.620 like, for instance, with booster shots. You know, Moderna and Pfizer, I believe, are already working

03:40:04.180 on booster shots to take care of the South African and British variations. If we do need to go through a

03:40:10.340 six-month trial process for those to get a perfect phase three, I would certainly hope that there would

03:40:17.780 be an option given to adventurous people, which would certainly include myself, who are willing to

03:40:23.620 take the chance that this isn't efficacious to get the vaccine before the phase three is done,

03:40:28.820 because we are in an emergency situation here.

03:40:31.460 Yeah, well, as should be obvious to everyone who has followed us this far, this is the beginning of

03:40:38.340 the conversation, not the end. But I know you and I will both, together and independently,

03:40:45.780 keep our attention on this front, and we'll certainly surface any good ideas we come across,

03:40:53.380 any organizations that are moving the dial here, whether it's in the philanthropic space,

03:41:00.420 or for-profit, or rumors of government actions that seem auspicious. This really just needs to be

03:41:09.860 kept front of mind here. The pandemic response, generally, and the SinBio privatization of the

03:41:18.340 apocalypse problem, more narrowly, this is really something that our generation has been tasked to

03:41:26.420 figure out. And I just want to thank you, Rob, for producing such a comprehensive and comprehensible

03:41:33.860 document for us to all get started with.

03:41:36.260 Well, it was absolutely a thrill to be able to present it on your show, Sam,

03:41:39.940 so thank you so much for that.

Making Sense - Sam Harris - April 24, 2021

Special Episode： Engineering the Apocalypse

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