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

Episode Date: April 24, 2021

In this nearly 4-hour SPECIAL EPISODE, Rob Reid delivers a 100-minute monologue (broken up into 4 segments, and interleaved with discussions with Sam) about the looming danger of a man-made pandemic, caused by an artificially-modified pathogen. The risk of this occurring is far higher and nearer-term than almost anyone realizes.  Rob explains the science and motivations that could produce such a catastrophe and explores the steps that society must start taking today to prevent it. These measures are concrete, affordable, and scientifically fascinating—and almost all of them are applicable to future, natural pandemics as well. So if we take most of them, the odds of a future Covid-like outbreak would plummet—a priceless collateral benefit.  If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe.

Imagine we're in another pandemic, and the disease has been deliberately engineered to be more contagious and way more lethal than COVID-19. That's right, it's a man-made pandemic. And the virus is so deadly, it kills roughly half the people it infects. So if you and your spouse catch it, at least one of you will probably die. And maybe you both will. Likewise, any other duo. You and your best friend.

You and your kid, the president and vice president, and an uncontrollable outbreak is underway. Next, imagine this outbreak sweeping through a power plant. Do the lights stay on? With half the staff dead or dying and the other half thinking they're next? And if the power goes out, how do we reach the internet? And with no internet, how do we find out, well, practically anything that we need to know to navigate this unprecedented existential threat? Now imagine you're a frontline worker at the power plant or caring for the sick or delivering food. People are getting wiped out at 50 to 100 times the rate of COVID. It's a coin toss as to whether you'll survive if you get sick. Do you report to work? Or do you hunker down with your loved ones at home until you all get

really hungry? Supply chains disintegrate in situations like this. The grocery stores that actually open sell out, not just out of toilet paper, and they don't get restocked. And pretty much everything else disintegrates too. For all of its horror, COVID hasn't shut down the power, the water, law enforcement, or the flow of information. But something this lethal could just shut them all down. And while you may be more imaginative than I am, I just can't picture civilization surviving an encounter with something this deadly. And the problem is, we're on a collision course with some version of this scenario.

Hi, I'm Rob Reed, and I've been worried about artificially modified viruses for a few years now. My background is that I'm a longtime tech entrepreneur who went on to become a writer. I write science fiction for Random House, and I'm also a science writer and science podcaster. A while back, I wrote four articles for Medium about artificial pandemics and other subjects. That led to an episode on my own podcast, which is called the After On Podcast, and mostly considers fairly deep scientific issues in ways that non-experts can follow. That particular episode was a conversation with a thinker and entrepreneur, Naval Ravikant, and it led directly to a talk that I gave on the TED conference's main stage about a conversation with a thinker and entrepreneur, Naval Ravikant, and it led directly to a talk that I gave on the TED conference's main stage about a year and a half ago.

I'll be integrating some of that earlier work here and then building on it in this short series. In the course of it, I believe I'll persuade you that an engineered pandemic will almost inevitably happen eventually, unless we take some very serious preventive steps. And I'll tell you exactly what those steps are. We'll also talk about the science and techniques that are at play here, about the sorts of people who might actually want to inflict a pandemic on the world, and what drives them. But first, a big spoiler. It may not sound like one, but I'm an incurable optimist. I wouldn't be telling you all this if I wasn't convinced this story can have a happy ending. And more than anything, this series is about navigating our way toward one. I'll start out with a strange claim that we actually got rather

lucky with COVID. Not in an absolute sense, obviously. This is clearly the most horrifying year humanity's endured in quite some time. But compared to what might have happened, in terms of sheer deadliness. Now, I say this with the caveat that it's hard to know exactly how deadly COVID is in percentage terms. We can't just use simple ratios of deaths to officially reported cases, because huge numbers of cases never get diagnosed. Many people who catch COVID never get symptoms, for one thing. And for those who do get sick, testing capacity is notoriously inadequate, so countless cases go undetected. But adjusting for all this murkiness, the World Health Organization estimates that between a half a percent

and one percent of infected people die. And in many age groups, it's a tiny fraction of one percent. And I'm saying we got lucky because there is no biological reason why the death rate had to be this low. I mean, take SARS. It killed about 10% of the people it infected. That's an order of magnitude worse than COVID. And we were lucky with SARS, too, in that people got so obviously sick so fast, patients

were easy to identify in quarantine before they spread the disease very far. So fewer than a thousand people died of it. But if SARS had been like COVID, and spread like mad when people were still asymptomatic, or thought they just had a cold, we'd be living in a very different and badly diminished world right now. And SARS is a kitten compared to Middle East Respiratory Syndrome, or MERS, now. And SARS is a kitten compared to Middle East Respiratory Syndrome, or MERS, which kills over a third of its victims. So we're incredibly lucky MERS just doesn't happen to be very contagious. And then MERS is mild compared to H5N1 flu, which kills about 60% of the people who catch it, making it even deadlier than Ebola. So thank God it's insanely hard to catch. How insanely hard?

Well, the World Health Organization tallied every instance of H5N1 over a decade and came up with just 630 cases and 375 deaths. To put that scale in perspective, lightning kills about 60,000 people in a typical decade. So H5N1 is barely contagious at all. In its natural form, that is. But unfortunately, there's an artificial form of H5N1 as well. It exists because several years ago, some scientists started poking at the virus in hopes of understanding just how dangerous it could be. Since it was plenty deadly, but barely transmissible, they set out to create a contagious form of it. And you heard me right. They deliberately produced an artificial version of this ghastly virus

with a terrifyingly high potential to spread easily between people. This incident is the basis of the grim pandemic scenario I opened with. A contagious, modified form of H5N1, killing half the people it infects. The researchers made this monster by manipulating its genes via passing the virus between several generations of ferrets, ferrets being common stand-ins for humans and virus research. Eventually, they had a strain that could pass from ferret to ferret without any contact through the air. The head of the Dutch team, Ron Fauciet, candidly admitted that his creation was, quote, probably one of the most dangerous viruses you

can make. Over in the U.S., the National Science Advisory Board for Biosecurity didn't disagree. In a press statement, it said that the modified virus's release could result in, quote, an unimaginable catastrophe for which the world is inadequately prepared. Coming from an organization that's not known for drama, the words unimaginable catastrophe are bone chilling. If that's not scary enough for you, I'll add that this work wasn't done in the world's most secure labs, literally, because both the Wisconsin and Holland facilities were certified biosafety level 3, which is a big notch below the top rating of biosafety level 4. This isn't very reassuring,

given the history of deadly substances erupting from profoundly secure labs. Think of the anthrax attacks of 2001, when the lethal spores found their way from a U.S. army lab to the offices of the Senate Majority Leader. Or consider that the last person killed by smallpox caught it because a British lab let the bug escape after decades of globally coordinated efforts had eradicated it from the entire planet. Or consider Britain's 2007 foot and mouth disease outbreak, which began with a leak from a biosafety level 4 lab. Incidents like these make it blindingly clear that any pathogen can potentially escape from any lab, because humans are fallible, and so are labs of any biosafety level. Knowing these facts,

what kind of person brings into existence a pandemic-ready bug that could be a hundred times deadlier than COVID, that could kill a majority of the people it infects, and perhaps be wildly contagious? In this case, not evil people. These were virologists who thought their research would help us face subsequent natural mutations in H5N1. But they were shooting dice with our future. And given their equipment and sophistication,

they didn't need to ask any outsider's permission to do that. They may have run things by an internal review board of some kind, but they only needed outside permission to publish their results once they were done. And they did encounter some speed bumps on that front. But no regulator, no judge, no outside body of neutral citizens was in a position to say, don't you dare take that gamble, however small it may be, on humanity's future. To say your judgment alone does not give you clearance to perhaps bet millions of lives on your assistant never screwing up or on your lab not being just a little bit imperfect. I call this sort of thing privatizing

the apocalypse. By this I mean that at the dawn of the Cold War, playing chicken with doomsday went from being something no one could do, because it was impossible with pre-atomic weapons, to something that two people could do. Kennedy and Khrushchev, Nixon and Brezhnev, Reagan and Gorbachev, etc. This transition traumatized generations, but the leaders represented giant countries with hundreds of millions of citizens, which made the act of risking annihilation a perverse form of public good. This approximate situation is still with us, and there's obviously plenty to dislike about that. But at least we've only needed to keep a fairly low number of decision makers in line.

People who spend years looking after a nation's well-being, who have major international obligations they hopefully take somewhat seriously, and who are subject to certain checks, balances, and fail-safes. None of that's true for an autonomous researcher running a lab who decides to make an apocalyptic pathogen in the general name of science. Even if the odds of it escaping are small, the decision to play chicken with doomsday has effectively been privatized. Which is plenty scary when the folks who get to toss the dice in these situations are very few and far between, and are generally, you know, good guys, white cowboy hats. But as we'll soon discuss,

the casino is about to throw the doors wide open. Not because anyone thinks that's a good idea. Very few people have even considered this issue, which is a big part of the problem, but rather because relentless advances in technology are about to make these kinds of gambles and these kinds of potentially genocidal powers very widely available to far more people than we can keep an eye on, and to people we can't keep in line by threatening with wrist slaps, like delaying publication of their research papers. In the next section of this podcast, we'll talk about the terrifying proliferation of doomsday powers and who might abuse them and why. But for now,

consider the landscape this is happening in. COVID is our dress rehearsal for handling something much worse. And in lots of places, certainly including the United States, it's been one of the most disastrous dress rehearsals in the history of theater. It's like half the actors forgot all their lines. A quarter got bizarrely doctored scripts, which have them saying and doing the opposite of what they're supposed to do. The lights have caught fire, half the costumes didn't show up, and disease is spreading throughout the cast. To step out of the dress rehearsal analogy,

I'm referring to things like the ongoing disaster connected to adequate COVID testing and timely results, our early lack of PPE, our all but non-existent contact tracing, the lethal politicization of slowing infection via masks, etc. In an October editorial, the normally sober and understated New England Journal of Medicine frankly stated that, quote, the magnitude of this failure is astonishing. And remember, stated that, quote, the magnitude of this failure is astonishing. And remember, this is just a dress rehearsal. Opening night is coming. Which means that as we do the post-mortem on this botched rehearsal, it's vital that we start planning maniacally for the next pandemic. That we start

thinking obsessively about all the cannonballs we've had the great fortune to partially dodge lately. That we consider the next set of cannonballs which are inevitably on their way, and that we humbly acknowledge that no one's luck lasts forever. For one thing, the rate of diseases jumping over from animals to the human population is rising dramatically

as we encroach ever more on natural habitats. So nature is taking potshots at us with increasing frequency. As for artificial viruses, there's no taking potshots at us with increasing frequency. As for artificial viruses, there's no reason they'll hit us at nature's relatively leisurely recent pace of one major scare every five to ten years, because the cadence will be determined by the people behind them. All this means that humanity's future depends on keeping our guard up if and when we put COVID-19 into the grave. And I mean way up, preparing for absolute worst-case scenarios. Natural pandemics are random-case scenarios because evolution is

driven by blind chance. But nothing will be random about a virus designed by a malicious and murderous party. Unfortunately, we don't have a great track record for keeping our guard up after a major disease scare has passed. Despite all the close calls of recent years, civilian biosecurity funding fell by 27% between 2015 and 2019, according to The Economist magazine. Meanwhile, governments haven't exactly inspired the private sector to carry the ball. the ball. The Economist also tells us that after the swine flu pandemic petered out, European and American governments reneged on contracts with vaccine makers, leaving them hundreds of millions of dollars in the hole. Speaking to the New York Times, virologist Peter Daszak summed up the situation saying, quote, the problem isn't that prevention was

impossible. It was very possible, but we didn't do it. Governments thought it was too expensive. It was very possible, but we didn't do it. Governments thought it was too expensive. Pharmaceutical companies operate for profit. In light of this, we should consider the finale of one of the most popular TED Talks of all time, in which Bill Gates warns against the dangers of complacency. He wraps up by saying if anything good can result from the current outbreak, quote, it's that it can serve as an early warning, a wake-up call to get ready.

If we start now, we can be ready for the next epidemic. Unfortunately, Gates didn't get his wish, because as many of you probably know, he wasn't talking about COVID, but Ebola. That talk was recorded over five years ago. And of course, we were far, far from ready for the coronavirus outbreak that followed it. Now, as I said up front, there are many steps we can take to dramatically increase our resilience against pandemics, both natural and unnatural. And although we have a history of hitting the snooze bar hard enough to scatter alarm clock fragments into the next county, the wake-up call we're getting from COVID is uniquely thunderous. In response to it, I say we take inspiration from the ways our own bodies fight

off infections and build a global immune system to identify and destroy deadly new diseases on a planetary basis. This system can be agile and adaptive, just like the ones in our bloodstreams. We'll talk about the components such a system might have and the fascinating science and technologies underpinning each of them. And I think you'll agree that if we finally heed the warnings nature has been sending and resending and re-resending to us, we can navigate this danger. Bottom line, if you take only one thing away from this series, I want you to understand that a catastrophic pandemic is heading our way, but it's not too late to prevent its arrival,

if we can push our policymakers to rally to this challenge. Okay, Rob, that was terrifying. So before we jump into the topic of pandemics, engineered and perhaps natural, let's just get a little bit of your background here. How did you come to be interested in this? And I know you have a generic interest in science as a science fiction writer, but how did you come to be worried about this particular topic of the catastrophic risk posed by an intentionally engineered pandemic? Well, I guess the earliest thread of that actually goes all the way back to when you and I overlapped briefly as Stanford undergrads. At the time, I was studying

a ton of Arabic and Middle Eastern history. And after graduating, I went to Cairo on a Fulbright fellowship, where I spent a year doing research on the secular opposition, people who were pushing for a non-religious, non-dictatorial government, a faction whose political heirs ultimately, to a great extent, led Egypt's Arab Spring Revolt, although they didn't actually gain any power from that long story. And one person that I spent a lot of time with back then was a guy named Farag Foda, who was Egypt's most prominent secularist at the time. And the fundamentalists hated him because he was vocal, he was for a non-religious government,

and he was really brave. And really tragically, not long after my year in Cairo wrapped up, Farag was assassinated. And that kicked off a ghastly wave of terrorism that Egypt endured throughout the 90s and, you know, beyond. And it was a really big shift because there'd been almost no terrorism in Egypt for years prior to that.

And really, as a direct result of that, I got, you know, very focused on terrorism as an issue. And that's a focus that persists to this day. Fast forward, you know, significantly, I founded a company that created the Rhapsody Music Service, which some of your listeners might be familiar with. And although that's unrelated, just give a quick side note, Rhapsody, for those who don't know it, it's pretty fair to say was the first Spotify. After I sold that, I really became sort of a two-fisted person. I'm a tech investor with some of my time, but I'm also kind of a media creative type of person. And I've written a few books, a couple of which are science fiction

novels for Random House. And when I was writing the second science fiction novel, a book called After On, I delved into a whole bunch of the technologies that we'll be talking today, particularly synthetic biology. There was a subplot in the story that was connected to a symbiote terror attack. And when the book came out, I decided to do what I thought would be a very limited podcast series, just going deeper into the science of the various things that were in this science fiction novel. And then that podcast ended up taking on a life of its own. And I've now done over 50 episodes, quite a few with leading lights and synthetic biology. So that's really where the other thread came in. Yeah, well, one thing that one gets from your discussion thus far is that it really can't

be a matter of relying on there being no one willing to do this sort of thing. there being no one willing to do this sort of thing. There's a level of incredulity psychologically that one has to cut through here when you think about who is going to want to unleash a catastrophic pandemic upon the whole world. For some reason, it takes some convincing for people to acknowledge that not only will there always be someone who will, there will always be many people who will aspire to do that sort of thing. And many, you know, 10 is many, but there are probably hundreds, if not thousands, in any generation who would be willing to do such a thing. And therefore, it just can't

be a matter of messaging successfully to these people, changing their minds, preventing the wrong memes from lodging in their brains. The memes are already there, and therefore, we have to fundamentally make acquiring the technology so difficult as to dial down the probability that this will ever happen. So as things stand now, we're on a collision course with the democratizing of this kind of technology. Where should we start here to absorb this initial lesson? The first thing to think about is what kinds of things can we do to make the near future tools that, let's say, a less sophisticated person, somebody who's not a top mind in synthetic biology, might be able to turn to in 10, 15, 20 years. Tools that will be able to do things that the entire project of

synthetic biology can't possibly do today. And what we need to do is to really exercise our imaginations about what tools like that could possibly do in a short period of time. Because I would argue that there is a very different level of moral responsibility on inventors and scientists and regulators, when we're starting to develop and handle a potentially catastrophic exponential technology, exponential being that this is something that can go in radically unexpected places in a short number of years, then when we're handling a normal dangerous technology. So to use a somewhat silly example, whoever the medieval Chinese blacksmith was who first invented a firearm,

we don't blame that person for mass shootings. Mass shootings approached us at an incredibly slow speed over centuries, meaning it was on us to dodge those literal bullets or not. And we could have done things to make mass shootings difficult and rare, like keeping guns out of private hands. Now, I don't want to dive into a Second Amendment discussion because that could last for hours. I'll just say that whatever your position on gun rights, we can agree that society had ample time to decide whether or not mass shootings are a reasonable price to pay for today's policy.

This situation did not sneak up on us at an exponential pace. But it's very different when something's improving a thousandfold in a few years. Because while it's impossible for anyone to definitively predict where that trajectory is going to lead, the people closest to the technology have a much better shot at it than the rest of us, which puts a particular moral weight on them to ask what rapid changes could end up ambushing a society that just doesn't see them coming. So one example of this, the U.S. Department of Health and Human Services includes in its huge grip the CDC, the FDA, the National Institutes of Health, and clearly has all the intellectual and technical firepower it needs to be profoundly informed

about synthetic biology. But it was the HHS of all entities that posted the 1918 flu genome to the internet in 2005. When smart people like Ray Kurzweil, who's basically the godfather of exponential thinking, who really came out stridently against doing that, could have easily told them that this information might be catastrophically weaponized within a couple of decades. And we can't keep having failures like that, which means private sector leaders need to use their imaginations a lot, and academics, a lot about worst-case scenarios, be very transparent about them, and self-regulate more than any industry in history. And meanwhile, governments have to be unbelievably smart about syn-bio, synthetic biology, and they have to monitor the industry

relentlessly. And they have to regulate dangerous practices on a coordinated international level. And I'm a generally very free market oriented person. So I don't say any of this lightly. But this sort of thing is just necessary when we have a wildly promising exponential technology that we want to nurture and benefit from, but which also has a cataclysmic downside. And the funny thing is that we don't really have a good precedent or analogy that we can turn to to guide us. This wasn't the case with digital technology, another exponential technology. Whatever we think of super AI risk today, computing posed no innate existential risk for its first 50 plus years. It could surprise and delight us

with astounding unforeseen developments for years in a row, no real downside. So we just don't have a good historic map to turn to for guidance here. Hmm. You and I are recording this during the, hopefully the waning days of the COVID-19 pandemic. Let's hope. We're in this frustrating, uncanny valley of knowing that vaccine is everywhere, sitting on shelves, and it's being administered at a shockingly leisurely pace. California was just declared the worst state in the nation with respect to the velocity of its vaccination program. How we achieve that is anybody's guess. But many of us have drawn the lesson here that we have experienced a comparatively benign pandemic. I mean, it almost couldn't be more benign. It's worse than flu and then perhaps tenfold worse than flu, but it is still killing at most 1% of people infected

and disproportionately elderly people. So the impact of something tenfold more lethal or more is really difficult to picture, or rather it's easy to picture how catastrophic that would be because I'm not alone in thinking that, you know, this is a dress rehearsal we've experienced for something quite a bit worse, and we have just manifestly failed this dress rehearsal. Our response to COVID has been abysmal, and it's been abysmal even though the scientific response has been amazing. The public health response has been as inept as you could have ever feared, but the research response, the molecular biology response, the vaccine production response has been amazing. The Moderna vaccine was created

apparently before there was a single death in the U.S. from COVID. It's astounding that we have the juxtaposition of that kind of technical competence and the utter mismanagement of a public health response. And, you know, as we know and need not get sidetracked by, there's been a layer of political controversy and chaos that in part explains how bad we are at this, but not entirely. We're a society that can't figure out how to produce masks at scale, it seems, or Q-tips. So we have supply chain problems. It's been a colossal embarrassment and an excruciatingly consequential one, given the body count. And again, this is about as easygoing a pandemic as we could have hoped for.

So what lesson do you draw from this, given that what would be engineered, you know, would very likely be quite a bit worse? And as we know, and as you've discussed, and we'll discuss further in this series, there are natural variants of diseases that we're already worried about, which are quite a bit worse than COVID. And it's just by sheer luck that they haven't spread more efficiently than they have. So we know that almost everything on the menu is worse than COVID. And yet, this has unmasked our near total inability to respond quickly to a challenge like this. To summarize all that, frankly, the private sector has covered itself in glory.

And in many countries, certainly including the United States, the public sector has covered itself in shame. And we need to do much, much better than that. You mentioned order of magnitude. I actually think that's exactly the right way to think about hypothetical future diseases because, you know, movements of 25, 50% on different metrics are kind of hard to model out. But let's think about order of magnitude along two metrics, deadliness and transmissibility,

which is to say transmissibility, how contagious the disease is. Because particularly if there's an artificial pandemic, we can rely on the malevolent designers of that to dial things up significantly beyond where COVID is. And we also can't rely on nature, as you rightly pointed out, to keep things dialed down to where they are with COVID. So let's start with deadliness. As I mentioned in the recording, the World Health Organization puts COVID's case fatality rate somewhere between half a percent and one percent. So that could be dialed up by up to two orders of magnitude. One order of magnitude, and it's five to 10 percent. Two orders of magnitude, and it's 50 to 100.

And as you noted, these are not unheard of numbers. SARS kills about 10 percent of the people it infects. H5N1 flew over 50 percent. So there is no biological reason why the next pandemic, even if it's natural, necessarily has to top out at 1% fatality. And if it's artificial, we can rely on it topping out higher. As for transmissibility, the big number of courses are not, which is how many people the average sick person infects. And without public health measures, COVID's R0naught is two-ish or three-ish,

something like that. Estimates vary. To get a sense of what it would be like if the R-naught was much higher, think of the measles, whose R-naught can hit, I think, the 15 to 20 range. An example, if you get into an elevator a minute or two after someone with COVID leaves it, almost all the aerosolized particles will have fallen to the ground and you'll be extremely unlikely to catch COVID. But if you're unvaccinated for measles and a sick person leaves an elevator

two hours before you show up, you could very easily catch the measles. So imagine a one order of magnitude disease and transmissibility. Think of something as deadly as COVID, it currently is, but as contagious as the measles. The result of that situation would be that virtually everyone would catch it in very short order

and we'd have an unbelievably hard landing into herd immunity. I think that would be absolutely ghastly. The death rate would go north of what COVID is because hospitals would be overwhelmed, but I'm pretty confident civilization would survive. As for the death rate going up by one order of magnitude, 5% to 10%, I'm still confident society would march on, but a bit less so. Not because of what it would do to people who were lucky enough to seclude at home. They could probably still dodge the virus. But what it could do to supply chains,

like if there's a 5% to 10% chance of death, do meat packers show up at work or grocery store workers? And if you start having food supply outages, even small anecdotal ones, just imagine the pandemonium of hoarding that would ensue and the road warrior-like scenes that would unfold in stores. And we could barely handle a toilet paper shortage, which itself was kind of like the GameStop run-up. I mean, it was a reflection of crowd psychology, not of an actual supply chain

breakdown. Still, I don't think that's a civilization-canceling scenario either, but it'd be way more dangerous than what we're facing now. Now, those are two one-order of magnitude diseases beyond COVID. As for two orders of magnitude, all bets are off. I mean, I don't know if anyone shows up to work if there's a 50 to 100% fatality rate, or if there's an order of magnitude jump in fatality combined with one in transmissibility. And in that sort of scenario, I start worrying about staffing the electrical grid. Because if the power goes out for a sustained period over a national grid,

or God forbid, a global footprint, civilization teeters very, very quickly. So if there ever is a wide outbreak, and I'll come back to those words, wide outbreak in a moment, of a two-order-of-magnitude disease, the only way society could possibly survive would be with very meticulous contingency plans that are drilled at local and national levels,

and very, very careful to keep power, food, and law enforcement flowing. Plans which I'm sure we don't currently have. Now, a much... It was right behind the Q-tip plan and the mask plan. Exactly. Once the Q-tip plan was contingency plan, the survive a doomsday apocalyptic disease plan. Now, a much better alternative to ever facing a wide outbreak scenario would be to have an incredibly robust global immune system response to quash the disease the instant it shows up on a radically improved global surveillance network, which we're going to talk about a lot later in the series. So in any event, somewhere between one to two

orders of magnitude distributed between deadliness and transmissibility, I do think civilization teeters. And there's no way we could survive a wide outbreak, much more than one order of magnitude, without a radically improved public health game. There's a couple of threads I want to pick up on here. One is this distinction between natural and synthetic pandemics. You focus on the synthetic possibility, but really everything you say is just as relevant to anything nature might cook up for us. I absolutely agree.

And also, I think the boundary there is a little blurry because even in the case of natural pandemics, you're still talking about human behavior. I mean, anyone who's putting a bat on top of a pangolin and calling it lunch is teasing out these xenoviruses from the womb of nature, and that's one vector by which they get into our population. So we have to figure out how to modify human behavior across the board so as to reduce the likelihood of this kind of thing happening. And we already know that there are natural viruses and other pathogens that have very high lethality, and a single mutation could make them super transmissible in ways that they're not currently.

And we know that nature is running that experiment continuously. This is the Darwinian principle by which things change. principle by which things change. But there is one human behavior that I think we do want to shine a light on and very likely block, and that is related to the experimentation on H5N1 that you discuss. And this is what often goes by the name of gain-of-function research where biologists in studying how a pathogen might behave can actually modify its genome such that it acquires a different rate of transmissibility, say, right? So something that was not yet transmissible human to human becomes so, human to human, become so. And it's easy to see how well-intentioned people might think it wise to do such research, assuming they have extraordinary confidence that they're not going to accidentally leak one of these pathogens out of their labs. But we know so much about how difficult it is to be perfectly careful

in an ongoing way that after a few minutes of reflection, some of this research seems patently insane. What's your current view on the H5N1 research that you began speaking about? Well, so you made an important point, which is that gain-of-function research is done by well-meaning people. It's done with the public health agenda. These aren't mad scientists. They're trying to probe at the worst things that could conceivably happen so we can better prepare for them. And the whole debate that the scientific community has had, and to a lesser degree, society writ large, is actually geared off of precisely this H5N1 research that we've been discussing. There was, and to some degree remains, some confusion about the virulence and transmissibility

of the H5N1-modified viruses that were created. Some have questioned the consistency of the statements at least one of the researchers made. And also, the transmissibility that the research achieved was in ferrets. So we really have no idea how these viruses would behave in humans. Of course, they didn't infect humans. They could have been way worse than the ferret results. They could have been a dud. We don't know. So for this reason, I use the H5N1 incident both as a scary and thought-provoking historic fact. I mean, this happened and holy shit, but also as a bit of a metaphor, like a touchstone for conversation. And that what we can say is that a virus of unknown,

but potentially catastrophic power resulted from gain-of-function work in 2011, using the technology that time. And to assess what that means for our security, now we need to consider the speed with which the tools and techniques of synthetic biology have been improving since 2011 and the degree to which they've been spreading. And we'll get into much more detail on that in a later section, but short answer is these tools are improving with unbelievable speed. And just as rapidly, they're spreading to very large, widespread levels in academic biology and beyond. So the original H5N1 gain-of-function research was the roughest of

prototypes for what's possible now for a much, much larger group of people, which makes any clouded understanding of the human transmissibility of those original viruses, kind of immaterial. Anyway, to get back to what happened. In 2014, there was a series of blunders that the U.S. government committed in relation to some scary pathogens. In one incident, some live anthrax spores were mailed from one lab to another, and another one really crazy. Live smallpox virus was discovered in a forgotten FDA storage facility. And as a result of these and some other things, concern ramped up about deadly pathogens. And one result of this was a pause on government funding of gain-of-function research. Emphasis on pause and government funding. So gain-of-function wasn't banned by any means. This just meant the U.S. government itself wouldn't fund any of it.

And both of those projects had some U.S. government funding. As for private research, there was, I think the words were, request for a voluntary moratorium on gain-of-function. So nothing like a ban and certainly nothing like enforcement. Then after three years of careful thought, I'm sure, the government put together some ethical frameworks and other things. Government funding for gain of function was resumed. I think that was 2017. And then in 2019, funding for the exact two H5N1 research projects that we've been discussing resumed. So now it's all systems go for gain of function as far as the US government's concerned. And as for whether it should actually be practiced, I've given this a huge amount of thought, and I fully appreciate the conceptual value of anticipating the worst bugs that might arise naturally by developing them artificially first. But I still, despite that, do not believe gain-of-function research should be carried out at all. The first reason is that it is enormously possible

that nature will never get around to creating the ghastly things that we invent with our gain-of-function research. I mean, no highly contagious form of H5N1 has ever managed to evolve across however many centuries. So widespread gain-of-function research will inevitably bring god-awful pathogens into existence that would never have existed otherwise. And why do that? But an even better reason to never do any gain-of-function research is, as you pointed out, no laboratory of any level of security can be wholly immune from leakages and accidents. And history shows this very, very clearly. And if you'd like, I could run through a few quick and rather unfortunately chilling examples that illustrate

that. Sure. The first one that I often draw attention to was a smallpox leak that occurred back in 1978. And the timing is relevant because just one year before that, smallpox leak that occurred back in 1978. And the timing is relevant because just one year before that, smallpox had been eradicated from the entire world after a heroic 10-year effort. And right before that eradication effort, 2 million people a year were dying from smallpox still

in the late 60s after hundreds of millions had been killed in the first half of the century. Yeah, something like 500 million people died in the 20ths, after hundreds of millions had been killed in the first half of the century. Yeah, something like 500 million people died in the 20th century from smallpox. Crazy, crazy numbers. And so we can imagine the level of care and attention that must have been lavished on every remaining sample of smallpox one year after the eradication. But nonetheless, smallpox managed to escape from a British lab. It infected two people and killed one of them. So the last person in history to die of smallpox died as a result of a lab leakage. And as for biosafety level four labs, which is the very, very highest level of biosafety by an

international set of standards, and biosafety level four is extremely rare. There aren't a lot of them in the world. So this is the pinnacle. We can look at a foot and mouth disease outbreak in, or leakage rather, in Britain once again back in 2007. And again, this timing is relevant because just a few years before that, Britain's cattle industry had suffered a crippling foot and mouth outbreak. So high alert for foot and mouth in the UK. But despite that, the virus literally leaked out of this BSL-4 lab into the surrounding groundwater.

And then two weeks after that lab resumed work, it happened again. So we're at the pinnacle of biosafety in a country that's been blighted by this disease recently, and we have this leak. And in light of that, do we really want to do gain-of-function research into pathogens that might imperil civilization itself? And by the way, many very level-headed people believe that COVID itself might have leaked out of a biosafety level for a lab, the Wuhan Institute of Virology. Now, I haven't dug deep enough into that to fully form my own point of view on whether that would have been a leak or not, but it's definitely not just the realm of the tinfoil hat crowd. And then the last example, which is relevant for an additional set of reasons

as if it's not grim enough, is the anthrax attack of 2001, which killed five people. This was a week after 9-11, and envelopes containing anthrax spores showed up at some media outlets as well as the offices of a couple senators, including the Senate Majority Leader Tom Daschle. And as it happens, I was in Daschle's office that week, so this one's kind of seared into my memory. And it turns out that those spores came out of a high-security U.S. Army biodefense lab, probably at Fort Detrick in Maryland, although some people think it might have been another Army lab. Now, there's always going to be a swirl of mystery and conspiracy theory around this

one because the FBI's main suspect actually killed himself before any indictments or trials. But regardless of who took the spores out of the lab, it's hard to imagine a country at a higher level of alert than the US after 9-11, one week after 9-11. And it's hard to imagine a significantly more security-minded and security capable organization than the US military. And yet, even in those circumstances, anthrax made its way from the heart of the military-industrial complex into the office of the Senate majority leader. Again, well, proving two things. One, any facility can leak, but also showing us that safety measures, which

are meant to prevent accidents, are all but helpless against a malicious insider, because that's not the disaster scenario they're designed around. And, you know, the odds of there being an unhinged insider go up as you increase the number of places working with disastrous pathogens. The consequences go up as the pathogens become exponentially more terrifying than anthrax or even COVID, which again leads us to question why in the world would we ever do gain-of-function research? Yeah, yeah. Well, there's another variable here which you discuss throughout the series, the prospect that this technology will become increasingly democratized and you'll have high school students performing experiments that now

the most sophisticated laboratories would struggle to perform because there's some desktop piece of technology 5, 10, 15 years from now that embeds so much knowledge that you don't even have to be a person in the field of, in this case, biology, to do biological experiments that no team is currently, or few teams are currently capable of, you know, it's very easy to see how the consequences of this meddling will get away from you. And the idea that we are poised to spread the tech around to the level of high school students is fairly terrifying. But at the same time, there is something that's undeniably cool about high school students discovering things like synthetic biology and doing really cool things with it. And so, a little bit of a sidetrack, the most vivid evidence of syn-bio technology in high schools,

to me, is something called the iGEM competition. And iGEM is sort of an annual SynBio jamboree for students, which spun out of MIT a while back. And each year, thousands of students grouped into several hundred teams compete in creating sort of little SynBio marvels. And those teams come out of grad schools, they come out of colleges, and they do come out of high schools. I recently eyeballed the list of last year's teams, and I'd say about a quarter of them came out of high schools. And the high school projects I read about included a virus testing system that delivers PCR-like technology at home, which is not easy to do. there was a field kit you could take out of the woods to test wild mushrooms for toxicology. So pretty sophisticated stuff coming out of today's high schools. And I do think iGEM is a great thing, as I mentioned. And I don't think that we have to worry at this instant about a rogue high school kid doing something catastrophic, you know, with SynBio today. But we do have to appreciate

that this is the endpoint of the academic transmission channel, and it's wide open. So things that are only possible for today's tops in bio professors will rapidly diffuse to smart grad students, and then to smart undergrads, and then to smart high school kids, and eventually to dumb eighth graders, right? And we obviously can't put a biosafety level four protection protocol into every high school. So we either have to stop the diffusion of this technology, which I think would be tragic and also completely impossible, or we have to start building safeguards that selectively prevent dangerous practices down

the line, which is tricky because our intuitions reliably defeat us when exponential change is involved. I mean, there's a famous question of whether it's better to have a million dollars or a penny that doubles every day for a month. And our intuitions scream, take the million bucks, but it turns out the penny is a much better deal. And I believe we have this miswiring because our ancestors simply never encountered exponential processes when they were living on the savannah and they were evolving on the savannah. They had to solve all kinds of de facto Newtonian physics problems when they went hunting, when they fled predators, when they were cracking things open. So that kind of mathematical intuition

is very hardwired into us, but not exponential processes. So therefore, we have things like HHS naively posting the Spanish flu genome to the world. And rather than laugh at that, we need to be unbelievably concerned about what information and methodologies we're putting out in the world today. To spoiler alert a little smidgen from section two of the recording, the awesomeness of this, the speed of this advance in SynBio to me is best captured in looking back at the Human Genome Project, which lasted 13 years and cost about $3 billion and ended in 2003. So not in ancient history, at which point the team had basically read out a single human genome. And today you can have your genome read not for $3 billion, but for $300. And 2003 wasn't that long ago. It's a 10 million to one price drop.

Yeah. I mean, that's flabbergasting. Yeah. And so that is the kind of pace of change that we are simply unaccustomed to dealing with, that our ancestors were utterly unaccustomed to dealing with, that our ancestors were utterly unaccustomed to dealing with, that defeats our intuitions. And so I go back to the point I made earlier, that those who are deep in the process of creating this technology have a much, much higher moral weight on them to try to forecast the things that might otherwise blindside a society that doesn't see it coming. And there really needs to be a symphony of coordination between academia,

a self-regulating private industry, and really, really smart public health people to prevent catastrophic unforeseen circumstances. Okay, well, it will not surprise you to know that you have not yet made me an optimist, Rob. But happily, you've got further installments in this series to try. Absolutely. There's more to come and much more optimistic ones to come. We've talked about the apocalyptic nature of artificial pandemics. Now let's consider the reasons someone could possibly have for unleashing one. Doing this would almost certainly doom the unleasher. If he doesn't die of his own awful disease, he ends up in a post-apocalyptic hellscape.

That doesn't sound like a great incentive structure, so it's fair to question whether anyone would ever actually do such a thing. A doctrine called mutual assured destruction comes to mind. It got us through the Cold War, and basically said that since a nuclear slugfest would annihilate everyone, neither side would start one. The policy had some terrifying holes in it. But you gotta admit, here we still are. Meanwhile, a vial filled with an obliterating contagion has its own mad deterrence built into it. So if we could trust the Soviets with thousands of nukes, and it turns out we could, who couldn't we trust with that vial? When I've explored this issue in writing or in talks or interviews, I've come to gravitate toward a handful of examples that really help frame it.

On the question of whether anyone would ever unleash a doomsday virus, I often think of the Las Vegas shooter who murdered 58 concertgoers in 2017. For starters, unlike the Soviet Union, he was committed to self-annihilation, making him undeterrable by nature. Given that, would he have preferred to unleash something 100 times worse than COVID if he somehow had that capability? Obviously, we don't know if he would have done that. But we sure can't say he wouldn't have. After all, this guy, like countless other mass shooters, had no proven boundaries when it

came to inflicting death and untold suffering on as many strangers as possible. And there's really no reason to think he even grazed the outer limits of the horror he would have liked to inflict. So we can't say he didn't want to topple civilization. We can only say he didn't get to. Now, this guy was no rocket scientist, nor was he a world-class biologist. In 2017, that meant he didn't get to have a vial full of deadly man-made viruses. So we don't know what he would have done with one. But here's the thing. I bet he didn't know squat about ballistics either, and that he couldn't have designed a semi-automatic weapon any more than he could have hoisted himself to Mars. But he did get to have a private arsenal, which illuminates a critical point. Even if it takes geniuses to create a technology, and more geniuses to translate it

into functional tools, it may only take a sick lunkhead to operate those tools. Now, the frontiers of biology are generating extraordinary tools, and for now, they're both created and operated by brilliant people. But there's no reason why this has to be the case forever. In fact, the tools and techniques in question are set to spread far and wide, which we'll discuss in a bit. But for now, the key point I always make when discussing this topic is that when suicidal mass murderers really go all in, technology is the force multiplier. For a low-tech example of this, I often cite a series of school attacks that occurred in China several years ago. There was a rash of 10 of them. Just like in the U.S., they were carried out with the deadliest things you could find in the local stores.

But since this was China, that wasn't semi-automatic rifles, but things like knives and hammers and cleavers. Just like the Vegas shooter, the 10 attackers in China pushed their technology to its murderous limits. But all of them, combined, killed less than half as many victims as the Vegas shooter alone. To slide to the other end of the tech spectrum, consider the German wings pilot who decided to end it all in 2015. He wasn't armed with a knife or a machine gun, but with an Airbus 320, which he drove into a mountainside killing everyone on board, a lot more than twice as many people as the Vegas shooter, who himself killed more than any other mass shooter in history.

So again, in the hands of suicidal mass murderers, technology is the force multiplier. With this in mind, let's return to the problem of artificial superbugs. Here, the question isn't whether someone can make a bug that could potentially kill at the scale of a world war. That one was already answered twice when those two teams made H5N1 flu contagious almost a decade ago. So the real question now is how many people can create something diabolical? Because as the group of people who can grows,

our ability to monitor and deter them vanishes. To frame this, let's reconsider that situation in the Cold War, when just two heads of state held annihilating powers. The world ultimately spent trillions of dollars to monitor them and to deter them from hitting the red button. Early warning systems, diplomacy, vast militaries maintaining the balance of power, missile stockpiles so huge they could destroy the enemy even if he struck first, etc. All this to deter just two people from doing the unthinkable.

But what if we had to keep the chieftains of 30 nuclear arsenals in line? Or a thousand? There wouldn't be enough money or resources in the world to fund all that deterrence. So we're lucky that two is such a low number. We're also lucky that the heads of the superpowers were mostly serious, stable people who spent decades soberly making their way to the top. Now we could probably say similar things about a very different duo. the two head researchers who created the contagious form of H5N1. They were brilliant biologists, the heads of labs.

They had decent budgets, excellent equipment, and spent years cultivating their minds until they could do things that no scientist had done before. A decade ago, when they did their thing, the cadre of people who could create genocidal pathogens was a pretty elite club with really high admissions standards, ones that would tend to weed out loopy, erratic people. But what if that club grows and the hurdles to joining it plummet? Again, try to imagine an analogous world with thousands of sovereign nuclear powers. It's a very unstable picture.

Now, on the biology front, we're way past the point when just two-ish people in the world could groom a bug as deadly as the contagious form of H5N1. The reason is a new branch of science called synthetic biology, I'll call it SynBio from now on for short, is what's known as an exponential technology. That means it gets more powerful and cheaper in rapidly compounding ways. The output that cost $1,000 last year might cost $500 today, $250 next year, and before we know it, just pennies. When this goes on, things don't just get cheaper, but capabilities spread.

From nobody, to a handful of of people to masses of people. We've all personally lived through this with computing, another exponential technology. 15 years ago, not even Bill Gates could casually place video calls from his cell phone. But today, billions of people can. And I'm one of them. But that sure doesn't mean I know more about computing than Bill Gates knew 15 years ago. This sort of thing happens all the time with exponential technologies. Over just a few years, complete non-experts pick up capabilities that were initially beyond the top people in the field. That's pretty cool when it's video calls, not so much when it's

unleashing an artificial disease. To give a sense of how steep the exponential curve is in biology, I always cite the Human Genome Project. It lasted 13 years and cost about $3 billion. When it ended in 2003, the team had read and documented a single human genome. Today, you can have your genome read for $300. That's a 10 million to one price drop in less than 20 years. So the impossible is now affordable. And soon, it'll be practically free. Of course, lots of things are still extremely hard in SynBio. For now, only a tiny handful of truly elite scientists can generate viable replicating viruses from scratch, just from genetic code. And it's a good thing that capability is so rare, because the genomes of eradicated monsters like smallpox

and the flu that killed 50 million people right after the First World War are up on the internet for anyone to download. And yes, that means smallpox can now be created from scratch by anyone with the skills and motivation. Two researchers recently proved this point by synthesizing the closely related horsepox virus, which is extinct and harmless, with a $100,000 budget and some mail-order DNA. This definitively showed that highly specialized scientists can now cook up some smallpox. But that elite monopoly won't last, because rare capabilities routinely become widespread when exponential technologies are in play. Again, think of video calls.

The trailblazers on the edge of SynBio tend to be brilliant, career-minded, and highly non-murderous. But as the trail gets worn down and the tools get simpler, lower and lower levels of skill, expertise, and long-term dedication will be needed. And at some point, probably fairly soon, freshman pre-med students will have homework assignments that the entire field of Sinbio couldn't complete today. With this in mind, let's go back to that grim subject of suicidal mass murderers. The ones who hit those Chinese schools had simple tools and killed a couple dozen people between them. The guy who killed a lot more people than that in Vegas

had guns, which much smarter people than him designed to slaughter humans. The German wings pilot had a plane designed by people much smarter than him, and so on. Each killer hit the limits of his technology, but there's no reason to think they hit the limits of their ambitions. None of them was in a position to die while launching a pandemic.

But once again, that doesn't mean none of them would have, given the chance. It just means none of them got to. So how rare are these sorts of people? These days, the U.S. alone averages over one mass shooting per day, according to the Gun Violence Archive. A big proportion of the perpetrators are suicidal, and a big fraction of that subgroup, like the Vegas shooter, take every random stranger they can with them. We need to worry about this group as massively deadly

technologies become widespread. Because again, their death tolls reveal the limits of their technology, not the limits of their bloodlust. And no doubt, some people in this category have no upper limits. Each year, this group is replenished as hundreds of people throughout the world go on a final deadly spree. Think of those killers as being in a circle on a Venn diagram. It's very small and stable in size, but it's extremely significant. In a neighboring circle are those who could trigger the deaths of millions of us if they really wanted to. That circle is even smaller. It's barely a speck, but it's growing. It used to include just a few heads of state, as we discussed. Then in 2011, assuming their creation was in fact contagious between humans, those H5N1 biologists entered it.

And these days, quite a few more scientists are surely in that circle. Because in biology, the heroically difficult feats of 10 years ago are just a hell of a lot easier now. The enabling technology is simply moving so fast. For instance, the world's most celebrated and prominent gene editing tool, which is called CRISPR, didn't even exist when the H5N1 flu was modified. And today, CRISPR is taught in high schools. And post-CRISPR tools, which are even more powerful, are now cropping up and are also proliferating. So again, we have two circles in our Venn diagram. One contains the people who are going to snap this year and kill as many people

as they can. And the other contains those who could kill millions of us or more if they really wanted to. That second circle is set to grow with insane speed due to the proliferation of ever more powerful symbiotools and techniques, which means unless something changes, those circles are going to collide and intersect, and the world will be home to someone who wants to kill us all and is capable of producing or obtaining an annihilating pathogen. The deadliness of that pathogen could have absolutely no precedent, because for all its faults, a bug like the coronavirus has nothing against us. Technically, viruses aren't even alive. And many deadly ones actually

become less deadly over time, because killing off all your hosts is no way to win the game of evolution. So natural viruses will never go out of their way to maximally harm us. They just don't have ways to go out of. That wouldn't be true of someone who sits down to design a deadly virus. For instance, one thing that makes COVID dangerous is that some people are contagious without any symptoms. That period's thought to last a few days. So why not extend it to a month? The coronavirus won't take that on as a personal goal, but a designer might. A designer might also make something a hundred times deadlier than COVID, like a contagious form of H5N1 flu.

Now, this wouldn't be easy, but ease is a function of tools and skill. And we know the raw tools of DNA synthesis and editing are improving at breakneck speeds. As this continues, some profoundly skilled people with perfectly benign motives will probably design some profoundly deadly things. They might be virologists, pushing biology's outer limits. Graduate students doing thesis projects. Militaries exploring what their enemies might cook up. Counter-terrorism units doing the same thing. I expect that almost all the people playing this game will be white hat operators, precisely because of the brilliance and resources it'll require at first. But that doesn't mean their work can't be dangerous.

For starters, we've already talked about how many deadly bugs have found their way out of secure labs. And they could also escape in non-physical ways. Because although good guy scientists may make critters and petri dishes, they'll really be creating tiny data files. The H5N1 genome is just that, a packet of information, with just 10,000 letters in it. That's nothing.

A transcript of this recording would have way more letters than that. And data networks get hacked constantly. And when they do, the significant files go missing, then get copied, and copied, and copied. Just ask any music label, movie studio, or Fortune 500 company that let hackers get the intimate details of millions of customers. Like, ask Equifax. Now, when the first deadly genome gets swiped and spread all over the dark web,

technology may not be advanced enough for bad guys who are not elite scientists to do much with it. But the internet never forgets. And a decade or two later, the technology to synthesize genomes could be a million times more powerful and in a million labs. You see, injecting the time variable between the brilliant good guy who does the hard work and a later bad guy who abuses that work is really destabilizing. Because while the bad guy may not be brilliant

at all, a couple decades could give him access to vastly more powerful tools that make up for that. Again, think of the Vegas shooter who was no ballistics expert, but who stood on the shoulders of generations of them. Or think of whoever posted the genetic recipes of smallpox in the 1918 flu to the internet, they couldn't possibly have been thinking exponentially. Which means they either couldn't imagine a near future in which platoons of people could resurrect those diseases, or they didn't bother trying. With this in mind, please dial up your inner science fiction writer for a moment. Let's imagine it's the intermediate future, a few decades out, and every high school biolab has a benchtop DNA synthesizer.

These already exist, as we'll soon discuss, but definitely not in high schools because they're way too expensive. However, like the personal computers of the 1970s, they'll get much cheaper and better, and it's hard to imagine their descendants won't end up in high schools. Now let's imagine this high school printer can crank out a complete error-corrected virus genome if you input its genetic code. You can't do this with today's DNA printers. They can only produce batches of about 2,000 error-corrected letters of DNA, whereas viruses typically run in the low tens of thousands to hundreds of thousands of letters. But history's shown that 10 to 100x improvements are fairly short walks in exponentially compounding

technologies like SynBio. Recall the 10 million x improvement in reading DNA in the 18 years since the Human Genome Project. Next, let's imagine that modern tools make the complex process of translating a genome into a viable replicating virus easy enough for smart high school kids to master. Now everything I've described so far is so plausible, it verges on inevitable given enough time. If not in this decade, then a bit further out. And yet I've described an all but impossible world. Because remember, those genetic blueprints of smallpox and 1918 flu are already floating around the internet. And God only knows what other blueprints will

eventually join them. In our scenario, any smart but disturbed high school through postdoc student, along with millions of people working in life sciences, could start an outbreak. That world just can't exist, or at least not for long. So we need to do whatever it takes to avoid ending up on a glide path that leads to it. When I think of this kind of intermediate future, suicidally murderous individuals worry me, because the world produces so many of them. Groups with those motives are much rarer, but they're inherently scary too, because groups can be way more capable and formidable than

individuals. And some groups do have bizarre urges to sweep the earth of humanity. There's plenty of doomsday cults out there, and at some point one of them will get bored and decide to speed things along. Japan's Aum Shinrikyu cult did this. It gathered over a thousand members, including several biologists, and it meant to bring about the end of the world. But the tools to do that just weren't around in 1995, so it made its big move with a sarin gas attack in the Tokyo subway. When the next Aum Shinrikyu comes along, I doubt they'll limit their arsenals to deadly gases. Meanwhile, environmental, or maybe animal rights extremists, could decide that humanity doesn't deserve a future. Or consider the strange philosophy of

antinatalism, which argues that human lives are so unpleasant, the ethical thing is to minimize the number of humans living them. For now, the people who think this way just try to avoid having children. But who knows where that could lead? The crazy motives we can imagine driving someone to launch a doomsday pandemic

are terrifyingly broad. And that's not counting the ones we can't imagine. Meanwhile, the ways for dangerous, well-intentioned work to leak out are boundless. Okay, that's the bad news. But luckily, there is a way out of this. That's the whole premise of this series. But before we get to the right way out,

let's briefly discuss the wrong way out, which would be a technology ban. Because we can't stop Sinbio from advancing, and we'd be fools to try. If a worldwide ban is enacted, could we really trust China and Russia to respect it? Would they trust us? Could anyone trust North Korea? Unlike nuclear programs, which require vast industrial complexes and therefore can be monitored, biology can be practiced almost invisibly. So swear off of SynBio and you're giving some rival a SynBio monopoly. Again, think of North Korea.

This is a really bad idea. Much more importantly, we shouldn't want to stop SynBio in its tracks because its promise is almost boundless. It's already starting to revolutionize medicine and is set to save untold millions of lives. It holds extraordinary promise for the environment in the form of crops that need less pesticides, biodegradable plastics, and perhaps even biofuels secreted by engineered microbes. And it has some sci-fi wonders up its sleeve, like clean meat

that's molecularly identical to the real stuff, but is produced without animals, so there's no suffering in factory farms, and greenhouse gases are sharply cut. Yet another giant reason to forego a symbiotech ban is that our greatest allies will be people trained in this field. And while a tiny handful of such people will almost inevitably go rogue, as training proliferates ever more broadly, the ratio of allies to enemies will be staggeringly high in our favor. I mean, think about it. The bar to being a good guy is that you're

opposed to wiping out humanity. That's about as low as a bar gets. So the more symbioexperts the world creates, the safer we'll be on a certain level. So how do we put the good guys to work in protecting us? In the next part of this series, we'll talk about the right way out of this predicament. Okay, I'm back with Rob Reed. That was section two. Rob, you have raised this terrifying memory of what smallpox did to the world and the prospect that it could be resurrected. What's your thinking there?

Well, I'd say the thing that unfortunately gives us confidence that some people out there could resurrect smallpox today, if they put their minds to it, is that someone recently created the harmless but closely related horsepox virus from scratch. And they're very closely related. So if you can create one, you can absolutely create the other. And in fact, the researcher behind that indicated in one of his interviews that part of the reason why he did this horsepox work was to force the world to confront the possibility that smallpox could be resurrected. And so how many people could also create these viruses in addition to this researcher whose name was David Evans today? And in asking that, I think there's two things to note. The first is that the horsepox work was done in 2016. So this was almost five

years ago. Using the tools of its day and all kinds of syn-bio tools have improved dramatically since then. And secondly, it was done by a very talented team, which kind of constricts the group of people who could do this, because at the time it was actually the largest virus that had ever been assembled from scratch. So that was not a small thing to do. So who did this? Like I said, his name is David Evans, and he's a virologist at the University of Alberta. And when he's described his work publicly, both in a paper that he put out there and in interviews, he's basically said two things, and I'm, of course, paraphrasing here. One is that for good or for ill, the world's full of talented scientists who, like him, can stitch together disparate bits of widely published knowledge to create things that

don't have ready-made recipes on the internet. But he also said, you know, so that's the bad news, but he also said that doing what he did would require, you know require advanced scientific training, a very specialized lab, and a fair amount of inside knowledge, all of which I'm sure was entirely true in 2016, and all of which I'm equally sure is less true today. Now, I can't reliably place David Evans in the global constellation of virologists, but for what it's worth, and take it with a grain of salt, I found what looks like a bottomless list of the world's most influential

virologists online based on AI rankings, which presumably includes things like academic citations and whatnot. And he wasn't listed in the top 500. So take that with a big grain of salt. But it doesn't seem like he's the top virologist in the world. So if we triangulate from all that, I would say that conjuring up the horsepox virus and therefore smallpox would probably be hard, but doable for a high-powered academic virologist who's really determined to do it. And my gut sense tells me that's probably hundreds of people in that category, so not thousands, but not mere dozens. But that's a really high number when you think of the terrifying power each of those people could potentially wield if they went off the rails.

We are, in a very real sense, counting on all of those people to never go Columbine. The analogy to guns is not reassuring because guns do not have this exponential quality to them. You only kill as many people as you shoot. It's not like you unleash rounds of ammunition onto the world and they keep spreading and killing people. We know where the trend lines for all of this technology, really any technology, tend to go, which is to embed the highly specialized knowledge that was required to create the tech in the tech itself such that a person without any real knowledge can use it and leverage all of that power to whatever end.

And so, as you pointed out, you don't have to be a master of engineering of any kind or ballistics to own the most powerful firearm available and use it. And someday you won't have to be a virologist to engineer a virus if we don't manage to contain this technology. Yeah, and a really scary thing you kind of touched on is just the open-endedness of a symbio attack. I mean, every terrorist attack we've experienced so far has had inherent limits

to it. You know, there's only so many people on an airplane, there's only so many people in a building that's being attacked, or, you know, there's only so many people in a building that's being attacked, or there's only so many victims one person can shoot before the cops show up. But COVID makes it abundantly clear how open-ended a disease's damage can be. We're a year into this thing. We still have no idea what the final bill is going to come to. And what's also scary is to think about what would a dud of a SinBio attack look like? I mean, let's say someone who's really smart and really determined, who has completely mastered the best biological tools that'll be available, I don't know, let's say 20 years from now. What if that person sets out to cancel humanity and falls 99.9% short of that goal? I mean, that's 8 million dead. And just imagine how the U.S.

would react to an attack that kills on that scale proportionately in the U.S. I mean, just think of how we reacted to 9-11, which killed fewer people than COVID currently kills on a bad day. I mean, two wars costing trillions of dollars, civil liberty ramifications. The scary thing is that not only can we not afford to suffer a successful symbio attack, but we probably can't afford to experience a failed one. Yeah. Well, again, the analogy from COVID is depressing because this is just about as benign as you could imagine while being worse than the ambient level of contagion that's already there. I mean, it's like if this were any more benign, we would barely notice it, right? And it has brought

global civilization to something like a standstill. We don't know what the ultimate bill will be from this, but we know it is certainly more than a million dead globally and trillions of dollars. And again, this is just, you know, if it were any more like flu, it would be the flu. And so it's, yeah, just anything that would be properly weaponized with an intent to kill as many people as possible, you have to imagine, you know, this is the dud scenario, you know, and it's still, you know, scarcely tolerable. So, you know, we're talking about, by definition, people who would intend to harm vast numbers of people by doing something in this space. The prospect that this can happen by accident is something we've touched on, and that's also terrifying. But here we're

talking about the most malicious case. Who are we imagining would do such a thing? Well, it's an interesting question, and it's obviously a really important one. And what I personally go back and forth about is, is the risk greater from lone wolf individuals, or is the risk ultimately greater from groups of individuals, from organized groups? And on the one hand, groups are obviously way more dangerous on a one-to-one basis. Like if we compare a single group to a single individual with an identical goal, because obviously unlike the individual, the group of five people, let's say it can be five places at once. It can pool expertise that might be hard to find in a single person. It can pool resources. There are just countless advantages. But the thing is, it's not really a one-to-one comparison because lone wolf operators are

just way more common when it comes to suicide attacks. Even if we include suicide bombings, which are the works of groups, in those statistics, lone wolf suicide attacks are way more common. I mean, we had more than one mass shooting per day in the US last year, many of which were suicide attacks, and almost all of which were lone wolf operations. I mean, things like Columbine, where you have multiple shooters coordinating, are incredibly rare. So I worry about groups because of their capabilities, but I worry about lone wolves because of just sheer numbers. And it's also hard to find groups

in history that have been committed to total annihilation. I mean, the only one I can think of is Zoma Shinrikyo. And I mean, I bet even ISIS's leaders would have been horrified on their worst day by a plan to exterminate humanity. That kind of nihilism is just much easier to imagine in an unhinged individual than an organized group. But that said, groups aren't really historically known for focusing on trying to do things that are utterly impossible on a technological basis,

which has been the case with total annihilation up until now, thank God. And there are schools of thought that might just be a few deranged steps away from considering that. Like, should we be worried about what the outer fringes of the environmental movement, or maybe the animal rights movement might do, let's say, 10 years from now, if they think they can create an off switch for humanity, or maybe a particularly unhinged group of antinatalists? Yeah, I would divide this more or less as you have into two possibilities. One is ideological, and that is more or less what you would need to have a group do anything like this. There has to be a belief system, some kind of doctrine that makes sense of this kind of apocalyptic,

genocidal behavior and suicidal behavior, unless you've also vaccinated yourself against this pathogen, which is, I suppose, also a possibility, although then we're imagining very competent people doing this. Right. So, but in the case of a lone wolf, I guess it could be ideological. You know, one person can have a rationale for what they're doing that may seem consistent to them, and they may be alone in doing it, but there's so many more ways for people to just snap, and it doesn't even have to school shooter, right? You know, he may have some internal story as to why he's doing what he's doing, but it doesn't need to be of the sort that we saw with someone like the Unabomber, who, you know, published a disconcertingly coherent manifesto. And that was, he was a group of one, essentially. They really are very different problems, even though they're terminating in the same way. I mean, I know this from the space of just having to deal

with crazy ideologues and crazy people more than I would want, you know, and so you can have people who bend their attention toward you based on their ideology that disagrees with you and they criticize you and attack you and in the worst case pose a security problem. But then there are just crazy people who think you're sending them messages, right? And that's a completely different problem to think about and to try to mitigate. That's a completely different problem to think about and to try to mitigate. And when you're talking about truly democratizing this tech and putting it in the hands of people who could be starkly delusional, yeah, we clearly have to find some way of closing the

door to this. Yeah, and it's interesting to think of that starkly delusional side of it. I mean, kind of one chilling example, if you remember the guy who shot up the movie theater in Colorado, there was a Batman premiere dressed as a Joker. He was like a PhD candidate, I want to say, in some biological science with an NIH grant. So that level of delusion can actually penetrate into fairly high academic circles. And then as the technology proliferates into ever lower circles, that high bar matters less and less. And I never really thought of this before, but I guess an interesting question to ask ourselves, I just have no ideas. What percentage of that daily mass shooter population in the U.S., for example, is actually schizophrenic or in some ways deeply delusional.

I mean, we should know that as a society. I mean, I think, you know, if we kind of follow the logic of all this, we start realizing that suicidal mass murder could absolutely begin to pose a national security risk. And if we look at it through that lens, we should probably be treating every mass shooting kind of the way we treat the crash of an airliner, with an incredibly serious effort to figure out exactly what went wrong and what are the aspects of this case that might have provided warning signs and really get a real epidemiology of this phenomenon. And I don't know that we're not doing that, but I don't believe that we're doing that. And it's something that we really

understand a lot better. Yeah, that airline crash you referenced, the Germanwings flight where a pilot, it seems all but certain, intentionally crashed the plane. I mean, that's one of those cases where this is a sort of murder-suicide that most people have never even thought about, right? It's just one of the most horrific things you can imagine. But you can see how it's a very odd case where you could see someone being, I would imagine, in this case, suicidally depressed. Someone in that condition might be capable of doing something like that. And you've got to think it presents psychologically as different than arming yourself and showing up at a school and shooting people. It's a different act. It is, in fact, a more murderous one, but it is a more abstract one in some ways from the,

you would imagine, from the point of view of the pilot. The pilot's experience is he's just committing suicide, right? And obviously he knows he's got a couple hundred people on the plane with him who he's going to kill. But you could imagine that there's some state of the human mind where all of those deaths are really an afterthought and there's no kind of murderous rage needed to motivate the instantaneous murder of hundreds of people, whereas there would be if you're going to start killing people with a club out in the world,

or shooting them one by one. Or at least it does strike me as the method of creating harm really does select for a different population of people who would be capable of causing that harm. Yeah, there'd be a squeamishness that the pilot wouldn't have to overcome that somebody who's actually getting into the gritty business of killing people would have to overcome. Yeah, there's no, I mean, the moment you've bought into, you know, you want to commit suicide anyway, right? And, you know, for whatever reason, you're happy to kill a lot of people in the process. But after that, there's no, it's all hypothetical. There's no up close and personal encounters. There's no conflict. There's just a plunge out of the sky with you at the controls. And this is analogous to different actions in times of war, right? It's just, it takes a different kind of person to just drop a

bomb from 30,000 feet, knowing all the while that beneath that bomb there are hundreds or even thousands of people who are dying. That's different than, you know, trench warfare or, you know, any other sort of conflict that produces death. I mean, this is the example I give somewhere, I think it's in my first book, The End of Faith. I mean, when you find out that your grandfather flew bombing missions over Dresden in World War II, that's one thing. But if you hear that he killed a woman and her kids with a shovel, that's another thing. The visceral reaction to that difference is an appraisal of just how different a person you would need to be to do

those two things. And yet we know he would have killed many more people flying a bombing run over Dresden than he would have killed with a shovel. These differences matter when they interact with technological innovations because, you know, we are now in a world where you could kill a lot of people with what never seems like anything more than an idea. It is a kind of an abstraction even when you're going through the steps required to weaponize a virus. I mean, because on some level you're not sure what steps required to weaponize a virus. I mean, because on some level, you're not sure what's going to happen, right? You're just going to release this thing into the wild and let's see what happens. It's all hypothetical until it isn't, right?

And it's, I don't know, I just, I can see this kind of possibility interacting with mentally unwell people of various sorts, where the bar to initiating this kind of thing is quite a bit lower than other acts of violence that would not nearly be as harmful. Yeah, because most of that process of engineering this thing and even unleashing it would involve gazing at a computer screen, dabbling with lab equipment, you know, and the level, the bar to being able to brutalize somebody with a sniper in war from 500 yards. It's yet another thing dropping a bomb. And, you know, designing and releasing a pathogen might even be more abstracted than that. You can imagine people just deciding to do things that pose, you know, incredible downside risk, but it's still, you're never quite sure, right? So it's like you could decide, well, I want to get a lot of people

sick to make a point. There is this prospect that this could get completely out of hand and kill millions, but that's not my intent, but what the hell, right? It's the exponential part here that just makes this so scary, because you keep rolling dice of these sorts. And again, what we have with COVID seems like a best-case scenario. grim scenario I hadn't thought of before. You can even get somebody with a messianic complex who decides, oh, I'm going to release a minor pathogen to warn the world about this stuff. You know, warning shot here, and that could get out of control. There's all kinds of motivations that people could have on this. Well, whenever you have a destructive technology of this sort that can be unleashed by a single person, that variable alone is enormous. I mean, just the fact that it takes perhaps a dozen fairly technical people to produce anything like a crude nuclear bomb.

Right. The difficulty factor for one even super competent person is just too high. I mean, there's just too much engineering to do. There's just too many parts to get together. You know, moving the thing requires collaboration. I mean, it's just, you need some people. And when you take that away and you deliver into the hands of any single person technology

that is potentially even more destructive, it seems like it does change the game significantly. And groups get busted. Groups get busted because they have to communicate with each other. They get busted because somebody defects from them. They get busted because they have a lot of surface area with the rest of the world, and somebody's going to try to impress his girlfriend by blabbing about something. You look at the statistics, and I don't remember the exact numbers, but the number of terrorist plots that have reportedly been foiled since 9-11. And it's a pretty impressive number and a very small number of plots that actually went forward. But if you look at

somebody like the Vegas shooter or Omar Mateen, who shot up the nightclub in Orlando, you know, there's no coordination, there's no signal leakage, all the actions that those people took, you know, that most mass shooters take in preparing for their crimes are perfectly legal, you know, and so if it's one person, it's just almost, you know, undetectable. And I guess I'm swinging around to being all the more concerned about lone wolves more than groups as we talk about this. Okay, well, let's get back into it and listen to section three. A while back, I said the way out of this is to build a global immune system to identify and destroy deadly new diseases. And there's plenty of inspiration to take from our own bodies.

Our immune systems are simply amazing. They fight off countless attackers each year without us even noticing. And countless attackers are bugs the immune system has never encountered before. and countless attackers or bugs the immune system has never encountered before. Yet it fends off these completely unknown enemies because it's agile, adaptive, and multilayered. We need to build something like this for humanity as a whole to fight off new threats, whether it's an artificial disease or a natural one,

on a worldwide basis, early. The great news is we can do this if, after putting COVID behind us, to whatever extent we're able, we maintain our focus on the threat of new diseases much, much, much more intensely than we did after SARS, MERS, Zika, etc. As we'll see, doing this properly will take big investments, which can be very tricky to fund. But let's compare that to the cost of doing nothing. The Congressional Budget Office estimates that COVID will cost the U.S. alone $7.9 trillion in economic activity, while former Harvard president Lawrence Summers pegs the domestic cost at $16 trillion. Whichever estimate you use, it maps out to tens of trillions of dollars

worldwide from COVID, while an artificial bug could be vastly more deadly and destructive. Indeed, as I said earlier, I'm not confident that civilization could even survive something like a highly contagious version of H5N1 flu. I meanwhile can't imagine everything I'm about to discuss combined, costing even 1% to 2% of the bill that COVID alone is sticking us with. And these measures would come with a massive side benefit in that they defend us from natural diseases as well as artificial ones. That would include previously unknown enemies like COVID or dreadful annual reruns like the flu. Let's talk about the flu for a second. The White House Council of Economic Advisers estimates that it costs the U. Let's talk about the flu for a second. The White House Council of Economic

Advisors estimates that it costs the U.S. alone $361 billion a year in medical spending and lost productivity. This maps to over a trillion dollars worldwide. And as we'll discuss in a bit, we might all but eradicate the flu if we get just one thing off of my wish list. Not definitely, but we'd have a great shot at it, for less than 1% of the flu's annual cost. Modern life sciences, absolutely including syn-bio, are magical arts, and we can and should enlist them against ancient enemies, along with emerging ones. Now, as I said, this immune system should be a global thing, but global initiatives can take years to gin up.

So we can and should get started everywhere at national levels, although it would be best if we eventually do things collaboratively and cover the globe. I've divided the immune system into five components. The first is about making it much trickier for bad actors to hijack our syn-bio infrastructure and use it to churn out awful things. The second component is outbreak surveillance. The earliest days of an outbreak can make all the difference between derailing a disease and letting it go global. So we should monitor the biosphere for new outbreaks as carefully as we watch the skies for enemy nukes. As we'll see, some really interesting science could help a lot with this if it gets the right funding and prioritization. The third component is about hardening society against a symbio attack, or a natural pandemic.

In military terminology, a hard target has some protection and is tougher to destroy than a defenseless soft target. Like you could say the U.S. hardened its airports back in the 70s when it first equipped them with metal detectors, then hardened them again after the 9-11 attacks by creating the TSA. Component number four is about conquering viruses. This is all about getting ahead of the next viral outbreak with vaccines and medications that could just stop it in its tracks. There's a huge amount that could be done here. But again, it's all about getting the right funding from a society that tends to underinvest badly in these things. I call the last component battle infrastructure. What do we need in place to fight the next novel disease after it's broken out, to either stop it

from becoming a pandemic or to dampen a pandemic that takes off despite all of our other measures? At least one thing we'll discuss may sound like science fiction. The immune system I'll describe will be a dual-purpose framework. While some parts of it are specifically targeted at artificial diseases, some of it would also pay huge dividends in our never-ending battle against natural ones. So even if no one ever attempts to create an artificial bug, which I find almost impossible to imagine, it would still pay for itself probably hundreds of times over in saving lives, suffering, and economic damage. Before we start, I should say this isn't meant to be the last word in anything. It's instead a framework for thinking about how

to respond to an existential threat humanity faces, one that the COVID crisis has brought into much sharper focus in the year and a half since I gave my TED Talk about these things. It's not meant to be comprehensive. It can't be. For one thing, this podcast is meant to have a manageable duration. Also, so much is changing in syn-bio and infectious disease research due to COVID that one writer can't hope to have it all on his radar. There might be dozens of measures and promising technologies

worth slotting into each of my notional components. And if some form of this immune system does arise, I certainly hope it'll be that deep and rich. So my hope in this is to start a conversation, not to complete one. A conversation that could lead to a blueprint for an immune system more agile, multilayered, and adaptive than anyone can currently imagine. So on to component one, hardening the syn-bio infrastructure. A few minutes back, I mentioned the TSA. Most of us have a friend who likes to say that if they wanted to hijack a plane, it would be so easy because the TSA sucks. Next time that happens, ask your friend how many U.S. hijackings there have been since the TSA got started and cockpit doors were hardened. The answer is zero.

Not because it's become impossible to hijack planes, but it's tricky enough that hardly anyone bothers. So while we haven't made aviation invulnerable, because that is impossible, we've made it much, much harder to disrupt. This is what we need to do with the act of creating deadly artificial bugs. We can't make that completely impossible, but we can push it past the reach of most people, including people acting on urges that will eventually pass. This matters a lot with someone bent on suicidal mass destruction, because most suicide attempts and many mass shootings are driven by transient phases of extreme rage or despair.

An analysis of over 175 academic papers showed that less than 4% of those who tried and failed to kill themselves later successfully did so. Now, that's obviously 4% too many, but it shows that most suicidal phases are impermanent. Hijacking, of all things, is an interesting parallel. Believe it or not, it was once possible to hijack a plane almost on a passing whim. Between 1968 and 1972, there were 130 U.S. hijackings, almost all of them by domestic perpetrators. Many of them were radicals who just kind of wanted to go to Cuba. It got so bad, Cuba created a special dormitory for wayward American hijackers. Alarmed citizens meanwhile swamped the FAA with anti-hijacking suggestions,

like building trap doors outside of cockpits. Eventually, metal detectors and so forth dropped the ambient level of hijackings from about 40 a year to almost zero. Now, we clearly can't live with dozens of biological attacks per year, so we need to think carefully about hardening the products and services that create synthetic DNA. Luckily, this process is already well underway. that create synthetic DNA. Luckily, this process is already well underway. Back in 2010, the U.S. Department of Health and Human Services issued guidance for securus and biopractices. And by then, the industry had already founded

the International Gene Synthesis Consortium, or IGSC, which is all about biosecurity. Its member companies represent about 80% of the world's gene synthesis capacity, although nobody is quite sure how accurate that estimate is. The government's guidance asked the industry to screen its customers for bad actors and to look out for orders of dangerous DNA sequences. So the IGSC created a regulated pathogen database. Its members now follow special review processes for potentially dangerous requests and contacts the FBI when appropriate.

They also follow government watch lists of terrorists, people subject to export controls, and more. I discussed these issues with science policy expert Sarah Carter. She has estimated that IGSC members spend an average of almost $15 for each synthetic DNA order that they receive on biosecurity compliance, which is a very serious investment. So there's lots of great news here. The bad news is that the government hasn't once updated its guidance. That's a 10-year lapse in guiding one of the fastest moving industries in history. Plus, that ancient government guidance is just that, guidance. In other words, it's voluntary. And while it's impressive that the IGSC's members produce maybe 80% of the world's synthetic DNA,

is that really enough? I'll use an analogy that many current and former American high school students will identify with. When I was growing up, my five-town area, a couple hundred thousand people total, had exactly one liquor store that reliably sold beer to teens. Every young beer enthusiast knew all about that store. And for a while, there may as well have been no drinking age whatsoever. Now, there had to be 99% compliance with the liquor laws amongst liquor stores in our area, but that hardly mattered. So I'd say when the fate of the world might literally hinge on controlling deadly DNA,

80% self-directed compliance to voluntary guidance is nowhere near enough. That other 20% in the hands of companies that are doing their own thing is just a gaping hole. And even for its members, the IGSC is no real arbiter because it thoroughly lacks independence. Its chair works for an IGSC member called Thermo Fisher. And the other folks who give it bits of their time also work for one member company or another. So if you're wondering why the IGSC website has no phone number, it's because they have no phone. Now, luckily, I wouldn't call this a pure Fox watching the henhouse scenario, because Symbio executives have huge incentives to prevent Symbio attacks. As humans, they'd suffer as much as the rest of us. And even a botched attack that

hurts no one could lead to calls to shut down their industry. That said, any company's prime directive is to make money, and every IGSC representative has a day job in a company that has to make quarterly goals. So it's not surprising that in a recent SynBio industry survey, Sarah Carter wrote that the people she interviewed, quote, repeatedly emphasized that biosecurity considerations were not a priority for the industry overall, with very little attention paid to the topic by investors and in industry venues. Now, this isn't true everywhere. A thought leader in this field is Twist Bioscience, a relatively large and publicly traded SynBio

company and an IGSC member. A company representative told me that Twist treats the consortium's standards as a baseline starting point for their own biosecurity measures. They have a small, full-time staff of PhDs who drill down on every DNA order that could possibly be misused. And the list of sequences that trigger reviews goes far beyond the IGSC's regulated pathogen database. That said, not everyone has TWIST's resources, and the cost of synthetic DNA is dropping, while the cost of screening is increasing as databases of concerning sequences grow larger and more complete. This means screening is heating up a growing share of companies' margins, which increases the incentives to cut corners. And my contact at Twist said that

some companies are, in fact, opting out of the IGSC for profitability reasons, particularly internationally. This worries him, and he's not alone. The World Economic Forum and a nonprofit called the Nuclear Threat Initiative have teamed up to address it. They've proposed a common screening platform that's robust, open source, and given to all industry players for free or at a very low cost. In a 2020 white paper, they wrote, quote, development of a common mechanism for screening pathogen and toxic DNA would reduce the time and expertise required to adopt and implement synthetic DNA screening practices and thereby expand those practices

to a wider range of DNA providers. They hope to have this available this year. In their white paper, they called for governments to require DNA screening practices through legislation or regulation. And although I'm generally a very free market oriented person, I fully agree. Governments worldwide should collaborate on tough regulations to forbid the distribution of any synthetic DNA to anonymous parties or known bad actors. As for dangerous DNA, it has its uses in research and other settings. And there are gradations of danger which should be treated differently. But in general, it should only be provided to highly trusted customers with excellent reasons for needing it. And as for

pandemic-grade DNA, it should never be synthesized or distributed, period. I'll add that there's no reason to ever mutate living organisms in ways that could let them cause devastating pandemics. I'm looking at you, H5N1 flu, and those who modified you in 2011. Not even if the head researcher has the most angelic history and motives, because no lab is 100% secure, as we've discussed. Plus, lab security is about preventing accidental leaks, not deliberate ones. And it's always possible that some lab worker will pass through an incredibly dark year and decide to cause the world enormous harm. This is evident in the mass shootings that happen on a roughly daily basis in the U.S. alone. No social

class or level of education makes people immune to this. The regulators should be as brilliant as the people in the industry they oversee, and they should coordinate globally. Yes, the US, China, Russia, and others disagree on plenty, but they each have everything to lose from Symbio run amok. Finally, regulators need to move as fast as the industry. No more 10-year lapses. For one example of what happens when regulators fall asleep, that ancient US government guidance didn't foresee the rise of benchtop DNA printers, which could be the future of the industry. These generate DNA in users' labs, so they don't have to order it from companies like Twist. This is significant because history is full of transitions from the center to the edge. By this, I mean capabilities that used to be provided by specialists migrate into the hands of users themselves.

For example, getting photographed used to require a technician with pricey gear. To send text messages, people used to go to telegraph offices. Printing anything on paper required professionals with special equipment. All these things can be done by users themselves now. The list is endless. The move from the center to the edge is generally a wonderful and empowering trend, but there have been regulatory tragedies.

For instance, the explosion in child pornography has been partly attributed to the fact that pictures are no longer printed in photo labs where developers could spot something evil. At some point, benchtop DNA printers will be powerful enough to aid and abet an apocalypse. Long before that, they all need to report any dangerous sequences that they're asked to create, triggering level-headed review processes. Now luckily, this is already happening. The most advanced product on the market is called the BioXP, and I spoke extensively with its creator, Dan Gibson.

The way it currently ingests and processes raw materials requires close communication between its user and its manufacturer, a company called Codex DNA, which Dan co-founded. Codex is an IGSC member, and it doesn't let its printers synthesize any DNA without a review. Over time, BioXPs will become more autonomous in terms of the raw materials they process, but Dan says they'll continue to report all print runs back to Codex so they can be reviewed like any order to an IGSC member. So far, so good, but this won't be the status quo for long. For one thing, the current version of the BioXP is analogous to the Apple II computer in 1977, which is to say that revolutionary as it is, its capabilities are minuscule compared to what's coming. And with the passage of time, the limitations of the BioXP and its errors will melt away. Limitations like its current inability to crank out a virus-length

genome. Another factor is that someday there'll be cheap knockoffs of the BioXP's distant descendants and they'll be capable of things we can scarcely imagine. Because remember, a lone lab tech can now sequence a human genome in a few hours, something that recently took the entire field of biology 13 years. So we can count on the fact that someday, undergrads will be doing things the entire field of SynBio can't possibly accomplish right now. And many of them could be using knockoff DNA printers made by amoral companies that cut corners and ignore safety measures unless they're sternly required to follow them. By then, hundreds of thousands of people could have access to gear that could cause a terrifying outbreak. And we cannot count on all of those people never having a catastrophically

dark day. So there needs to be an iron set of rules and an iron culture about keeping dangerous DNA out of the wrong hands and the most deadly DNA out of all hands. And the time to create these universal rules is now, not a few months before distributed printers attain apocalyptic powers. This may sound like a terrifyingly tall order, and I'm sure government skeptics are particularly aghast at the need for brilliant and fast-moving regulators. But remember, in less than a century, we humans banished diseases that had plagued us for millennia, made 200-ton chunks of metal fly, and transitioned from slide rules to the internet. And I'm just talking about shaping an industry that's still in its infancy and is

leaning in the right direction, we can put a very serious lid on this. Now, that won't make it completely impossible for some disturbed person or group to make a profoundly lethal pathogen because like eradicating all hijackings, that is impossible, which is why our immune system has four more components. So let's talk about the second component, early detection. Early detection is everything in epidemics, especially when a new disease is stalking the earth, like COVID or any artificial pathogen that could be unleashed in the future. That's because in the first days of an outbreak, cases tend to grow exponentially. And we saw how profound

exponential growth is when we discussed SynBio's speed of improvement. COVID illustrates the cost of ignoring a novel disease's outbreak. A study published in Nature estimates that if China had implemented lockdowns and other measures three weeks sooner, the number of Chinese COVID cases could have been reduced by 95%. Had that happened, who knows if the disease would have reached the rest of the world? And the tragic fact is, China squandered much more early lead time than that, according to an investigation by the Wall Street Journal. The head of the country's own Center for Disease Control and Prevention learned about the outbreak not from some advanced disease monitoring system,

but from reading the news online. And by then, there were dozens of suspected cases. Why? Among other things, the journal reports that local hospitals didn't log cases in the China CDC's real-time tracking system. Plus, local authorities wanted to hide bad news from Beijing. National leaders later followed suit by hiding information from the rest of the world. This is not meant as national finger-pointing, because my own country's

CDC has a dismal COVID history. I instead want to show how vital early detection will be if a deadly artificial pathogen is ever unleashed. So how do you find the first signs of a pandemic? It's not like you can just Google it, or can you? One of the most fascinating COVID-related articles I've read was written by a data scientist named Seth Stevens-Davidowitz for the New York Times in April of 2020. In it, he showed that Google searches for the phrase, I can't smell, almost perfectly tracked the prevalence of COVID across the 50 U.S. states. Loss of smell had only just been recognized as a COVID symptom at that point, so the article's chart seemed almost magical to me.

In a conversation, Seth told me that Google is remarkably generous with their search data, and he didn't need any special access to write his piece. In it, he boldly predicted that eye pain would emerge as a COVID symptom. This was not recognized as a symptom at the time, but he'd seen searches for it spike by as much as 500% in countries like Italy, Spain, and Iran when they were in the throes of their COVID outbreaks. Sure enough, within a few months, news articles were identifying eye pain as a COVID symptom. If you'd like to hear a lot more about this, then I can squeeze in here and many other topics Seth has explored using data science. I interviewed him for my own podcast, which is

called the After On Podcast. I'm posting that interview simultaneously with Sam's posting of this episode, meaning that it should be available now. So could searches be used to predict outbreaks? Work by Bill Lampos of the Computer Science Department at University College London says yes. He and a team of researchers dug deep into search traffic across several countries and compared it to reported COVID cases and deaths. They found that search traffic pointed to national outbreaks an average of 16 days before case counts started to spike. This could be an amazing tool for countries trying to get early warnings of outbreaks before local doctors have even seen many patients. And in fact, Bill told

me that Public Health England is now using his COVID models as well as a search-powered flu detector that his team has built. I'd like to see this kind of work grow exponentially for our global immune system. Since we don't know what symptoms an artificial pathogen or any new disease would trigger, we should continuously scan the search sphere for every known symptom of every known disease. And yes, I know that sounds like an insanely tall order, but big data is called big for a reason. Any symptom spike outside of a seasonal norm, like the huge spike Seth saw in loss of smell searches in Italy, could be a signal. And if it's a cluster of symptoms, it could be a strong signal, especially if that cluster shows up in more than one place at once.

Now, building this would present all kinds of interesting data science challenges. As Seth and I discuss in our interview, the biggest one would probably be dealing with false positives. But Bill Lampos believes that such a system is buildable. Better yet, he wrote to me, quote, a moderate scientific research budget can support the development of a system like that. This translates to the very low millions of dollars to potentially get way ahead of something that could cost us trillions or even cost us everything. Of course, there are many offline places to search for emerging pandemics.

One of the best, and certainly most obvious, is in the bodies of sick people who turn up at doctor's offices. One day, artificial pathogens could strike anywhere. But meanwhile, we can greatly expand our virus hunting expertise by relentlessly identifying and neutralizing new natural diseases and hotspots where viruses commonly jump from animal hosts to humans. Southern China is one such place, and parts of Africa are others. SARS, MERS, Ebola, and perhaps COVID all jump from animals and are known as zoonotic viruses.

Zoonotics are especially dangerous because until the moment they jump, no human body has any immunity or experience in fighting them. An amazing program that's just rolling out in West Africa called Sentinel could be a role model for the developed world as well, as we gear up for a time in which new diseases could strike anywhere. One of its co-leaders is Pardis Sabeti, who has appointments at both Harvard and the Broad Institute. The Broad is basically a joint venture between Harvard and MIT, and is worth knowing about, because a huge proportion of the world's best genetic science is coming out of there. Sentinel is called, quote, a pandemic preemption system for the real-time detection of viral threats, and it's launching first in Nigeria.

It will be a multi-tiered system. Its creators believe that we are, quote, on the cusp of a new era. Ultrasensitive genomic technologies have the unprecedented ability to detect virtually any pathogen, including those circulating under the radar, and can be leveraged to create simple point-of-care diagnostics to be deployed anywhere. In parallel, powerful new information systems allow us to continuously collect, integrate, and share viral surveillance data. By unifying these tools into a coherent system for the first time ever, we can detect and prevent pandemics on the ground before they start." and prevent pandemics on the ground before they start, end quote. So basically, it's sci-fi grade genomics meets cloud computing. And it sounds pretty good, huh? Sentinel will be built around

a three-tier system with simpler tools out in the field and more powerful ones in regional and national centers, and data about every single infection flowing back to a central system for tracking and analysis. If a patient has one of the area's top priority diseases, Pardis expects that they'll be able to identify it within an hour and to identify any other known human virus within a day. When I asked her how long it would take to create a test for a previously unknown disease that they discover out in the field, she said a day to build it and a week to know that it works. Pardis absolutely believes we need something like Sentinel in the U.S.

and throughout the rest of the world, although her own focus is currently on West and Central Africa. And she shares my concerns about biosecurity. So could we afford a worldwide Sentinel system? I've seen the program's budget, And while it's confidential, I can say it's absolutely in the reach of any developed country and any less developed country with just a little bit of outside financial help. In the U.S., adjusting for cost of living factors and population size, I estimate it would cost in the low billions per year. This is a trifling sum, just compared to what we lose to the flu every year, let alone a pandemic like COVID. And it's negligible compared to what a truly nasty artificial pathogen could cost us if it goes undetected for a few critical weeks.

How else might we detect a new pathogen? Well, how about plucking it right out of the air? A handful of researchers are now pioneering bioaerosol science, including Mark Hernandez at the University of Colorado. One technology he's excited about is called Condensation Particle Capture, or CPC. This uses humidity to condense incredibly tiny particles out of the air. It then concentrates them into a little vial from which DNA and RNA can be sequenced. Next-generation CPC systems are small, roughly shoebox-sized. They're also networkable and cheap, about $1,000 each.

Someone needs to collect those little vials, so CPC doesn't provide instant results. But if the samples arrive at a robust enough lab, there's no limit to the number of pathogens you could test for. Mark and I talked about a plausible future CPC system, which could do analysis right inside the box with a miniature robotic lab. He believes that if the right R&D resources are applied, this could be achieved in about five years, and the system might be about the size of a ticket kiosk. These could be deployed at transit hubs and other places you'd want to monitor particularly closely. There was actually an early U.S. government effort to do something like this called BioWatch. It arose in the wake of the anthrax attacks of 2001 and was deployed in dozens of cities targeting six pathogens.

Although it got some terrible press, Mark says BioWatch wasn't bad for its day, that it did pull genetic information out of the air and achieved its goals to some degree. Another technology Mark is excited about has the fabulous name of spectrophotometric comb. This is more physics than biology and uses lasers to characterize gases and the particles in them. The proportions of gases we exhale change when we get sick, and tracking changes could be a fantastic early warning tool. A group Mark works with has proposed an experiment looking at the breath of mice infected with COVID to see how their exhalations change as they get ill. Unlike CPC, Mark could see

this technology one day plugging into a phone. Breathe into it daily, and it will get a baseline understanding of what you exhale when you're healthy. Diverge from the norm, and it will get a baseline understanding of what you exhale when you're healthy. Diverge from the norm, and it could mean something's wrong. As the science gets smarter about what different shifts mean, better early warnings could be delivered. And if millions or billions of people start to do this regularly to monitor their personal health, the aggregate data could amount to an amazing early warning system. Mark is one of over 100 contributors to a global microorganism survey called MetaSub, run by geneticist Chris Mason, a professor at Weill Cornell Medicine. Each year, researchers in 114 global cities, plus an outpost in Antarctica,

spend a day sampling an average of 50 local sites. Some sample the air like Mark Hernandez. Others sample wastewater. But most of them swab surfaces in places including public transit systems, shopping malls, hospitals, and homes. You could think of this as a microorganism census, but it could be converted into a massive disease surveillance network by doing swabbing and analysis on a daily rather than yearly basis. Chris Mason ballparks that a budget of about $3 billion would enable this with extremely deep genetic sequencing, which would uncover even highly rare bugs in each environment. Like everything discussed in this series, that's nothing compared to the annual cost of the flu, let alone a devastating pandemic.

And about half of that cost is for reading genes, costs which are continuing to drop dramatically. Over time, this could let hundreds of additional cities join the survey for the same budget. Or the budget could be increased to expand coverage, because after all, it is peanuts compared to the steaks. Over time, investments in R&D could result in robotic systems to do the swabbing automatically

and do the geneticbing automatically and do the genetic analysis right on the machine, potentially enabling far more sampling or allowing more to be accomplished on the same budget. The bottom line is disease surveillance is an incredibly promising frontier for improvement if we prioritize the right investments today. the right investments today. Okay. Well, Rob, in thinking about how to solve this problem, we have to think about how to pay for the solution. What is the role of money in this equation? Well, I think there's two things to think about. How much is it going to take? And is society actually going to be willing to make those investments, given that we know

society basically hit the snooze bar after SARS, after Zika, after a bunch of other things. This time around, there's definitely promising signs. I do think that COVID's wake-up call is uniquely noisy. And the Biden administration has, of course, drawn up a mega billion dollar pandemic budget. But with almost all the conversation, understandably enough, focused on the immediate project of fighting COVID, it's a little hard to tease out what permanent changes will be made to our pandemic readiness. ideas starting to circulate. And also, the real test won't be what we're doing against pandemics in 2022, but what we're doing in 2032, if we've been lucky enough to have a quiet decade. Like, do we lose focus and let our capabilities atrophy after COVID's a distant memory? And for this reason, the right way to look at this, and I think the only way to look at this, is through a national security lens, in that we spend massive amounts on defense every year, even though the huge majority of our military capacity isn't being used at any given moment, because we want to be prepared for an extreme military emergency that's never happened before. And since pandemics are huge

national security risks, that's definitely how we need to budget for them. And viewing through this lens, I'd say, for example, the odds of another pandemic happening vastly outweigh those of an all-out nuclear war happening, right? billion a year, according to at least one report that I saw, maintaining its nuclear arsenal, while the world as a whole spends about $70 billion a year. Now, that kind of annual budget would fund every pandemic preparedness measure I'm going to mention in this series many times over. So it's a highly precedented level of investment to make against a major national security risk, and an investment that I think would do the trick of defending against future pandemics if it's spent wisely, which, of course, governments don't always do, but they can in a pinch, and this is a pinch. But it needs to be a relentless investment year in, year out across even pandemic-free decades.

So again, the analogy has to be defense spending, which, like an even bigger example, is counterterrorism, which the US has spent trillions on since 9-11, including two world wars. And all that shows we absolutely have the resources to fund almost any imaginable pandemic immune system on a national or global level. It's just a matter of political will. Yeah, and the point I would make here, which I think we've made at least a couple times already, is that everything we're saying about defending against a syn-bio attack applies to natural pandemics, right? I mean, even if we manage to completely solve the problem we're mostly focused on here, you know, we manage to keep the tools of SynBio out of the hands of all the bad

or crazy people that could ever want to wield them. We still have this massive risk, which we know is never going away, that nature will produce the next pandemic. That, you know, if it doesn't wipe us out, it still can be much worse than COVID, unimaginably worse than COVID and its effects on civilization if we can't immediately deal with it. So every step we would take here to prevent bioterrorism, we should be taking anyway to prevent the bioterrorism of Mother Nature. Yeah, that's absolutely the right lens to look at it through. And every countermeasure we're going to talk about, or pretty much every one, is equally applicable to natural pandemics.

Then on top of that, just look at the flu. Even if we never face another pandemic again, which is awfully unlikely, the White House Council and economic advisors put the annual cost of the flu in the U.S. alone at $361 billion a year. That's lost productivity as well as medical spending. That maps out to a trillion dollars a year and hundreds of thousands of lives worldwide. There's plenty of ways to recoup any investment that we make against these things. Yeah. So how do members of the IGSC screen for dangerous DNA? How is any of this being monitored? Well, the good news is it's actually a really interesting and ambitious precedent, and it's a great place to start. We start thinking about hardening our syn-bio infrastructure

against being hijacked. So I'll start with a quick overview of the market for long error-corrected strands of DNA and RNA. Those strands are mostly assembled by specialized companies for customers who don't want to create their own advanced DNA synthesis capability, which is almost everybody because that's very expensive to build. So it's kind of like how people used to get their photos developed at drugstores rather than building home dark rooms, right? Now, the centralized DNA creators are almost shockingly unregulated. There's just this voluntary guidance, which the government issued over 10 years ago to keep dangerous DNA away from bad guys. Guidance which has never been updated.

But luckily, the industry itself doesn't want a Hindenburg moment, you know, like a catastrophic biosecurity lapse, because that could lead to massive regulation or even the industry getting shut down, which is why we have this self-regulating body called the IGSC, which doesn't really have its own staff or resources, but its members jointly maintain a comprehensive database of pathogen genomes. That's the main function of the IGSC, as far as I can tell. And the members screen all of their orders against that list. It's pretty impressive.

And every order is tagged either red, yellow, or green. So if there's no meaningful overlap between the order and the genetic code of any known pathogen, the order is marked green and it sails right through. That's about 95% of orders. But about 5% of orders are yellow, and that means there is significant overlap with some stretch of DNA in a pathogen. Those orders are very carefully reviewed for maybe an hour or two, and it usually turns out that the overlap is with a benign stretch of DNA, like maybe it's a housekeeping gene or something like that. But every so often, a yellow order becomes a red order because the genetic code that someone's requesting is directly connected to some kind of dangerous machinery in a pathogen. And those

orders take several hours to review. And sometimes they're ultimately proved, sometimes they're amended. And in some cases, I understand they're actually reported to the FBI. Now, the thing that's interesting is this review work is done by bioinformaticians, I mean, very often PhDs. So it's a very thorough apparatus, and it's also very expensive. And the industry is doing this on its own already. It's a hell of a start. But its expense is why some companies are just opting out of the

whole thing and don't join the IGSC at all, because none of this is required by law. And the IGSC has the statistic that it represents 80% of total industry capacity. But that was really just an educated guess that someone, and nobody can seem to remember who, made many years ago. And I'm totally confident in saying that it's very outdated because the IGSC has exactly one Chinese member and China's SynBio capacity is growing like mad because it's a huge government priority. So what should change? Well, the guidance on SynBio safety, first of all, has to stop being voluntary. It has to stop being 10

years out of date. It definitely has to apply to 100% of the industry. And it's got to be internationalized through careful cooperation with China and everyone else. And that's a very tall order. But the great news is that the starting point that the IGSC has coordinated can absolutely form the core of the first layer of our global immune system of hardening up our syn-bio architecture. Because if it's universalized, it would, without question, just hugely reduce the number of people who could do something awful with synthetic DNA. Because working around universal restrictions would just require so much more planning, so much more stealth and skill than simply ordering something from a rogue supplier that doesn't implement any protections. So we have a great start, but it does need to be universal. And, you know, again, it has to be up to date. Ten-year lags don't cut it. But what is the mechanism that would enforce compliance internationally here? Certainly if you're talking about a rogue state, well, it's in the very nature of being

a rogue state that it is not compliant with international demands. Again, North Korea is a perfect example. But even state-level misbehavior aside, even within labs or individuals within other countries, what leverage do we or any collective we have to make sure that this compliance is truly international? Yeah, I mean, there's two dimensions of that. One, how do you get IGSC-like regulations enforced by all countries that have private syn-bio industries? And that is challenge number one, and it's an ample challenge. But there are, I'm sure there

are many industries that have relatively universalized regulations throughout the world, in part because that's in the interest of industry, to not have to comply with rules and countless jurisdictions that might be different and so forth. But that's hard enough, and I don't want to minimize that. But state actors are a whole other wrinkle. Because if we look to the Montreal Protocol for reassurance, the hole in that analogy is that state actors themselves didn't have big chlorofluorocarbon projects of their own. Those were industrial ingredients. They were coolants for air conditioners. They were making foam packaging for McDonald's, that sort of thing. So in that case, governments were regulating society, which they're perfectly happy to do.

But sovereign governments get really grumpy about restrictions on their own actions. And so it's not hard to imagine the Chinese state or the US, for that matter, secretly developing governments in bio capabilities to stay ahead of the rest of the world. So, you know, in addition to an internationally coordinated IGSC-like system for keeping private industry safe, we definitely need something like the Nuclear Non-Proliferation Treaty for SynBio amongst nations, which is a really tall order. And it's not something I have a ready-made playbook for. But I will say that as we scale up all of our national protective layers, it's really important not to neglect the international side of things. And this has to be a feat of very

significant and determined international diplomacy without any question. determined international diplomacy without any question. Hmm. So are there any lessons to draw from, you know, on this point of cooperation and its enforcement internationally from our experience with China and COVID? I mean, there's so many ways in which cooperation almost happened and then failed, and then we're still trying to figure out to what degree rank deception is the story of what China has done here. What lessons do we draw from COVID? Well, it's obviously not an encouraging example on so many levels. I mean, the denialism, the suppression of people spreading the word about the outbreak, the fact that people in regions like Wuhan are often afraid to report

bad news up to Beijing. So there was stonewalling internally, according to that very extensive research that I cited in the recorded material by the Wall Street Journal. There was obviously stonewalling on an international level. But what we can hope for, and I don't think this is a naive hope, is that a lot of people in a lot of countries are looking at all the botched responses to COVID and saying never again. And they're saying it with the kind of determination that carries over across years and across decades. And, you know, the kind of encouraging thing, in a weird way, is that I think China's disease detection system might have actually been up to the challenge of containing COVID. But for some tragically delayed responses, which Beijing will presumably do everything possible to avoid in the future. And from that, my optimistic side says the world may be closer

than we think already to adequate warning and detection systems. And where I get this from is a fascinating paper in the journal Nature, whose lead author is Shenji Lai, L-A-I, at the University of Southampton. And it analyzes China's so-called non-pharmaceutical interventions against COVID, which is a fancy term for quarantines, lockdowns. It's a fancy term for welding people into their apartments. Exactly. And masking and that kind of thing. The non-pharmaceutical interventions, the NPIs.

And the paper's analysis goes into a lot of depth and says that these interventions had been implemented a week earlier. China's COVID cases could have been cut by about two-thirds or cut by something like 85% if they were implemented two weeks earlier or 95% if the lockdown and so forth happened three weeks earlier. So, you know, did China have three weeks? if the lockdown and so forth happened three weeks earlier. So, you know, did China have three weeks? And the answer is these interventions started, I think it was on the 23rd of January. And as early as late December, this fairly heroic doctor that some people have probably heard of named Li Wenliang first sent a message to some fellow doctors warning of a SARS-like outbreak in Wuhan. So yeah, that's over three weeks of lead time. And since this was a lone doctor, you know, basically successfully tuning

into the pandemic just from his narrow personal experience, I think we can safely assume the local health authorities, who would have had much broader access to data, had to be aware of something. Now, this is just terrible to even think about because a 95% drop in China's cases may well have prevented the global outbreak. But it's also, it feels just really unlikely that a delay like that will happen again in a post-COVID world. There's just going to be so much more urgency about any warning signs. And there's meanwhile, a ton of things we can do to dial up the sensitivity of early warning systems throughout the world, which we'll talk about. And all that together gives me real optimism about our ability to detect and hopefully also snuff out potential pandemics,

whether they're natural or artificial. Is there any more that you've uncovered on the monitoring front, or just how we can pay attention to what's happening in the world? Because again, this is the kind of thing that by its very nature will emerge by stealth. I guess some maniac could decide to take the Bond villain approach to this, saying that if my demands are not met, I will be releasing the doomsday virus on New Year's Eve. But generally speaking, we're just going to hear about people getting sick somewhere, and we're not going to know what's going on or for how long it's been going on unless we build some system by which we detect these things earlier and earlier.

Yeah, I mean, I would definitely like to draw attention back to that Nigerian system called Sentinel, or it's being rolled out in Nigeria, called Sentinel that I talked about in the recording, which just to quickly review is, I think they call it a pandemic prevention system using real-time detection of viral threats or something like that. The expectation with Sentinel is that they'll be able to empower community health workers to diagnose any of a region's most common viral infections or highest priority viral infections, so probably the common ones along with rare scary ones like Ebola or whatever, within an hour, and to basically diagnose any known human virus within a day by pushing things up the chain to a central

organization. And, you know, my back of the envelope math on that, as I mentioned in the recording, is that it would cost in the low billions to trot out something like that, for instance, in the US. And you've got to ask yourself on a certain level, why in the hell haven't we done that? And part of the answer is that some of Sentinel's technology is very new, and also the amount of genetic sequencing that it involves would have been impossibly unenforceable just six or seven years ago. But the bigger reason is the American healthcare system is just this baffling thicket of overlapping jurisdictions.

Some things are managed by 50 different states. Other things are managed by 3,000 different counties. And at least for now, a nationally coordinated system like Sentinel seems to be completely beyond us. I mean, just one example from yesterday's New York Times. An editorial in yesterday's Times said that 20 million COVID vaccines have essentially gone missing in the US,

which is a huge number when 40 million vaccines have actually been injected so far. And I think the intent of the editorial was that they've gone missing from the standpoint of the federal government, which basically means the federal government is pumping out the nation's scarcest and most precious resource into 3,000 counties and 50 states and losing all track of it. And we obviously need to do better than that. And when it comes to disease surveillance, we need to do what Sentinel

is bringing to Nigeria, this real-time radar of viral infections. And obviously, counties can't build that. It needs to be a national system. And I think it would have to hinge on radically expanding testing and diagnosis of all respiratory infections. I mean, flu, rhinoviruses, minor brushes with a common cold, the whole shebang, which we don't currently even attempt. I mean, have you ever in your life had a flu diagnostic? Like, has a doctor ever said, hey, you don't have the flu, you have a rhinovirus, or you have influenza A, not influenza B? I mean, basically no one has ever experienced that because people usually recover from these things and collecting the data didn't seem important. But this has got to change, because the only way we're going to know if something new and dangerous is emerging is if

we track the full national inventory of viral infections as close as we can, which basically means, in my mind, a project warp speed for diagnostics, for testing, not just COVID testing, obviously, but every respiratory infection we know of. And I understand the Biden administration plans to invest a lot in tests. And I don't know how much of that is for the current crisis and how much of that is ongoing, but we basically need a whole new category of diagnostics, ones that can test for multiple diseases and which are reliable, which are cheap as hell, and above all, can be taken at home. Because we want to track these things much more closely,

but we don't want to trigger an avalanche of new doctor visits. We just don't have the capacity for that. And most people wouldn't bother with a doctor visit for a mild infection anyway. So these tests should be in every home. They should be free. And somehow the results should be automatically logged with the national cloud. Like maybe you need to scan some kind of coded display on the test with your phone to get the results.

And all of this disease information needs to go into a real-time integrated system that's inhaling lots of other data as well. I mean, something kind of like NORAD, the super high-tech military command that scans the skies for nukes and enemy planes. Like a disease tracking center that's staffed 24-7 by data scientists looking at data from all kinds of sources, like all those diagnostic tests, also online data, search engine queries, and so forth, like we talked about. And hopefully we're smart enough to invest in a bioaerosol grid and the technologies I talked about for pulling viruses out of the air in public spaces,

that data should also feed in continuously. And hopefully we're also smart enough to build a hugely expanded version of MetaSub, that academic project, which tests surfaces and wastewater and air samples for viruses in over 100 cities, that data would feed into. And it should also be dialed into, obviously, the local public health systems. So if there's an alarm signal somewhere, you can get boots on the ground and see what's happening. Now, that's quite a wish list, but we could build something like that, and it would be an amazing layer two for our global immune system. Yeah, well, there are at least two parts to this that are distinct. There's the actual diagnostic end of it where you have to swab the door handle on a bank or the keypad on an ATM

or somebody's nose or get a saliva sample, and then you need to take all the friction out of the system that allows those samples to be processed and analyzed. But then there's just this massive information integration problem and, you know, prospective and retrospective search of the data, looking for patterns. And I got to think on that second piece, once again, the 20% time, companies like Google and Palantir and these other major tech corporations that have so much engineering talent, that could profitably be spent there. And it's got to be shouldered as a responsibility by every smart person who has something to contribute here. My fear is that we will solve COVID. The vaccines will ultimately get distributed and they will work, you know, if not in the first volley, maybe the second,

right? We still have these variants now that could be outrunning some of the vaccines. But you can imagine us putting this behind us fairly conclusively, and then that ushering in a kind of roaring 20s-like spirit of, okay, well, we've reset everything, you know, hallelujah, and that we could lose the lesson that we really must draw from this, which is we can't let this happen again. Again, this is a dress rehearsal that we have manifestly botched in almost every way, apart from the speed with which we produced vaccines. And yeah, so I do worry that once we get out from under this, we will lose the sense of urgency and just assume, okay, this sort of thing only happens once a century anyway,

so we can go back to sleep. Yeah, I mean, and that's why I'll come back to the idea that this absolutely needs to be viewed through a national security lens. And maybe just because it is so damn good at lobbying for hundreds of billions of dollars every year, we kind of hold our nose and put it under the Department of Defense because, you know, they sure know how to lobby for dollars. And it's got to be something that is done relentlessly year in and year out, like we do with funding military capacities that at almost any given moment are 99% unutilized. And we've become okay with that as a society because we know that we someday might need to draw on emergency capacity. But the other thing is that the IT work, I mean, I'm just sort of glibly

describing something like NORAD. I assume NORAD works really well. I don't know. I've never been there. But what we do know is that the IT contracting that the government has done for all kinds of things has at times been completely catastrophically inept. And just look at the debacle of the vaccine rollout. The New York Times editorial that I just mentioned about the 20 million vaccines that have gone missing also mentions that the federal government gave Deloitte a $44 million no-bid contract to develop software for states and others to use during their vaccine rollouts. And the product is simply catastrophic. A lot of health departments have completely ceased to use it. A lot of health departments have completely ceased to use it, and we can't have that level of incompetence and that lack of seriousness invade or infest somethingir can allegedly do than from the kinds of projects the federal government has overseen. I mean, it's hard higher level of seriousness as we tackle this thing. And again, maybe this gets back to that

20% time notion, not that you would want this natural detection grid to be staffed by part timers, but maybe people who are intent on careers in SynBio view things from a linear standpoint and say, maybe I'll give 20% of my career to doing work in the public interest. And so maybe we could have some really, really top-flight people from academia and private industry see to it these systems are outstanding and work incredibly well. Yeah, yeah. And I'm sure there's a role for philanthropic organizations here to point resources in the right direction and just lobby for this being a priority.

Some of the most important work that can be done here, I think, is just to make the case that we need to allocate the resources at the government level. And this is the problem we've run into all these long years with climate change. We're still barely at the starting line because the war of words has been so difficult to win. And we really need to figure this one out. Somehow, I think this is less abstract to most people than the risk of climate changes. But we're also living in a country where it seems that at the time of this recording, something like half the country is fairly carefree about the prospects of catching COVID

and quite worried about getting vaccinated for it. It's the absolute inverse of what you would think would be psychologically possible. So we obviously do have a major messaging problem here, which also requires a commitment of resources. And that is in large part the purpose of this podcast. So, Rob, let's listen to the fourth and final section of your, by turns, fascinating and harrowing meditation on the future of SynBio and global pandemic. on the future of SynBio and global pandemic. This brings us to the third component of our immune system, which is hardening society against future pandemics. So what can we do to toughen things up?

Well, probably dozens of things. And as I said earlier, this podcast can't be a comprehensive list of everything we could do. But I'd like to lay out a couple of intriguing possibilities that might just be game-changing. For now, they're both unproven, but they're examples of the types of investments we should be making, in some cases tiny ones, to bulk up our arsenals. The first is a very particular ray of light, of ultraviolet or UV light. As you may know, UV is invisible to human eyes. It's carved up into various bands and sub-bands, just like radio.

UVA and UVB light from the sun shine through our atmospheres and cause sunburns and skin cancer. A higher frequency band called UVC light doesn't get through, but we can make it ourselves down here with lamps. UVC has lots of energy, so much that it kills microorganisms by frying their DNA. You may have seen it sterilizing things in hair salons. It's also used to sterilize operating rooms in hospitals and buses in some countries. But only when those places are empty. Because again, UV light is bad for us.

Or at least, most of it is. The UV-C spectrum has its own little neighborhoods. One of them is called Far UVC spectrum has its own little neighborhoods. One of them is called far UVC, and fascinating research shows that it may not damage human tissue at all. David Brenner, a radiation physicist at Columbia, has done most of the groundbreaking work here. In a July 2020 interview with TED's David Bielo, he explained that light around the 222 nanometer wavelength just can't penetrate the dead cells that form the surface of our skin and our eyes.

He's exposed the skin and eyes of mice, as well as human skin to it. And there's no sign that it gets through that outer layer to do any damage. But viruses and other bugs are much tinier than our cells, and this light zaps them. David Brenner's experiments have shown that it kills off airborne thugs like

influenza and coronaviruses. He'd like for far UVC lights to be in indoor spaces everywhere and to be switched on safely in the presence of humans whenever outbreaks occur. He's calculated that 99.99% of the pathogens in an enclosed room could be knocked out by these lights in just a few minutes. Now, this wouldn't sterilize diseases out of existence. After all, it takes seconds, not minutes, for a sick person to sneeze on you in the subway. But it could bring the ambient level of pathogens way down and completely sterilize surfaces. In other words, while it wouldn't make the built environment virus-proof, it could harden it quite a bit. But there's a puzzle here. Dangerous UV wavelengths

aren't all that much longer than far UVC. It's all measured in nanometers. So why can the bad UV penetrate our skin when far UVC can't? I talked to a Scottish physicist based in Australia named Charlie Ironside who explained this. Different materials absorb and reflect different frequencies of light. And the proteins in our cells happen to be highly absorbent right around that magic 222 nanometer wavelength. And when light is absorbed, it decays away exponentially as it enters the material. So boom, our outer layers of dead cells are bulletproof, or at least very opaque, at 222. dead cells are bulletproof, or at least very opaque, at 222. To make far UVC today, you need clunky tubes,

which are big, ugly, inefficient, and generate way too much heat. Charlie has spent decades working with LEDs and has issued a call to arms to the industry to make far UVC LED products. If things work out, he thinks they could even be integrated into smartphones, letting them act as germicidal wands. No more need for hand sanitizer. But lots of research and development would need to be done. And as Physics World recently pointed out, nothing's going to happen until safety is proven beyond a doubt.

David Brenner's intriguing experiments notwithstanding, this is yet to be done. If you're like me, you're wondering, why in the world not? Safety studies would cost in the millions, in a world that's losing trillions to a pandemic, a world which will, without question, face future pandemics. And this could be a game changer, or it could be a dud. But we'll only find out if we put it to the test. Our global immune system has to fund research that could strengthen our pandemic readiness, especially when next steps cost so little, and excellent research shows that the results could be transformative. This brings us to the BCG vaccine.

BCG prevents early childhood tuberculosis and has been given over 4 billion times since the 1920s, more than any other vaccine. It's so safe, it's given to over 120 million infants each year. And there have been signs that it fights many diseases beyond tuberculosis for almost a century. Way back in 1927, a Swedish study found that BCG vaccinated children turned out to be three times less likely to die from any cause. More recently, a 25-year study of over 150,000 kids in 33 countries showed the vaccine reduced lower respiratory tract infections by 40%. Then a very recent study in Greece showed an 80% drop in respiratory infections amongst older adults who were given the vaccine, as well as a 50% drop in all other

forms of infection. And BCG's superpowers go far beyond this. It's now a frontline treatment for bladder cancer, and there are promising signs that it might even help to prevent cancer from arising in the first place, and possibly even prevent Alzheimer's. BCG seems to work its magic by strengthening the innate immune system over the long term. Think of this as being your body's first responders. It's the innate immune system that instantly kicks in when something punctures your skin or when you first get an infection. It's ready to fight anything, unlike the adaptive immune system, which creates highly effective specialized responses to specific enemies, but needs time to get started. So could widespread BCG use help foil a pandemic? Well, as early as March, people started noticing that countries with long-running BCG programs,

like Japan, generally had much lower COVID infection and death rates than countries with no BCG programs, like the U.S. A rigorous study of this effect appeared in the July 28th edition of the Proceedings of the National Academies of Sciences. To control for things like socioeconomics, population structure, and urbanization, the researchers looked at a set of what they called socially similar European countries, and they found that for every 10% increase in a BCG coverage index, COVID death rates dropped by 10.4%. An intriguingly stark example was found in Germany. Back when the country was divided, East Germany pursued a policy which has yielded far more BCG

coverage in today's elderly adults, who are of course the most vulnerable group to COVID. And today, the death rate from COVID is 290% higher in Western Germany, the opposite of what we'd expect to see, given that Western Germany is the far more prosperous region. Is all of this just a coincidence? Of course, it could be, which means this screams for multiple clinical trials. They should be run in places like the U.S., where almost no one has ever had the vaccine. Researchers would then give one group of people BCG and another group a placebo, and then compare COVID infection rates between the groups over time. Although some BCG COVID trials are in fact underway, I'm still stunned by how hard it is to raise tiny research funds for such

obviously important work. As I was researching this, I got to know two scientists who were proposing some exceptionally well-designed research into BCG's benefits for an extremely vulnerable population to COVID. They're from one of the world's top and best-known universities, but instead of running their trial, they were hunting for a few million dollars in funding during a pandemic that's costing the U.S. alone $7 trillion, at least. Again, this is insane. Even though BCG, like Far-UVC Light, could admittedly turn out to be a flop, we won't know until we fund the inexpensive research that tells us. You might question why this research is still important, with so many COVID-specific vaccines entering the market. The answer is that we have inexpensive research that tells us. You might question why this research is still important with so many COVID-specific vaccines entering the market. The answer is that we have an entire

planet to vaccinate, almost 8 billion people. Some of the new vaccines are expensive with limited production capacity, whereas BCG costs as little as 7 cents a dose and is made by 22 different manufacturers throughout the world. And COVID aside, this could be a game changer for future pandemics. BCG's greatest superpower seems to be fighting respiratory infections of all types. And a huge percentage of pandemics, as well as novel diseases with the potential to become pandemics, are respiratory in nature. SARS, MERS, COVID, flu, tuberculosis itself. You get the picture. And God forbid we ever have an artificially modified H5N1 outbreak. But if we do, boy, will that be a respiratory nightmare. If a future pandemic could be greatly softened by a precautionary BCG

vaccination program, we'd be fools not to do the inexpensive research to either prove or debunk BCG's efficacy. And again, if we do decide to vaccinate people, BCG costs as little as seven cents a dose. So giving the largest totally unvaccinated country, the US, full coverage would cost peanuts. If you'd like to learn a lot more about the BCG vaccine, tuberculosis, and more, I interviewed a brilliant Harvard epidemiologist named Megan Murray for my own podcast, which again is called the After On Podcast. Her academic focus is tuberculosis, and she knows tons about BCG and its potential. Our interview runs for well over an hour and goes into much more depth than I can cover here. more depth than I can cover here. That episode may or may not be posted by the time you're hearing this, but if it hasn't been posted, it's the next one in the queue, so you'll be able to access it

quite soon. The last method for hardening society that I'd like to highlight doesn't hinge on cutting-edge science, but on plain old public policy. It is to greatly increase the social safety net that keeps people from sliding into states of extreme despair. Though it may be hard to feel empathy for suicidal mass murderers, we have to accept that all of them arrive at profoundly dark places that few of us can even imagine. These are not swift journeys, and all involve some form of mental illness, be it extreme depression, uncontrolled rage, pathological narcissism, schizophrenia, or something else. We need to study the case histories of everyone who snaps in this way and greatly increase our vigilance and generosity in detecting and treating the relevant conditions. Here in the U.S., a de facto

policy of emptying asylums for the mentally ill back in the 80s has done us no favors. More broadly speaking, every single one of us can be a white blood cell in this global immune system by each doing what we can to ensure that no one goes unloved. This brings us to the fourth component in our immune system, which is conquering viruses. But before we talk about viruses, let's briefly discuss bacteria, which can be extremely dangerous. They cause things like cholera and bubonic plague, which can be extremely dangerous. They cause things like cholera and bubonic plague, which still bubble up in places with overwhelmed healthcare systems. Plus there's so-called superbugs, which resist all antibiotics. These killed about 700,000 people in

2016 and could be over 10 times as lethal by 2050, which means they could significantly exceed the death toll of even COVID. We're desperately underinvesting in new antibiotics, and this urgently needs to change. That said, almost every major epidemic since antibiotics were discovered has been viral. Influenza, polio, mumps, yellow fever, measles, dengue, AIDS, SARS, MERS, COVID. And as for true pandemics, only viruses cause them in the modern era. So why are viruses such tough customers? Ironically, it's because there's not much to them. They lack the basic machinery of life and don't have any cells. So they infiltrate our cells. That doesn't leave us many targets when we go after them, because we don't want to wipe ourselves out along with a virus. Bacteria, on the other hand, are cells, ones which are very different from ours. That gives us loads of targets when we fight them. And many of our

antibiotics are broad spectrum, which means they can wipe out all kinds of bacteria, sometimes too many. This makes it almost certain that the first deadly artificial pathogens will be viruses. So does a second factor, which is that bacteria are radically more complex than viruses and are therefore much harder to engineer. Other deadly critters, like the parasites that cause malaria, are more complicated still. Complexity also makes it almost certain that early man-made bugs will be modifications of existing viruses, not completely artificial ones, because it's currently beyond

anyone's capacity to make complex, functioning viruses from scratch. So how should we face the threat of artificially modified viruses, terrors like that contagious version of H5N1 flu, which has already been created. Well, I'd say exactly how we should have been facing natural viruses for decades, steps that probably could have stopped COVID in its tracks. There are two main sets of tools to consider. The first is vaccines to prevent viruses from infecting us in the first place. The second is therapeutics, a fancy word for medicines to help us fight viruses if we do get infected. The trick is that so far, both sets of antiviral tools have

been very narrowly targeted at very specific diseases, rather than having the broad spectrum disease fighting power of many antibiotics. So let's start by talking about therapeutics. Here, Johns Hopkins Center for Health Security senior scholar Amesha Dalja sums things up, writing, quote, the existing armamentarium, by the way, I love that word, of antiviral drugs is rapidly expanding and now covers several viral families. However, very few existing antiviral agents have spectrums of activity that even slightly But it's not hopeless. In a conversation with me, Amesh pointed to several viral therapeutics that hit multiple targets. One influenza treatment has proven effective against Ebola.

Another medicine fights members of four virus families, herpes, pox, adeno, and polyoma. And something called ribavirin, which was name-checked in the movie Contagion, can help treat hepatitis C and E, influenza A and B, parainfluenza viruses, Crimean Congo hemorrhagic fever, metanumovirus, new and old world hemorrhagic arena virus, and SARS. Although it unfortunately has what Amesh calls serious toxicity issues. So what do we do with all this? Amesh told me he'd like to see a serious multi-year program to test every antiviral medicine that's ever been developed against every dangerous viral family. Though reluctant to put a firm budget on this, he said it could cost several billion dollars and take several years.

Chump change in light of what we're up against. And this would give us something crucial that we lack, a complete understanding of what our existing weapons can already clobber. For now, we make these discoveries haphazardly or reactively, like when the Ebola medication remdesivir proved to have some effectiveness against COVID. There may be some truly broad-spectrum wonders in our viral toolkit already that we just don't know about. So let's figure this out. Amesh also calls for us to proactively develop new antivirals to cover full viral families, like all coronaviruses. Pull that off and you've

tackled SARS and MERS, as well as four causes of the common cold, plus, above all, COVID. Just imagine where we'd be now if we'd launched a successful campaign against the full coronavirus family right after the SARS crisis in 2003. With a powerful anti-coronavirus treatment in our arsenal, COVID fatalities could have been a tiny fraction of today's death tolls, and society and the economy could have been far less disrupted. Amesh notes that it usually takes about a billion dollars to get a drug to market. Big bucks, but small change compared to what's at stake, even if you do this for every viral family that sickens humans,

of which there's just a couple dozen. Although there are a few viruses that don't currently infect us that we should probably sharpen some weapons for. Remember those zoonotic viruses? Something called the Global Virome Project keeps a wary eye on bugs that haven't yet jumped to humans, but may one day do so. Like so much of what we're discussing, all these antiviral measures would bring massive benefits against natural pathogens as well as artificial ones. And strictly in light of the endless costs that natural diseases inflict on us, we'd be crazy to skimp here. Also, there are things that could help bring the costs down, like software-based modeling and screening of drugs against specific diseases, a new field that's showing lots of promise and appears to be very cost-effective.

Now, of course, the other side of the viral defense equation is vaccines. And here we'll start by talking about the flu again, because lots of smart people have been calling for a universal flu vaccine for years. By this, they mean a vaccine that works against all strains of the influenza virus. So if you stamp out seasonal flu, you've protected people from rogue versions of H5N1 flu for free, along with countless other variations. A universal flu vaccine would also hopefully be good for multiple years, unlike the annual vaccines we currently get. There are lots of good reasons to get blanket protection from

influenza. As we've already seen with H5N1 flu, it can be hacked in terrifying ways. It also kills three to five hundred thousand people worldwide each year and costs over a trillion dollars in global economic activity. Plus, it mutates constantly, reinfecting people who recovered from earlier strains. Those mutations can also trigger deadly pandemics, as happened in 1918 and three times since. Finally, the current vaccine is just so inadequate. It's only 10 to 60 percent effective depending on the year, and its manufacturing is largely based on 1940s technology. One of the top people who has long called for a universal flu vaccine is Harvey Feinberg, a former dean of the Harvard School of Public Health and a former president of the

National Academy of Medicine. He told me that he thinks it would cost just $1 to $200 million to fund a fully dedicated effort that would have, quote, a very good chance, end quote, of developing a universal flu vaccine over about 10 years. You heard that right, just $10 to $20 million a year. And he points off that even if he's off by an order of magnitude and it costs $1 to $2 billion total, it's a staggeringly good deal. Now, you could spend this money only to find out that a universal flu vaccine is impossible with today's science. only to find out that a universal flu vaccine is impossible with today's science. Harvey puts those odds at at least 25%, and maybe in a stretch as high as 50.

But if we take the worst possible numbers from all of his ranges, and figure it's $2 billion to get just a 50-50 shot at saving the world a trillion dollars and hundreds of thousands of lives each year. It's still the deal of the century. And of course, there's no reason to stop with the flu. Harvey thinks similar programs against other viral families would cost similar amounts and face similar odds. If given the budget, he'd start with universal influenza and coronavirus vaccines. He thinks we'd learn enough from this to make later efforts targeting other viral families faster and cheaper. So again, let's say we take the worst possible number from Harvey's ranges and launch universal vaccine programs against all of the couple dozen virus families that

sicken humans. This one-time moonshot program would cost less than 5% of what the flu alone costs the world every year, and less than 1% of COVID the flu alone costs the world every year, and less than 1% of COVID's bill. Even if artificial bugs are forever pure science fiction, this is an investment humanity cannot afford not to make. And no, you wouldn't have to get all those shots, although you'd be wise to get the influenza and corona ones. Instead, we'd stockpile these vaccines and have them ready

in case something is bad or worse than COVID emerges from one of those many viral families. And as with viral therapeutics, just imagine if we'd had the foresight to launch a family-wide coronavirus vaccine program in response to the SARS outbreak in 2003. Society literally could have been inoculated against COVID before it even raised its head.

On to our global immune system's final component, battle infrastructure. So let's say the worst happens and an evil artificial bug or something nasty and natural is on the loose. What do we need in our arsenal that we'll wish we had invested in today? As a first step, Harvey Feinberg thinks we should adopt a national security mindset toward pandemics. And I fully agree. These can be threats on the scale of a world war, after all, which calls for a unified command. And Harvey believes the head of it should carry, quote, the full power and authority of the American president to mobilize every civilian and asset needed to win the war. That's the

approximate opposite of how the U.S. at least met COVID. One small example of dozens, the federal government here triggered a bidding war between the 50 states for critical equipment and supplies by refusing to coordinate purchasing and distribution. This turned the states into rivals rather than allies, while prompting hoarding and backstabbing. In the words of the Wall Street Journal, quote, Some states turned against each other. One refused to give another contact information for lab supplies, fearful of being outbid. Governors kept shipment details secret.

Other governors dispatched state police to airports to guard their cargo, end quote. A bigger example, the federal government left it to each state to concoct its own defense and public health strategy against COVID. Of course, by definition, states don't have National Institutes of Health or National Centers for Disease Control. Thus badly underpowered, states made their best guesses as to what might work, resulting in a stew of conflicting policies and even quasi-border controls against citizens of other states. might work, resulting in a stew of conflicting policies and even quasi-border controls against citizens of other states. Could you imagine approaching something 10 to 100 times deadlier

than COVID with this sort of flailing? The virus would finish us. Harvey also thinks voluntary quarantine should be more widely practiced and available on demand. By this, he means offering temporary accommodations to people who have been exposed to protect the people they live with. This is important because close, extended indoor contact is the surest way to catch someone's infectious disease. Just consider how badly COVID spread in nursing homes. Now, it may seem heartless to suggest that someone consider separating from their housemates or family, but saying you should quarantine at home is an invitation to infect everyone there, while only getting ad hoc, homespun medical care,

unless you happen to live with a doctor or a nurse. Is that less heartless? Or more? Imagine someone's instead offered a free stay at a hotel that's been shuttered by a pandemic. Harvey outlined a compelling pitch to me. You could stay somewhere other people would pay hundreds of dollars a day to live in. You'll have room service because that enables social distancing. You'll have 24-7 Zoom access to everyone you love via in-house broadband. Okay, you won't get spa services, but you will protect your family for the next 10 to 15 days.

Quarantine locations could have trained personnel ready to manage mild infections much better than most people's housemates. And if things turn ugly, someone under quarantine could be transferred smoothly and directly to a hospital. We haven't seen much of this sort of thing outside of a few places like New York City. Perhaps partly because China adopted a very coercive approach to this with what they called fever clinics, which gave the practice a bad name. It also takes forethought and perhaps some earmarked funding to set up a more comfortable voluntary program. And COVID caught the world unawares. But we have no excuse for letting the next pandemic sneak up on us. Especially if it's something much deadlier and more contagious than COVID, a complete lack of quarantine could really sink us. To all this, I'll add the dead obvious suggestion

that personal protective equipment, ventilators, and other defensive tools should be stockpiled to a degree that verges on absurdity, and that all nations should try to establish highly local supply chains for this critical gear. Also, this stockpiling should not be limited to governments. Just as all homes are mandated to have smoke detectors, home stockpiles of N95 masks, hand sanitizer, and other essentials should be mandated by law, and perhaps paid for with government funds, to ensure high compliance. I say this as someone who tends to be highly anti-regulatory by nature. But if we get whacked by something much worse than COVID, we cannot afford months of supply outages, hoarding, price gouging, and counterfeit products on the personal protection market like we saw at the start of this pandemic. And if you think all this sounds like a totalitarian imposition, recall that personal hygiene and PPE use don't just affect the person practicing or not practicing them.

They affect everyone, because scofflaws and free riders infect the rest of us. So this isn't a matter of personal freedom, like choosing to eat junk food. It's a matter of civic obligation, like refraining from drunk driving. In this spirit, universal PPE stockpiles should be accompanied by a predefined set of rules and levels. For instance, if a region goes to a certain infection level during an outbreak, universal mask wearing in public becomes mandatory. Everyone knows the levels, everyone knows the rules, everyone has the gear at home, and there are no excuses.

Another relative novelty we should consider seeing more of is challenge trials. These involve testing a vaccine by deliberately infecting healthy volunteers with the disease it targets. Now I know that sounds insane. So let me explain the rationale using COVID as an example. Big COVID trials inject tens of thousands of people. Half of them get the vaccine, half get completely inactive placebos.

Then everyone waits until a couple hundred people come down with the disease while going about their ordinary lives. If most or all of the sick people turn out to have gotten the placebo, in other words, if the people who got the vaccine don't get sick, then the vaccine's a winner. There are two issues with this approach. First, it takes a long time to recruit tens of thousands of people to take an experimental injection. Second, it can take months for enough people to get sick on their own to generate statistically significant data, which is normally fine.

But what happens if thousands of people are dying each week? If your vaccine works and you could have saved several months by running a challenge trial, tens of thousands will die waiting for the results. Compare that to the number of test subjects who might die from deliberate infection. In the case of a COVID challenge trial, that number may actually be zero. The reason is you'd probably mostly allow young volunteers to enlist, people who are quite unlikely to die from the disease. And instead of signing up tens of thousands of participants, quite unlikely to die from the disease. And instead of signing up tens of thousands of participants, you'd have just a couple hundred. Why? Because you don't have to wait for a small percentage of a huge group to catch the disease to get the couple hundred infectees it takes to determine

efficacy. Because in challenge trials, everyone's infected. And at least with COVID, if they're all healthy and mostly in their 20s or 30s, the odds are decent that literally no one out of a couple hundred participants will die. But what if one or two volunteers do die? Isn't that unconscionable? Well, compare that to the tens of thousands of people who could end up not dying if your vaccine works. When are one or two lives worth more than tens of thousands of lives? Well, when lawyers are involved, for one thing. And that's one reason why we don't see challenge trials, because the loved ones of someone who dies in one might sue the trial manager, whereas the anonymous masses who die waiting for a vaccine trial to run its course have no one to sue but Mother Nature. And she doesn't pay up. Another reason is that doctors are deeply squeamish about imperiling anyone in their care, as they should be. Not only

do our moral instincts scream this, but the Hippocratic Oath famously says, first do no harm. The culture of medicine is built on that foundation, which of course is hugely admirable, but it makes it hard to put the good of the many ahead of the good of the few, if the few happen to be under your care and the many are countless strangers. Now, an important moral dimension to consider about challenge trials is the mindset of the volunteers. If they're fully informed of the dangers, as they absolutely must be, what are their motivations? Well, if they're not being paid, they're probably signing up because they're willing to take a risk to help fight something awful that threatens society.

People join the U.S. military after the 9-11 attacks for somewhat similar reasons. Those volunteers put their lives on the line too. Many of them died. And society didn't reject their offers of service, so should it reject people who volunteer for challenge trials? These aren't hypothetical beings, by the way. Tens of thousands of people have volunteered to participate in COVID challenge trials via an organization called One Day Sooner, and no one's taken them up on that offer. I could fill a podcast twice as long as this one exploring the nuances of challenge trials and their morality, but I'll leave it to you to decide where you come out on this complex issue. And if you really want to dive into a rabbit hole, Google the term trolley problem

while you're thinking it through. Now, the one good thing about any future pandemic is that it'll happen in the future, of course, giving SynBio's exponential momentum some growing room, which is great because as I said early on, SynBio itself and the countless people who will one day practice it at doctoral levels, high school levels, and everything between, are our best defense against evil uses of biology. So I'll close on an appropriately optimistic note, describing one of the coolest things I see in SynBio's midterm pipeline, which is teleporting vaccines. And yes, I mean that metaphorically. But only just.

To appreciate how valuable this could be, let's imagine an artificial pathogen, or something natural and much more lethal than COVID, is on the loose. Having taken the various precautions I discussed earlier, we have an effective vaccine that targets its viral family. But it's incredibly deadly out there, and all supply chains are fragile or breaking. It also takes months to manufacture hundreds of millions of vaccine doses using standard methods,

let alone billions of doses for the entire world. In this situation, you'd want the vaccine available everywhere now, not in a few lucky places a few months from now. You'd also want as few miles between you and your personal dose of that vaccine as possible. So wouldn't it be great if vaccines could be printed right at the local pharmacy? Or better yet, in your living room?

Enter the BioXP, the DNA printer I talked about earlier. It will soon be able to directly convert the four basic genetic letters, A, G, C, and T, into DNA or RNA strands, giving it unlimited flexibility in what it can write, just as four-color inkjets can produce any imaginable image. Its creator, Dan Gibson, actually invented it with vaccine production in mind, particularly RNA vaccines, a new technology which is behind the wildly exciting vaccines from Pfizer and Moderna. And here's where his teleporting term comes in. Imagine you have the genetic code of a working vaccine at the center of your system,

at the Centers for Disease Control in Atlanta, say. If you now print that genetic strand in thousands of pharmacies and doctor's offices, you've basically teleported it throughout your network. Now, simply printing a strand of RNA doesn't give you an RNA vaccine. There are several additional steps, often referred to as fill and finish. Dan says the BioXP team is building these steps right into the machine. He believes fully integrated systems should be operational at pharmacies and doctor's offices within three to five years. As for consumer-friendly home systems, he puts those in the 10-plus year time range, which I'm sure sounds like science fiction. But most of what's happening in SynBio today would have sounded like science fiction to

the top people in the field when the Human Genome Project was wrapping up just 17 years ago. As with most of what everyday folks do with computing today, compared to the minimal things that were possible on the world's most powerful computers just a few decades ago. That's the thing about exponential technologies. They can deliver science fiction in short time frames. Of course, they can also enable evil or disturbed people to wreak terrible devastation. But they can enable the rest of us to prevent that devastation if we have the foresight to do it. As we come to the end of this survey of what could go wrong with

engineered pandemics, which is practically everything, and what we can do to protect ourselves, there's lots of reasons for optimism. There are many steps we can take to nip tomorrow's problems in the bud. Most of them have huge dual-use benefits in fighting the natural diseases that clobber us constantly, and their costs are tiny compared to their benefits. To finish making this case for optimism, let's dial up your inner science fiction writer one more time. Imagine it's 10 to 15 years from now. A smart person with a biology background and a crippling emotional disease has decided to inflict a devastating pandemic on the world. He has access to a DNA printer with the raw horsepower to crank out

any viral genome and tools we can scarcely imagine today, which easily translate printed genomes into replicating viruses. Worst of all, the dark web has given him the genetic code of that contagious H5N1 flu, which those researchers created all those years ago. Only it's an upgraded version, which some darkly motivated biohackers have made wildly contagious, way more than COVID. But luckily our deeply disturbed protagonist lives in a world in which we have the foresight to defend ourselves from his attack years before he even thought of launching it. Strong laws require all DNA printers, not just 80% of them, to scan for deadly sequences before printing anything. So the only

way to make his virus is from scratch, using methods that only a few elite scientists ever bothered to learn many years ago before it became automated. That's a huge win right there, because with that one step, we've radically constrained the number of people who could do something awful. In other words, the population of one circle in our Venn diagram, those who could kill millions, has plummeted, greatly reducing the chances it ever intersects with the other circle, which contains the people who'd like to kill millions. But let's say this person actually is an aging elite scientist who still knows the obsolete methods of making viruses from scratch, and that he somehow infects a few people with his creation. Now our early detection system kicks in.

We're monitoring the air, wastewater, and surfaces in hundreds of cities daily, with tools that are several generations beyond what we have today. And everyone with a viral infection is diagnosed and logged the moment they show up at a clinic and many more are feeding in data from simple rapid tests they take at home. So unlike with COVID, the very first victims light up the global public health radar. If we're lucky and smart, by then virtually all humans have had a universal flu vaccine anyway, which would stop an H5N1 outbreak in its tracks, since it's in the influenza family. We've also made huge investments in therapeutics for influenza, along with dozens

of other viral families, which can help cure the unvaccinated people who get sick. And if somewhere in the world there's a large unvaccinated geography, and the epidemic gets momentum there, we can fall back on our unified command for fighting disease. There's plenty of masks and ventilators, and no one's in a bidding war to access them. And within hours of that local outbreak, vaccines are teleporting into its pharmacies and even some living rooms, killing the outbreak in its crib. So that's my case for optimism. We do have time to create our global immune system before this happens.

It can be multilayered, and like our own immune systems, agile and adaptive, with a diversity of tools to tackle whatever threat emerges. The case for pessimism is that this immune system will not build itself. We've botched so much in the face of COVID, and if we respond to COVID's hoped-for defeat in the same way we responded at the end of SARS, the snooze bar could be the end of us. So for all my optimism, there's absolutely no room for complacency. The new era in biology could put us in the best position we've ever occupied in relation to disease,

but only if we make the right investments and take the right precautions today. Okay, well, I'm back with Rob Reed. Rob, you finally brought us to something like a glimmer of daylight here at the end. Let's talk about how we might yet survive. How would you characterize your own outlook here at the moment? How optimistic are you? I would say that I'm extremely optimistic for somebody who has really marinated as much as I have in the twin dangers of suicidal mass murder and the relentless exponential advances in bio. Not happy topics, and I've been marinating in them for much longer than I'd like to since even before the pandemic. But for somebody who has really grappled with

those issues, I got to say I'm wildly optimistic because the science and technology that's in the pipeline is just so promising. And the dead obvious things that we fumbled during COVID should be incredibly fixable, especially with a post-COVID mindset, which should give us all the political will we need to invest in fixing them. And so definitely optimistic. And I think it's important to highlight that, because the last thing you want to do in talking about this stuff is to bring people directly from a state of denial to a state of despair, because you don't do anything in either one of those states. The first one, denial, you

don't see a problem, and in despair, you think it's hopeless. And in either case, you're equally motionless. And I think this is actually a problem that the environmental movement had. I mean, I'll just pick on an inconvenient truth, which I thought was absolutely brilliant. But I did think it had the tendency to put people on an express train from denial to despair. And there's definitely no need to despair here. We can absolutely harden our syn-bio infrastructure to make it really, really hard for any but the most brilliant and determined people to do something lawful. That is doable. We can definitely invest in pan-viral vaccines and therapeutics. I mean, the cost of investment is trivial compared to the likely returns and all the

rest of us. And in doing that, really make ourselves a hard target for future pandemics, whether it's artificial or natural. So yeah, on the balance, I think there's just so much we can do that can be so helpful. Okay, so let's talk about some of the topics you raised in this final chapter. Where are we with the far UVC light technology? So far UVC has had unbelievably promising signs in the lab. But so far, it's been relatively small academic studies, and we need

more. I mean, the next step really is to do rigorous FDA quality tests that fully establish whether these wavelengths annihilate pathogens, as we think they do, without damaging human health, which is obviously unbelievably vital if we're going to contemplate exposing people to these lights for long periods of time during flu season or in the case of a pandemic. The signs are really promising, but we do need to do more. And if things really work out, unlike almost any of the other measures I'm talking about, this one could be really expensive if we go all in, but we'd only go all in in an incremental manner, starting with that relatively cheap step of proving this stuff out. And this could easily turn out to be a complete flop for UVC light.

But like I said in the recording, that's completely fine. Because while we're testing this, we're also hopefully testing things like the BCG vaccine and dozens of other things. There's just some incredible super weapons against pandemics, almost inevitably, in the tech and scientific pipelines. We just need to turn over the rocks. So anyway, if far UVC light is everything we hope, the next thing we'll need to do is figure out how to make LED lights that emit them, because the current bulbs are just huge, they're clunky, they're unbelievably expensive, and they throw off way too much heat for use in public spaces, just way too much maintenance and everything else. Now, getting LEDs to emit far UVC light will take significant R&D work. I mean, the whole history

of LEDs is one of the industry turning its attention to new wavelengths of light and figuring out how to make them after some heroic R&D efforts. And figuring out how to make blue LED light was actually particularly difficult. And there's a really interesting story behind that, which we won't go into. But the LED industry is good at this. And it basically is all about really precisely tuning the alloys of the LEDs, semiconductors. But far UVC has already been demonstrated in an LED in the lab, I think in Japan. So we know it's possible. It's a matter of bringing the science into technology. And once the technology is dialed in, we would need to build a fab or a

fabrication plant to build the LED bulbs, which is probably a multi-billion dollar proposition. So like I said, not cheap, but one that we would never take unless we had high confidence this was going to have a huge ROI for society. Then once we're making the bulbs, the question becomes how many bulbs and who pays for them? So if these things actually work, we'd clearly want them in public transit. I mean, just imagine how much safer a subway car would be if 99.99% of the pathogens in it are killed every few minutes, which is what the science at MIT shows is possible. And we'd also probably want to put them in big public spaces.

So basically, we'd have a lot of local governments buying bulbs, installing them, maintaining them, et cetera. As for where you go beyond that, it's probably a bunch of private decisions, like stores and restaurants might install them if customers call for them or want them. Maybe more to keep safe from flu and flu season than pandemics in normal times. And maybe businesses will install them in offices, also with flu in mind, to cut down on sick days, which would pay for an awful lot of balls. which would pay for an awful lot of balls. So the bottom line, if UVC becomes widespread, it'll cost a lot,

but it'll be a lot of justified incremental investments made by people who are thinking rationally. And the path to it, a real wide deployment, feels like it should be less than 10 years. It's not going to be right around the corner. There's a lot of work to be done, and building a fab takes time, but this is absolutely something in the intermediate future, if it makes sense. Well, on the other end of the spectrum here, we have this BCG vaccine, which I only just heard about during COVID.

Describe what this is and why we can't get access to it, even though it seems like an incredibly promising vaccine for a variety of reasons. Well, what it is and why we can't get access to it here in the U.S. are kind of the same answer, which is that it's a tuberculosis vaccine. It's frontline for infant tuberculosis. So it's given, you know, shortly after birth to a high majority of the babies who are born on Earth in any given year. But it's never been given in the United States because, well, it was developed in the 20s. And we definitely had a tuberculosis problem back then. So I can't really say why we never had it. But the US, I think by the time universal BCG programs started kicking in, I think it was much later than the 20s. It was invented in the 20s, but I think it's more like 50s, 60s, even 70s before countries began implementing universal

vaccine programs. And by the 50s, you had the first antibiotics, and antibiotics can be quite effective against adult tuberculosis, also against infants. And so I think there just wasn't a huge TB problem in the US by the time these vaccination programs really started coming online. And there is this unbelievably promising data going all the way back to the 1920s about BCG protecting against all kinds of things other than tuberculosis, above all respiratory infections and broad spectrum protectionpectrum protection against respiratory infections, the most recent study of which was quite recent. I think it was concluded just last

year in Greece. And in that case, they were basically taking older adults who were checking out of hospitals, I think people 55 and up, and half of them got the BCG vaccine and half of them did not, got a placebo. And the statistic was that 80% or those who got the vaccine had an 80% reduced incidence of any kind of respiratory infection and a 50% reduced incidence of infections of all kinds. So there's all this really intriguing data. And then of course, there was that unbelievable data that was in the proceedings of the National Academy of Science that showed this huge inverse correlation between national BCG vaccination rates and COVID cases. Now, the thing is, most of this data, not the Greek study, but most of this data is

what epidemiologists call ecological data, which means it's data about groups of people rather than individual case studies. And also it comes from observational studies rather than hands-on work with injections and patients. So that inverse correlation amongst countries, classic ecological data. But obviously to get a vaccine approved for a specific disease, you have to track cause and effect in individual subjects. In other words, you have to do a classic double-blind test with control groups. And a full phase three trial for FDA approval is generally beyond the reach of academic budgets, and the people who have been poking at BCG are mostly academics. Whereas pharma companies,

they're just not going to spend their limited capital on testing a seven cent vaccine that's in the public domain. There's just no money in that. And I hope I'm not over pimping my podcast here. And if I am, just tell me. But I'll be posting a really detailed interview with a Harvard epidemiologist named Megan Murray about all this stuff, probably shortly after you post this conversation. And Megan actually is hard at work on developing and trying to fund a phase three trial, despite being an academic and this normally being a pharma thing. And we're counting on her to do this rather than Pfizer, because it's a market failure. There's just no deep-pocketed players who are incented to do this

research. And we really need to fix this for two reasons. The most obvious one is that if BCG actually can protect against COVID, and we don't know, but if it can, even if it's a long shot, figuring this out would totally change the global vaccination timeline. Because there's 22 BCG manufacturers throughout the world, and there are distribution channels for BCG into almost all the developing world with armies of people who know how to store and administer the vaccine. And it's obviously just morally urgent to speed up vaccinations in poorer countries. But it's also in the selfish interests of rich countries that are about to get all the Pfizer and Moderna vaccines they need, because every person that COVID infects is another

opportunity for it to mutate. And COVID is incredibly prone to mutation, as we're seeing from these terrifying new strains, at least one of which is, you know, the South African one is partly resistant to vaccines. And so if we take our guard down after, you know, wealthy countries are vaccinated, if COVID keeps rampaging amongst billions of people, we can pretty much count on a new strain emerging, which can steamroll through all of our hard-earned defenses. And so we need a great phase three trial test of BCG against COVID, whether it's Megan's or someone else's, even if it's a long shot. Because I mean, this test would cost tens of billions of dollars, not the billion plus we spent on each candidate for Project Warp Speed, because there's no vaccine to be developed. It's just a test. some huge philanthropists like Bill Gates, who have started investing in BCG with an eye toward COVID, but we shouldn't sit around and wait for somebody to gift this to the world. It should just be an immediate public investment. And the other reason to do this, to study BCG much more deeply

beyond COVID, is this apparent protection against respiratory diseases in general? Because, you know, if that, you know, the initial trial in Greece, which is, you know, very promising, but very initial, that pattern holds up. It could be a real game changer against the flu, against future pandemics, which are almost sure to be respiratory in nature, against all kinds of things. But there's a lot to be studied, like how frequently does BCG need to be given to have this effect? Does it work in all age groups? Is it particularly effective against a certain class of respiratory infections and so forth? And again, we shouldn't be waiting for someone to gift this to the world, particularly because an initial set of academic studies would

cost very, very little. Yeah, we have to become increasingly sensitive to market failures in this domain, in public health generally, but across all of the fronts of where we're running something like existential risk. We've been living with the problem of producing antibiotics in a market that can't effectively incentivize it. So we have antibiotics that are losing their power over really every bug that concerns us, and we're meandering toward a time that will be indistinguishable from the 1920s and 30s when we simply didn't have the drugs that could solve our most basic infectious disease problems. And the reason is there's not enough money in it. You know, you take a new antibiotic, costs a billion dollars to produce, and you take it once for 10 days in your life, and then that's

it. That is if you're unlucky. Most people don't have to take them, any specific new antibiotic ever. And yet, if you need it, this is the one drug that's going to save your life. the one drug that's going to save your life. So we have to, and this is the role of government or major philanthropy, on some level, we just have to say whether it makes any market sense in any rational time horizon for a business person, we have to spend money on these things. Yeah, we've basically stood by as multiple antibiotic companies have gone out of business in the US. And it just allowed this market failure to propagate to the point that, you know, who's even developing new antibiotics? I can only think of a couple of companies that are even in that business anymore. And we're not really talking, we're talking more

about viruses than bacteria, obviously, in this series, but that is an equally glaring issue. And, you know, something that, you know, one estimate that I saw, you know, super bugs could easily be killing millions of people per year within 10 years. Yeah. So what are the prospects of developing vaccines for whole classes of viruses, a universal flu vaccine, a universal coronavirus vaccine. What have you uncovered on this front? Well, this actually ties to what you were just saying about market failures, because it seems, talking to some pretty informed people in this domain, that a universal flu vaccine effort would probably have very good chances of succeeding, at least 50%, which is a shot worth

taking. And the budget that I was quoted was probably in the range of $200 million over 10 years, with kind of an extreme, like, why don't we just for safety go up an order of magnitude budget of $2 billion over 10 years? And you look at those numbers and you remember that the flu is costing the US alone $361 billion a year in lost productivity and medical spending. And it's just flabbergasting. And I couldn't believe my ears when that budget estimate was quoted to me. And it couldn't have come from a more informed person, who is Harvey Feinberg. He's the former president of the National Academy of Medicine and the former dean of the Harvard School of Public Health. And more to the point, he's done a lot of work studying the

potential for universal flu vaccine, including at the Sabin Vaccine Institute. And so this is just another stunning market failure. I mean, if you can spend, let's take the worst case scenario, $2 billion over 10 years for the chance of saving $361 billion a year, even if there's a 1% chance you should take that. And according to Harvey, it's probably more like a 50% to 75% chance. And once again, to go back to what you were saying about antibiotics, why this isn't happening, well, pharma is not going to do this because it's a lousy business proposition to make a cheap vaccine that people might only use just once. I mean, one of the

models for universal flu vaccine is one and done in a lifetime. You'll hopefully never need again. Or maybe it's even if it's annual every five years. I mean, pharma companies just won't do this unless they're presented with non-market incentives. And so there's that. But then obviously, this is also just a shocking failure of public policy, because the ROI on this would be profound. Now, the optimistic way of looking at this, which I prefer, is to say there's just so much low-hanging fruit here. And Harvey Feinberg believes that, you know, much as we could create a universal vaccine effort for influenza, we could do that against any arbitrary number of viral families. And as I think I mentioned in the recording,

you know, he would suggest we start with influenza and coronavirus, get good at that, and then start tackling more. And there's only a couple dozen viral families that actually infect humans. And there's probably also a couple of other zoonotic diseases out there, viral families that don't currently infect us that we want to be careful of. But even if you multiply this out by every family we can think of, by $2 billion over 10 years, the numbers that come back are just minuscule, just compared to, I mean, like I said earlier, compared to what we spend maintaining our nuclear arsenal on an annual basis, just minuscule compared to anything that seems like a comparable. And, you know, especially when we think of how quickly these COVID vaccines were created, just days in the case of Moderna. So we're obviously in a completely new age when it comes to vaccine science, which screams for

just ambitious new goals for vaccine science. Yeah, and we've not only accelerated the time it takes to produce the vaccine itself, but we've accelerated the approval process. And it sounds like we could accelerate it even further if we changed our cost-benefit analysis in how we do research. I mean, obviously, we're doing research now under duress with a global pandemic, crushing economies and killing hundreds of thousands of people, even just in the United States. But what role would challenge trials play here? Because this is something that many people first heard about in recent months under COVID, but they're controversial. How do you think about this? Well, I think the right way to look at it, I mean, it's ultimately an ethical question. So

we can safely say that there's no quote-unquote right answer to this conundrum. But I do think that it helps a great deal to put concrete numbers on the assets and liabilities in terms of human lives of the two approaches. So to just quickly review, a challenge trial would involve deliberately infecting a much smaller number of people than you would have in a normal trial with COVID. The numbers are really, really stark. A normal COVID trial, you're talking tens of thousands of volunteers. They get that huge number of people because they need to wait until there's essentially maybe 200-ish people have come down with COVID from that vast base of 30, 40, 50,000 people.

And once 200-ish people have definitively tested for COVID, they can basically take off the blinders and figure out which of those people were in the control arm of the trial, which of those people actually got the vaccine. And based on that, you can come up with these exciting numbers like 95% effective. Now, if you're just doing a challenge trial and you know all those people are going to be infected, instead of 50,000 people, you might just need 200 people or maybe a little bit more, you know, just in case, you know, some data points bounce out for some reason. So that really collapses the timeframe. And to compare a challenge trial with a normal trial, let's imagine, I mean, I don't know exactly how long a challenge trial would take, but

recruiting 200 people would be harder on a per-person basis because you're asking them to submit to a hell of a lot more than just an experimental vaccine. You're asking them to contract COVID. But as I said in the recording, 20,000 people, I think it is, have already expressed a willingness to participate in challenge trials through a group called One Day Sooner. So there's a ready body of people. Recruiting presumably would not be anywhere near the challenge that it is with 50,000 volunteers. And then in terms of the timeframe, you're infecting them on day one. So you're not waiting months and months and months for people to contract things.

It seems logical that this timeframe could collapse into a very, very low number of months. Let's talk by comparison about the AstraZeneca vaccine, because I was able to find, cobble together a detailed timeline on that. Its last phase of trials started in the UK on May 28th, and they eventually recruited, it was a smaller trial, 23,000 volunteers, mostly in the UK, but also in Brazil. Now, there was some weirdness with this trial that people might remember. There was a pause to it because of an adverse reaction in one of the volunteers, but that was only a six-day pause, turns out. So it generally proceeded along its timeline. And the results of this trial were reported out on November 23rd. So in other words,

it ran for just under six months. And most of that time was spent recruiting all those volunteers and then waiting for enough of them to test positive for the trial to have a statistically significant result. Now, during that six-month period from May to November, over a million people died of COVID worldwide, while what turned out to be an impressively effective vaccine was slowly and methodically tested. And we can probably assume that other vaccine trials had similar timelines. I just happen to know the dates with AstraZeneca. Now, a challenge trial obviously wouldn't have been instantaneous, but it would shave

months off that timeline, not weeks, during a time when thousands of people are dying every day. But it would have involved deliberately infecting a couple hundred people with COVID. While most of them would have presumably been younger volunteers, so fatality rate would have probably been extremely low, it's all too likely that one or more of those people would have died. And it's also likely that very few of those 200 people would have caught COVID on their own. So how do you balance the ethics out of that? I mean, the numbers are enormous. Hundreds of thousands or a million people dying during the running of this trial versus perhaps a tiny handful or even one or even no people dying in a challenge trial.

But it's very much like the trolley problem, isn't it? Yeah, except with the variable of consent here, which I think is ethically decisive. So there's no argument against someone deciding to consent to a challenge trial once they understand the risks they're running and the possible benefits. And as you say, it's surprising, but it is just a demonstrated fact that you can find people eager to serve on this front, and you can find people eager to take all kinds of risks that any individual listening to this might never entertain themselves. Once there's a one-way ticket to Mars offered, you can be sure

there are going to be thousands of volunteers willing to die on Mars. There's a spirit of wanting to advance the human project and be part of something great. And in this case, In this case, again, there are relevant variables here around just how widespread the illness is at each point when trials are being run. I mean, that affects how long you have to wait around for people to catch the virus naturally. Yeah, it totally affects it. And it affects the perceived odds for anyone enrolling in a trial. perceived odds for anyone enrolling in a trial? How different is a challenge trial if this virus is burning so quickly through the population that you seem guaranteed to get it anyway? But I do think consent is the master variable here ethically. And yeah, we certainly should be talking about running challenge trials

under circumstances like this, where we're having to respond to a pandemic that is burning out of control. It would be different if we're preemptively trying to design a universal flu vaccine or a universal coronavirus vaccine under conditions where we don't feel like we're currently losing thousands of people a day to a pandemic. But it is very interesting. And it's amazing that so many people volunteered. It's great. Yeah. I mean, I guess it's kind of like the people who volunteered for the U.S. military after 9-11. Yeah. They were, you know, there was a big surge of signups, and these people

were certainly signing up to risk their lives. And the government didn't tell them, no, we're not going to accept your service. And in a sense, because I don't think there was any serious conversation about a challenge trial at all in this COVID period. Was there? I mean, I don't think there was. I remember it being spoken about, and obviously people volunteered, but I think most of the conversation I heard about it was going on in the UK and not in the US. Yeah. I mean, and another thing to think about, which when it comes to this regulator saying, no, you can't do that type of thing is, it's interesting that, I guess, both, well, certainly the Russian vaccine, and I believe the Chinese vaccine as well,

have started coming out, there's starting to be some independent research that's signifying that these are actually reasonably effective vaccines. And in both cases, the countries started administering the vaccines without waiting for phase three data, which at the time was generally viewed as or discussed as being a particularly bad idea, at least work, you know, maybe that's another policy that policymakers should consider, along with challenge trials, when future problems come up. Because, you know, imagine if, and it's always easy to do something looking with the benefit of hindsight, but imagine if the FDA said, okay, you know, Moderna has come up with this vaccine, it's going to go through rigorous trials. It hasn't yet, but we're in an emergency time here. So any U.S. citizen who is courageous enough to take the chance and is willing to sign,

you know, a thick legal document saying that they're not going to sue or anything is welcome to take this vaccine. And, you know, it's an experimental vaccine, so there could be bad effects, probably unlikely, because I think they'd already done a safety trial before phase three, but, you know, may not work against COVID at all. We could kind of imagine perhaps millions of people, I mean, I would have certainly entertained that idea if there'd already been a safety trial on this thing. I mean, why not? And if millions or tens of millions of people have been vaccinated with Moderna and Pfizer, Johnson & Johnson, whoever knows what else, during the six months

of trial times, we might already be seeing the end of this thing already. Yeah, the safety stage is the most important part from my point of view. I mean, whether it's effective or not is obviously important, but it's the first do-no-harm principle, which I think everyone is rightly focused on, especially with a vaccine, because you're not, as has been pointed out many times before, this is a medication you're giving to healthy people, by and large.

This is not an intervention, a new form of chemotherapy when all other forms have failed you. So what do you have to lose? In this case, you have a lot to lose if the vaccine is basically unsafe. And I guess the novelty of the current batch was relevant here. The more work we do in this area and the more any new vaccine has already been pre-characterized by similar vaccines in the past, you know, working by a similar mechanism, perhaps the safety concerns get dialed down quicker.

Yeah, but particularly, and you're right, with the mRNA vaccines, this was a completely new type of vaccine and safety testing was especially important. But now that we have seen that these apparently are very safe vaccines, yeah, I do hope the policymakers take a different approach, like, for instance, with booster shots. Moderna and Pfizer, I believe, are already working on booster shots to take care of the South African and British variations. If we do need to go through a six-month trial process for those to get a perfect phase three, I would certainly hope that there would be an option given to adventurous people, which would certainly include myself, who are willing to take the chance that this isn't efficacious to get the vaccine before the phase three is done, because we are in

an emergency situation here. Yeah, well, as should be obvious to everyone who has followed us this far, this is the beginning of the conversation, not the end. But I know you and I will both together and independently keep our attention on this front and we'll certainly surface any good ideas we come across, any organizations that are moving the dial here, whether it's in the philanthropic space or for-profit or rumors of government actions that seem auspicious.

This really just needs to be kept front of mind here. The pandemic response generally and the SinBio privatization of the apocalypse problem more narrowly. This is really something that our generation has been tasked to figure out. And I just want to thank you, Rob, for producing such a comprehensive and comprehensible document for us to all get started with. Well, it was absolutely a thrill to be able to present it on your show, Sam. So thank you so much for that.