Drew Endy is a member of the bioengineering faculty at Stanford University and BioBricks Foundation president. His research teams pioneered amplifying genetic logic, rewritable DNA data storage, reliably-reuseable standard biological parts, and genome refactoring. Endy helped launch the new undergraduate majors in bioengineering at both MIT and Stanford; he also co-founded the iGEM competition, a global genetic engineering “olympics” engaging thousands of students annually. In 2013, the White House recognized him for his work on open-source biotechnology. Endy has served on the U.S. National Science Advisory Board for Biosecurity and the Committee on Science, Technology, & Law; he currently serves on the World Health Organization’s Smallpox Advisory Committee and is a member of the Defense Innovation Board.
CTC: The COVID-19 pandemic has shown how vulnerable we are as a society and economy, both the United States and the rest of the world, and in turn, there’s been a lot of discussion on whether the bioterror threat of a nefarious actor deploying a deadly pathogen needs to be revisited. In a recent CTC Sentinel roundtable discussion, Lieutenant General (Ret) Michael Nagata said that “the likelihood of a future terrorist using a highly potent, clandestinely produced, difficult to detect/identify/track, easily transportable and dispersible, and quite lethal biological weapon is rising significantly.”a From your perspective, how easy or difficult would it be for a state or non-state actor to employ a pathogen or biological weapon?
Endy: It sort of depends on what their objectives are. If their objective is to create fear and uncertainty and doubt and the doing of that requires a small integer number of casualties in one or a few locations, launching a biological attack looks pretty straightforward. If their goal is to cause mass casualties at the scale of a coordinated WMD attack where they’ve weaponized both the payload and the delivery systems in a biological context, then suddenly that’s not only a bioweapon; that’s an integrated system. So it depends on the objectives and the scale related to the objectives. There’s plenty of examples of natural pathogens that have been weaponized in a conventional sense through history, and there’s also reports of the modulation of pathogenicity of natural agents, and some of the easiest to find literature is the analysis and assessment of the Soviet bioweapons program and the work there, for example, to increase the consequences of being infected with a pox virus to try and push casualty rates or lethality rates up into the 90th-plus percentile. That was all pursued, at least as I read the literature, using the tools of genetic engineering that were state-of-the-art in the 1980s. And thankfully, we didn’t experience any of those in a deployed sense.
But now if you fast forward 30-plus years to the tools we have today, I think it’d be foolish to claim you couldn’t make worse the properties of a bio threat agent with the knowledge and capacities that now exist. Still, it’s much more plausible to cause a disruption in a culture, in a body politic, in supply chains and operational capacities with a very limited scope attack versus deploying something that would directly incapacitate half the population of the continent. Those are the bookends.
CTC: With those bookends in mind, in recent years there have been several cases involving ricin, including a jihadi terrorist plot in Germany disrupted in 2018.1 There’s also the famous Amerithrax anthrax letters attack in the United States in 2001. But apart from these cases and a small number of other exceptions, biological weapons have not emerged as a viable threat from non-state actors, even on those bookends with respect to a limited scale. From a scientific perspective, can you explain why this is so, given some of the devastation caused by viral pathogens, such as Ebola and more recently the COVID-19-producing virus SARS-CoV-2?
Endy: Good question, but I want to reflect the question back and question the question. Is it a scientific question to explain what you’re reporting and observing? Meaning if one were to attempt, if I understand your question correctly, to explain ‘why have we not seen more bio attacks,’ whether it’s bioterror or otherwise, but especially at the level of sub-state actors, ‘why aren’t we seeing more given that we’re almost two decades post Amerithrax?’ Is the answer to that question based in science? Or is the answer to that question based in culture and politics and other things, or what’s the balance or ratio in responding to that question? I just want to pause and ask, is that a fair reflection, at least as I’m setting up to answer your question a little bit more?
CTC: It’s a fair reflection, and it would actually be helpful if in your responses, you could unpack some of those different dynamics that would impact, one way or the other, an organization or state’s ability to conduct a limited biological attack.
Endy: So one thing to acknowledge is, and this is a soft claim but I’ll frame it as a question: to what extent is there a sort of moral demarcation that keeps most people from purposely causing harm with biology? If we’re all biology to begin with, which we are, then maybe we’re each inheriting a little bit of prohibition regarding the use of bioterror or bioweapons. To what extent might this be helping to mitigate the potential and actual acts of misapplying biology to cause harm? It’s hard to know that, but I suspect it’s there and very real.
Of course, a ‘soft’ frame of reference for avoiding harm via biology could be eroded in the blink of an eye, it seems to me, if anybody, especially at the level of a state, came out and said, ‘No, this is on the table again. Biology is on the table again as a platform for inflicting harm or projecting political power.’
But, critically, we’re not operating in such a “bioweaponeering” regime right now. Thus, to jump to your question—‘what’s the scientific side of it?’—on the one hand, there’s a pretty big international scientific research community in biology. On the other hand, a lot of the people who would be interested in causing harm to other people start by not knowing very much about bio, which is good for the moment.
There’s also, as has been well documented in the bioterror preparedness literature, a lot of discussion about what’s called tacit knowledge—it’s one thing to read something in a paper that’s published in the peer-reviewed literature: ‘This is how you build a virus from scratch using a DNA synthesizer.’ But even though you might have that entire recipe published in the public literature, the recipe doesn’t really enable you to go into a laboratory and repeat the work directly because the operation of the physical processes in a biological lab is much more akin to a trade that has the accumulated inherited skill of practice that, historically, can only be gained almost through an apprenticeship, if you will. And so that’s called tacit knowledge.
So, to recap, one obstacle to the weaponization of biology is the cultural prohibition that we inherit. The second is the ‘bio-beginner’ bonus that creates a significant moat for people who might choose to cause harm via biology. Then the third is when you try and cross that moat, you’re encountering the barrier of tacit knowledge—just because you have the recipe doesn’t mean you [can] ‘bake a soufflé.’
The impact of a biological attack would depend on scope of the bad actor’s objectives. How many casualties were there with Amerithrax? Dozens. What was the consequence of that? Massive orders of magnitude bigger. So that was a terror attack; it worked in that regard. If you’re trying to use natural biology in that way, I don’t think there’s a lot of scientific limits. If you were trying to use and adapt natural biology to get to something that poses a more widespread threat to the population, that’s trickier. It’s just at the frontier of the science.
CTC: In recent years, we’ve seen the norms for chemical weapons erode, with chemical attacks by regime and terrorist forces in Syria2 and the use of nerve agents against Russian dissidents.3 Do you see that potentially happening in the bio realm?
Endy: It’s a great question, and it highlights a big gap for me in our strategic portfolio, which is basically sustained thinking and scholarship that leads to bio-strategy. Let me give you an example. Most might be well familiar with the concept of mutual assured destruction, or MAD, through nuclear weapons. Well, what about the possibility that a non-nuclear power could be incentivized to develop as a bio power to create heterogeneous mutual assured destruction, where you would attempt to counter the power projection of a nuclear power by reciprocating with bio power. Suddenly, you don’t need the isotope centrifuges. Rather becoming a ‘bio power’ is relatively affordable as a state-level program and it’s hard to detect or thwart. And, if you’re operating in the strategic regime of MAD, you don’t need to deal with the targeting issue. You’re willing to—because you’re up against the nuclear power [that’s] threatening to wipe you out—take everybody out with your bioweapon “dead hand.”
So we may be stumbling into a near future where suddenly geopolitics plays out in new ways and the nuclear powers, which have entrenched themselves in a geopolitical position of privilege, suddenly find themselves being outmaneuvered from underneath by emerging bio powers, who due to non-proliferation of nuclear, can never get access to that power projection, but attempt to counter it with the dead-hand bioweapon. It’s absolutely horrifying to think about this and talk it out, but the meta point I want to make clear is, where’s our strategic thinking on this? Where do we have the sustained conversations and scholarship that enables us to develop a coherent bio strategy?
One of the consequences when we wind the clock back to 2001 and the post-anthrax reaction [is] what did we do as a nation? One of the things we did was we increased the civilian budget for biodefense. It went up to about $10 billion a year, matching at the time the Missile Defense Agency budget, and some of that money got allocated to build semi-classified BL3s, BL4s—Biosafety Level Three, Four labs. Imagine you’re another nation, and you’re looking at the United States at that time and you’re trying to make sense of what the United States is doing in response to anthrax. The first thing you’d observe is the U.S. has freaked out about bio and bioterror, plenty of evidence of that. The second thing you’d observe is ‘They’re spending public treasure on capacities, including semi-secure/secure BL3, BL4 facilities.’ Now, if you’re a generous nation state looking at the U.S., you’re going to go, ‘Wow. They’re really taking this seriously, and they’re really building the capacities to be responsible with respect to future risks in the bio space.’ But if you don’t trust the United States, you might be concluding, ‘Wow. Looks to me like the U.S. is taking steps towards re-weaponizing biology. I’m not sure I can trust what they’re doing.’ And so there’s the potential in the absence of holistic coherent strategy for bio security broadly to create this ‘autoimmune’ geopolitics that recapitulates the dynamics that led to the weapons programs in the early 20th century in the first place, which was basically ‘Japan’s doing it, the U.K. is doing it, the United States better do it, everybody’s doing it.’ I suspect and am concerned that it’s a lot easier to trip back into such geopolitics than we might understand. Regardless, I absolutely want to highlight: where’s our sustained scholarship and work on bio strategy? It just feels like a gap we need to be resourcing to address.
CTC: To pull on that thread a little bit, regarding bio strategy and need for more research in that area, as you know well, when we talk about nuclear strategy, there’s the need for a credible deterrent. And so this is where it sort of intersects with potentially our space, looking at political violence and terrorism: would a state try to utilize a proxy to establish some form of credibility as potentially an emerging bio power?
Endy: That’s a really interesting question. I hope not, but it’s a plausible scenario. It would violate various norms, and it’s horrifying to think about.
Looking at it from the opposite direction, would a state demonstrate a functioning public health system as a way of projecting a capacity to make pathogens obsolete within their civil society, as a type of deterrent? The positive demonstration of a capacity to make a pathogen obsolete is a form of power projection.
Conversely, a weak public health system may invite attacks. If you wind the clock back to the rationalization of the standing down of the U.S. [Offensive Biological] weapons program under Nixon,4 there are three planks in that argument. One was we already have plenty of weapons systems so we don’t need more. Second, because we have the leading economy, in the grand scheme of things, we prefer expensive weapons, and biology is cheap [so don’t do bioweapons]. And third, we don’t know how to target, so you’d risk tactical blowback if you go to deploy a bioweapon.
I used to think—and this returns to the science aspect of your earlier question—‘we need to be very mindful of the potential for scientific advances to enable targeting because if targeting becomes possible through CRISPRb or genomics or any bit of science or engineering capacity in the bio space, then suddenly one of the three pillars of the argument against nation-state bioweapons goes away.’ However, what COVID-19 is revealing is you can target a nation-state (or even specific communities) not on the basis of science but on the basis of politics and behavior. The targeting question becomes, ‘does that group have a functioning public health system or capacity to lead their citizenry to effectively limit the impact of a pathogen or make it obsolete?’ What COVID-19 reveals, as a natural pandemic, is that the United States is projecting bio-vulnerability. And I have been surprised by this. I thought that the way we would see the possibility of targeting would be based on scientific advances, not via the civics or the culture aspects of things.
CTC: You just mentioned CRISPR. With some of these emerging technologies, the democratization of information, and the reduced costs of gene synthesis lowering the entry into this bio realm, can you give us a broad sense of what capabilities are required to bio-engineer a virus or modify an existing virus to increase its potency?
Endy: When you put the qualifier in there of increased potency, that’s a wild card, right? To really do that well, you’d want to have a functioning laboratory that was operating with reasonable biosafety so [that] you weren’t risking yourself or your workers. If you were just trying to recapitulate something without trying to make it worse, so to speak, as a pathogen, that seems much more straightforward. So let’s start with those examples. We have the example of the virus which produces the disease COVID-19 being sequenced in China [after the onset of the outbreak], that information defining the genome’s sequence going on to the internet out of Shanghai, and the next day in Switzerland, that sequence information is being reordered for synthesis such that within less than a month, the laboratory in Switzerland has made from scratch infectious COVID-19 particles without any physical transmission of the virus.5 So that’s transmission via internet, and you’re using DNA sequencing to read out the information in China and DNA synthesis to write or print out the genome in Switzerland or Europe. The cost of printing DNA, when I first started teaching in 2003 back at MIT, was $4 every letter. So anytime you press an ATCGc keypad, every letter press is four bucks. So back then, you were maybe looking at about $100,000, $120,000 to make a virus genome. Today, depending on how much you’re buying, it’s 10 cents to one penny a letterpress. So if it’s a penny, what is that? 300 bucks? It’s basically noise to print the genetic material for a virus encoding a pathogen.
When we say viruses, what are we talking about? There’s of course the virus which produces COVID-19, but there’s the hemorrhagic fevers like Ebola. There are the flus. In 2016, we had the example of a laboratory in Alberta, Canada, building from scratch the horse pox virus genome, and that was done with a team of three people.6 Now, to be fair, the people who did that work, David Evans and two postdocs, are best in world at the doing of that work. So the tacit knowledge there is off the charts, meaning they know how to do things that nobody else has really figured out. But just from a budgeting perspective, you’re talking about a couple person months of labor and a couple thousand dollars’ worth of DNA fab and that gets you access to a whole category of pathogenic agents that don’t need to be made worse to trigger a lot of disruption.
Returning to your earlier comment—because this is important to think about—what was the reaction to the recent use of chemical weapons, and did we lose some moral high ground there by not calling it out more strongly? How would the world react to a nation-state that started to play around by not making anything worse, but just demonstrating that they could remake pathogens on demand? And maybe there’d be a ‘laboratory accident’ proving that these were pathogens that could cause disruption. And that nation-state would declare, ‘Oh, yes, we’re going to be better,’ but suddenly everybody would know that that nation over there had state-of-the-art pathogen-on-demand capacity. Well, suddenly they’d be recognized as an emergent bio power. And they wouldn’t have to do much more; they’d be toeing the line of what was acceptable internationally. In other words, I don’t want to get too hung up on threats involving making things worse than what we find when we start with nature. I think that’s a valid topic, but there’s so much bad stuff out there to begin with.
CTC: To segue from that, given the increased number of do-it-yourself bio labs set up by amateur scientists and entrepreneurs,7 what is the risk of such a lab being set up and used by technically proficient bad actors to create a bioweapon?
Endy: Can you tell me what the distribution of mal-intentioned actors are because I can’t possibly answer your question unless you can give me the probability density function for people’s intentions. I’m serious. I’ve gotten this question for 20 years now. If we were meeting in person, I’m just going to tell you what we would do at this point: we would get up and we would walk around the engineering quad at Stanford and we’d go into the Huang Engineering Center because, in the basement level of that building where there is a big open area for students to do their homework and stuff, there is also a ‘temple.’ It’s a recapitulation of the Hewlett Packard garage. And it’s much more expensive than the original one because it’s made out of etched glass and it’s got some vintage oscilloscopes that they made and stuff like that. So I work at a place where we build temples to garages. And we celebrate the garage-istas because they’re building our capacity to have a functioning economy and a functioning technology base that allows us to have world-best tooling that allows us to do world-best discovery and world-best innovation, and from there world-best defense. Of course, we have to wonder to what extent, if these sort of capacities get deployed and everybody’s got their garage biotech shop down the corner, could they be misapplied? But to answer this question, we really have to understand the distribution of mal-intentioned actors? Period. Full stop.
Meanwhile, I don’t see how we maintain discovery in and tinkering with biology as a practice that only occurs at institutions. In fact, everything I’ve seen indicates things are going in the other direction; bioscience and technology are becoming even more accessible. And, there’s ongoing erosion of the institutions that have attempted to contain bio technology, starting from the discussions in 1975 around safety and containment protocols for safety related to genetic engineering—biosafety not biosecurity. So we’re inheriting a very lumbering institutional containment framework for biotech, and it’s just eroding. Let me give you some projections. Right now, we have DNA synthesizers that are based on chemistry called the phosphoramidite chemistry that requires dissolving the ingredients in anhydrous acetonitrile, [that is] acetonitrile without water in it. So when I just start putting those words together, most people will go, ‘I don’t have any of that. I’m not even sure what that is.’ So if the DNA printers today require an esoteric chemical just to operate, what that means is DNA printers aren’t going to be in most places because I know I don’t have anhydrous acetonitrile in my kitchen or in my pantry. And I wouldn’t want it because [it’s] just a pain to deal with and dispose. I mean, it’s a mess. But that’s first-gen DNA synthesis. Second-generation synthesis—which is showing up now—is using enzymes, biology itself, to make the DNA. So in all of us, in our bodies, we’re making DNA all the time—DNA polymerase that copies DNA—and there’s even terminal transferences that make DNA without a template, that make DNA from scratch in our body. Now, our body’s operating in water. It’s not operating in acetonitrile. So everybody’s got water mostly, and everybody’s got enzymes. So we can imagine a future where the DNA printers are personal. Everybody’s got a pocket or desktop DNA printer, if they want it, and the input to that DNA printer is the internet. A little bit of electricity and we’re done.
So one of the things that makes our discussion today timely from my perspective is I think we’ve got this window of opportunity to recognize what some of the trends are, and we have to figure out how to articulate victory with respect to bio defense, bio security, and bio overall. This window of time—it might [border on] a decade, but it’s not a lot more than that, I would say anymore—is our last chance to get to the first layer of victory conditions. If we don’t address what’s happening now—and I can just pick on the trends you’re identifying: things are getting easier, we’re understanding more about how natural systems work, more people are getting access to biology, the [COVID-]19 perturbation is revealing that we’re not prepared for natural things—then by the time we get to 2030, it will be too late.
When I think about the conversations I’ve been part of over the last two decades, a lot of leadership conversations, we came close to getting a bio strategy going, but we never really got to the starting line. And so the current situation is very professionally depressing, I’ll say—not personally depressing but professionally depressing—because it just represents a collective failure of leadership over two decades. Another way of saying it is—and you picked up on this in some of your notes—we’ve just been dallying about in the bio space, we’ve just been playing, we haven’t been taking biology seriously. That can’t be true anymore. We have to be incredibly serious about biology.
CTC: Microsoft founder Bill Gates in April said that a bioterror attack with a pathogen with a high death rate is potentially the next big threat facing the planet after this COVID-19 pandemic.8 Do you share that concern?
Endy: It’s up there. I think there’s another one that regrettably is appearing, and it’s just the functioning of a civil society as a liberal democracy. I think that’s superseded for the moment the bio threat, and I say that not to diminish at all the scope of the bio threat. It’s just very, very interesting to me in a horrifying way to see how fragile certain operational aspects of our society are [and] what might happen if that goes sideways. In other words, there’s cultural terrorism, there’s economic terrorism, there’s political terrorism, and there’s bioterrorism. I would say something at the intersection of those first three categories is more pressing and more concerning to me than bio is right now. Again, this is not to defer or diminish the bio threat because I think it’s off the charts. I would agree with Bill in that regard. But I think all of us have taken a little too much for granted what we’ve inherited as a functioning liberal democracy. So I would say the number-one priority is basically to renew our democracy for the 21st century.
Critically, a vibrant economy provides the best conditions to renew American democracy. And the bioeconomy has the potential to be a huge jobs and growth driver. But it also can strengthen American democracy in other ways. Let me get to that by asking a question: what would make a bio economy a uniquely American bio economy? I think that’s a really important question because it sets up something both amazing, wonderful, and fun. Normally when we think about biotechnology, we start by thinking about life (i.e., medicines, health, food, fuel, shelter, all the things biology makes). And of course, an American bio economy would advance those things and mitigate the negative things. But, an American bio economy would be unique in the world and would lead the world if we also did two other things: an American bio economy should uniquely advance not only life but also liberty and the pursuit of happiness. And by liberty, we mean citizenship, the standing of an individual with respect to the capacities of biotechnology as it manifests in society so that we are not having bio technology imposed upon us but we have the option of understanding and participating in having the bio technology that allows us to be citizens, not merely consumers or subjects or objects. And then pursuit of happiness is that wonderful strange diverse mystery.
If we don’t have a functioning civil society where people feel that they’re citizens, we won’t be able to make COVID obsolete and we’ll be even more vulnerable to bio.
CTC: And, of course, a pandemic can put further strains, to put it mildly, on civil society. With regard to the threat posed by biological agents, post COVID, do you see contagious ones as being the most dangerous?
Endy: Infectious agents causing contagions would allow bad actors to target societies that don’t have a functioning public health system. So they’re useful against those types of targets because they can get everywhere. Places that have a functioning public health system can deal with it and get back to business, but places that don’t just go into this spiral—and I think you’re right, with respect to the coupling between biological attack or event and civil society disconnects and deterioration. But let’s say a bad actor was trying to target a place that did have a functioning public health system that could deal with a contagious outbreak, then that bad actor might look at a different type of threat agent where the harm being caused did not require transmissibility but was a one-time shot. It would burn out super fast, but if dispersed in an appropriate way, there would be a significant impact. And so, assessing the danger posed by a hypothetical contagious pathogen A versus a hypothetical non-contagious pathogen B depends on what the bad actor’s target is and what their target’s vulnerabilities are.
CTC: On the one hand, COVID-19 may result in biosecurity being taken more seriously by the citizenry in the future. But on the other hand, there is the possibility that many see it as an every-hundred-year event and may feel, ‘Okay, we get through COVID-19, we’re good. We’re not going to have to deal with this again.’ How do you see this playing out?
Endy: Great question. You would have to be an ignoramus to take that position, right? You have got to document the frequency of bio events. For example, how long ago was it that we had a nurse quarantined in New Jersey by order of the governor because of Ebola?d How long ago was there great concern over MERS?e It’s just a generation ago that there was acute concern over HIV. We’ve also seen seasonal flu flaring up. Anybody who’s taking that position is really ignorant and needs to be educated about the frequency of bio events in nature. But you’re totally correct that people take that position. And that’s one of the reasons why there’s been a lack of sustained critical thinking and scholarship about bio strategy that looks at the whole picture, bioterror but also bio flourishing.
CTC: Are there other things that, in your view, prevent policymakers from taking this more seriously?
Endy: Look, there’s something really fundamental I’d like to mention here. We tend to operate with a posture that biology happens to us. It’s nature’s will; it’s God’s will. And so that’s why, for example, the entire strategic posture with respect to epidemiology is ‘wait for something to happen and then react and then when we make investments; the best we can do is get better at reacting.’ But I challenge you to teach me of another domain, another theater of potential conflict or risk, where the correct strategic posture is ‘wait for the bad thing to happen.’
CTC: We definitely don’t do that in counterterrorism.
Endy: Yet uniquely, to your question, in biology, ‘wait then react’ is our posture. We’re just letting biology happen to us. Some of our leaders say, ‘Eventually, the [COVID-]19 will go away.’ Well, until recently, this was indeed correct because for most of human history until one generation ago, biology did happen to us, and you just had to react. But starting a generation ago, we human beings got the capacity to express human intention directly into living matter. Genetic engineering got going in the 1970s. And now with DNA printers, we can directly code into biology, into the genetic material. So what this means is there’s a complementary way of thinking about biology, which is ‘we’re happening to biology.’ So as soon as you start talking about bioterror or bio war, we’re driving the biology to cause things to happen. But if most of our society is operating in a frame of reference [that] biology just happens to us, then the best we can do as a strategy is ‘let’s get better at reacting,’ which is approximately what’s happening. But if we can express intention in biology and we can take action by driving the biology, then we have to, at least in part, adopt a complementary strategic posture, which is we have to get ahead of this thing.
CTC: What does that look like?
Endy: Well, first thing is we have to do is express victory conditions in qualitative natural language. Go read the National Biodefense Strategy document.9 I like that the United States of America has one and am grateful for all the hard work in preparing and advancing the document. Yet, I don’t think anybody could recognize the document as presenting a strategy. Instead I can recognize it as a collection of tactics and an accounting of all the things that are happening. Critically, one of the things that’s embedded within this document is very Orwellian: we will always be at war with biology; biology will always be a threat to us. Stated differently, there is currently no articulation of what victory would look like. Without a clear articulation of victory conditions we risk perpetual failure.
So let’s start by articulating what victory could look like. For example, one goal should be to make infectious diseases obsolete. We’re going to start with natural infectious disease, but we’re going to cover the whole spectrum. Bioterror events, bio warfare agents, our goal must be that we’ll make them all obsolete: we’ll make bioweapons obsolete; we’ll make bioterror obsolete; we’ll make infectious disease obsolete. That’s our goal. That would be a clear victory. If we could do that, we would secure victory for a whole category of bio threats.
But how could we do that? We have no chance of victory today. Why? For many reasons—public health for one, as already mentioned. But also because we don’t understand biology well enough. For example, the fundamental unit of life is the cell. It’s the thing that builds all of us: every plant, animal, and whatnot. Yet there is no cell on Earth that we understand completely. Even for the best studied cells, nobody knows what about a quarter of the componentry essential for the cell to be alive does.10 Now the good thing is in the year 2020, we understand this mystery well enough to know what we don’t know and likely why we don’t know it. And so it’s plausible, for the first time ever, to lay out a plan of attack for fundamental research that would get us better measurement tools and better modeling tools so we could operationally master the fundamental unit of life, the cell. I don’t know how to secure biology when the fundamental unit has a quarter of its componentry that nobody understands; everything I don’t understand is a potential vulnerability attack point. So I have no chance of reaching victory conditions if I don’t have operational mastery of the cell.
However, it’s plausible, for the first time ever, to get to this type of operational mastery. Evidence of such operational mastery would be profound. We would demonstrate operational mastery of the cell by building cells from scratch. We would be able to take a lifeless ensemble of molecules in tubes and put them together and get a reproducing cell. Some nation on earth is going to do this for the first time. I would view this feat as akin to orbiting a satellite for the first time. The orbiting of a satellite is demonstrating that you can climb up out of the gravity well of the earth and begin to get out into space. Similarly, the making of a cell from scratch is demonstration of climbing up out of the ‘life well of the earth.’ A life well is the constraint on life in one position in spacetime, and life on Earth is currently constrained by the life that comes before us, the lineages, and the requirements of being able to reproduce and evolve. And so demonstrating operational mastery of the cell is enabled and realized by climbing up out of the life well, by constructing cells. What’s interesting is when we get up there, it won’t be like being in the deep void of space. Instead we’ll have the capacity to construct the fundamental unit of life to do whatever we want. The good thing is we mostly want to do good things with biology, almost exclusively.
This brings me to one thing that I think the Pentagon has gotten really correct in bringing biotechnology into the portfolio of strategic technologies for defense. The Pentagon decided that Defense doesn’t want to own biotechnology, because there’s a flourishing civilian bio economy and that’s where most of the leadership is. And so the U.S. defense strategy for biology should make sure that the United States has the world’s leading bio economy so that everybody, including Defense, can get world-best biotechnology on demand.
At the risk of sounding like a broken record, I’m of the opinion that there needs to be a holistic strategy for biology, inclusive of biosecurity, bioterror, and bio flourishing. I think such a strategy also has to recognize that there are two key trends playing out. One of the things that’s happening in biology is that DNA read [sequencing] and DNA write [synthesizing] technologies get biology onto the network. Together, they make genetic material convertible into sequence information and sequence information convertible into genetic material. Genetic material is the stuff that instructs how life behaves. The superpower of the internet is it disconnects information from location and it lets information be redistributed to other times and other places. So when biology goes on the network, what that means is biocapacity suddenly becomes decoupled from location; it becomes transmissible as information. So we’re heading towards a networked bio economy—a bio net, if you will. Any security strategy, any bio economy strategy, in my opinion, has to ponder what a network strategy is for biology.
The reason why recognizing the need for network strategy is important, to give you an example, is usually when people think about competition in biotech, they think about keeping up with the Joneses. They think about Moore’s lawf metaphor, exponential improvements in computing and DNA sequencing and synthesis. While valid, as soon as you’re dealing with a network, there are different strategies that come into play for keeping ahead of others. One is the establishment of coordination solutions, meaning somebody develops network-based solutions first. Thereafter, everybody goes to the existing solution. For example, if we need to search the web, we’re probably going to connect to Mountain Viewg and use Google’s platform, maybe some others, but it’s very, very hard to displace an entrenched coordination solution. What this means is that there are winner-take-all, first-mover strategies that come into play. And so, just as the United States benefited, for example, by having a world-leading information networking technology that we projected globally that got us a lot of soft power and capacity, which we have still, if a bio net shows up and we’re not driving it and deploying it, and it’s somebody else’s bio net, then forget about our capacity to monitor it, to do intelligence gathering, to interdict threats as they’re emerging. So we need to recognize that biology is going on the network and we need to adopt network strategies for bio.
The second trend that is playing out is much more esoteric but equally important—we’re leaving ‘lineage land.’ Right now, all of life on Earth derives from lineage, so we’re on lineage land. There is a new world of biology that hasn’t been reached yet, but it’s out there, which is lineage-agnostic biology. It’s leaving the life well, as mentioned earlier; it’s demonstrating operational mastery of the cell. Why does that matter? Well, right now if I want to download bio code and do something with it locally, I’m downloading a research project. It’s not like downloading Mandalorian from Disney Plus, where I just get to watch it with my kids, right? I’m downloading a research project; I’d need a laboratory. But let’s imagine I want to download bio code and it lets me brew a medicine where I’m field-deployed right now and I’m not going to want a research project, I just need that medicine made in 90 minutes. Well, that means I need to understand everything about a cell well enough to compile code and operate in the cell with 100-percent reliability. That means I have to get to operational mastery of the cell. That means I have to, from an engineering perspective, be able to build cells. Whoever does that first is going to have a huge advantage. If China builds cells first, then my students will want to go there because that’s where world-best bioengineering will be. We just have to recognize that if somebody gets to that before us, our branded leadership in bio is totally gone. And that’s up for grabs this decade: the building of a cell.
So now let’s pull it together for U.S. policymakers. We need a bio strategy. As one example, here’s my favorite working bio strategy. It has three parts. First, we need to demonstrate operational mastery of cells by learning to build them. Second and third, we need to build and secure the bio net. And we have to do this now, within the decade, so that we can translate these advances as infrastructure undergirding a uniquely American bio economy that projects power while advancing life, liberty, pursuit of happiness. If we do this, then we have a chance of taking infectious disease off the table. If we don’t develop and implement a coherent bio strategy, it’s game over, not to be dramatic.
CTC: The analogy here is the moonshot, the need to articulate getting out of the life well in terms of a bio defense or bio strategy. Let’s pivot to something you thought was important with respect to the bio defense strategy, which is recognizing that there’s a need for a strong civilian private sector bio economy space. If the United States is going to lead not just with respect to biology and biosecurity but in other spheres as well, it needs to get right the nexus between government, private industry, academia, and the research community.
Endy: I’m totally with you, and you’re right in connecting it to other things. Biology does not stand alone. So let me give you the nerd framework. Civilizations run on joules, bits, and atoms: energy, information, and knowledge. So how do we provision joules, bits, and atoms, and how are we going to do that heading out to the rest of the 21st century? Whoever does that best is going to be world leading. Biology is really interesting because it operates at the intersection of energy, information, and atoms, literally. Photosynthesis on Earth harvests about 90 terawatts of energy from sunlight on average at any instant. Natural living systems use this energy to organize molecules into the things we eat and use and so on. Ninety terawatts is about four and a half times what civilization runs on. Human civilization [is] now powered by about 20 terawatts. So another reason to recognize biology as a strategic domain is that it’s simply operating at a planetary scale at this intersection of joules, bits, and atoms, which is what people demand and civilization organizes.
Now let’s bring biology and connect it to some other things—and this is literally one of the most exciting technical advances I’ve stumbled across in the last year—you can reengineer metabolism of microorganisms like yeast for brewing, which normally are fed sugar, to instead grow on another carbon molecule called formate. Now, why do you care about formate? You don’t really need to, except if you go talk to the chemical engineers, they’ve demonstrated that you can take electricity, split water into its elements, and fix carbon from the atmosphere and make formate from atmospheric carbon dioxide. By doing this, you can use, say, a kilowatt hour of electricity, make formate, and grow biomass from that electricity originally. A kilowatt hour of electricity can get you a gram of biomass, and it looks like it’ll probably get us about 30 grams of biomass. Ten cents of electricity, 30 grams of new biomass. That’s amazing. That suddenly implies that I’m going to have an electro bio synthesizer. I’m going to have a machine that I can plug into the wall, and the internet, and feed with atmospheric carbon and water, and I get biology out. Well, that’s like the personal computer, but it’s the personal bio synthesizer.
The other thing is by ‘feeding’ biology with electricity, you can piggy-back on advances in energy generation systems. One of the most remarkable transformations in the last decade is what’s happened with the return on energy for photovoltaic solar panels.11 The key question here is, ‘How much energy does it take to make the solar panel? And how much energy does the solar panel generate?’ Do you ever get your energy back? What’s the return on energy? And in the last decade, the return on energy for photovoltaic went greater than one, and it’s now averaging about 20-fold. Meaning over the lifetime of the panel, I get 20 times more energy than it took to make the panel. This means we’re transitioning to an electricity generation abundant civilization. Never been true before. In the biosphere, why that matters is, if I can go from electricity to biomass, suddenly my capacity to wrangle molecules to manufacture materials is no longer capped by that 90 terawatts of natural photosynthesis. It’s just a question of how much electricity can we make. And, for the first time ever, it doesn’t look like there’s a hard ceiling on electricity generation.
So if we take this more integrated framework and put [in place] a bio strategy and an overall strategy, for the first time in human civilization, it’s looking to me like we can pull off the nerd rapture. We can provision energy, knowledge, and stuff sufficient to support 10 billion people without trashing the rest of the planet. That gives the United States the option of being awesome. This gets back to the citizenship topic. Suddenly, you start to take seriously the question about what fraction of the population, local or elsewhere, is incentivized to be a mal-intentioned actor. And if I want to take bioterror seriously, if I want to take bio war seriously, I have to drive that number to zero. One way to do that is to wait for mal-intentioned actors to show up and then put mass-on-target to interdict, but I’d much rather get ahead of that and just preempt people from being mal-intentioned in the first place by creating better conditions for life, liberty, and the pursuit of happiness. I’m not naïve. I recognize we’ve got to deal with some bad actors inevitably. But it’s so interesting to me that we’re literally sitting on capacities that for the first time in human civilization seem like they have the potential to enable flourishing. If only we embrace that possibility and make it true. And, just to be really clear, I do not mean this as some hippie academic out in California. I mean this as an operational protagonist wanting to see this deployed practically at a planetary scale.
CTC: But between now and the nerd rapture, we’re in a danger period, right?
Endy: Totally. Totally vulnerable.
CTC: Back in 2007, you co-authored a report, “Synthetic Genomics: Options for Governance,”12 which, in a very granular way, looked at some of the ways you can put steps in place to mitigate the threat. We’d love you to walk us through your thinking on that now. Given that technology in synthetic biology continues to advance and spread,13 what steps are key to lowering the risk that a mal-intentioned actor with some scientific knowledge is going to do something which could have a planetary consequence?
Endy: Frankly, all the effort that went into what became the federal guidelines in the United States for sequence screening upstream of DNA synthesis—and I mean this in a very profound way, not a cynical way—with hindsight, most of that work was securing a nascent technology and nascent economic activity from political attack. It did almost nothing to secure the nation from bio attack. It simply allowed a very fragile technology to emerge as an economic activity.
The context, which we’ve touched upon, is the post-anthrax attack. It’s a bioterror regime. And I remember talking with the director of DARPA in October of 2003, briefing out on this synthetic biology study. One of our recommendations was to systematically and unapologetically advance DNA synthesis as a technology, because it allows for the decoupling of design of biology from its construction, so that people could specialize as DNA designers or DNA builders. Well, the net impact of that briefing was to help cancel all public funding for improving DNA synthesis, because our recommendation was only received as potentially increasing political liability and public health risks.
So, four years later, those 2007 guidelines were developed in a context where everything was getting shut down. Yet, we were genuine in our belief that DNA synthesis is a critically important technology for the nation’s well-being, economic security, and physical security. But there wasn’t executive leadership, there wasn’t air cover, so to speak, within the culture or politics for that. You can go back and find a tape of me sitting before the Energy and Commerce Committee in the House next to Craig Venterh and Jay Keaslingi and Tony Fauci.j And I remember Tony is holding up the federal guidelines for DNA sequence screening, and he’s representing them as being sufficient to mitigate risk. And he’s doing his job, but of course, the reason we were there is that Dan Gibsonk on Craig Venter’s team had shown how to do assembly of genes and genomes inside yeast, without needing to use commercial gene synthesis. And so I’m going to myself, ‘Yeah, Tony, I appreciate what you’re doing. You’re securing the biomedical research enterprise from political vulnerability in this context, but everything is not okay.’ Meaning these guidelines don’t prevent a mal-intentioned actor from doing something absolutely bad, and I think if you want a postcard evidence of the potential for this, the researchers up in Canada, as I touched on earlier, had no problem building a pox virus from scratch, running through these commercial providers.14
I’m not saying the commercial providers are irresponsible, but what I am saying is that it’s very difficult to regulate this kind of activity. A DNA synthesizer is essentially a printing press for genetic material, and you’re attempting to regulate the press by having the people operating the press check everything going through the press. It’s just nuts. That’s not how you do it for the written word. Instead, we should look at how we govern speech and the press. And the way we do that is we distribute the responsibility for governance to the places where the speech is being performed. We might have some central oversight and we’ll have the courts, if you will, to adjudicate controversial experiences, but structurally, we’ve made a massive mistake if we continue forward with a centralization of screening-based approach. It just isn’t matched to the problem. And by the way, a centralization approach is also probably incompatible with a liberal democracy. But nevertheless, sequence screening is an easy thing for people to latch on to because it feels like you’re doing something. I get concerned when it becomes the only activity in the name of biosecurity.
Let’s talk about the ultimate DNA synthesizer. It’s an enzyme, which means it’s a genetically-encoded object. It’s going to be programmable with three wavelengths of light—two to set the base and one to say add a base or not. It’s going to be operating inside cells. And so you’re just building DNA from scratch inside cells, wherever you have cells, which is everywhere. And so what’s your governance framework for that? It can’t only be some centralized screening approach. While we might need centralized capacities for intelligence gathering and so on we better also have a culture that understands how to handle lawlessness and obscenity in speech—as it related to building DNA—and distributing the governance of that.
CTC: So is what you’re saying that it should be self-policing? That it should be for the bio industry, bio sphere to be on the lookout, to be careful in what they do, to have certain procedures, in terms of knowing who they’re selling stuff to and so on?
Endy: I would not say self-policing. I would say it’s distributed governance with scaled connections into common governance, shared governance, and centralized governance. But it has to be a system in which there is a degree of bottom-up consensus on the rules of the road. When it comes to speech, we’ve grown up in a society where we’ve been educated about what’s okay and what’s not okay. If that doesn’t exist, good luck. Good luck policing what people say. You can do it, but it’s not a democracy anymore. If you want to police what everybody is saying through a central authority, I don’t know how you do that and have democracy. Let me ask you a series of questions and maybe your readers can think about this too, so be patient. How many people should have the option of learning to read and write? Most would say everybody. Primary education is a basic human right. Next question, how many people should have the option of learning to read and write Python or C++, a computer language?
CTC: Many would argue as many as would want to or need to for society to flourish.
Endy: And so everybody can have the option, and we see programs like Code for America and Computer Science for All. You can predict my next question. How many people should have the option of learning to read and write DNA? The genetic material that instructs how living systems behave; the stuff that’s at the intersection of joules, bits, and atoms; nature’s nanotechnology operating at planetary scale; the organisms that define or impact everything we care about. How many people should have the option?
CTC: Many would argue everybody.
Endy: I’m with you, but then we have to immediately confront the window of vulnerability that we’re exposed to. Now is our chance of establishing leadership in synthetic biology sufficient to guarantee our position as a nation, as the world’s leading bio power of the 21st century, so we can project values. And we have to wrestle with the governance frameworks that recognize that it’s not just an elite scientific enterprise that is strongly institutionalized and can be self-policed through command-and-control institutional authority. We have to also realize the democratic enabling of our citizens as citizens of a 21st biocentury.
CTC: Just to play devil’s advocate, one could ask a different question. Not everybody should have access to nuclear materials like plutonium, right? If biology, just like nuclear science, can be the source of us destroying ourselves as a planet, the human race, is there not an argument for hitting the brakes?
Endy: Yes, one option is hit the brakes. What’s the opposite option? Floor it. Okay, so let’s play those options out. We hit the brakes. But does that work out well for us? Well, we’re still dealing with natural events like the current pandemic, and we’re going to be watching from the sidelines what everybody else does in biology. In fact, we are already starting to do this. We were successful in installing a strategy for synthetic biology at the Ministry of Science and Technology in China in 2013. And they’re running with it. We were successful in doing the same in the United Kingdom. So I think we’re already behind practically in synthetic biology. China’s farther ahead of us with respect to industrialization in their bio economy, and Europe is farther ahead of us with respect to fundamental science and synthetic biology and cell building. That was not true five years ago. It’s definitely true now. I can give you the architectural fly-through of the Institute for Synthetic Biology at the Shenzhen Institute for Advanced Technology, and it’s a half-a-billion-dollar facility. We have nothing like that in the United States. And that’s just one of many. We’ve already seen what happens when we pump the brakes. The result is we’re already behind. For example, under the Obama administration, suddenly you couldn’t talk about synthetic biology in the United States government because it was perceived as being too close to genetic modification, and we never addressed that issue within the food supply culturally.
The other possibility is we floor it. We decide biology’s a strategic domain, there’s massive risk here, and we’re increasingly vulnerable until we have a chance of getting to some better foundational knowledge and better capacities. But we’re going to have to own the risks and associated responsibilities, and we’re going to have to declare we’re going for victory and there’s qualitative risk and increasing risk until we figure it out. I don’t like being in that position either, but given a choice, I would probably adopt the latter strategy rather than hitting the brake again. One key reason for this is that one crisis facing our planet is natural species going extinct. Let’s just float this observation as an orthogonal dimension for just a second: do we care about species in nature going extinct? Some people care quite a lot. Over my lifetime as the human population doubled, the natural biodiversity index dropped by a factor of two. If you want to talk to people who are very comfortable intervening in nature, talk to conservation biologists who are desperately worried about natural species going extinct, which is an irreversible loss. They are willing to intervene in ecosystems, they’re willing to field deploy biology, they’re willing to consider releasing engineered biology like gene drives to cause invasive species to go extinct, to preserve the natural species. It’s a totally different culture, totally different psychology. So I wish I would say we have the option of pumping the brakes or slowing down. But, I don’t think we have that option practically, and I don’t like saying that because there are risks associated with flooring it. But I think if we are mindful about it and smart about it, there’s a way forward.
Let me just flip it around. The Combating Terrorism Center is naturally focused on biothreats. Is there an equivalent organization where I can have the equivalent conversation about our strategy for bio flourishing? I don’t think such a center exists, by the way. I haven’t found it. And so if we only have the conversations in reaction to the Hobbesian possibilities of mal-intentioned actors and the state of nature as a state of war, all we’re going to get is reactive strategy and maybe we should slow down, but the extrinsic crises and urgency created by natural phenomena and things at the intersection of civilization and nature, I think, are increasingly going to drive people to action. In other words, there’s a space that’s been created, it’s going to get filled with something; we should act to fill it with the most awesome thing possible.
CTC: We’ve spoken about how to try to prevent or at least make more difficult a future biological attack. But let’s assume a bad-intentioned actor with some tacit knowledge in some bio lab somewhere cooks up COVID-19 2.0, how can we prepare for that? It has been noted that there is a significant positive feedback loop between preparing for the next pandemic and preparing for the first global bioterrorist attack.15 What are the things that we can do to prepare for and mitigate the impact of a major bio-attack with an engineered pathogen?
Endy: We’ve got to start with culture and leadership. We have to get to a frame of reference, which is we’re not going to let biology happen to us. Number-one most important thing because with infectious disease, we actually have plenty of examples of dealing with it, whether it’s the eradication of smallpox or the nation-states that have dealt well with the COVID-19. We need to get out of a mindset of ‘biology is just happening to us,’ that’s [the] number-one thing. Because from that, you get the dream of victory, and from the dream of victory, you can get action and ownership, not just imposition and compliance. I mean, it’s irresponsible to ask people to comply and to give up things when it’s not coupled to, ‘here’s what victory is and why you’re sacrificing now to get to victory.’ It’s like, really, the best we could do is bend the curve? Like your prize is you bent the curve, good job. Come on. That’s pathetic. That’s a victory? We bent the curve? Gosh. There are many other things we can do as well. You know the example, if you want people to build a navy, you don’t order them to cut the trees down and weave the canvas, you teach them to love sailing and the endless ocean, right? Martin Luther King’s speech wasn’t ‘I have a plan for mitigating …’ It’s ‘I have a dream.’ Where’s our bio dream? Where’s our infectious disease dream?
CTC: So you’re talking about getting the best and the brightest into this field in United States, into the scientific field, the need to convince them that this is an enterprise they want to be involved in. And getting better vaccines and better medical countermeasures?l
Endy: But I want to be really careful because we float those techno improvements as a patch that obviates the responsibility of leading. Like we’ll solve this problem with some magical technology by being magical technologists, as opposed to this is actually something that we’re in all together. There’s a relationship between personal health and public health, and that we’re all in this together in certain ways.
Yes, obviously, advances in biological science can play an important role. I gave you the example of the virology institute in Switzerland building COVID-19 from scratch so that they could do vaccine work. Despite all the concern two decades ago and the shutting down of public funding, the use of DNA synthesis has resulted in better pandemic response: for example, when it comes to the automated generation of attenuated vaccine candidate virus genomes.
What would be something that we could do better? It took a month for that genome to be built in Switzerland. So there was a month latency. I thought Craig Venter did a nice job in giving people the vision of a technology-enabled public health system in response to a pandemic, be it natural or intentional, which would detect where things were happening at the time they were happening, upload that information on the web, transmit that information at the speed of light, and people could be compiling prophylactics and vaccine candidates faster than the planes were landing with infected people.16 So you can have a speed of light public health bio defense system; it would require the equivalent of a hurricane satellite warning system. Imagine a bio weather map. This century we’ll have enough sequencing capacity to sequence the DNA of every organism on the planet. Like literally every base on earth, we’ll sequence. So now let’s just imagine a bio surveillance system. We have a bio weather map. We can see when things are happening. We can transmit that information over the network. We can instantly develop, using computer algorithms, attenuated vaccine candidates. We have enough experience with trialing against scaffolds for vaccine vectors that we just integrate the new sequence specific to the novel pathogen such that we have a vaccine on demand.
A lot of what’s playing out here reminds me of what I read about France coming out of World War I. They were facing some decision-making puzzles around how to invest the nation’s treasure in defense. And having just experienced trench warfare, one of the ideas is to build a better trench. Two factions are arguing that case. There was a third faction, which is basically saying the threat landscape is changing due to mobile infantry and what that means is the threat landscape is going to become more agile, such that you could no longer predict exactly where the attacks are going to happen. Thus, the strategy should not be to make a better trench, rather to create an agile defense system that can react appropriately wherever the threats might arise. Apparently, the third faction lost these conversations and France made the Maginot Line, which almost worked. Who is one of the leaders of that third faction that lost the argument? Charles de Gaulle. Has an airport named for him now. He was strategically correct, but politically didn’t get it done. Some of our posture today reminds me a lot of that period of French history. We’ve got the national biodefense stockpile, and to a significant degree, we’re just deploying fixed assets. But the threat landscape inclusive of bioterror is increasingly dynamic. All the advances in knowledge and tooling suggests that the threat landscape is becoming more agile, and so we need technology capacities that allow us to be better responsive in real time, but we also have to anticipate, we can’t only react.
CTC: So the threat landscape is changing, the strategic environment is changing, the innovative landscape is obviously continuing to evolve related to synthetic biology and the biological arena. We discussed trade-offs in terms of do we pull the brake or do we hit the gas related to a field like synthetic biology or innovations in biology in general. You’ve noted that hitting the brakes may see the United States fall further behind countries like China in the biological domain and outlined why the winner in this race may be able to establish a position of supremacy in this arena. This is all set against the backdrop of a shift in the U.S. defense enterprise to greater focus on near-peer threats and strategic competition, with obviously an emphasis on China. Can you speak a little more to how you see the geopolitical competition over biology playing out?
Endy: I think there’s been a lot of complacency that just because the U.S. has been leading in bio since the modern biotechnology era that this will always be true. But according to the indicators I see, we’ve lost our lead, not by a lot but a little, and it’s not that we can’t get the lead back.
As I already noted, with respect to industrialization and translation, we’ve lost our lead to China. With respect to fundamental science, I think we’ve lost our lead to Europe. And when I talk about losing the lead, I’m speaking not about biology overall but synthetic biology specifically, which is the tip of the tip of the spear of frontier biotech. The reason I care about that is because there’s the Moore’s Law thing playing out, which is basically tools beget tools. So if you fall behind on that exponential, it’s increasingly difficult to catch up. But as we were discussing, network strategies lead to coordination solutions, and once coordination solutions get entrenched, you cannot displace them. So it’s a one-time, winner-take-all scenario. But I don’t think we should see it as a U.S. versus China strategy. It’s who’s going to lead the world with what set of values and then anybody who chooses to unsubscribe from that set of values is disconnected from everybody else. And so I think the U.S. position should be, let’s just make sure we’re leading the world with respect to an open and networked bio economy.
Let me make one more point here. We don’t want to own biotech; we want best-in-class biotech available to us. And so that means the United States has to have the world-leading bio economy. And so we need a strategy to enable the awesomeness associated with that. When we’re talking about pushing the go button increasingly—not the gas pedal, but the go button—the thing to focus on is the doing of the goodness, the doing of the good things, the making of things awesome through biology, and the mindfulness around that related to security and public health. We definitely don’t want to become hyper consumed around only mitigating the things we can imagine.
CTC: To wrap things up, what is your message for the CT community? What do they need to understand and what do they need to worry about when it comes to bioterror?
Endy: In answering this question, let me make a prediction. What’s going to happen in the next 10 years is biology will be recognized as a domain of strategic importance in a holistic way around the world. It’s going to be recognized as strategic for the economy, strategic for security, and in democratic countries like ours strategic for citizenship and values. So there’s going to be some new terms we can anticipate. One of those is bio power—is your nation an established or emerging bio power? Can you project power, economic or otherwise, via biology? As soon as this type of rhetoric and framework shows up, the landscape within which anybody working on bioterror will change, and suddenly biology and biosecurity isn’t the fringe thing that we have to worry about every now and then, with budgets that wax and wane, but recognized holistically as a strategic domain.
There will be and must be sustained interest in bio strategy that accounts for everything from bioterror to public health to bio economy, to bio leadership and so on. And when we think about bio leadership, then we also have to think about the struggle to articulate victory, that the end game can’t be perpetual war or perpetual failure. We have to set a dream that is better than that, that puts some stars in the sky that animates all of us to pull together. There’s a prescription here without a doubt; this prescription is arriving because I think the options of not doing any of this simply gets us into a near future where all the vulnerabilities that we expect are increasing [and] are really going to accelerate in their ‘increasingness.’ If we get to 2030 like we’ve been playing around for last 20 years, it’s just not going to be good. And that’s an understatement. And so there’s another prediction. And I’d like to escape this second prediction by filling it with something positive. It is our responsibility now in this decade to lead ourselves and others to a type of operational victory. And the community of people who are worried about mitigating mal-intentioned actors in biology are essential to victory, essential to flourishing. We can’t have the bio economy without mitigation of mal-intentioned possibilities, and so really bringing it all together and making it coherent and holistic at a national and global scale, bio strategy and bio victory, is something to focus on and to work together on. CTC
[a] Paul Cruickshank and Don Rassler, “A View from the CT Foxhole: A Virtual Roundtable on COVID-19 and Counterterrorism with Audrey Kurth Cronin, Lieutenant General (Ret) Michael Nagata, Magnus Ranstorp, Ali Soufan, and Juan Zarate,” CTC Sentinel 13:6 (2020).
[b] Editor’s note: According to the U.S. National Library of Medicine, “Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism’s DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.” “What are genome editing and CRISPR-Cas9?” U.S. National Library of Medicine.
[c] Editor’s note: This refers to the “acronym for the four types of bases found in a DNA molecule: adenine (A), cytosine (C), guanine (G), and thymine (T).” National Human Genome Research Institute.
[d] Editor’s note: In 2014, a nurse was forcibly quarantined in New Jersey after she returned from West Africa where she had been treating Ebola patients. She was discharged several days later after testing negative for the Ebola virus. “New Jersey Releases Nurse Quarantined for Suspected Ebola,” NBC News, October 27, 2014.
[e] Editor’s note: According to the Centers for Disease Control and Prevention (CDC), “Middle East Respiratory Syndrome (MERS) is viral respiratory illness that is new to humans. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries, including the United States. Most people infected with MERS-CoV developed severe respiratory illness, including fever, cough, and shortness of breath. Many of them have died.” “Middle East Respiratory Syndrome (MERS),” Centers for Disease Control and Prevention, updated August 2, 2019, accessed September 2020.
[f] Editor’s note: Based on a principle articulated by Gordon Moore (later co-founder of Intel), Moore’s law “states that the number of transistors on a microchip will double every year or so.” M. Mitchell Waldrop, “The chips are down for Moore’s law,” Nature News Feature, February 9, 2016.
[g] Editor’s note: Google’s global headquarters complex is based in Mountain View, California.
[h] Editor’s note: Dr. J. Craig Venter is a leading scientist in the field of genome research. See “About,” J. Craig Venter Institute.
[i] Editor’s note: Dr. Jay Keasling is a Professor in the Department of Chemical & Biomolecular Engineering at UC Berkeley’s College of Chemistry. See “Jay D. Keasling,” UC Berkeley College of Chemistry.
[j] Editor’s note: Dr. Anthony Fauci has been the director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID) since 1984.
[k] Editor’s note: Dr. Daniel Gibson is a Professor in the Synthetic Biology group at the J. Craig Venter Institute (JCVI). “About,” J. Craig Venter Institute.
[l] The FDA defines medical countermeasures, or MCMs, as “FDA-regulated products (biologics, drugs, devices) that may be used in the event of a potential public health emergency stemming from a terrorist attack with a biological, chemical, or radiological/nuclear material, or a naturally occurring emerging disease.” “What are Medical Countermeasures?” Food and Drug Administration, accessed September 2020.
 Columb Strack, “The Evolution of the Islamic State’s Chemical Weapons Efforts,” CTC Sentinel 10:9 (2017); “Death by Chemicals: The Syrian Government’s Widespread and Systematic Use of Chemical Weapons,” Human Rights Watch, May 1, 2017.
 Editor’s note: For more on this decision, see Jonathan B. Tucker and Erin R. Mahan, “President Nixon’s Decision to Renounce the U.S. Offensive Biological Weapons Program,” Center for the Study of Weapons of Mass Destruction Case Study 1, National Defense University Press, October 2009.
 Editor’s note: For a perspective from an FBI official on DIY labs, see Kristina Hummel, “A View from the CT Foxhole: Ed You, FBI Weapons of Mass Destruction Directorate, Biological Countermeasures Unit,” CTC Sentinel 10:7 (2017).
 Editor’s note: “National Biodefense Strategy, 2018,” The White House, September 8, 2018.
 Editor’s note: Khagendra P. Bhandari, Jennifer M. Collier, Randy J. Ellingson, and Defne S. Apul, “Energy payback time (EPBT) and energy return on energy invested (EROI) of solar photovoltaic systems: A systematic review and meta-analysis,” Renewable and Sustainable Energy Reviews 47 (2015): pp. 133-141.
 Michele S. Garfinkel, Drew Endy, Gerald L. Epstein, and Robert M. Friedman, “Synthetic genomics: Options for governance,” Biosecurity and bioterrorism: biodefense strategy, practice, and science 5:4 (2007).
 J. Kenneth Wickiser, Kevin J. O’Donovan, Michael Washington, Stephen Hummel, and F. John Burpo, “Engineered Pathogens and Unnatural Biological Weapons: The Future Threat of Synthetic Biology,” CTC Sentinel 13:8 (2020).
 Editor’s note: Kupferschmidt.
 For example, see “A View from the CT Foxhole: A Virtual Roundtable on COVID-19 and Counterterrorism with Audrey Kurth Cronin, Lieutenant General (Ret) Michael Nagata, Magnus Ranstorp, Ali Soufan, and Juan Zarate,” CTC Sentinel 13:6 (2020).
 Editor’s note: See J. Craig Venter, Life at the Speed of Light (New York: Penguin Books, 2013).