A View from the CT Foxhole: Drew Endy, Associate Chair, Bioengineering, Stanford University.

• Author: Hummel, Stephen

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." (3) 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 souffle.'

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 Syria (2) 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...