Latest / 80,000 Hours Podcast / #70 - Dr Cassidy Nelson on the 12 best ways to stop the next pandemic (and limit nCoV)
Transcript
- Robert Wiblin: Hi listeners, this is the 80,000 Hours Podcast, where each week we have an unusually in-depth conversation about one of the world’s most pressing problems and how you can use your career to solve it. I’m Rob Wiblin, Director of Research at 80,000 Hours. Today’s episode is unusually spontaneous and going from conception to release in just a few days. Last week, after we released Howie and my discussion of nCoV, I was thinking it would be great to have a follow-up about what governments should be doing to prevent and manage pandemics, in order to get some good ideas circulating while the policy reform iron is still hot. And as it happens, on the weekend I was hanging out with my friend Cassidy and, it turned out that her and her biosecurity research group at Oxford have been busy working on literally exactly that question. So I figured, if she was going to be explaining all this to me, why not pull out the recording gear and share her views with everyone else at the same time. After a brief update on where we are with nCoV, we work our way through 12 specific policy ideas, and I try to push on each of their pros, cons and uncertainties. While these proposals are especially pertinent today, they were probably also good ideas a few years ago, and should look equally sensible in a few years’ time. All large scale pandemics start with just the first few hundred cases, and we might be able to greatly limit the damage they do if we get better at early outbreak detection and containment. To get there we need both new science and technology, and new ways of organising people to respond intelligently and immediately. I didn’t emphasise this in the interview nearly as much as I should have, but each one of these approaches is not only a policy option available to governments, but also a career option open to some of you listeners. Among others, we discuss several biomedical research projects for scientists, various kinds of policy analysis for economists and others, regulatory reforms for security experts, and scenario planning for people working in medicine. One thing I love about pandemic preparedness as a problem is that there are so many sensible ways to tackle it, all across government, academia, medicine, business, the military and security studies. The surface area of the problem is huge. So I’m sure there’s at least one person in the audience who can pick up and run with each of these ideas in their own life, and help move the needle on humanity’s safety from contagious diseases. I apologise ahead of time if there’s any audio or editing issues — we’ve put this episode together on a very accelerated timeline so we can get these proposals out there before nCoV becomes widespread in the US or Europe. As always, if you notice something we should address or have any other feedback for us, drop Keiran and me an email at podcast at 80000hours dot org. Oh and one thing we forgot to mention is that Cassidy was just accepted into the Emerging Leaders in Biosecurity Fellowship being run by the Johns Hopkins Center for Health Security. We spoke about that back in episode 27 with the centre’s Director, Dr Tom Inglesby. If you’re interested in working on biosecurity, that program is a fantastic way to advance your career and so you should definitely apply. You can hear the pitch for why it’s so valuable in that episode with Tom, and we’ll stick up links to the program’s website in the blog post associated with the episode. Applications for that will next open this coming November. Alright, without further ado, here’s Dr Cassidy Nelson. Today, I’m joined by Cassidy Nelson, a research scholar at Oxford University’s Future of Humanity Institute where her research centers on global catastrophic biological risks and the threats posed by advanced biotechnology. Cassidy is also a PhD student at Oxford focusing on mathematical modeling of pandemic scenarios. Before moving to the UK, Cassidy studied and practiced medicine in Australia with a focus on hospital and laboratory based medicine, human biosecurity and communicable disease public health. And, she also happens to be the person that Howie and I turned to, to listen to our conversation about nCoV before it went out last week to make sure we weren’t saying anything too egregiously wrong. Thanks for coming on the podcast, Cassidy. Cassidy Nelson: Cheers. Thanks for having me. Robert Wiblin: So we’ve ended up doing this episode and I hope we’ll be able to get it out really fast because we were chatting the other day and you mentioned that you were meeting some people in the UK government to give them advice on how to better control and manage pandemics, I guess with a particular focus on nCoV which everyone is talking about just now. And I was like, “That is perfect because I was just thinking that it’ll be great to do an episode to draw some attention to hopefully not stupid policy ideas that people might be willing to implement right now while so many people are thinking about what government can do to stop nCoV from getting into their countries”. Cassidy Nelson: Yeah. There’s lots of interest in this space at the moment and there’s lots of ideas flying around, so happy to be here talking about a few. Robert Wiblin: Before we get to that though, how did you end up working on global catastrophic biological risks? My colleagues have told me that 80,000 Hours had something to do with it, but I don’t know the details. Cassidy Nelson: Yeah. So I originally came across 80,000 Hours and effective altruism as a movement as well back in Australia in 2016. I was four years out of medical school and I was really thinking about which specialty I was going to go into. I was a bit uncertain about which type of career path would be best and have good impact. And I was actually googling how to have more impact with my career that I came across 80K. Years before, I had discovered Peter Singer in some philosophy classes in my undergraduate actually, and had gotten quite involved in thinking about extreme poverty, thinking about animal rights, but had somehow missed the EA bandwagon and so in 2016, coming across the 80K website, a lot of the writing on there really resonated with me. It really made me realize how much impact I’d have working in clinical medicine, seeing one patient at a time, and that initially led me to public health and then through some 80K career coaching, led me to think about biosecurity and more consideration of the long-term future, which I’m now very much focused on in my work. Robert Wiblin: I guess someone reading Peter Singer and then googling how to have more impact with their career. It’s kind of the archetypal perfect target audience for 80,000 Hours. It’s hard to believe that anyone exists in reality doing that, rather than just someone on paper as part of our strategy document. Cassidy Nelson: Well, I’m really glad that the resources were available to me at the time, otherwise I might’ve still been a bit lost looking for myself in a medical career. Robert Wiblin: Yeah. I guess you would have seen articles on like how many lives does a doctor save? Cassidy Nelson: That’s right. That’s one of them that I came across. Robert Wiblin: And then maybe our biosecurity problem profile or something like that? Cassidy Nelson: That’s right. And then thinking through about how many people could potentially die in a pandemic as well as really appreciating that even if you have low probability events, the scale of the impact that they’d have, both on near-term considerations as well as the long-term future really resonated with me and has really shaped my decisions that have led me to be living in the UK today and working on this today. Robert Wiblin: Fortunately, we’ve got a big update to the biosecurity and pandemic preparedness problem profile coming out in the next few weeks. You never want to say the next few weeks, but at least within the next few months. Cassidy Nelson: Yeah, my colleague Greg Lewis has been working hard on that. So I’m looking forward to seeing that out there and seeing more people getting interested and involved. Robert Wiblin: Yeah, we’ll have something even better for the next doctor who’s googling “How to have more impact with my career”. Alright. I guess I don’t want to spend too much time focusing on nCoV specifically because hopefully we can think about timeless policy ideas for pandemic preparedness. But before that, is there anything you want to say about where we stand with the nCoV today as of Tuesday the 11th of February? Is there anything that’s useful to put things in context? Cassidy Nelson: Yeah. So I thought the podcast that you and Howie did a week or so ago now was quite good and that you were able to cover a lot of ground and talk through a lot of the different issues. You also did a really good job of conveying uncertainty which I really respect. I think a few people in this space, including some people in the US have not been so good about conveying uncertainty. So what I could say from today is what we know is that we do have more than 43,000 confirmed cases globally. More than 99% of those being in China. We have more than a thousand deaths now. It looks like this outbreak is continuing to grow, although the latest case numbers from the last few days seems to show that the growth rate itself seems to be slowing down. Cassidy Nelson: Whether that is a true representation of the situation is a bit hard to tell when you have data collection problems where if you think about the cases as a pyramid, and you’re only collecting the very tip of that pyramid and you don’t really know the size of that pyramid going forward, it can be very misleading depending on how you’re ascertaining cases. So I think looking at the situation now, I’ll just say outright, I don’t think it’s a GCBR, a global catastrophic biological risk. However, I do think it is quite a concerning outbreak in terms of thinking through, “Are we prepared for an outbreak of this scale”? An outbreak that is already overwhelming resources and response efforts in places like China and are there things that we could be doing drastically differently that might be able to prepare us for the next one which might be considerably worse? Robert Wiblin: Yeah. Last week, Howie and I gave a probability of something like 20% of whether we’d be able to contain it, and ultimately, in the next six to 12 months, the pandemic would die out. What do the odds look like now? Cassidy Nelson: The latest that I’ve been reading, and, I would encourage some people if they’re interested in this outbreak specifically, the best resources I’ve been coming across are from a mix of places, but especially here in the UK, Imperial College London is releasing some great reports that are able to go through the missing data in great detail. And, what their reckoning is, is that we’re detecting less than 10% of actual cases at the moment. And they’ve made predictions again with high uncertainty, but the predictions that the outbreak should peak in Wuhan in about a month’s time, in China within two to three months, and then in the rest of the world, there might be peaks depending on import rates within several months after that. Cassidy Nelson: All of that, unfortunately, is not something that can be forecasted very well when we still don’t have just even base understanding of some elements of this disease. I think the other place that people could be looking to as well is the Johns Hopkins Center for Health Security who have been doing a really good job of relaying information both from the US perspective as well as from a global perspective. And so, I’d encourage people to continue reading about this as time goes on because it’s going to evolve as we develop more understanding and get more information. Robert Wiblin: Yeah. I guess that’s not a containment scenario, right? It’s more like it’s burned out because so many people have got it already. Cassidy Nelson: My personal view based on this data is that it’s not likely that we are going to be able to contain it in the same way that we contained SARS, for example, where we were able to stop transmission completely just over 8,000 cases. We’ve already obviously massively exceeded that in terms of just the confirmed case numbers. What I think is possible is that we either get to a stage where the outbreak peaks and then dies off completely in the places where it already is established. And there haven’t been good examples yet of outside of China, a very much sustained transmission. Whether or not that’s going on and it’s going on undetected is an open question, and I have suspicions that that might be the case and I’ll get to that in a moment with regards to how we’re actually detecting cases. But, if it does just peak in China and then go off, it might completely disappear and so we don’t have cases anymore in a year or so time. The other outcome that we need to consider and that some have already raised in the biosecurity community, is that this might become endemic. Just like we have other coronaviruses, including seasonal coronavirus that we see come up every wintertime and you actually have peaks and waves of an outbreak, it’s quite possible that this is an emergent coronavirus species that ends up going down the endemic route. Robert Wiblin: Yeah, so it kind of becomes like the flu, but it’s just a different kind of flu? Cassidy Nelson: Yeah, exactly. Or other respiratory viruses. Yes. Robert Wiblin: Yeah. Do you have a sense of how alarmed authorities in the US and UK are? Cassidy Nelson: There’s signs that they’re quite alarmed. In the US, they’ve done things as drastic as announcing travel bans which is quite an extreme measure. In the UK, there’s obviously a lot of concern and just in the last day there’s been evidence of a super-spreader event, which is an anomaly that you do see in outbreaks at times where you have a single person who generates a much larger number of cases than the average. So this particular person on a return from Singapore and stopping by in France for a vacation, ended up infecting at least 11 people who have been confirmed from a single case. And these types of events lead to a nonlinear transmission route, a nonlinear transmission curve. And so things like this do cause a lot of concern in places like the UK, that you might have this sudden inject of a lot of cases which could lead to the worrying scenario if you do get sustained outbreak in a place like the UK or the US. Robert Wiblin: That person wasn’t especially sick themselves, right? They were just spreading it everywhere despite having modest symptoms. Cassidy Nelson: That’s correct. At least according to the reports that person had very modest symptoms and was only isolated, not because they themselves were that unwell, but because they wanted to stop them transmitting. And that in itself is also a worry. While it’s good for the individual to only have mild symptoms from a case like this, people who are infected and only develop mild symptoms also don’t go stay at home and stay in bed, or go to hospital and stay in a hospital bed. They’re ambulatory and they walk around and even though they have milder symptoms, so they might be, what we call like excreting less virus than someone who’s extremely symptomatic, they’re also walking around potentially getting into contact with more people and therefore actually might be more contagious than the extremely unwell person. That can sustain an outbreak and can make it very difficult to contain. Robert Wiblin: Yeah. Okay. Let’s move onto policy. We don’t want to only think about options that are available for nCoV because I suppose for some options, it’s already too late. We would need to plan years ahead potentially to do some things. But I guess there is this interesting phenomenon where every time there’s a pandemic, people are very interested to figure out what can we do right now, and I suppose they end up kind of fighting the last fire. Do you think that there’s a problem that each time we try to figure out what can we do about this pandemic right now and then don’t think about what can we do to plan ahead to put in place processes that will be able to stop the next thing? Cassidy Nelson: Oh, very much so. I get very worried that as a species, in general, we’re quite reactive and we’re not very good at being proactive and events like this really show the need to be proactive. That being able to scramble in the moment to come up with countermeasures, to even be able to come up with a diagnostic test, it means that you’re always several steps behind where the outbreak is actually at, at any given moment. So in many ways, we need to be thinking of policy for the next outbreak to be able to plan now for that. However, at the same time, I do think there are things that we can do for outbreaks in the moment as it were. There can be ways that we can think through, with current moments like this, what we could be doing differently. Cassidy Nelson: I think, in general, with regards to funding and interest as well, that we do really have a focus usually on things that are very temporally relevant. And we’ve seen this before in 2009 in swine flu where there was massive amounts of funding going into certain public health measures. The world, in many places, never had a pandemic plan in their national public health system before. Many places like Australia developed a pandemic plan specifically because of 2009 swine flu. However, the followup to that years later isn’t always there. So people don’t necessarily go in and see once you’ve injected money and resources into this, what the actual ongoing steps are. Is there ongoing interest or does interest dry up and you don’t actually get the changes that you need having a self sustaining mechanism? Cassidy Nelson: The other good example of this is in 2001 of anthrax in the United States that you had a sudden investment in deliberate biological advantages which is something I personally very much care about with my work at FHI. And you saw in 2001 a high interest in being able to protect the nation against deliberate biological threats. And you had things like the BioWatch program come out, which took billions of dollars of investment into doing environmental biosurveillance which was quite revolutionary at the time, but turned out to not be as effective as people would have hoped. And then you had very much a trailing off of that interest. And that’s exactly what we don’t need in these situations. When you have events that only occur occasionally and you have interests that wax and wane, you will never ever be prepared properly. And so sustained funding, sustained interest is what we really should learn from something like this. Robert Wiblin: Well, I guess you need policies that are useful in a wide range of scenarios rather than just focusing on something that would narrowly work in a very specific case that you’ve already seen. I guess I think putting in place a policy that only works if they decide to use anthrax isn’t that helpful because 1) They can just adapt to that and then use a different thing. But then there’s all kinds of different diseases that terrorists might use and a policy that’s so brittle that it only helps in this one case doesn’t seem so good. Cassidy Nelson: And that brings me to one of the policy recommendations that I was going to talk through, which was this idea that as much as it’s nice to have a national pandemic plan like many countries do, like the UK does, like the US does, like Australia does, we need a national pandemic plan. The pandemic influenza plan on its own is just always going to be disease specific. It’s not going to account for things, for example, like this novel coronavirus where we don’t have vaccines against it like we do for flu; at least we have baseline vaccine that you could potentially adapt. We also need, for events where it’s not as common, you need to be able to test systems if it’s not going to happen that often, you need to be able to do things like pandemic tabletop exercises where you actually trial the system that isn’t activated that often because you’re not seeing events that often to be able to actually see where the failures in the system are actually going to be so you can address them before the real event itself. Robert Wiblin: In your normal research, I guess we’ve been using this term ‘global catastrophic biological risk’ which is this jargon for, I guess, the worst case scenarios, basically; so a new disease that doesn’t kill 2% of people but kills like 50% plus, so it’s a massive threat to humanity or I suppose other cases where it’s been done deliberately as say a weapon by a state or something like that where it’s easy to get these worst case scenarios. How much do you think that the policies that would deal with nCoV and other similar pandemics like that overlap with the ones that would help with these GCBRs? Cassidy Nelson: It depends. In some ways, they are the same response system that you would be wanting to deploy in a GCBR event versus a “normal” pandemic event. In other ways, the responses that you’d need for something truly globally catastrophic require not just a scale up of what the normal system is, but a completely different strategy. So depending on the aspect of the response, but depending on the aspect of how you’d want to prevent such things, they do differ quite a bit. I do think though there’s wins to think through ways in which the combinations go hand in hand because I think, especially with regards to policy changes in government, it would be hard to get through legislation and through policy changes in general, that only tackle global catastrophic events and have no relevance to natural pandemics. Robert Wiblin: Yeah. I suppose inasmuch as you’re worried about active use then you can focus on how do we regulate the technologies and the labs and what agreements can we have between states to discourage them from producing biological weapons? There’s a whole category there that doesn’t really carry over to natural pandemics. Then there’s also a case where it has a 50% mortality rate and is spreading a lot and you can imagine the normal healthcare system completely breaking down and you potentially need to rethink, “Well how do we treat this completely”, because you can’t just use the normal processes because they’re not going to be functioning. Cassidy Nelson: That’s exactly right. It’s really beyond just a scale up of what your health system is. Most health systems around the world are functioning at 95% plus capacity on a daily basis. You can’t inundate a healthcare system with cases of a new pandemic pathogen and expect it to continue to work. So the idea that you can just isolate cases in existing isolation: beds in hospitals and hope that you just don’t exhaust that system just really doesn’t work for global catastrophic risks. So thinking through, instead of just exhaustion of systems as they were, alternative routes for which you could get patient care, alternative routes for which you could isolate symptomatic patients so that they’re not transmitting the disease, is really important to think through. Cassidy Nelson: And unfortunately, there have only been limited examples of countries really being willing to think through things of this level. There’s some countries that have made some public statements about plans, about things like home isolation or home care, but in very limited and specific circumstances. Not thinking through different ways that you’d really get on board with tackling a very large scale, highly lethal pandemic pathogen. And to your point with regards to prevention of deliberate events too, you’re right, there’s a very different strategy that you go through thinking about how you prevent a malicious actor from misusing biology to cause harm than you would, for example, thinking through the origins of a natural flu pandemic or other viral pandemic. And those strategies differ drastically when you’re dealing with it, though the responses very quickly start overlapping because both of them are punctuated by the fact that you have a sustained disease propagation through your population. Robert Wiblin: Have we learned anything from what the Chinese are doing or what they’re struggling to do? I mean, I think a week ago, we were looking at the quarantine numbers that they were giving out and just seeing the explosion of the number of people that they were supposedly containing because they’d had contact with someone who had the disease and I suppose the hospitals are just getting flooded with patients or at least at some point they were. Is there anything we can learn from that about how do you deal with the sudden explosion in the number of cases you have to deal with? Cassidy Nelson: Yeah, so I’ve been amazed at the response that’s happened by the Chinese government. Both, with regards like you were saying, to quarantine where they were contact tracing on average 11 to 12 persons for each confirmed case, which as you can imagine, completely exploded very quickly and they’ve contact traced more than 400,000 people and put them in medical observation: home quarantine like setups. We’re not entirely sure of all the details of exactly what that home quarantine entails, but just that sheer number that they’re at least doing a daily phone call into is just massive on a system, and is just not sustainable in the long-term. What we’ve also seen, like you were saying, is the idea in China of being able to actually create an entire hospital in under 10 days with more than a thousand beds and being able to have it open and functioning. Cassidy Nelson: I don’t think you could do that in most Western countries. It would be very difficult to get to those levels as well as quarantining whole cities. We’ve never seen a quarantine of this scale before or stopping human movement of this scale before. All of those I think in some ways are encouraging in that China’s obviously taking this really seriously and has learned some lessons from SARS. It’s a little bit scary from a personal citizen point of view I’d imagine for many people in China. However, what I find it even more disturbing though, is that despite all these measures, the case numbers were not really coming down for quite a few days and now that they might be coming down, at least according to the confirmed case counts, it isn’t terribly reassuring to me given the ample growing evidence that there’s a lot of undetected cases that are already present in Wuhan and outside of Wuhan as well. Cassidy Nelson: What this means to me is that it showcases that even in a state like China, where you could enact these measures, that maybe it’s just that 19th century public health just doesn’t work. The idea of isolating symptomatic cases and quarantining non-symptomatic contacts is just not feasible as a true way to reduce transmission in your population. And that maybe we just need a drastically different approach to how we do public health, how we do outbreak containment, and that we probably need to start considering that soon, especially for a worse pandemic that I worry that we might face this century. Robert Wiblin: Yeah, I guess if the shutting down of travel inside China, I guess especially around Wuhan is the first time that that’s been attempted on that scale, I suppose there’ll be tons of epidemiological papers getting published, trying to learn from this N equals one of whether it’s worked or not. We might not be able to figure it out. Cassidy Nelson: I’m sure there’s going to be hundreds of papers that come out of this outbreak. Yeah. Robert Wiblin: I guess speaking of travel restrictions, that’s one thing that I guess some governments have done. So the US has done that, or they’ve cut off flights from China to the US. Is that right? Cassidy Nelson: They’ve cut off flights from certain areas of China into the US, though they are allowing US citizens back into the US. Robert Wiblin: And the UK hasn’t done that? Cassidy Nelson: That’s correct. Although British Airways has closed off some flights to China or almost all of them now, I think. Robert Wiblin: Yeah, well I suppose perhaps the number of people going on tourist trips to China might have declined, so perhaps less interesting commercial flights there. So that’s been super controversial. There’s a common sense way in which you’d be like, “Well, this is the place where tons of people have this disease. Why don’t we stop them from coming at least for a while and then that will slow down the spread or perhaps will be able to contain it”. It’s easy to see the immediate appeal of that. What’s the case against it? Why is it so controversial whether it helps or not? Cassidy Nelson: So travel bans, like you were saying, seems like a common sense response, and a lot of countries therefore have really, in a knee-jerk type reaction way, started instilling this. If you look at the evidence based behind travel bans, it seems that in most cases, especially with the rapid moving respiratory virus, that it really just doesn’t work. And a lot of this evidence came out of 2009 swine flu. There’s some good Australian modeling papers on this as well. But if you look at the synthesis of all this literature, what it seems to show is that travel bans for these types of outbreaks, if you can get above 90% of the travel stopped from the place of origin, it seems that you could delay the peak of the outbreak by about three weeks plus or minus. Cassidy Nelson: And so that sounds great on paper, but three weeks actually… if a vaccine takes more than a year to be developed, let alone manufactured on scale and you don’t really have any other public health response besides the one you already do, delaying the peak really doesn’t change the magnitude. So you still get the same number of cases overall and it doesn’t change the final outcome of the outbreak. What it does do though, is cause a whole downstream sequence of events. One of the more obvious ones is the economic impacts that travel bans can have. And for a place like China, we’re already starting to see what this actually might do. China is the main manufacturing hub of things such as antibiotics, of personal protective equipment, PPE, which are gloves and masks, and it turns out you do need those things in pandemics and for normal healthcare system functions. Cassidy Nelson: So the other thing that I worry about travel bans doing is that you get people who want to not show that they’re from a place where the travel ban has come from. So they’ll take flights that stop in a few places and then end up in their destination. They want to get out or they have their own business reasons to get out. They won’t show up in the way that we’re doing diagnostics now, which, to get a diagnostic test for this outbreak, you either have to be epidemiologically linked back to Wuhan or a confirmed case, or you have to have severe pneumonia and all other tests for all other etiologies have come back negative. So if you have travel bans in place and you have cases wanting to hide their connection with China or with Wuhan, you can get cases really quickly going undetected. Travel bans, so if you could get them to 100%, which is very difficult to do, they do work on paper. Cassidy Nelson: They work in modeling and there might be some scenarios where you’d actually would want to do that. You could consider doing that if, unlike in this case where you already had free flow of people for more than a month from China to other countries before we really started detecting this outbreak in large numbers. And so therefore, there’s good reason to think that you already have local transmission going on from China. So putting in travel bans now, you’re going to stop the flow in, but you’re already going to have local transmission going on. If you have an outbreak which you think that you haven’t had local spread yet and you can do a hundred percent block, for example, if you’re an island nation and you can stop land border crosses. There’s good reason to think that in extreme pandemic scenarios, and there’s been some researchers out in New Zealand that have looked at this specifically, that maybe travel bans are, even with the economic impact that you’ll incur, are worth considering. However, it’s just a more nuanced conversation than travel bans as a knee-jerk reaction to every outbreak scenario. Robert Wiblin: Okay. So the case where it looks good is, say, if you’re Fiji, you can really cut off the people coming in. It already hasn’t gotten a foothold in lots of other places or it probably hasn’t already come in before you put in the ban. And I guess the fatality rate is so high, or the level of damage that it does is so high, that you’re willing to pay a large cost to stop people from coming in. Doesn’t it still have this problem that, say your Fiji and there’s a very bad disease going around… at some point you’re going to have to reopen the border again. right? You can’t keep doing this. Well, I mean, I guess you could keep it going for months, but what are you going to do it for years? And then at that point it will get in presumably, unless it’s managed to completely burn out by that time. So it seems again like you’re maybe just delaying it rather than truly preventing it. Cassidy Nelson: That’s what I worry is that even if you have been successful and you have stopped those first few cases getting in, by doing a travel ban early enough, you are most likely just delaying cases in your country and that might get you something if your response can be rapidly upscaled in some meaningful type of way. But if it can’t, which it seems like most public health responses at the moment, starting today or starting in three weeks doesn’t make that much difference. You might just be economically hurting yourself with no real gain. There’s another more complicated picture to this too about what travel bans actually have on a world stage point of view which is that if you have travel bans against a place like China and I’m a Southeast Asian country that is very worried that if I suddenly start having a bunch of cases, people make trouble bans against me as well, which I don’t economically want, I don’t have a very good incentive to actually go look for cases. I might actually be disincentivized from disclosure. You might hope that you don’t have cases, but you’re not going to actively go look. And I think there needs to be a massive change to how we think about finding and ascertaining cases that really requires the world not responding in these knee-jerk ways that makes countries really balk back against being truly transparent about their actual caseloads. Robert Wiblin: Okay. So three weeks isn’t enough to come up with a vaccine. I guess possibly it could be enough to do some early research on which existing antivirals might help a little bit and get like a bit more evidence in that time. I suppose it’s enough time to get a little bit more clarity perhaps on the fatality rate of the disease. So I feel like we have a better idea now than we did a month ago, although we’re still super unsure. Why can’t healthcare systems or governments do more to prepare? In the UK is the NHS say, you know, setting aside beds or figuring out what are they going to do when it gets here, given that it seems that it’s likely that at some point it’s going to end up going through the UK in a pretty large scale? Cassidy Nelson: Not many health systems have beds to set aside. There’s not many places in the world where that’s a feasible option. I mean, this is the type of planning I’d hope you’d do before an outbreak, but the idea of, “Do you send people to the GP” and “How quickly can you get a test result back”? If you send people to hospital and it takes a few days to get a test result back, you might actually just be exposing people to cases. Maybe it’s better to keep people at home and do testing at home so you don’t actually have this bringing into a central point where you have vulnerable populations like you do in hospitals or in GP practices that are being exposed. So I think in many ways, you don’t get that much by delaying for a few weeks. Robert Wiblin: So basically they’re going to end up muddling through with whatever their plan is whenever it arrives in reality. So I guess it sounds, in theory, you could do a whole bunch of planning to try to help within those few weeks, but the reality is that there’s not capacity to even do that. Cassidy Nelson: And so this brings us to some points on quality of data that you could get in the early stages of an outbreak which unfortunately we haven’t seen that well. I mean, China’s been arguably a bit more transparent than they were with SARS. They released the genetic sequence, the whole genome of the 2019 nCoV virus fairly early on. But in terms of actual granular data on, for example, onset dates of their cases and the number of tests that they’re performing, they’re reporting on confirmed cases, but we don’t know what the denominator is of that, of how many people they’re actually testing. You could get more data if more data was available, but very few countries are willing to share that or allow others to access it. Robert Wiblin: All right. So travel restrictions don’t sound so good. But maybe let’s talk about some of the ideas that you would like all of the incredibly powerful listeners who are in government right now just waiting to implement good policies to prevent nCoV and future pandemics affecting their countries to implement. Yeah. What’s number one on the list? Cassidy Nelson: Yeah, so I think just because we’re talking about a current outbreak, it’s good to just talk through some response elements first. So we already touched on a few of these, but I think it’s important to get a bit more into the details. The first one that I’d be most excited to see initially is a drastic new change to how we actually do diagnostic testing. This includes both the technology behind diagnostic testing, as well as the protocols by which we go through deciding who gets tested. So at the moment, what we have is a system where you have to know of a pathogen first, know its genetic sequence and usually you develop a specific test to that pathogen. At the moment, the most common types of testing are PCR testing, which is polymerase chain reaction, and it allows you to detect a pathogen that has a certain section of its genetic code match this test that’s very limited in terms of anything new that comes out. You always have to know about the pathogen beforehand, have to have designed and validated a test against that. In the last few years though, some new technologies that have come out that are based on metagenomic techniques, which are pathogen agnostic diagnostics. So you don’t need to know anything about the pathogen beforehand. You can put a clinical sample on and it will tell you all of the DNA that is in that sample. And so you’d be able to do things like bioinformatics testing on this and be able to actually work out, “Oh, it matches against my RSV or CMV or other known viruses, or this is completely new and it doesn’t match anything in my bioinformatics data set”. Robert Wiblin: How does this work? So what, you take a sample from someone and I guess you break down the viruses and bacteria and then you sequence all of it? Cassidy Nelson: Yeah. It sequences everything. So you’d imagine like 98% of it is just human DNA, but bioinformatically you just push that out and you usually don’t care about the human DNA, and then everything that’s left over you’re able to analyze. Robert Wiblin: Is this affordable? Cassidy Nelson: So this has started being used in places like in 2014 in West Africa when there was some diagnostic conundrums going on in the Ebola epidemic going on there. Metagenomic sequencing, especially based on nanopore technology, which is a fascinating way to do this is quite expensive in terms of the reagents that are being used, but the costs of that are coming down and the accuracy of it is going up. I personally think though that these platform agnostic ways of looking at pathogens is really the only way forward if to be on top of diagnostics. There’s really always going to be a one step behind type picture if we have to wait to characterize a new pathogen and then design a new test for it based on PCR type methods today. Robert Wiblin: So the idea is we would just make this the normal way of diagnosing people with contagious diseases. So people come into hospital, they’ve got symptoms and you’d do the sample and you try to sequence everything. You see all the viruses that are going through there. And then you can see whether any of them are weird and whether there’s a pattern of some new disease showing up, hopefully really quickly. Cassidy Nelson: Yeah, and there’s been great studies that have come out looking at like fever in return travelers, for example: 60% of them never get a diagnosis, but there’s something causing their fever. People have gone on using metagenomic techniques and have gone, “What is the pathogen here? What do we actually have”, as well as other diagnostic conundrums. So people have been starting to do this. It hasn’t been adopted on a wide scale yet, but I’d love to see this adopted and you’d be able to have this in all healthcare settings. So you could have this in your emergency department. You may first limit it to just severe cases. So if you have a severe case of pneumonia or another disease, you don’t have any etiology that you’ve been able to find, you’re able to do these types of tests. Cassidy Nelson: This would mean that not only would you be able to have a reliable diagnostic from the get-go before an outbreak begins and then for those first few cases, you might actually be able to instead… on average globally, we have about a 20 day lag in between first outbreak cases and detection of an outbreak for new emerging diseases. That’s way too long. If you could detect those first handful of cases of a new disease, you’re much, much more likely to be able to contain it. Robert Wiblin: Is there a way that this is cheaper? Cause it’s just one machine that tests for everything rather than having to have lots of different tests, where it’s like you test one thing and then it comes back negative– Cassidy Nelson: It’s reagent limited though. So the reagents themselves cost money. Robert Wiblin: What’s a reagent? Cassidy Nelson: Reagents are the chemicals that are being used to be able to actually chemically process the samples. Robert Wiblin: What’s this nanopore thing? Cassidy Nelson: So nanopore is fascinating. I think your listeners would be interested in reading more about it. Nanopore is a protein that actually allows DNA to pass through it and it’s able to read nucleotides one at a time as it passes through this small molecule that literally has a pore in the middle of it. Does that make sense? Robert Wiblin: Okay. And how is that different from just normal sequencing of DNA? Cassidy Nelson: So PCR testing, what you have to do is, is you have a small piece of DNA that you know about and you amplify it. So you go in and you make multiple copies of it and then it comes up as a positive on a band because it’s able to detect that that’s present in the solution that you’ve put it in. This is a very different way of detecting DNA. This doesn’t have to amplify your DNA, so you don’t have to replicate the number. So there’s 1) and 2), You literally just put it through this little molecular machine and it’s able to read all the nucleotides that pass by it. It looks at the electrical charge of the nucleotides that are going by and is able to tell you which nucleotides. Robert Wiblin: It just reads it out. Cassidy Nelson: It just reads it out and it theoretically can read any length of DNA as well. It is not limited to truncated little portions of DNA. Robert Wiblin: Is this in beta testing or is this just a thing that does work that’s expensive? Cassidy Nelson: It’s been used for a while now. There’s companies in the US as well as in the UK that have employed it, but there’s two limitations to it at the moment. One is the sensitivity of it. So the accuracy of its reads are not nearly as high as other sequencing techniques and the other’s the reagent cost. So the cost of the reagents that you have to put into it for it to read a sample are still quite expensive. Robert Wiblin: Okay. So nanopore is the thing that we’ve been talking about that sequences all this stuff. Cassidy Nelson: Yeah. Robert Wiblin: All right. So if this is the first best policy for how we’re going to start detecting– Cassidy Nelson: So pathogen agnostic approaches to diagnostics… So what this means is, is that you cannot only detect pathogens that you’ve never come across before and be able to get a sense of, “Oh, this is something new that’s caused the death in this person”. Not only that, but you would, theoretically, if you could make this as ubiquitous as possible in healthcare settings, you wouldn’t need to. What they’re doing in the US right now, which is, you know, they’ve tested 400 people for nCoV, but they could be testing a lot more and they could be getting a better sense of how many people have mild cases. At the moment, protocols only let you test if you have a link back to China or severe pneumonia, and what that will always mean if you have, what we’re seeing now, which is that there are at least some cases that are mild or maybe even just asymptomatic. You never fully know what the actual infection load is on your population because you don’t have a good sense of how many people are actually infected until you can confirm and test. Robert Wiblin: Okay. So we could really clarify where it is and isn’t and I guess also what the actual fatality rate is and what’s the distribution of the severity? If we just started sampling or testing a representative sample of people in a particular place, rather than just testing the people who are really sick. Cassidy Nelson: Yes. I’d love to see a cohort study that just did this proper testing and actually got to the bottom of how many low symptom or asymptomatic cases there actually are. Robert Wiblin: Okay. So we want to get this everywhere. Anywhere that any pandemic could start. Is that realistic anytime soon? It seems like cost and just the difficulty of getting this into poorer countries might be a bit of a challenge. Cassidy Nelson: If you could get poor countries though to be able to buy like licensure to be able to manufacture the reagents on their own or other such things, you could imagine that, as opposed to relying on countries shipping all these reagents to places around the world, you’d be able to have in-house development. I don’t think it’s the easiest thing to do by any means. However, I do think because it would be such a game changer in these early moments of outbreaks, that it’d be worth investing in overcoming these challenges. Robert Wiblin: What’s the worst part of this idea? What makes you most worried that it isn’t as good as it seems? Cassidy Nelson: The accuracy. So like I was saying, the reads that you get are unfortunately not as accurate as you would hope from sequencing. And what this means is that when you bioinformatically analyze your samples, at the moment you need expertise to be able to actually interpret that data. A normal emergency room department doctor, for example, would not be able to interpret the reads that you get off of this at the moment. You need a much more rigorous system to be able to tell you things about the actual data. Robert Wiblin: Yeah. Is it because you need to take account the possibility of partial matches because there’s just going to be errors in it so you can’t look for an exact match? Cassidy Nelson: Yeah. It requires expertise and a bit of bioinformatics knowledge to properly actually understand the results coming out of this. Robert Wiblin: Okay. All right. Pathogen agnostic testing. I love it. We want to get this out everywhere. What do we actually want the government to do? Cassidy Nelson: Invest in being able to figure out ways to make it more feasible to have it ubiquitous in healthcare settings. More accurate reads and a pathway so that other health systems can also have this type of technology. Robert Wiblin: So we want the government to buy lots of these machines or invest in the stock of the companies that make this stuff or, I don’t know, to give prizes for them if they meet like particular benchmarks? Cassidy Nelson: I think more research and development in this area is either through prizes as a way to go about doing this or thinking through other incentive structures that you could do for development. Robert Wiblin: Yeah. Do you know if these are being developed by academics or by dominant institutions or is it mostly companies that are making these? Cassidy Nelson: It’s mostly companies that I’m aware of. So there’s diagnostic companies in the US and I know of Oxford Nanopore here in the UK. So it’s mostly been private companies doing the investment. Robert Wiblin: Okay. So I guess we could pay them to do research or, I suppose, you could do for profit in investment or just promise to buy lots of machines if they reach a particular level could be another aspect. Just say, “Well, the NHS will buy tons of these once they’re good enough. Cassidy Nelson: That would be a very good incentive. Yeah. Cassidy Nelson: Okay. I guess, is there any way of promoting this that’s not expensive? Is there any way of promoting it on the cheap? Cassidy Nelson: You could have a design prize to see how do you make reagents less costly. Cassidy Nelson: Okay. Cassidy Nelson: So you have private companies. You have academics as well who I know are quite interested in nanopore technology in general. The other way you can do this is through ARPA-like structures and as we know, in the US, DARPA and IARPA programs have been really quite revolutionary in being able to get hard technological problems solved. The UK has also shown a lot of interest in forming their own ARPA. Robert Wiblin: ARPA is Advanced Research Projects Agency. It’s part of the US government’s science and tech funding. Cassidy Nelson: Yeah, that’s correct. Cassidy Nelson: It seems like the Defense people might really love this because I suppose it was very good for protecting us against natural pandemics, but it also seems like it’d be really useful for biodefense if you want to protect against North Korea or whatever kind of crazy people who might be developing diseases. This seems like the kind of thing that they’re really into. Cassidy Nelson: Yeah, I think it’s a win across a lot of fronts. I think it helps you against natural pandemics. It also helps you if we had an accidental or deliberate release of something engineered. If you were able to sequence what you have, if it’s a novel pathogen, it gets you far steps ahead. Robert Wiblin: All right. Okay. So that’s idea one. How many things do we have on the list? Cassidy Nelson: There’s 12. Robert Wiblin: Alright, I’m going to have to cut down on my follow-up questions. What’s number two? Cassidy Nelson: So in a similar vein, thinking through vaccine platforms. So platform technologies in general I think are quite promising. At the moment, the way that we’re designing vaccines, we have a pathogen in mind and we develop a vaccine that’s able to go against that. If you’re able to take a step back and think through ways in which we could have more underlying platforms that would be able to apply across a range of different viral species, you would be many steps ahead when, for example, you have a new coronavirus come out and we already know about other coronaviruses and we would hopefully be able to have some vaccine candidates that would be more readily adjustable to be able to apply to these. This requires a very different fundamental way of funding. Cassidy Nelson: And there have already been some initiatives that have looked at ways you can actually get new vaccines to licensure a lot more quickly than the 10 to 15 plus years that we see for most vaccines. And one of the most prominent ones at the moment is CEPI, which is the Coalition for Epidemic Preparedness Innovations. They were announced in 2017 and currently have a 16 week target from detection of a new pathogen and a candidate vaccine that they can be contesting. They then have a 30 week target for a million doses of that being manufactured. I have two mindsets about this. 1) That’s aspirational and has never been done before. It’s never been done by them or anyone else before. We’ve never had a vaccine for a novel pathogen released in those types of time frames. So it’s good. At the same time, I also don’t think it’s fast enough. I think having a million doses in 30 weeks after your first few cases for especially the types of pandemics I worry about is too long. Robert Wiblin: So both impossible and insufficient. What is it that’s taking up 10 years, normally? Seems like a long time. Is it safety tests? Cassidy Nelson: So the design build test of vaccines as well as other pharmaceuticals unfortunately is a very slow, laborious process. Robert Wiblin: Is this including the whole time of coming up with candidates and seeing if they work and then it doesn’t work and then you go back and try to come up with another one? Cassidy Nelson: That’s correct. As well as phase one clinical trials which looks at just safety. For example, like we don’t have a SARS vaccine and SARS happened 17 years ago, and one of the reasons is, is that most of the candidates we’ve come up with, failed phase one trials, which is where you trial in a small, like 20 to 80 people group and you just look at safety. You haven’t even looked at efficacy yet. That’s phase two and three. Cassidy Nelson: I see, and I suppose it’s hard to test efficacy on that one, because what are they going to do; give them SARS? Cassidy Nelson: It’s hard to test efficacy. But if you fail safety in the first place, if you cause liver failure in someone, you don’t really move on. Cassidy Nelson: So, okay. They want to take it from 10 years to four weeks? Cassidy Nelson: It would be great to get a vaccine in four weeks. Yes. Cassidy Nelson: Seems like a long time to cut it down. Cassidy Nelson: Again, I think we need to stop being limited by how we’re approaching novel tech design and drug and vaccine design in today’s day and age. I think that we have tools in our toolkit that we just really didn’t have in the 20th century when it comes to vaccines, where we could really start using things like machine learning and other techniques to actually go, “How do we do this in silico? How do we do this before we have to put it into an animal model or a human, and actually be able to get a much better sense of a vaccine candidate being both safe and efficacious before you actually get to the human test phase”. You wouldn’t be able to eliminate the human test phase, but if you could get a head start on being able to design these through investment in vaccine platforms, I don’t think it’s a completely intractable problem or insurmountable. It just will require a radically new approach to vaccine development. Cassidy Nelson: So by vaccine platform, do you mean some approach from going from a pathogen to a vaccine that hopefully isn’t so specific to a given pathogen? Something that’s more of a generic way of producing an immune reaction. Of anticipating what vaccines to make and I guess maybe to scale them up much more quickly as well than manufacturing. Cassidy Nelson: Yes, that’s exactly right. So people have talked about this from a universal flu vaccine point of view, which we haven’t been able to do quite yet, but there’s some promising avenues down that. Robert Wiblin: What’s a universal flu vaccine? Is that just one shot that then protects you from all flus? Cassidy Nelson: It’s the idea of being able to either have a vaccine that protects you against all different flus and flu mutates quite quickly as an RNA virus and is able to, as most of us know, each vaccine that you might get each year doesn’t protect you the following year because the virus has changed too much. So a universal flu vaccine would be able to protect you ongoingly. Robert Wiblin: All right. I love it. Okay. So we’re going to make vaccines faster. Are there any particular groups that need funding here or any particular research projects or businesses? Cassidy Nelson: I’m encouraged by CEPI’s role. They’ve run into problems. They chose four diseases to begin with and they chose them because there’s not a good economic incentive for these diseases to have vaccines developed against. And that’s because there’s just no guarantee that they’re actually going to lead to sustained outbreaks and therefore companies that are making vaccines don’t have an incentive to roll the ball and risk pouring a billion plus dollars that it takes to develop a vaccine into something where they never get it sold. Cassidy Nelson: They’re worried about the possibility that there won’t be a terrible pandemic. Is there a problem where if they come up with a vaccine that’s really good, then spot vaccination would be able to control the pandemic really quickly and so they wouldn’t be able to sell enough doses of the thing because they stopped it from spreading. Cassidy Nelson: I mean that’s a conundrum of a lot of cures I guess that you’d have for any pharmaceutical or vaccine that you’d be developing as a company. Cassidy Nelson: Okay. Is there anything more to say on this? What’s the biggest weakness? I suppose it just sounds technically ambitious? Cassidy Nelson: It’s very technically ambitious. But again, I’m optimistic about us being a bit more ambitious with this. I think in general, we really won’t be making much headway unless we start getting a bit ambitious with these types of projects. Cassidy Nelson: We manufacture vaccines in eggs or something? Don’t we have some really primitive way of actually developing them? Cassidy Nelson: That’s correct. So the main way, especially with flu vaccines, there’s a few different ways, but the mainstay is that you are reliant on chicken eggs in which you inject an antigen that’s able to make the response against and then you’re able to then extract that from the egg and use it as a vaccine. It’s useful because it works, but it’s also limited by things such as egg supply, which we’ve seen actually in some vaccine manufacturing problems. I was involved in that when I was working in communicable disease in Australia with the flu vaccine. So there’s different ways that you can think about how you could do this where you don’t need eggs or you can use it in some other vat type way. Robert Wiblin: Yeah. I guess naively it seems to me that we want something… I suppose we have yeast that makes insulin. So we want to get some little microorganism that can just churn out where we’ll chuck in the DNA for whatever antigen of the virus that we want to get the immune reaction to and then just get it to churn out that stuff in great quantities. Is that one vision? Cassidy Nelson: That would be a great research project that I’d love someone to solve because it is a hard problem. But I don’t think there’s any biological reason why it’s not solvable. Robert Wiblin: Okay. All right. Let’s move on. What’s idea three? Cassidy Nelson: So, idea three is in a similar vein and it’s thinking through broad-spectrum therapeutics. So, not only do we want to be able to diagnose disease and prevent it with vaccines, but being able to treat the unwell with effective therapeutics can be quite difficult in outbreaks and we’ve seen that with this outbreak at the moment. It’s especially hard for viral diseases in which we have very few broad-spectrum antivirals available that are effective. I think, again, it’s ambitious, but thinking through ways that we could incentivize development into broad-spectrum therapeutics where you could have candidate treatments that are potentially able to work against certain pathogens. And we’ve had two that have actually appeared in this outbreak that seem to have some efficacy. However, I think we just mostly got lucky with that. I think if we had a truly novel pathogen outbreak from a completely new viral family for example, that we’d be very hard pressed to have any therapeutics that actually work. Robert Wiblin: Yeah. So, this is something like having antivirals or antibiotics. I guess we developed antibiotics that for almost any bacteria, we have some antibiotic that kills it, I guess, at least until they develop resistance. Is there some reason why technically we haven’t been able to come up with broad-spectrum antivirals in the way that we’ve come up with broad-spectrum antibiotics? Cassidy Nelson: Yeah. So, there’s a few reasons that viruses are just notoriously harder to develop pharmaceuticals against than antibiotics. It depends on a few different things. One of the ways that it’s a lot more difficult is that viruses are usually hidden intracellularly. They’re harder to access, so you need to be able to either have the antiviral uptaken into the cell itself. Viruses have all sorts of ways of being able to hide themselves against the therapeutic responses. Robert Wiblin: They’re co-opting the cell’s own machinery to replicate themselves, right? Cassidy Nelson: That’s right. Robert Wiblin: So attacking the things that they’re doing is attacking the human cell itself. So you’d get big side effects. Cassidy Nelson: Yeah. And a lot of disease actually can come down to our own immune systems trying to clear infections but ending up causing more tissue damage than the actual damage from the culprit pathogen itself. And antivirals in general as well seem to work on very specific mechanisms that are only usually specific to certain viruses and are harder to make more generic than the ways that we’ve been able to harness our knowledge of how bacteria, for example, how they divide and being able to stop that process which seems to be a bit more shared across a range of different bacterial species. Robert Wiblin: Okay. So for a broad-spectrum antiviral, I guess we need to target some very fundamental common element that most viruses have or that most pathogens have? It seems like antivirals and antibiotics, they’re things that have a particular shape that lock onto some part of some process and then inhibit it and make it hard for it to go about its business. That’s basically what’s going on. We’re trying to come up with something that’s just the right shape, like having the right key for the right lock. To mess with that but nothing else. Cassidy Nelson: A lot of it comes down to keys and locks. Robert Wiblin: I studied biology in high school too! Cassidy Nelson: But there’s other ways you can think about it. You can think about the ways that you can help your own immune system clearing infections as well. If you can just put a little a homing beacon on a viral particle so that your own immune system comes around and scoops it up. It’s straightforward. Again, the solutions to these are not readily available because they are hard problems. But again, I think we need to be thinking outside of the box and we need to… Instead of the current approach where we have specific pathogen and then have specific treatment developed for it, it’s these more ambitious projects that are actually going to make a difference in novel pathogen outbreaks. Robert Wiblin: Yeah. Is this something that has already got a lot of attention? I’m interested actually to ask that for all of the three things that we’ve talked about so far. Are these things where people have been banging their head against a wall for a long time or…? Cassidy Nelson: They’ve all been talked about in the literature to some degree. They’ve been pursued to some degree by places like the WHO and the US government’s NIH and others. To the degree that they’re pursued versus disease-specific treatments though, I think that they’re more neglected. And so I think that if you change the portfolio where you went, “No, these are really priority areas that… Yes, they’re a lot harder to solve than single disease therapeutics, vaccines or diagnostics, but they could make a massive difference for such a large range that they’re worth it.” I do think there are ways that you can have traction. Robert Wiblin: So all of these three suggestions, they all have this character of not being focused on one particular disease. We’ll have generic screening for new pathogens, we’ll have generic ways of developing vaccines faster. The methodology for making and scaling up vaccines and then the methodology for producing an antiviral that doesn’t target any one thing in particular, it’s just targeting everything. Is there a reason why that stuff doesn’t get funded as much? Is it harder to draw attention to the idea of improving vaccine technology as a whole rather than a vaccine for a specific disease? Cassidy Nelson: In my experience, like I was saying before, I think we have been mostly reactive and not proactive. So we very much have honed in on disease threats that are emerging and that we are faced with. We’re not, until probably recently, really thinking through what we’d call disease X scenarios, which is not a specific disease but the idea that something new that’s emerged might be a massive threat to the human species. And so, I really think this type of conceptualization is fairly new to most circles. It’s just very much a different way of looking at a problem. It looks a lot harder– Robert Wiblin: It’s not how a typical doctor thinks about it. I guess they think about that particular pathology, particular conditions. Not about medical technology as a whole. Cassidy Nelson: Exactly. It’s harder to think in this broad-term way and it’s messier, but also a lot quicker as well. But I think it’s important. I think it’s important and I do think it’s not something that we should throw our hands in the air because it’s so difficult. Robert Wiblin: Yeah. Okay, so this stuff doesn’t fit quite as neatly into typical funding and I guess career progression perhaps. And I suppose also people just aren’t appreciating the size of the prize here, or just how important it is to have these generic technologies that can tackle new pathogens because we haven’t yet had a pandemic that kills half of people. It’s not quite in the forefront of people’s minds how bad things could get. Cassidy Nelson: I mean recent events may have changed this for some people, but in general we’re kind of complacent when it comes to thinking about infectious diseases. Those don’t really, especially in the Western world, seem to affect us that much on a daily basis and we don’t realize how vulnerable we are as a population to viruses that are even emerging from nature, let alone engineered ones that could be potentially much worse. Robert Wiblin: Okay. And I guess the biggest weakness of the broad-spectrum antiviral is just that, again, technically it’s really hard? Cassidy Nelson: Yeah. I don’t want to downplay that at all. It is technically very difficult. However, I do think there’s at least some momentum that we could get there and we’d at least have some candidates that could maybe be adjusted in that four week period that you could then tail to a new virus. Robert Wiblin: Nice. All right. Idea four? Cassidy Nelson: Yeah, so we touched on this again before, but I think it’s an important one. Thinking through instead of each nation having a pandemic influenza plan, having a pandemic plan. And so the way I’d conceptualize this is that we’d have a plan that’s both pathogen agnostic again, so it’s generic enough that you could tailor it to any pathogen outbreak, and then it’s adaptable too depending on different factors of what you’re actually facing in that outbreak. The transmissibility, the R nought, the mode of transmission as well as things like how fast moving it is, what the incubation period’s like. I think that this is harder for countries to do and that’s why they haven’t, for the most part, developed a generic pandemic plan. However, I think we’re seeing now that you can’t really just take your influenza plan and then– Robert Wiblin: Import it over. Cassidy Nelson: Import it on top of nCoV or other things. Robert Wiblin: Why is that? Cassidy Nelson: Why can’t you import it over? Robert Wiblin: Yeah. Cassidy Nelson: Because influenza’s not just a different disease, but we already have different countermeasures available for it that we just really don’t have for nCoV. For nCoV we actually got a bit lucky with the diagnostic side of things. We were able to develop a diagnostic in a few weeks. But that’s mostly because it was so similar to SARS that the PCR tests, if you actually look at the laboratory testing for it, its positive case-control is actually SARS. And so it’s so genetically similar, especially in the region where you’re doing the PCR testing. So the genetic region that we’re actually doing the testing on is so similar that it only took a little bit of tweaking to make this diagnostic test. Cassidy Nelson: For novel pathogens that aren’t from a viral family we’ve come across before, you would actually struggle for quite a bit longer. We didn’t have a SARS test, for example, for nine months actually to get to the point, and that was well after the outbreak was over. We had one that was developed in April/May, but it only returned positive after about 20 days of infection. So you had to be infected for about 20 days which is well after you’ve stopped being– Robert Wiblin: How the hell did they control SARS if they couldn’t even diagnose people? Cassidy Nelson: It’s amazing that they did. It’s amazing. So the way that they were diagnosing people is just based on symptoms. And I’ve done some research into this as a part of my PhD actually. But the sensitivity of the case definition they’re using… Case definition is how you define if someone’s infected or not infected. The sensitivity of the WHO case definition was 26% which is extremely low. It means the majority of cases that actually have the disease wouldn’t turn up as a positive based on the definition. Cassidy Nelson: I mean it’s even in the title. SARS stands for severe acute respiratory syndrome, which is the most nondescript way of defining a disease. And so you can see how much you struggle if you can’t even sort out who’s infected and who’s not. I’m amazed that we controlled SARS. Robert Wiblin: Did we just get lucky? I don’t understand. Maybe I should get someone on the show who can explain how we stopped SARS. Cassidy Nelson: Yeah. So we got lucky in a few ways. One way we got lucky is that it seems that there wasn’t, looking back on it, there isn’t any good evidence that people were transmitting while they were not symptomatic. So that makes it easier to control. We were also able to isolate cases. At the beginning, it took several days before when you started showing symptoms and when you’d be put into isolation. We were able to get that down to under two days which is phenomenal of public health services be able to do this. Cassidy Nelson: The other thing with SARS is that you had a nonlinear transmission as well which was fascinating, but also in some ways perhaps helped in that most cases actually only generated about one extra case. And then you had a few super-spreaders. So you had a famous Hong Kong hotel. I don’t know if you know the story behind this, but there was a doctor who treated cases in mainland China who came back to Hong Kong and he was on the ninth floor of a hotel and infected almost everyone on that floor. Even people he never met but just because the air was circulating. And that, they reckon, led to about 70% of the cases in Hong Kong due to this one person. So these super-spreader events are scary and they can massively cause upswings in your outbreak. But it also means that most of the other cases are not transmitting as much. So if you can get– Robert Wiblin: So if you can stop the super-spreading then– Cassidy Nelson: If you can stop the super-spreaders or if it’s only really that super-spreaders are occasionally happening, and most other people are only generating one extra case, really strong isolation can really make you control your outbreak. Robert Wiblin: Okay. All right. Sorry, what was the– Cassidy Nelson: Yeah, sorry. So that was generic pandemic planning. There are a few things that I think this is important for. Being able to have it adaptable to new diseases that might not look like influenza or things that you’ve seen before. The other is thinking through that often you won’t be able to just, especially for large scale pandemics, you can’t just scale up the response that you would for smaller scale outbreaks. You can’t just turn up the dial as it were. You might need to adapt a different strategy at different points, and there might be trigger points for which times you need to do that. Most healthcare systems are already functioning at 95% plus capacity. And so to think through how you’d actually maybe not bring all your pandemic cases to a hospital that already has cardiac patients, that already has other people with other diseases that you want to continue treating, especially if– Robert Wiblin: And that are especially vulnerable to getting sick with it. Cassidy Nelson: Who are especially vulnerable to getting sick. And what we’ve seen in other outbreaks before is that nosocomial infections, which means you acquire them in a healthcare setting, really propagate pandemics. In SARS, in Taiwan and a few other places, more than 50% of cases were acquired in a hospital. Robert Wiblin: There was a bunch of that with Ebola as well, right? Cassidy Nelson: And there was that with Ebola as well. So you need to think of a different strategy as opposed to just scaling up. So I think that’s a really important point. Robert Wiblin: If and when, probably most likely when, nCoV gets to the UK or the US, do you think there’s a case that they should be telling people who have low level symptoms to stay at home? I guess if people need a respirator then they’ve got to go into hospital. But, short of that, maybe they should just be staying in their room and trying to not go anywhere near their housemates as much as possible. Cassidy Nelson: I think there’s something to be said for, if your health system can deliver this, not having people who especially are mild cases going into GP surgeries or into hospital emergency rooms and potentially infecting other people in the process while they’re waiting. Especially if you have a few days delay anyway to getting diagnosed. If you could set up your system so that you could do at home testing of people and also at home care of the milder cases where people are either cared for at their home or they’re checked in on if they only have very, very mild symptoms but they’re able to stay isolated and not transmitting it to others, that’s a much better system than bringing everyone to a central convening point where there’s vulnerable populations. And some places have started thinking through this about, “Don’t come into hospital. Call us first,” and then working through this. Robert Wiblin: France is doing that.. Cassidy Nelson: France is doing a phone call system. In the UK they’re recommending calling 111. I’m not sure what happens after you call 111, but they’re obviously thinking through different ways as opposed to just saying, “Come immediately into hospital,” which is not what you want to do with a transmissible disease in every scenario. Robert Wiblin: So the general suggestion is do a generic pandemic plan or plan for a whole bunch of different scenarios. Did you have any other ideas of what kind of actions are likely to end up in that plan? Cassidy Nelson: I have personal ones of thinking through a plan like that could be something that, especially thinking through GCBRs and larger scale events where you really want to protect the survival of populations, that having strategies in place, having thought through, “What are the triggers at which you think you need to invoke in the next level of that strategy”, if that makes sense. Having that preplanned out can save you a lot of time on the ground in the middle of an event itself, instead of having to scramble to think of, “Okay, what is actually the best solution here”?I think it’s hard to predict everything. It’s hard to plan for everything. But I think you can have various permutations of at least plausible scenarios in which you can have done some pre-thinking in peacetime, as it were, that really help you in an outbreak response situation where you need to be making rapid decisions. Robert Wiblin: Yeah. In the episode between Howie and me, we suggested that people should have food at home so that in one of these worst case scenarios, the option is open to just stay at home and not go out. And I guess ideally, from a public health point of view, it would probably be very nice if lots of people just had so much food at home that, at the drop of a hat, people could just decide that they’re not going to leave the house for the next few weeks. And then that can be used as a way of stopping the spread of a disease. Is that on point? Cassidy Nelson: I’d hesitate to caution people that this pandemic or this outbreak, as it were, was going to get to that level necessarily, because it’s all still uncertain. But yes, things like that, things like social distancing in general. The reason that biology is scary in this way is because it infects human hosts and then it’s able to spread human to human. But it needs to be able to have a transmission pathway to be able to do that. You distancing yourself in a larger scale outbreak is one of the best ways to protect yourself, so if you have resources at home that’s quite good. Cassidy Nelson: That brings to another point in a pandemic plan something that you’d really want which is if you had a large enough outbreak, things such as long supply chains can get really affected. That’s both for food, especially in places where food production is not at the levels needed to sustain a population. It’s also for essential items such as your antibiotics, essential medicines, respirators and personal protective equipment, PPE. And it’s something that for this outbreak right now, we might actually see downstream effects if China’s production of things like gloves and respirators and antibiotics go offline because there’s less people working or because trade is affected. Cassidy Nelson: That can actually seriously affect healthcare systems. For a lot of healthcare systems, you only have a few days worth of supply. We saw this with normal saline back when there were some Caribbean extreme weather events. Normal saline supplies were affected in the United States and other places around the world as well as heparin at the moment. Because of African swine fever in China, heparin supplies around the world, which is a very essential medication for a range of hospital uses because it stops clotting, has been affected and is still being affected right now. Cassidy Nelson: Being able to think through, “Okay, if I don’t have domestic stockpiling of enough extent or if I don’t have production, are there ways that I could either have a system where I just turn online production of things like gloves, of things like respirators, of things like antibiotics? Maybe it’s not economically feasible for me in the UK to be making all of those things at cost at times. But if I had a system in place where I could at least turn on production of those types of things and therefore get around the problem of supply chain cutoffs.” Robert Wiblin: Okay. So the general suggestion is do a whole lot of game planning on how you’re going to deal with this stuff? Cassidy Nelson: Yes. That’s a pandemic plan that’s adaptable and generic. Yes. Robert Wiblin: Is there any case against prioritizing doing this? What’s the argument against it? Or maybe this is just too common sense. Cassidy Nelson: I guess, done poorly, maybe you’ll get surprised by something that you haven’t planned for. But I guess that’s part of how well you plan. I guess for some of these things, especially if you need to massively increase the capability and capacity of your healthcare systems, that could cost quite a bit. However, I think there are ways that you could think through about things where it’s only in these scenarios themselves that you suddenly start spending a lot of money on doing this. For example, the supply chain idea or changes to how you do healthcare system response. Robert Wiblin: I was kind of surprised to find out that this hadn’t already been done. Are there any countries where they have done this? Cassidy Nelson: I was surprised that there wasn’t really pandemic plans before 2009 in a lot of countries. And then only then are there really pandemic influenza plans. Yes, there are countries that have thought more through generic pandemic planning. A lot of them haven’t framed it in this kind of way. They’ve either looked at public health emergency response planning, which is the generic way that they’re looking at it, and then they look at a whole range of scenarios that aren’t just infectious disease contagious scenarios. Or they’ve looked at things, like the US, for example, has done a bit of planning around if smallpox was released or other pathogen specific scenarios. I think again, it’s quite ambitious to be thinking through so many permutations. I think the payoff that you get from having done that hard background work just pays for itself in an event where it’s unprecedented. Robert Wiblin: All right. What’s the fifth idea? Cassidy Nelson: The fifth idea is thinking through a different approach to how we do travel bans and having it much more evidence-based than the knee-jerk reactions that we have. I don’t think it’s the case that in all scenarios we shouldn’t do travel bans. I think there are a few trigger scenarios in which they are a good idea. I just think that doing it in this ad hoc way can cause more harm than good and we need to actually think through the pros and cons. Robert Wiblin: Okay. So it’s just the thing that people jump to right away. Cassidy Nelson: It’s a thing that a government can do. Robert Wiblin: And be seen to be doing it. Cassidy Nelson: Exactly. Robert Wiblin: Okay. Basically this is, “Do a proper cost-benefit analysis of under what circumstances, probably fairly unusual circumstances, it would be worth having a travel ban”. Cassidy Nelson: That’s correct. Robert Wiblin: Okay. All right, I’m not going to ask if there’s any downsides to that. It does seem probably worth putting someone on that. What’s the sixth idea? Cassidy Nelson: This idea is a little bit of a departure from what we’ve been talking about, but data sharing. At the moment, what we’ve seen is a real reluctance to provide and share granular data on outbreak cases. China’s not alone in this. I think most countries, if they were the ones experiencing this outbreak, would also have similar reluctance to be sharing data. I think we need, as a global community, a really different approach to this. At the moment we have what the WHO is relying on, which is the International Health Regulations last updated in 2005, which showcases internationally the absolute maximum countries need to do when it comes to things such as a public health response, support of other member states and data sharing. There are requirements under the International Health Regulations to share certain data with the WHO, and then the WHO is able to share what member states agree to out of that. Cassidy Nelson: I don’t think this is nearly enough because I think what we’re seeing now, it’s very frustrating that we do have expertise in places like the UK and the US that really could be helping understand this outbreak a lot more if we had access to de-identified data of things like onset dates of cases, testing numbers and other such things. We’d have a much better idea of what the case fatality is and what responses actually work. I think this is more of a international relations type problem, which is not my area of expertise. There’s a lot to be gained if we actually established, in peacetime, ways to share public health data rapidly in fast moving outbreaks. Robert Wiblin: Why are countries so reluctant to release this information? It seems China is already getting slammed. How much worse can it be if they release more data on the specific cases? China is a cagey country in general. But I guess it sounded like you were suggesting that other countries might do the same thing. Cassidy Nelson: I think countries would fear backlash. It’s politically sensitive for some of these things. It can be politically embarrassing for other countries to realize if they were too slow to act at certain stages or they had problems with instigating certain parts of their response. Having too many cases looks bad and they might rightfully fear things like travel bans or effects on their economy or trade. Robert Wiblin: Yeah. It seems they’re not especially careful about being very strategic about what they share and what they don’t. It seems in many cases it’s just that there’s not that much damage to it. There had been a bunch of papers that I’ve seen that have descriptions of a hundred different cases of people who had it and how long did it take, did they recover, and what symptoms did they have. So there is some information showing, it’s just not everything that we’d want. Cassidy Nelson: There are Chinese authors and international authors on a lot of those papers. It’s much better than what we saw for example in SARS, or in MERS as well too, which also had problems around data sharing in the Middle East. However, it seems that no country has really lead the way with going, “No, we want this, we need this and we ourselves are willing to give up our data”. I think you’d have problems with most countries actually wanting to really be as transparent as possible with this type of data. Robert Wiblin: Is there any way of having international multilateral or bilateral treaties that make it more mandatory with punishments for not following up? Cassidy Nelson: Well, that’s what the International Health Regulations mandates, at for least member states, but it’s not a mandate to release publicly. It’s a mandate to share with WHO and other member states. Robert Wiblin: Then they can’t pass it on necessarily. Cassidy Nelson: It’s specified in there what the absolute maximum is that can be passed on. Robert Wiblin: Okay. What can we do? I guess it’s convincing countries to do the follow through on this, to actually follow those regulations. Do we need to change the International Health Regulations so that there’s more punishment for not following them? Do you have any idea? I suppose this is the international relations aspect. Cassidy Nelson: It gets politically sensitive for all sorts of reasons. I do think though that if as a global community, we just decided that information sharing of outbreak data is just too important to really fall by the wayside. That we really want to make it mandatory in ways that’s transparent, not just as a reporting mechanism to the WHO, but as a transparency mechanism to the rest of the world. I do think that it could be quite hard to do this, but that we could make headway. Robert Wiblin: I wonder if you can have a pre-commitment thing. Any government in the moment doesn’t want to share this data, but if they’ve put in place processes that inexorably go about the process of sharing all of this information, and it’s difficult to stop because the law says that the government can’t prevent the data from being released. So they’d have to go to parliament and change the legislation and do all these other things. No one’s going to want to do it in the moment, but if you don’t know if you’re the government that’s going to have to release this information, maybe you’re willing to pre-commit future governments to do it because it seems like a good idea? Cassidy Nelson: That sounds good to me. Yeah, it would be nice to see. We see this ,for example, in another area that I’ve been involved in, the Biological Weapons Convention. And there’s confidence building measures that countries report every year. Unfortunately, only about 40% of these countries report them on time and very few actually report them publicly. It’s voluntary if you make them public or not. The ones that do though, like the US and the UK, I think could showcase that we can actually do this. We can actually show that we’re committed to this, and you could do something similar here with regards to public health outbreak data. Yeah, you just need to get some momentum going on this and then make it an international norm that public health emergencies step beyond these kinds of political considerations. Robert Wiblin: Can we pay countries to share their data? I suppose as an economist, we’re just like, “Show them the money”! Yeah. Can you think of any ways that data sharing arrangements could backfire? That maybe it’s good for countries to not share their information? Cassidy Nelson: Well, there’s selfish reasons to not share your data. Like I was saying about travel bans before, if countries sometimes are transparent about their number of cases, they rightfully have a concern that there’s going to be restriction of travel and trade against them. The incentives aren’t really always in the favor of sharing. The other thing I’ve thought about before with regards to this is pathogen sharing, which I do feel has nuances that could be quite risky as well too, but on net, quite useful. It’s good to share genetic data on new viruses and bacteria that are causing outbreaks. However, sharing live pathogen itself is what you really actually need to be able to develop things like vaccines instead of what we did in this outbreak, which is waiting for cases to appear in your country unlike places like Australia. Cassidy Nelson: CSIRO, in Australia, was able to take clinical samples from an Australian patient and culture the nCoV virus and grow it en masse so that they can now lead, for the CEPI response, the vaccine manufacturing. If you didn’t have an Australian case though, and you only have genetic data, it’s quite hard to just boot up a virus from scratch. From a risk point of view, I get a bit worried about viral design, but being able to have rapid sharing pathogens, so you can actually have your countermeasures getting developed a lot quicker. I feel like there’s massive strides we could be making in terms of ways we could be approaching this in the world. Robert Wiblin: Okay. I suppose this is a nice one that doesn’t cost anything in the budget: committing to showing the data. What’s the next idea? Cassidy Nelson: Okay, so now we’re moving on to prevention. So this is now thinking outside of this outbreak, which we already kind of have been, which is thinking before you’re in an outbreak scenario, what are the things that you can do to actually prevent one from occurring? I get very excited about preventing these types of events from happening. I think it’s much worse to be scrambling and responding, even if you have the best response possible. It’s always better to be in the world in which you prevented it in the first place. One of the first ideas which I think could be something that’s quite feasible in the next decade or so is environmental buyer surveillance. Cassidy Nelson: This is the idea that you could actually do widespread environmental sampling and be able to detect new pathogens before outbreaks actually occur. This can occur in a few different places and in a few different ways. It comes back to, in many ways, the metagenomic sequencing that we were talking about before. The idea that you could go out and take samples in environments, especially things like taking air samples in places like airports and going out and sampling wildlife that comes into contact with humans, and being able to detect new viruses, new bacteria, that have a potential of causing a pandemic in our species before you have your first few number of cases. Cassidy Nelson: I think this requires a really new approach though to how we actually go out and gather data. There’s been some efforts, especially after anthrax in 2001 in the US, to do biosurveillance in some ways; the BioWatch program was set up. You can see it when you go to the US and you go to their metro lines and whatnot. You’ll see this thing that looks like a sophisticated vacuum cleaner that’s literally sucking the air and then sampling it for things like anthrax and other dangerous pathogens. Unfortunately, for various reasons, I won’t go into too much detail here, it didn’t work that well and it wasn’t as cost-effective as you want. I think with modern day technology and things like metagenomics, you could actually detect new pathogens before we have outbreaks. Robert Wiblin: Okay. So this is similar to the idea of doing a full spectrum screening for patients who come into hospitals who have diseases that we can’t easily identify, but we’re going to do it just in random places. We’re going to grab samples from airports and do the same thing more or less. Cassidy Nelson: Yes. Robert Wiblin: I guess one case against this would be that it’s super expensive. You’re just going to have to sample so many things and it just has the same cost issue. Is there also a concern with false positives that we’re going to be sampling so many things that we’ll constantly be worried. Presumably there’s new viruses and new things appearing all the time. How are we going to tell which ones are actually dangerous? Cassidy Nelson: We’ll have to get much better at actually being able to predict pathogenicity from viruses, which is also fraught with some risky problems I might go into it in a second. Detecting a new pathogen, for example, I could go about in the world today and detect some new types of viruses. People have been doing this for a while now about going out and just detecting new species. How do I know that it could even infect a human cell? It actually turns out to be very hard to predict. That can it not only cause an epidemic, but can it even infect a human cell isn’t as straightforward to predict at the moment. However, our ability, especially with machine learning techniques and other new approaches, I think are going to massively make a difference in being able to make these types of predictions a lot more accurate going forward. Cassidy Nelson: I also think there’s a lot that you get from gathering a sheer amount of data. That there are ways that we could massively upskill ourselves as a species. That would require quite a few iterations of being able to do this and then realizing, “Wow, there’s a lot out there we’ve just never detected or seen before.” But the more that you get used to the idea of, “No, this doesn’t cause disease” and “This is unlikely to cause disease”, and you get a bit more of a granular picture, you start getting that sorted out with the more you’re able to sample. Robert Wiblin: There you’re saying that the more we sample, the more we get a picture of what’s normal, and the easier it is to detect what’s new and concerning? Cassidy Nelson: Yeah, correct. People are doing this on metagenomics on humans at the moment of going like, “What in the gut microbiome is actually normal and what’s not normal? What correlates with the disease state and what doesn’t”? Robert Wiblin: So it’s a bit like how the immune system is trained to identify antigens? Cassidy Nelson: Yeah, that’s a good analogy. Robert Wiblin: Yeah, I suppose as we collect more and more samples. Okay, is machine learning actually going to be able to do these things? It’s like, we’ll have machine learning and machine learning will “solve the mysteries of the universe” and be able to tell just from a DNA sequence whether something can infect a human cell. It seems hard to me. Cassidy Nelson: I agree. It seems hard. What you really need is to have a really good in silico representation of what a human cell is actually like. Robert Wiblin: Well obviously, but what does that mean? Cassidy Nelson: I think we’re making good progress and good headway. I’m encouraged by fields in protein design and other ones where we’ve gone from a world where we really design-build test cycles in a variety of fields, really have only in the last few years where we actually can accelerate some of these steps with machine learning. Robert Wiblin: What’s in silico representation? Cassidy Nelson: In silico representation. Robert Wiblin: Oh, in silico! Cassidy Nelson: Yeah, sorry. Robert Wiblin: That makes sense. Interesting. Do you have any similar skepticism for… Maybe this problem just sounds like it might be the first one that I’m a little bit skeptical of whether it’s practical. Cassidy Nelson: I agree. I think this would require massive infrastructure investment and like I said, an upswing to our actual understanding, especially being able to interpret all this data. If you suddenly started collecting this amount of data you’ll very quickly need to find better ways of mining through it. Robert Wiblin: Yeah, I suppose it’s not that I know that this is impossible. It just seems that simulating something so complex as a virus in the human body. It seems like so much is going on that I don’t know. Something within me is skeptical about whether that’s possible. Cassidy Nelson: Bio is a hard problem and unfortunately none of the– Robert Wiblin: You should try economics. Cassidy Nelson: I agree with you that it is complicated. Robert Wiblin: Many things are hard, yeah. Cassidy Nelson: It is complicated. I remember working in a research lab 10 years ago where we became famous for simulating a single beta cell in the pancreas that could release insulin and it was phenomenal at the time. You realize just how much is going on in any given cell. However, I do think there’s headway that you can make. I don’t think any of these things completely protect you 100%. I don’t think environmental biosurveillance is going to detect every virus or bacteria before it causes disease in humans. I do think if you could reduce the risk by 60% or something, you’ve made massive headways in this area, so I’m cautiously optimistic. Robert Wiblin: You mentioned that we do the first thing first, which is testing the people who are sick and then having really improved the technology for scanning that and made it a lot cheaper, then this one starts to seem a whole lot more practical. Or maybe this is something that’s going to take more like decades to produce than something that we can start scaling up in the next few years. Maybe I’m wrong about that. Maybe I just don’t realize how advanced the technology has gotten in this area. Cassidy Nelson: With tech development, in general, there’s different ways you can think about the speed of progress for this. Like you can imagine, without “Manhattan Project style” approaches to solving really difficult problems, how long it actually takes to do moonshot type projects. This is why I think this is an area where unless you get major buy-in instead of just trickling in a few million dollars for one PhD student to do a project or something like that. You actually had a government that really just went into a full mode of, “I want to get secure from biological threats”, you will see a very different type of technological response. Robert Wiblin: What was wrong with the thing that the Americans did? What was it called, the biosurveillance program? Cassidy Nelson: BioWatch. Robert Wiblin: BioWatch, yeah. Cassidy Nelson: It had what you alluded to earlier of lots of false positives. It only is able to test for, I think, eight different pathogens as well. They break down quite a bit. It cost a lot of money as well. It seems that, in general, this type of approach to the way their testing is actually done in that machine is pretty rudimentary compared to modern day standards. I do think the aspiration, at least the intention, was actually quite good. Robert Wiblin: It was maybe an idea that’s a bit ahead of its time. Cassidy Nelson: It was a bit ahead of it’s time and also the followup and the iterations that you would have needed for it just didn’t eventualize. Robert Wiblin: Yeah. Okay. What’s the next one? Cassidy Nelson: This is a little bit of a departure from what we’ve been talking about before, but I’m thinking through about getting more transparency around laboratory accidents. When I think through pandemic scenarios, I generally divide them into three main categories of natural, accidental and deliberate, as the broad categories of things that I’m concerned about. I’m particularly concerned about laboratory accidents in places like BSL3 and BSL4 laboratories because these are the laboratories that can be working on dangerous pathogens that are capable of causing epidemics and outbreaks in humans. Cassidy Nelson: There’s concerns, especially with certain types of experiments that are going on and different ways in which pathogens are being modified in ways that they’re not being modified in nature, that a laboratory accident could cause an outbreak that is worse than what we’d see from a natural pandemic. At the moment there’s not much transparency around how frequently accidents occur. We do know that there’s historical examples of outbreaks occurring from laboratory accidents, but generally the industry, and not just in the UK and the US but around the world, has been very low in transparency about how frequently accidents occur. Until we have that type of information, there’s not much we can do to start tackling biosafety problems that might be putting us at risk as a population. Robert Wiblin: Yeah. In the conversation with Howie, he pointed out that there was a BSL4, I think the most secure biosecurity lab in the UK, twice, two weeks apart, managed to release foot and mouth disease right next to a farm where they had cows. It was actually a release of the disease. Cassidy Nelson: Through the wastewater, yeah. Robert Wiblin: That caused the whole foot… Cassidy Nelson: The foot and mouth disease epidemic in 2007, yeah. Robert Wiblin: I was astonished to find out that they don’t have to declare these breaches of BSL standards if a disease escapes. I guess in that case people found out, but they tried to hide it or they tried to delay people finding out. Is there any case for not having transparency here, just to consider the other side? Should people be able to keep secret the things that they do that endanger the future of human civilization? Cassidy Nelson: No, I can’t think of any reason, no. Robert Wiblin: Is it expensive to post the PDF online of the thing that you did? Cassidy Nelson: It’s embarrassing to have a needlestick injury. I don’t think this is a good reason, but you can imagine laboratories might start worrying that they actually might be liable for causing outbreaks. This is something that many haven’t considered, about the liability that they’d actually have if they caused a sustained outbreak. So transmission beyond just their own staff, which would fall under occupational health and safety or other such roles. Robert Wiblin: Yeah. We actually talked about this in the episode with Owen Cotton-Barratt ages ago. Maybe it was episode 28 from memory. I think he was saying that labs should be liable for the external damage if they release a pathogen and then lots of people die, or it causes massive economic harm. Then they should be liable and therefore they should have to get insurance ahead of time to cover the payouts that they would have to pay if they were legally liable for the damage that they did. This would appropriately price the cost of doing these experiments. That if it’s not worth getting the insurance because the insurance premiums are really high because it’s very dangerous, because you could do $10 billion of damage to the economy if you mess up a pipe. Then it’s sending the right price signals to people about how many external costs there are to the research that they’re doing. Cassidy Nelson: Yeah. Robert Wiblin: I suppose that idea has a bunch of other practical problems that we discussed on that episode. Cassidy Nelson: It does and we’ve had someone look into this before for us. There’s a lot of nuance to it, but I do think there’s things to be said there and there’s not many people that are thinking through these types of effects in this type of way. Robert Wiblin: Okay. That one seems really good to me. Do you anticipate problems getting that out? I imagine perhaps that scientists working in these labs won’t be keen on this? Who wants to have to announce their mistakes? Cassidy Nelson: Yeah. Also, how public and transparent should that type of data be? I guess another point against it, again, the human behavior element of it: if you have to report, does that discourage reporting? How do you get incentive structures? I’ve talked with biosafety officers in US laboratories before about how the culture of labs actually can be affected depending on how you instigate these rules. Robert Wiblin: Yeah. There is this problem that if you tell anyone, then you have to tell everyone. It does mean that it creates an awfully strong incentive to tell no one at all. To keep it secret completely. Cassidy Nelson: Yeah. We saw at Fort Detrick, there was a military lab that was recently shut down because of biosafety breaches and whatnot which I think is a good thing. It shows that if there’s safety breaches, there’s going to be shutdowns. However, you can imagine you might not want that to be known if you know that that’s going to be the outcome for your lab and you have an incentive to obviously keep your job and your lab running. Robert Wiblin: Yeah. So that was the other side of the coin. What’s the next idea? Cassidy Nelson: Something that we’ve thought about quite a bit at FHI is DNA synthesis screening. At the moment, there’s massive upswing in the number of academics and private companies who order DNA that’s been synthesized by companies off-site. At the moment there’s no country that legally requires that DNA to be screened for dangerous pathogens sequences, for example. There’s quite a few companies that have signed up for screening on their own accord and there’s been international consortiums brought together to go: “It’s actually really important to screen your orders”. However, there’s no legal mandates in which to do this. This really came to light after in 2006, actually, a UK Guardian newspaper, some of the journalists there decided to order a 78 base pair sequence of smallpox to a residential London address. And 78 base pairs is not enough to be a danger to the public so the public wasn’t at risk. They wrote up this expose about how really they shouldn’t have been able to do this. That they shouldn’t have been able to just mail order a sequence of smallpox to a residential address. Robert Wiblin: It should have been flagged somewhere. Cassidy Nelson: It should have been flagged somewhere. There’s been international momentum at being able to get screening up. Some companies have voluntarily signed up for this. However, the quality of the screening that they do if they choose to, as well as the fact that they only screen over a certain size, they usually only screen over 200 base pairs so they don’t screen oligos and shorter sequences, means that you have a real security problem with regards to people being able to potentially order– Robert Wiblin: Just chop it into tiny pieces and then put it back together again or? Cassidy Nelson: That requires quite a bit of technical knowledge. I don’t want to portray the idea that it’s easy to make your own live virus or anything like that, but it does worry me with regards to going forward. We’ve known about this problem for more than a decade now; how do we regulate an industry that could be a real source of risk? The other thing is that even if as a company, if I want to screen my orders that takes time; what do I do when I get a suspicious order? Is there a reporting mechanism in place? It’s not totally clear if that’s the case. Robert Wiblin: You just phone them up and you’re like, “We noticed that this was smallpox, I’m just curious what you’re planning to do”? That’s an awkward conversation, perhaps. Cassidy Nelson: But it becomes a real security problem and I also worry that if we don’t govern and regulate this properly, what you’ll do is, which is what a lot of countries have done, which is switch their orders to India and China, which don’t have these types of oversight mechanisms you can voluntarily put in place. I feel like there’s a lot of wins to be made with having Western countries lead on making this governance and regulation much stronger and working with DNA synthesis companies so that it’s not an economic hit to them and making it so that the screening itself is much more reliable than what we see at the moment. Robert Wiblin: It seems like this is a problem that desperately has to be solved. I suppose there’s problems with each of the solutions. If you create a big database of all of the worst things, then that seems like it’s a bit of a hazard as well given we don’t have good computer security. I mean you have to create a database of everything to compare it with, right? Cassidy Nelson: And so this comes– Robert Wiblin: Do you really want to stick that all in one place for someone to steal? Cassidy Nelson: Exactly. It’s very hard and so that comes into the problem of knowing something is dangerous. You’ve now put that information into the world and that’s fraught with its own problems. I think that this needs a lot more careful consideration and I would hate that this is another category in which we wait for something nasty to happen before we actually go, “Oh wow, we really need to get secure in this type of way”. Robert Wiblin: What’s the specific idea for politicians and bureaucrats here? Is it to fund more people to research how to address this? Cassidy Nelson: Yes. Like IARPA in the US has thought through different ambitious projects about how you could do DNA screening better. I think there’s still traction that we need to make to be able to improve these methods from an actual research point of view. I do think that there just needs to be more interest in this, as well as buy-in from private industry. You need to get DNA synthesis companies on board with these mechanisms and for them to not see it as a– Robert Wiblin: Just a pain in the ass. Cassidy Nelson: Yeah. Because it is for them. And it takes time. If you get false positives, you have to have a human reader on this and they’re dealing with a lot of mail orders every day, there’s a lot of DNA being made. Robert Wiblin: How hard is it… Well, it just seems like you’ve got the sequence, compare it to a database, see if it matches a bunch of dangerous things. Maybe I’m just completely naive about how hard this is, but it’s getting done by computers, I guess. Cassidy Nelson: But then you need someone with bioinformatics knowledge to be able to then– Robert Wiblin: Interpret it. Cassidy Nelson: Yeah, interpret it. You need to contact the person ordering the DNA to go, “What are you doing”? You need some mechanism in place for if you want to inform the authorities and DNA synthesis companies want a one day turnaround. It’s amazing; the cost of DNA synthesis has gone down exponentially. It’s phenomenal to look at the graphs of how much this has been accelerated which is an amazing thing for science. There’s areas of biotechnology at the moment that are accelerating faster than Moore’s law. This field is rapidly growing and I am net very excited about scientific developments, however, I think when it comes to thinking through nefarious actors and malicious ways of doing things, we really need to get on top of this and we need to get on top of it soon. Robert Wiblin: I know that IARPA was looking into this a couple years ago– Cassidy Nelson: And still ongoing projects. Robert Wiblin: It’s an ongoing project? So it hasn’t died? But I guess we would like more people to be looking into it and trying to run with some of the ideas just making sure that this area of research and policy design doesn’t peter out. Cassidy Nelson: Yeah, and then getting buy-in from companies. Robert Wiblin: I’m a little bit surprised that the companies don’t see this as a big potential threat to their business. If they have some disaster where someone does request about it, it could ruin them, right? It seems, I don’t know, maybe I don’t understand their business or perhaps I have lots of time to think about these things that have never happened before whereas if you’re actually running a DNA synthesis business you have a lot of things to think about than aren’t this. Cassidy Nelson: I can’t speak exactly to their incentive structure, but I’d imagine that’s why they’re having any buy-in at all and why they’re voluntarily agreeing with international consortiums. I do also think that they’re competing with international companies and what they have as an advantage is, for example, their screening and also quality as well is another buy-in but time frame for turnaround as well too. If they can screen and they can cut corners in any way, especially when the cost per base pair is extremely low, it’s really hard to want to get the most up to date screening methodologies and have a whole full time person or more on staff to look at all the red flags. Robert Wiblin: I guess, the economist in me says, “Well, in that case, we need to say that these companies overseas that aren’t following these regulations, they can’t import things into your country until they follow the rules.” I think in part the EU is designed, for example, to allow you to have regulations that increase costs for your companies but are good for the country without facing unreasonable competition from other groups that aren’t following those regulations that are good for the whole world in neighboring countries. For example, the US could say, “These DNA synthesis companies in China: you can’t import stuff from them until they follow these screening procedures that meet our requirements.” Then all the companies in the US have to follow these rules, which means that they’re not at a competitive disadvantage against other companies if they do it. There’s a whole bunch of implementation problems here, but I guess in principle that seems like it could work. Cassidy Nelson: No, that makes sense to me. Unfortunately– Robert Wiblin: But I suppose you’re pissing off a whole lot of people by doing this. Cassidy Nelson: I feel like this would have been easier to do about 10 years ago when these companies were just taking off. Now the sheer scale and size will make it very hard to get these through, but I think ultimately that is what we’re going to need. There needs to be regulation and governance on that scale. There needs to be a way to implement it as well, and to control import as well is another way that you can do this. Robert Wiblin: I guess then you get leakage of someone who really wants to do something bad just leaves the country and goes to another country where they’re not following the rules and gets– Cassidy Nelson: That’s another concern which is that if you actually want to do something– Robert Wiblin: It’s very hard to get to 100%. Cassidy Nelson: Exactly, but I think you can reduce a lot of the risks this way and I do think it’s an obvious area that we can begin to tackle. Robert Wiblin: What’s next? Cassidy Nelson: That leads into thinking about Dual Use Research oversight as well too. Dual Use Research of Concern, which many of your listeners might be familiar with, is research that can be used for both good, it has good applications, but also it can be used for nefarious purposes. There’s been various prominent examples of Dual Use Research, especially in the last 10 years or so, for example, research on highly pathogenic avian influenza where two labs, one in the Netherlands and one in the US, purposely modified avian influenza to become human-to-human transmissible. Avian influenza has a high mortality rate. Much higher than your usual flu. But it isn’t readily able to be caught person to person. Most people who get it are working in intensive agriculture or with wild bird populations. But they were able to modify the virus so that it could be airborne transmissible between a ferret model which is what we use for influenza. Cassidy Nelson: It’s a very similar respiratory system model for influenza comparable to humans. This type of research is dual use in the sense that we can understand things like how would a very dangerous virus become transmissible between humans. At the same time, publishing that, and publishing how those mutations happen and what modifications need to be made to be able to make it that way is extremely concerning from a point of view of someone taking that knowledge and information and then perhaps using it to create a biological agent that could cause a lot of harm. This type of research is very difficult to regulate and govern. It’s not only just difficult to regulate and govern, I know that my colleague, Greg Lewis, has written on this before about unilateralist action of the fact that even if 99 out of 100 researchers decide, “I’m not going to modify flu viruses to make them more transmissible”, all you need is one to do it and then publish it and then that information is out in the world. Cassidy Nelson: There’s a bias towards information availability. These are really difficult problems and they’re not easy to solve but we need people to be thinking about this. We need better oversight of research at every phase of the research cycle, thinking through when grants are made about dangerous research. Thinking through experiments that might be churning up dangerous results and then publication phase where maybe the risks outweigh the benefits in terms of getting certain information out into the world. No country, in my opinion, is doing this very well yet and there’s a lot of gains to be made if we’re able to do this better. Robert Wiblin: Are there any other cutting edge cases of Dual Use Research where it seems dangerous or controversial? Cassidy Nelson: Yeah, there’s quite a few examples like horsepox in 2018 was an example of two Canadian researchers taking an extinct pox virus: that’s a cousin of smallpox, and they were able to, from strands of DNA, reconstruct it in the laboratory for less than $100,000 and cause it to infect cells. Horsepox doesn’t– Robert Wiblin: They were doing this as a proof of concept? Cassidy Nelson: They were doing this as a proof of concept. Pox viruses are known to be quite difficult to construct from scratch. They’re very large. They’re over 150,000 base pairs and globular in structure. There’s a few reasons why they’re a bit difficult to actually think that you could go from just genetic sequence to a live virus. There’s been a lot of community prohibition on doing this type of research because we’d be worried about something like smallpox being made from scratch… which genetic information is available. They were doing this. The reasons that they said were so that we could start making new smallpox vaccines. However, there was a lot of pushback to publishing the methods by which you can make pox viruses from genetic sequences as it’s a bit risky to have out in the open literature. Robert Wiblin: It sounds bad. They went ahead and did this without getting lots of buy-in from other people and convincing them that it was good? Cassidy Nelson: Correct. They tried to publish in a few different papers. Science rejected them and a few others did. Eventually PLOS One said yes and published their paper. Robert Wiblin: I suppose they just test whether it’s a sound paper? PLOS One is designed to not have lots of editorial standards, right? Cassidy Nelson: Yeah, it was interesting though when one of the journals rejected them. Their actual reasoning that they posted was that, “We are unable to publish your paper because we wouldn’t be able to deal with the administrative burden of publishing something so controversial”. So it wasn’t that it was dangerous to the world, it’s just we didn’t– Robert Wiblin: The paperwork involved! Cassidy Nelson: In the same way we don’t want to deal with what the influenza research, for example, had to deal with which was a big backlash against Science about publishing something that could be dual use. Robert Wiblin: When it was published, I guess, many scientists were not keen on this or many of their colleagues? Cassidy Nelson: There was a big push back, so unlike PLOS Biology, there’s a really good back and forth both from the original authors of the paper as well as from people like Tom Inglesby at The Johns Hopkins Center for Health Security and Kevin Esvelt and others who really laid out why exactly this type of research shouldn’t be in the open literature and why we need different standards for publication. Robert Wiblin: It sounds fun. I’ll look it up and we’ll stick a link to it in the blog post for the show. The suggestion here is more research on how to solve this. One thing I worry is maybe these problems are just super intractable and we’re always going to be like, “Well, we need more research because we haven’t really got a great policy idea here.” But we’ll come back in 10 years and it will still be just as hard and just as messed up. Cassidy Nelson: I don’t know if we need more research. I think we need more oversight. Robert Wiblin: Oh, okay. So we’re actually at a point that we don’t need to think about this more, we need to put in place better processes? Cassidy Nelson: I think in the same way that we have ethics committees for experiments on animals and humans, we can think through having people who are biosecurity minded. You won’t capture 100%, but I think having people that think through the risks of having certain information out in the open literature could be a good way to think through about how we disincentivize this type of Dual Use Research from being published. Robert Wiblin: This is a new oversight panel of dangerous research areas where rather than consider the risks to the people in the lab or the animals you’re experimenting on, the people you’re giving the drug to, it considers the risk of the whole world of doing this work or of publishing it, which I guess currently doesn’t exist or only exists in a very ad hoc fashion? Cassidy Nelson: Most review panels don’t consider these types of biosecurity concerns. Talking with editors of journals, they’re also unsure. It’s very unclear where the responsibility lies. Is it with the editor of a journal to sit down and decide on what dual use should be published or not published? And obviously, people are biased. As a researcher, you want your research published. You might have different incentives. At the moment there isn’t a very good committee for this. There’s also not a very good committee, in a different respect, which is something that a paper by Marc Lipsitch goes through which is risk to non participants. You think especially for contagious diseases, we, at the moment, have become quite good at realizing how do we pre-conceptualize potential risks to participants in a research study? We’re not very good at conceptualizing risks to the general population or public and thinking through, “Do we actually have any duty of care towards non-participants in research studies”? Robert Wiblin: Seems even more because they’re not consenting? It’s almost worse. Cassidy Nelson: Yeah, so there’s a good argument to say that not only should we care but we actually have a duty to; they didn’t consent to this research being done. Robert Wiblin: They’re completely innocent third parties. Cassidy Nelson: Yeah. So if I’m doing research, modifying dangerous pathogens and it’s a non-zero risk to the person in the neighboring town because they could be affected if an outbreak occurred, how do I even start thinking through it? How do I do a risk assessment that takes them into account? I do think that this is hard but I think that’s not a reason not to do it. Robert Wiblin: Doing nothing is a choice. It’s a choice to just not consider the risk at all or to consider it in a very ad hoc and inconsistent way and allow people to shop around for whatever journal doesn’t care– Cassidy Nelson: That seems to be what happens and so this unilateralist action is quite scary. It’s always going to be biased towards information. Robert Wiblin: We should say some of this dangerous research should happen because even though it’s dangerous, there’s a high enough probability that it will produce some really useful information or lead to a breakthrough that will reduce risk even more on the other side. You can have something that’s very risky but it’s risk reducing on net in expectation. Cassidy Nelson: Yeah. People forget sometimes Dual Use Research is dual because it’s good as well. It’s not just making weapons or something like this. But you’re right, actually working out the net sign of a lot of this research can be really difficult. I think you can get at least a general sense for most research to some degree. Robert Wiblin: If you really can’t tell the sign, if you’re just super unconfident about it, then it doesn’t seem like it’s probably a top priority project. If you’re just unsure whether this is good or bad for the world, I don’t know, why don’t you find something that’s good? That you’re confident is good. I suppose you’d be like, “Well, it’s a 55-45 scenario, but the 55 would be so valuable.” I don’t know. Cassidy Nelson: But it’s hard. You can imagine– Robert Wiblin: People disagree. Yeah, is there anything more say on this? Any unintended consequences we got to avoid or something specific that policymakers should be doing? Are there any individuals we should be funding? Who should we send money to? Cassidy Nelson: No, as much as it’s a headache to get your funding application in and your ethics committees approved and all this type of stuff, I do think really having some biosecurity minded people involved in each stage of the research cycle is necessary. There’s just not many people that are thinking in the biosecurity mindset for these types of things. Robert Wiblin: What number are we up to now? I’ve lost count. Cassidy Nelson: We’re on number 11 next. Robert Wiblin: What’s number 11? Cassidy Nelson: Number 11 is doing pandemic tabletop exercises. This is something I’ve become quite excited about over the last two years. It comes back down to pandemic plans as well too, but I think in terms of both government buy-in to start realizing the extent that some of these risks could pose, as well as thinking through until you actually trial a system where your actual breaking points are and where your gaps are in your knowledge and your response capabilities. It’s only when you start exercising these things that do these things come out. Some of the best exercises I’ve seen have come out of The Johns Hopkins Center for Health Security. Two years ago they did Clade X which was a deliberate release scenario. They also did Event 201, named, because on average, the global health community deals with 200 outbreaks per year so Event 201, the name was the idea that what if there’s an extra one that was extremely bad and caused a pandemic. Cassidy Nelson: They were able to go through, especially a lot of the economic effects in that exercise. I was also involved in Australia in a smallpox release exercise in the Pacific. Like a pretend scenario, of course, but thinking through about if we had smallpox come back again, what are the vaccine pipelines for that? What is the world prepared for, for a disease that we know quite a bit about but that we haven’t seen in more than 40 years? I think these types of scenarios really showcase and bring people step-by-step through the way of a plausible scenario to an outcome that they really don’t want to be in realizing, “I need to make policy changes on how I’m approaching pandemic planning”. Robert Wiblin: Do we have any evidence for how well tabletop exercises tend to match reality when things play out? Because you can imagine there’s a whole lot of stuff. Well it’s like you’re playing a board game and it’s a high level of abstraction and so there’s all kinds of details that are probably getting missed. I suppose, at least you managed to notice the things that are wrong at that level of abstraction that you’re operating at. You can be like, “Oh, there’s this piece of our whole plan that’s missing”. Cassidy Nelson: I agree. It’s quite unclear. I’ve looked into this especially for state or local level exercises about how much that actually gets translated into policy. It seems very variable about how much actually changes in terms of planning. It’s also very hard unless you get buy-in from funding. When I worked in communicable disease control in Melbourne, there was a lot of interest in pandemic funding and we had a person who was on pandemic flu and others but because you’re a public health department that’s dealing with limited resources and you’re dealing with communicable disease control day in and day out, it’s very hard to then plan for larger scale things. Cassidy Nelson: Unless you get a lot of resources invested from higher levels up and going, “This is something that needs priority because, yes, it’s less likely than your day-to-day communicable disease cases but it can be much worse”. It’s very hard. I think the answer is it’s quite variable. I get a sense, at least from the people that attend these exercises, that at least the buy-in, in the moment, is quite a bit stronger than just talking at people’s stats or something like this. Robert Wiblin: Okay, so it’s a way of both carving out time to think about this thing because it’s like, “We’re doing this exercise.” That’s a concrete thing that you got to take some time away from your normal job to do. Then I guess it forces people to think in a more near mode, where you’re playing out this scenario and thinking, “Well, what would we actually do here?”, rather than just thinking in some vague sense that they’ve got it handled. Then, I suppose, people can go back and be like, “Well, these are the things that went wrong in the tabletop exercise. Here’s things that we could improve”. But maybe that could go wrong. It could be that the simulation of the tabletop exercise draws the wrong conclusions about what are the biggest weaknesses because it is not very accurately modeled, say, or that you can get follow through. Cassidy Nelson: It’s usually pre-planned. The scenario is not like “play your own adventure type thing”. Usually they’re pre-planned in terms of the outcome and whatnot. I think you get updates on participants. Robert Wiblin: So there’s no way to win where you’re like,” Oh, we did these things.” I suppose the idea is, well, they’re going to be limited by what the capacities are that are in place at the moment and so this is what will happen in this case given the plan that we currently have. Cassidy Nelson: I’ve been very surprised with some of them that I’ve attended, especially with senior people in government who, for example, I don’t say this derogatorily, but they don’t realize things like, “What do you mean we don’t have a vaccine in a few weeks? We can’t just do that type of thing”? Even just realizations like this of going, “What are the actual feasible timelines for things on the ground today?” I think that people have very different preconceptions about what actual health system response can look like and realizing that the timeframes for things are very different than what their preconceptions were. I think, in itself I can’t see how that doesn’t plant seeds. Robert Wiblin: Is this mostly bringing in people who really don’t know a ton about this scenario, who are non-experts in the area and then getting them to understand how things will actually work, broadly speaking? Cassidy Nelson: I’ve seen a mix. Usually, you have experts in the area mixed with decision makers who are in positions that would be either the ones dealing with the response, who would be leaders in the response, in various aspects of the response, or formerly were in those types of positions, which I think is quite useful because those are the people that you really, really want to be understanding the nuances of the situation. I think any system that’s untried will always have this problem of you’ll have this general sense of, “Oh, I think we’ll do something in this scenario and I’m sure it will work out”, and only when you start examining it in detail and just going through a scenario exercise realizing– Robert Wiblin: Oh, this is going to involve 10,000 people who we don’t have. Cassidy Nelson: Then what happens if any of us get sick as well? There’s nuances to infectious diseases that really are different than any other disaster. Robert Wiblin: Are there any other pros or cons of this idea that you want to flag? Cassidy Nelson: Tabletop exercises can mislead if you– Robert Wiblin: Design it badly. Cassidy Nelson: Design it badly or unnecessarily scare, I guess. I feel very sorry for The Johns Hopkins Center for Health Security at the moment. Their latest exercise, the Event 201 one, involved a coronavirus and they’ve received a lot of backlash in this current outbreak of people saying like, “Oh, they planned this one all these terrible things”, and they’ve unfortunately received a lot of negative press online which is extremely unfair that they just happen to choose something that was likely to cause an outbreak and– Robert Wiblin: Maybe they need to come up with a fake name next time. I suppose, I know whenever I’m planning to release a plague to kill millions of people, I always do a tabletop exercise and post it on YouTube first. It’s just common sense really. Jokes aside, I feel really bad for them. There are just a lot of loopy people out there. Cassidy Nelson: It’s terrible because they’re obviously extremely good at what they do and they’re almost getting punished for how good they are. Robert Wiblin: Yeah, they were so good that they picked it up surprisingly closely to how it’d be. Cassidy Nelson: And it makes sense that we’re seeing a coronavirus. Anyway, so there’s backlash that you can get in these types of ways that I do think, again, this is more of misinformation control and being very clear that tabletop exercises are obviously fictional and whatnot which they made very clear but maybe– Robert Wiblin: Not every random person on Twitter knows that. Is this expensive to do or is it hard to get buy-in from people who come along? Cassidy Nelson: It can be. It depends on the participants that you want and how public you want to have it. It doesn’t have to be. I’ve been involved in some where you had actual situation rooms and it took all day. Those are quite fun and actually, I think you do get a lot of bang for your buck when you are having people having to take on the roles that they’d have to be taking on but yes they do– Robert Wiblin: That does sound quite fun. I suppose I was never into Dungeons & Dragons or anything like that but this is like a better version. Cassidy Nelson: It’s interesting. And like I said, it’s very interesting to see the preconceptions people have about vaccine timelines and other such things. Robert Wiblin: I see. Cassidy Nelson: It doesn’t have to be that expensive but a lot of the time, people do put production value into these types of things. Robert Wiblin: Are there any groups in particular, where someone in the audience who might be listening from some government agency, where you would be particularly keen for them to go and do it? Cassidy Nelson: I’d be very excited for most national governments to be doing this on a regular basis and to think through a large range of scenarios. Not just doing pandemic flu, but thinking through things like, what would be different if you had a deliberate biological event? What would be different if the type of virus or bacteria that was spreading was quite a bit different than things like influenza? What happens if we need to support other countries where there’s a lot of problems with misinformation? There’s a lot of different scenarios that can happen with biological events and so I think they’re worth thinking through. Cassidy Nelson: Others that I think could be thinking through this quite a bit are central services like electricity companies and other such things where you need a certain functioning level of staff to be able to keep things running. It’s amazing how when you start looking into this, about how important it is to have not just this whole of government response which is talked about in this way in many circles, but also the public-private partnerships where you’d need things like your electricity companies and others to be able to keep services going in a pandemic scenario. Robert Wiblin: I was thinking; should anyone be storing water for this situation? It seems like there’s no way this is going to interfere with the water supply. That’s if you’re in a place where water supply is incredibly insecure to begin with like if you’re using desalination plants then it’s a bit more insecure. Cassidy Nelson: Singapore is unfortunately very insecure when it comes to water. Robert Wiblin: How bad do things have to get before we worry about whether the water and the electricity and the gas is going to keep flowing? Do we have any sense of that yet? Or is that one of the many questions that we should be trying to figure out? Cassidy Nelson: It’s hard to know but people have done some estimates about worker absenteeism/they’re absent because they’re either at home taking care of sick loved ones, they themselves are sick, or they’re too scared to go and work/if public transport or such things were affected? What are actually the bare minimum number of people that you need to keep things like electricity or water plants or waste collection going or hospital services which would obviously be a mainstay in such an event. There are quite a few people that you need and– Robert Wiblin: The electrical grid is a daily high-wire act. There’s a lot of things that can go wrong with it and it’s impressive how much redundancy we have to try to keep it going. Cassidy Nelson: Well, one of the more morbid things I’ve looked at before is things like cremation rates and other such things which you’d have to also be thinking in this kind of this more morbid– Robert Wiblin: How to dispose of bodies that would be infectious? Cassidy Nelson: Correct. And thinking through that and you need people to be able to be helping in this. I think there’s a lot more community resilience than people realize when it comes to widespread events. Robert Wiblin: Because people rise to the occasion sort of thing? Cassidy Nelson: Yeah, and people have worried before about healthcare worker absenteeism and whatnot. Being a healthcare worker is putting yourself at risk because you’re putting yourself in a scenario where it’s a higher concentration of the unwell. But it’s amazing what you see in terms of the resilience of communities to actually power through and be able to keep coming into work and realizing the role that they’re playing in keeping the entire response going. I think there needs to be more research done to make sure that those types of things can… What are the minimum points? What are ways that we can keep that going for as long as possible, especially when you’re thinking through larger scale events? Robert Wiblin: Nice. All right. Number 12. Cassidy Nelson: Yeah, okay. So this gets us to the end. Number 12 is a wrap-up one of we need to coordinate all of this. Coordination of all this, especially because we’ve talked through a lot of different aspects of this and some of this may be just a standalone type of things that a government would take on or an industry would take on, for example, for the platform technologies or whatnot. I do think there’s something to be worthwhile said about a coordination role for different agencies. This is something we’ve been thinking about from the UK perspective which is thinking through having things like a biosecurity leadership council. At the moment, we have a synthetic biology leadership council in the UK. They work to help get evidence-based policy into the UK Government and coordinate things within the synthetic biology community as well as in the policy scene. Cassidy Nelson: You could imagine that you could have a lot of biosecurity initiatives undertaken in the same way if you had a convening body that coordinated people as opposed to the very spread out community that you have at the moment. The other is thinking through having a research and development center where you’d have this type of biodefense of the 21st century being undertaken, as well as a more formalized way in which you link up security and biological communities. So there’s some roles in the US, for example, that link between the FBI and the biohacker/biological industries communities and is able to keep this breadth of what is actually going on in developments in the space as well as more risks and security concerns as well. Robert Wiblin: This is creating new people who are responsible for making these and other good ideas happen? Cassidy Nelson: Yeah. Robert Wiblin: Is there a reason that there aren’t people who are already responsible for this? I guess this just costs money and there’s a lot of things to worry about in the world so this just hasn’t reached the top of the list? Cassidy Nelson: That’s correct. Like in the UK there was a biological security strategy released in 2018. One of the things that it called for was someone to have oversight over Dual Use Research of Concern, but no one’s been assigned that as a task. There’s not a single person that’s really responsible to make sure that in the UK there’s oversight of Dual Use Research of Concern. I think formalizing this into a single person or into a single body in a government structure or council or other such thing is a good way to make sure that you have coordination and action in this space. Otherwise, it just gets lost in the ether as it were. Robert Wiblin: Are there any arguments against doing this or any reasons why it wouldn’t be such high priority? Cassidy Nelson: I guess sometimes there’s councils that get formed that then end up like a cog that’s off its gear: it turns and it doesn’t actually do anything in the real world. There’s a lot of failure modes to such things taking place. I think though, if there’s buy-in and you have the people who are forming such bodies actually want to make change in this space, it seems to be the only way that you get proper coordination. There’s just not much understanding of biosecurity in the wider world. If you work in an academic lab in a university, you probably know quite a bit about biosafety because you’ve had to do a lot of biosafety courses. Cassidy Nelson: You probably haven’t really thought through about security concerns of like, “What if a bunch of reagents went missing”? Or “What if someone was ordering a bunch of DNA”? Or thinking through, “What if I publish this and someone used the research I was doing with all the good purposes in the world, but I did research that could enable someone cause harm”? So having someone or a group that’s able to govern and oversee this wider picture, I think, is really the main way that you get traction in these spaces. Robert Wiblin: Do you want to do any prioritization of this at all? Is there any one that you’re particularly psyched about that? Any that are more droppable? Cassidy Nelson: A lot of what we’ve talked about is very ambitious. I’m okay with that. I think if you’re working with a LEGO set, you really need to start thinking about different building materials. There’s some point you just need a different building material. I think we need a very different approach to how we’re doing proper biosecurity going forward, especially for the risks that are possible this century. One that I’ve been most excited about recently, in that I think it’s on the closest time horizon, would be diagnostic testing and metagenomic approaches and doing more ubiquitous metagenomic sequencing. So that covers both your biosurveillance side of things as well as testing in an outbreak and doing that early outbreak response. In general, from like a policy standpoint, I think having more generic pandemic planning, thinking through a bunch of different permutations could really get a lot of traction on potential scenarios that we might be faced with. Robert Wiblin: How optimistic are you that some of these ideas might get up in the next couple of months? At least in some countries as the current pandemic focuses their mind. Cassidy Nelson: I think people are rightfully quite concerned when they think about this pandemic. The security that you might think you have from a modern day health system really isn’t able to deal with these types of scenarios. I think there’s a lot of interest in having solutions in these areas. Whether or not that interest will be translated into things like knee-jerk travel bans or whether they’ll be translated into things like a fundamentally different approach to how we do vaccines and diagnostics. I remain cautiously optimistic. CEPI’s announced that they’re going for it. They’ve put the green light for places to try to develop vaccines in 16 weeks. If they could prove that, then it might give people hope that that timeline can just be reduced and reduced. I do think that these problems look big to people when they look at them, but I think that’s a time to put your head down and not your hands in the air. Robert Wiblin: I guess getting into this has been a pretty big career shift from just being a normal doctor. Did you ever just practice medicine in a hospital without any particular focus on this kind of thing? Cassidy Nelson: Yeah, I decided on clinical for five years and then communicable disease for just under a year. Robert Wiblin: Are you glad you shifted? It sounds like 80,000 Hours might have been responsible for you ending up doing this. How should we feel about that? Are you happier in your life? Cassidy Nelson: I massively credit 80,000 Hours for being easily googleable when I needed it and very much so: I was searching for a while, for more than a year trying to find what specialty fit my interests before realizing… I loved clinical medicine, but it also felt very limited. I was not able to articulate that until reading some articles on 80,000 Hours about doing shift work in a hospital always means that no matter how efficient you are and how good you are at applying clinical guidelines, you’re just seeing one patient at a time. Cassidy Nelson: I’m really glad to have shifted. I feel like not only have I moved into an area where you can make a big difference, I also feel really excited about putting a career into protecting against these types of risks because it worries me that we really are not prepared for large-scale pandemic events and what that can mean for people alive today, what that can mean for our long-term future. I really hope that I can contribute to this space in some positive type of way. Robert Wiblin: This stuff seems really fun. There’s so many margins to push on. So many concrete things to think about. So many places that are working on things that can be funded. It seems exciting. Is that impression right? It’s also slightly terrifying, perhaps? Cassidy Nelson: Yeah, I go from being a bit worried and feeling that worry, to actually feeling quite excited. And you’re right, I do think that as much as some of these ideas are very much… There’d have to be a lot of buy-in and investment, I don’t think there’s no physical reason why they’re not tractable and with the rate of technological development that we’ve had, I think, at least some of these can be ticked off in the next few decades. That really excites me. I know it sounds silly but I get quite excited by the idea of getting to the end of my career and if someone was a naysayer, “None of these events ever happened”, I’d be so happy because it meant that we got good at the first time as a species to think through how are we going to be proactive against these things and stop them three steps up the line versus having to deal with a scenario that I wouldn’t want any conscious being to have to go through which is what I’d imagine a large scale pandemic would end up being like. Robert Wiblin: Well, fantastic. Thanks for going through so many different ideas and dealing with all of my stupid potential objections to them. We’ll be talking with your colleague, Greg Lewis, I think, in a couple of weeks; the guy who’s overwhelmingly responsible for writing up this new problem profile on pandemic preparedness. Cassidy Nelson: Yeah, he’s been working hard on it and I’m looking forward to people being able to read it on 80K. As this interview showed, I’ve been quite involved with thinking through some UK policy ideas and working with some people who are also working in UK policy, so if any of your listeners are interested in helping out in this area, if you’re thinking about contributing, feel free to get in touch with me and I can get you in touch. I do think there’s a lot of areas that can have action at the moment and that’s exciting. Robert Wiblin: Likewise. If you have any responses to this, Rob@80,000hours.org: I’d be very interested to hear from you. Someone actually sent through a bunch of policy ideas when I posted this on the Effective Altruism forum. There’s one that I think he thought was interesting, which was, if we’re going to run out of protective personal equipment– Cassidy Nelson: Personal protective equipment. Robert Wiblin: Like masks and couldn’t we find some way to heat them up enough to deactivate viruses that are on them which is an idea that I’d never heard before. Cassidy Nelson: Also, we autoclave a lot of equipment in hospitals and other ways to sterilize them. I get excited about PPE, it’s not as a sexy area as other areas like designing new vaccines, but you can actually save a lot of lives if you could find new ways of approaching things like gloves and masks, making them more effective, making them reusable in a reliable way. And heating them up in the oven, I think, we’d need a little bit more evidence behind it about how many viruses they kill? How many minutes you’d have to do that? There’s lots of interesting work in this space. I think that could be quite positive for the future going forward. Robert Wiblin: Yeah, if nCoV reaches London where we’re at the moment, should we consider shutting down the tube or discouraging public gatherings to avoid it spreading a lot? Or is it maybe just it’s going to end up going through a lot of people anyway and that just slows things down and it doesn’t really change the ultimate outcome? Cassidy Nelson: Yeah, so I’ve thought about mass gatherings quite a bit before. We also have the Olympics coming up in Japan. I don’t want to give any prescriptive advice here with regards to this, but it is true that social distancing, including things like avoiding places of mass gatherings is a very useful way to slow transmission. Once transmission gets enough that that actually becomes an option that makes sense. Thinking through new ways about how we can go about our daily lives. I don’t think we’re at that stage yet though, and I really hope that London doesn’t get to that stage either but I do encourage your listeners to keep up to date. Not unnecessarily worried by any means, but keep informed about this outbreak because there’s still a lot of uncertainty. Robert Wiblin: My guest today has been Cassidy Nelson. Thanks for coming on the 80,000 Hours podcast at such short notice, Cassidy. Cassidy Nelson: Cheers. Thanks for having me, Rob. Robert Wiblin: I hope you enjoyed that episode. I’ll let you know when our new written problem profile on this topic is out. If you’d like to chat to Cassidy or her various contacts about UK policy careers, whether on bio or any other longtermist focus areas, you can contact her at cassidy dot nelson at gtc dot ox dot ac dot uk. In the meantime if you want to learn more: Number 4 – Howie Lempel on pandemics that kill hundreds of millions and how to stop them Number 12 – Dr Beth Cameron works to stop you dying in a pandemic. Here’s what keeps her up at night. Number 27 – Dr Tom Inglesby on careers and policies that reduce global catastrophic biological risks As I mentioned at the start, there’s a discussion of the excellent Emerging Leaders in Biosecurity Fellowship which Cassidy is about to enter, in episode 27. And there’s Howie and my conversation from February 3rd in your podcast feed. If you want to follow nCoV we’ve got a lot of great resources in the blog post attached to that episode. The 80,000 Hours Podcast is produced by Keiran Harris; and transcriptions are by Zakee Ulhaq. Thanks for joining, talk to you in a week or two.