Combating the Coronavirus (w/ Balaji Srinivasan)
ASH BENNINGTON: So one of the things that you talked about on Twitter is the viral funnel. Can you explain that a bit? BALAJI SRINIVASAN: Yeah, so I tweet about this in March. But, basically, there's lots of different efforts flying around and where do you want to help. So, ideally, where it saves the most lives, given your skills. So the funnel model comes from startups. You've got a bunch of leads at the top of the funnel. These are people who might be out there. And then some of them click and land on your website. And some of them click a little bit more, and they end up in a cart. And then some of them all the way convert and so on. And maybe they renew the subscription or they churn. It might seem like trivial startup lingo. But you can apply the same thing to the virus. You've got this group of healthy people out there. Then they're exposed. Then some of them get infected. Some get sick. Some of them actually die or recover. That's similar to like the SCRI models, the epidemiological models, and so on. And so you can think of interventions at different portions of the viral funnel. For example, like for healthy people, masks, social distancing, lockdown, vaccines, tests, those kind of things you can do on healthy people. When you talk about if someone's exposed, you do more tests. You do CT scan. You do not just PCR, but you might do sequencing or whatever if you think they're being exposed to a strain that you want to know about. If they're infected, then you'd actually isolate them. You need hospital beds or some kind of quarantine area. You're going to potentially need drugs. If they're really sick, then hospitalization, PPE for MDs and nurses and, if they're recovered, maybe serology tests. And so now, once you kind of had that funnel, when you say, OK, I'm doing PPE, you're actually at like stage four of the funnel because you're helping sick people, because you're giving PPE to MDs and nurses. Oh, but maybe you might help at the top of the funnel as well because some of those masks could go to people who are healthy. So, in this fashion, you can kind think about where you want to allocate resources. And, really, the best thing you could do is stop healthy people from getting sick in the first place. So that's why, for the last few weeks of March and early April, I was helping out Jeremy P. Howard launched Masks4All, which was very effective in basically shifting policy on this, where the Surgeon General was, at first, saying, oh, people, you shouldn't wear masks, and then literally recorded himself making a video wearing a mask, which is good. I'm glad they turned around on this. But, essentially, that common sense intervention is something that, we think, will significantly reduce the spread of the disease. So the idea of the viral funnel is to prioritize different things, interventions, based on the impact from the funnel. ASH BENNINGTON: The frightening thing about hearing you discuss that is it sounds as though that sort of thinking hasn't broadly taken place at scale yet. It sounds as though the basic sort of staging and framework of this is still at the position where it is a novel idea. BALAJI SRINIVASAN: Yeah, so the thing that has been concerning to me about this whole way is this whole thing is rear-wheel drive, where the folks with scientific, technical, mathematical, management backgrounds are not in politics. And they're generally not in the media either, at least as writers. And so what then means is the folks who are talking about what to do and the folks who are responsible for making the decisions are just-- there isn't a critical mass of folks who know what a virus is, for example. And so you just have-- it's not a partisan thing, by the way. It's the federal bureaucracy. It is the mayor of New York and the White House. It is the FDA and the CDC. All major media outlets have had "just the flu"-type stuff, and not just "just the flu" but masks don't work and then masks work, just face plant after face plant on this. So I think, yeah, I'm pretty concerned about the fact that the folks who I think of as competent are outside of the loop on making decisions on this or are doing kind of rear-wheel drive. You're tweeting frantically to try to get the attention of somebody as opposed to just being in the position to make decision yourself. ASH BENNINGTON: Another suggestion that's getting a fair amount of traction is this notion of immunity passports. This is something I spoke about into the mainstream media at this point. Could explain that concept and tell us where we are with regard to being able to actually execute on that? BALAJI SRINIVASAN: Yeah, so that's something-- basically, immunity passport's a proof of health. That could help reopen the world, whether it's based on serology testing, which is, hey, do you have antibodies like immunity in that sense, or some other kind of test. Essentially, for example, in Asia, people have forehead thermometers, and they stand outside of buildings. And they kind of scan people as they walk by. And that's not a perfect test because people can be asymptomatic and still pass and so on. But it gives you some signal. And so you can start thinking about defense in depth. You have, for example, wearables like your Fitbit Aria. There are studies going into whether that gives you signal. There's your forehead thermometers. There's certainly your self report. There is a digital diagnosis of whether you're close to somebody else, contact tracing. Were you close to another positive? Can we send you a signal on that basis, which smartphone manufacturers can do now? I know it's Orwellian. But they can. Another test is these kind of thermal scans from afar. There's these really high throughput CT scans of the Chinese have, where it's really fast and it can do a bunch of them quickly. There's obviously PCR. There's sequencing. And so you start to have a defense in depth. Right and it's something I tweeted about, I said, China is going to build the third Great Wall as a function of this. There's a Great Wall, the Great Firewall. They're building the Great Biowall of China, like a gigantic biodefense wall of testing and other kinds of things, eventually vaccines, just fortify themselves in many different ways so, if the virus breaks through one fortification, it doesn't break through another and yet another. And so that's, I think, a good mental model also for proof of health or these immunity passports, where you have a series of tests that are done on somebody. And, in China, the way of doing it is green code, yellow code, red code. Your WeChat has either green, yellow, or red, corresponding to your current virus status. So green is you're fine. Yellow, you've been exposed and need to be quarantined. You can't travel between cities and so on. And red, you're known to be infected. And so that digital status is contagious just like the virus is. If a red walked into a crowd of 20 greens, it would turn yellow, for example. At least, that's my-- that's one's understanding of it. So that's the kind of stuff that all goes into something like this immunity passport. And, frankly, in a sense, it already existed because you need vaccination certificates to immigrate to a country. The US has needed that for a long time. You get a cool vaccination certificate. So this is kind of like that. A vaccination cert is, are you going to bring a deadly virus into our shores? That's the same reason to ask, are you bringing in snails? Or you bringing in animals and stuff like that? They'll always ask those kinds of questions, the agricultural things. So we want to know, are you bringing something that can reproduce of its own accord and maybe get out of control, something that has no natural predators? All the type of stuff, unbalanced ecosystems. And I think that's what this is. It's like a vaccination cert. It's like one of those questions about whether you're bringing in animals, except it's applied to a virus. And it's also done obviously in a much more intrusive and realtime way. ASH BENNINGTON: And, on the treatment side of this equation, you talked about the expanded, the "right to try". Tell us a little bit about what that is and why it's relevant for getting the kinds of treatments that we need to see. BALAJI SRINIVASAN: Yeah, so what the FDA did in February was basically catastrophic. It's now known that they prevented emergency use authorizations for tests and, in so doing, turned a containable epidemic into a catastrophe. What essentially happened was labs that could have run tests that would have shown that the coronavirus epidemic was actually-- it was spreading, they were prevented from running tests by the FDA for a critical 28-day period and only really allowed to run on the 29th. Once the tests actually started to run, it was clear that we had a massive outbreak on our hands. And so where things might have been nipped in the bud because what happened was the lack of testing gave everybody a false sense of security over the course of February, when the fire was still at a relatively early stage. So that's my point. My point is, that's potentially the greatest failure in the history of not just the FDA, maybe of the greatest failures ever in the history of the United States. It cost the country trillions of dollars, tens of millions of jobs, simply because bureaucrats didn't approve tests fast enough. And that's just something that's perceptible to people. It's a catastrophe on such a scale that's perceptible. Most of the times that something is denied for multiple sclerosis or like colon cancer, it's not visible on that scale. It's not something where everybody has a stake in it, where it's super-- there's lots of eyes on it. It's more deniable. So with respect to the FDA, there's been pads to route around it in the past. And, critically, those pads don't say, no regulation. They just say a different regulator to put some competitive pressure on this regulator. So some of them, for example, compounding pharmacies are one where pharmacists have some discretion in order to kind of mix drugs together to get a new drug. Off the little prescription by MDs-- you can have a drug that's approved for purpose A that a doctor, in their own discretion, can prescribe for purpose B. There's been CLIA and clinical labs, where you can, basically, go and have individual labs that are not necessarily FDA-regulated but they're regulated by a different agency also under HHS-- under CMS. So HHS' parent, it's got FDA, and it's got CMS. Under CMS is something called CLIA, and CLIA works with state regulators to approve clinical labs, to rollout tests. And then, of course, there's other countries. And so each of these are pathways that are outside of the FDA. And if the FDA wants to shut them down, usually, they've been kind of waging a war against lab tests and compounding pharmacies and so on for a while. Right-to-try is yet another pathway outside the FDA where, basically, people have, as it sounds like, the right to try a drug. And they just have state regulators sign off on it and then, under some circumstances, give notice to the FDA because the procedure for actually getting approval to use a drug is actually extremely bureaucratic normally and that person is dying. And so now you just give a notice to the FDA rather than going through that whole rigmarole. The one thing also, by the way, a lot of the FDA stuff, where it blocks things, it causes failure to apply rather than necessarily failure to get approved. And those are similar in outcome. But failure to apply is less measurable because it's top of the funnel. It's such a complicated and timeconsuming process that people don't even put in an application. And, therefore, it's harder to detect the full impact of what it is they're doing, if that makes sense. Because many of these companies and labs that were turned down for these authorizations, EUAs, may not have filed formal applications. They just got informal feedback that, you know, OK, they can't get one in time. So what does this have to do with expanded "right to try"? So, right now, there's all these different pathways outside the FDA for drugs via off label, for labs via CLIA, for drugs, again, via compounding pharmacies, for which everything via going internationally like medical tourism. An expanded "right to try" would basically just expand all of this. And one model would be something where these-- like, for example, this Western States Compact. California, Oregon, Washington, and also Colorado, Nevada have joined this, OK. So this Western States Compact now could basically say, look, we're going to have Stanford, UW, Berkeley, UCSF, and Cedars-Sinai, which are all very legit, based on the west coast. We could throw in UC Boulder, something like that. And those are universities that will work with state regulators to approve drugs, diagnostics, and vaccines, and what have you. You do the same thing for this Upper Midwest Compact, where the Mayo Clinic is working with the local regulators to approve things. And same thing in the Northeast, you have Harvard and MIT. And same thing in the New York [INAUDIBLE] Area Compact, you have Columbia and Cornell. And, by doing this, now suddenly you've got four or five six, effectively, regulators in-- and each of these regions has like 80 million people or something fairly big. They're essentially European countries. But, now, there's competition for the FDA. And you're not giving up on safety. You're not giving up on quality. What you've got, though, are folks who have an incentive to balance quality with speed and with cost, which really, really matter in a pandemic, very obviously so. But it's also true at other times. It's just not somewhere where everybody's eyes are on it. ASH BENNINGTON: Are you optimistic about our ability to actually execute on this in a reasonable time frame in a way that can get actual results for this particular crisis? Or is this something that we're look out for, potentially, mitigating future issues? BALAJI SRINIVASAN: So expanded "right to try" would be, if not a silver bullet, certainly a very, very useful bullet that can be tried right now that's unlock a lot of biomedical innovation. And I think, frankly, it's the only way-- yes, the horse has left the barn in some ways. The fire is going to burn for quite a while. But we need to-- even if this fire burns the US more than it burns other countries-- and it looks like it will-- we still need fire hoses. So we have to unlock that biomedical innovation even if-- I shouldn't say too little, too late because it would be great if this had been done five years ago. Five years ago, for example, the Apple Watch had a bunch of diagnostic, great stuff in it that the FDA forced them to either take out or nerf. This report of the Wall Street Journal, for example. And so, had that been in there, had-- for example, 23andMe, the FDA ran a campaign against them, if we had 100 million people with genome sequences, maybe we'd know the pharmacogenomics and immunogenomics of this thing. So, yes, it would have been much better had we done this five years ago, 10 years ago. But today is better than never. And that'll at least give us the technology where, in six months, we'll be in a very-- even in a few months, we'd be in a very different place if you have "right to try", expanded "right to try".