Tuesday, July 28, 2020

Out of the Crisis #16: Robert Schooley on why we weren't prepared, long-term thinking, and how to make decisions for the greater good.

Dr. Robert Schooley began his career just as the HIV-AIDS pandemic was coming to the forefront. He's dedicated his life to infectious disease research even as funding for infrastructure and national attention to this area of medicine have declined. Now, he's temporarily slowed his work on phage therapy to combat multi-drug resistant bacterial infections in order to help lead the civic response to the CoV-SARS-2 pandemic. Though mistakes have been made in the way the U.S. has handled the virus, his perspective and experience make him confident we'll find our way out. "Humanity's been through these infectious crises before with plague and smallpox and influenza," he explained to me, "at times when we had many fewer tools and much less insight than we do now about what we were dealing with."

There's a lot of work to be done, though, including finding ways to separate public health efforts from both politics and profit. Currently, he says, "we're essentially letting capitalism kill capitalism by not coming up with a way as a society to figure out how to commoditize these tests, and have them become a public health tool."

He hopes one of the outcomes of this pandemic will be that it helps us on all fronts to "make decisions that are sounder in terms of greater good for more people over a longer period of time."

We talked about why America was so unprepared to fight the virus, focusing on the legacies we leave behind, his experiences during the HIV-AIDS crisis and much more. Ultimately, he hopes we'll all make decisions according to one simple question: "What would you want for the people that matter to you most? Think about that as we make policy for what affects everybody else in the world. Because every decision we make, in varying degrees, has an impact on more than just us."

You can listen to my conversation with Robert Schooley on Apple, Google, or wherever you like to download podcasts.


A full transcript of the show is below.

Highlights from the show:

  • Robert Schooley introduces himself and talks about his quarantine circumstances at work and home (2:36)
  • His perspective on the current state of the crisis (5:02)
  • How he got into infectious disease research as a medical student (7:53)
  • The early days of the HIV epidemic in 1979 (11:30)
  • Antiretroviral drugs and research on an AIDS vaccine (15:02)
  • The similarities and differences between COVID and other pandemics (21:17)
  • How the virus entered the US and how it has spread (22:47)
  • How science-driven policy and response could have affected the pandemic's trajectory (27:38)
  • The first community case transmission (29:09)
  • The missed opportunity to prevent deaths (32:13)
  • The marshmallow game (34:35)
  • Was this kind of pandemic inevitable? (37:00)
  • The failure to invest in public health resources that would have helped manage SARS CoV-2 (39:40)
  • The two most important lessons of the pandemic (40:59)
  • What the U.S.'s focus on the short-term has done to the country (43:32)
  • A legacy built on sustainable health, climate, education and economy (44:20)
  • The problem with having a short investment horizon for drug research (45:12)
  • What's happening at UCSD and in San Diego (48:44)
  • The testing plan and how it could be a model for other institutions (51:27)
  • What companies need to do to bring people back safely (55:48)
  • The problem of test scarcity (57:27)
  • How to lower the cost of testing (59:48)
  • Why separating politics from science is the key to moving forward (1:01:35)
  • Creating systems and structures for isolation cases without punitive measures (1:02:41)
  • Phage therapy and bacterial infections (1:05:07)
  • Making decisions for the greater good, for more people, over a longer time (1:09:21)
  • The roadmap for exiting the crisis (1:11:37)

Show-related resources:

Transcript for Out of the Crisis #16, Dr. Robert Schooley


Eric Ries: My name is Eric Ries, this is Out of the Crisis.

Why are we still not ready? Right at this very moment, a second wave of the pandemic is brewing, and we are repeating the same mistakes. If we don't learn the lessons of the pandemic, hundreds of thousands will die. We're still casting about for blame and looking backwards, as if this is over. But we have to learn from our mistakes to prevent an unimaginable tragedy.

I don't believe this is as straightforward as saying if only we had stopped traveling sooner or if we had more Purell on hand we would have been better off. Why weren't we ready? Why are we still not ready? These seem like complicated questions to answer, but it is not impossible. There is a science to this.

Dr. Robert Schooley is a genuine expert. He has seen this before. He started his career on the front line to the HIV AIDS epidemic. Since, he has dedicated his life to infectious disease research, despite seeing the decline of funding infrastructure and national attention to this area of medicine. Now he is on the leading edge of infectious disease research at the University of California, San Diego, and has been a leader in the civic response to the pandemic.

Dr. Schooley is a rare person who understands deeply the many ways we could have been better prepared to fight COVID and the consequences of our inaction. In our conversation, he detailed the many, many mistakes we made along the way and most critically, how we can avoid them next time. Because this is not over. Dr. Schooley is now leading the charge for the Herculean effort it will take to reopen the UCSD campus. If it works, it will be one of the most comprehensive testing programs in the country.

It will require frequent and convenient testing for all students and faculty, 10s of thousands of people. It will have huge implications for the rest of us, helping us understand what will be required to reopen and to live in the new normal. However, the part of the conversation that will stick with me the longest I think, was when I asked him of the more than 100,000 deaths we have seen in the pandemic so far. How many were preventable? His answer; pretty much all of them.

Here's my conversation with Dr. Robert Schooley.

Robert Schooley: I'm Robert Turner Schooley, professor of medicine at the University of California San Diego. I'm a biologist and a member of the infectious disease division here at UC San Diego and have been involved in viral research, particularly RNA viruses, since HIV came along in the 80s. And have gotten increasingly involved in our response to the Coronavirus.

Eric Ries: Well, Dr. Schooley, thank you so much for taking the time. I know this must be a very hectic and busy time in the university. First of all, how have you been doing? How are your colleagues holding up in these difficult times, how's your family, what's the quarantine and the crisis been like for you?

Robert Schooley: Well, the family is doing fine. They're all home as many of us are trying to work from home and keep things going. The university is right now on kind of a summer quasi-hiatus. I think what people don't realize sometimes about research universities is that we never really shut down because we have a research effort that goes on year round. Of course, our students are here for three quarters of the year and the outbreak, for the most part truncated the last part of our last quarter and the summer is usually quieter. So the university is kind of quiet like it normally is in the summer as far as the students are concerned, but this summer has been a bit different because much of the research effort has been shut down. And except for those of us who have been doing research on Coronavirus, the campus has been really pretty quiet.

The hospitals have been busy. We continue to see quite a few cases here in San Diego County. Our biggest cluster of cases comes from the south part of the county near the border with Mexico. We have a large number of American citizens, American green card holders who have gotten sick in Mexico and are coming back to the US for care. And that's causing a bit of a challenge for the hospitals in the southern part of the county and for our hospital in the southern part of San Diego. With quite a few new cases every day we see about 160 new cases in San Diego County daily and we're not that large a county.

Eric Ries: So from your perspective, just looking at the big picture, where are we in this crisis?

Robert Schooley: Well, until about three weeks ago, I was hoping that we were beginning to see the end of the tunnel. The overall number of new cases in the US had been decreasing. We were beginning to see some parts of the country where the virus had been totally out of control in the early part of March to early April. New York, New Jersey, beginning to really see the epidemic in the rear view mirror, and things are still looking reasonably good there. But what's happened since then is the epidemic has taken off in other parts of the country. Both in parts of the country where it's just beginning to get its foothold, in the Midwest. But more so in the southeast and the Southwest where as the people went back to work, they didn't understand that going back to work also means going back to work and realizing there's still a virus out there and wearing masks in public and being careful about socializing.

And what's happening now is in some states, we're seeing the kinds of expansions of new cases that we saw in the early part of March. And we've had over the course of the last two weeks, of course, a lot of activity around the demonstrations and all around the country where we've had large numbers people out many without masks, a lot of yelling, a lot of pepper spray, and we haven't yet begun to see what impact that might be having on the outbreak.

What we're seeing the last couple of weeks is what happened over Memorial Day weekend. And I'm really concerned that we're headed into a new wave of infection that is going to be just as bad as the first wave. We've had 110,000 deaths now. And by the end of the summer we could have a total of 200,000 deaths if the current trends continue.

Eric Ries: I've also heard some reports that the way that police and authorities have responded to the protests using tear gas, pepper spray, locking people up in confined spaces in the name of riot control, those seem like just the perfect conditions to maximize viral transmission.

Robert Schooley: Yeah, I think this is absolutely on the money. There's no better way to do that than to confine people in small places with no personal protective devices with coughing and sputtering from pepper spray and tear gas. So the response to these demonstrations has certainly not helped us with epidemiology, among other things.

Eric Ries: I really wanted to speak with you because this is not the first epidemic that you have lived through, and lead the charge in helping to understand and reverse. Talk a little bit about your career, how you got into infectious disease research, why that was interesting to you. And if you don't mind, maybe say a little bit about your work with HIV and some of the earlier research that you lead for prior epidemics.

Robert Schooley: Well, I got into infectious diseases as a medical student, because I found the combination of the diseases we dealt with, big ones that we ... for the most part had antibiotics for in those days, we focused mainly on bacterial infections. And when patients came in, we could make a diagnosis and do something for them. They got better quickly, most of the time. And we really could do a lot for them.

Also, it is a cluster of diseases that disproportionately affected people at the other end of the economic spectrum. And I was training in East Baltimore at the time and most of my patients were intercity members of the Baltimore community. And I felt that since most of their disease version, a lot of their disease burden was infectious disease related.

Getting involved in that area of medicine was really quite exciting and very rewarding seeing people being able to respond to the drugs we had at the time. I went to the National Institutes of Health for my infectious disease fellowship thinking that I would continue to work on bacterial disease. When I got there, there were very few people working on bacterial disease. Almost all of the work at NIH in the section I went to focused on immunology. But there was one guy who was working on virology named Ray Dolan who had just come back to the NIH, from his fellowship in Boston and was heading up a virology lab.

At the time, virology was not thought to be very interesting because we didn't have good ways to diagnose specific viral infections except antibody responses. And those don't happen until somebody is either better or has died. And we had no drugs for them and the party line with antiviral drugs was that we wouldn't have any because viruses used the machinery of the cell to replicate. There was no way to separate them from the cells in which they grew to have therapeutic agents drugs that would work.

And as I began to go into the lab and work on the immunology of Epstein-Barr virus, the virus that caused infectious mononucleosis working with Ray Dolan and Tony Fauci, who at the time was really quite young. I got interested in some of the new antiviral drugs that were just beginning to come along to treat some of the herpes virus infections, herpes zoster, herpes encephalitis, herpes simplex encephalitis, herpes neonatorum. Herpes simplex can be a devastating disease in children.

And the paradigm shift occurred, that began to occur, that many people didn't think would happen that we actually could separate the pathogen from the target with drugs for viral diseases. And so I got quite interested in a combination of viral immunology and viral therapeutics.

After finishing three years at the NIH, I went to Boston and worked at the Masters General Hospital as a fellow.

Eric Ries: And now it's the early days of HIV.

Robert Schooley: Yep, I arrived in 1979. And the week I finished my fellowship was the week that HIV appeared in MWR. And initially it was a disease that was thought to be rare, was going to be seen mainly in New York and San Francisco. And I remember the first grant that I wrote about it, the scientific critique was it's a very interesting grant, scientifically compelling, but we don't believe we can fund it because there will never be enough diseases in Boston to study. Not enough people with disease in Boston to study.

Eric Ries: Wow.

Robert Schooley: I think for a long time for the first year or so, people really thought that this was going to be a very rare disease that was interesting immunologically, but would not have much societal impact. I got very interested in it because I had been working on some of the immune modulatory changes that herpes viruses had in transplant recipients. And one thing that happened was patients who have been received kidney transplants or lung transplants or liver transplants, if they got severe herpes virus infections, their CD4 cells went down and CDA cells went up. The ability to measure CD4 and A cells was really just happening in the transplant group that I was working with was one of the first to do that.

They were interested in whether or not these changes we're seeing with rejection, of the kidney, of the organ. I became interested in whether or not these had anything to do with viral infections. We found that whenever anybody got one of these herpes virus infections, they had their T-cells, we call them invert. The so-called helper cells decreased as their suppressor cells went up, as we called them in those days. And when HIV came along, we didn't know what caused the disease. At the time we didn't know about HIV, but with age we saw the same immunologic changes. And as these helper cells went away, people got the same kinds of infections I’d been seeing in the transplant patients that I was seeing in the hospital as a consultant. And so it was a fairly easy scientific shift into this new disease, which began to be much more pressing and to be much more ... It was much more clear that it was not going to be a limited problem. I also became fascinated by the patient population. I'd grown up in Alabama and had really very little insight into the MSM population.

If you'd asked me growing up in Alabama about how many members of the MSM community there were in Alabama, I'd say there must be at least 100, I don't know. But when Aids came along, what it did was it forced the whole community. They've been working all along beside us and kind of suppressed because of the stigma.

And in those days of being in that population, this disease forced them out of the closet and into the hospitals. And they encountered the same thing in the hospitals that they did in life. Their doctors didn't want to take care of them for a while. We didn't have anything we could do for them specifically, beyond trying to treat their infections. Young people my age were dying. The average survival if you came with pneumocystis, the time was six months. And I'd been used to infectious diseases in my younger career as a specialty in which we had drugs we could treat people with and who got better quickly.

So with AIDS, it was a very different story. And having had the experience with any viral drugs with herpes viruses, when the first drugs that came along for HIV to be studied became available. I got involved in the early antiretroviral trials, with AZT and drugs after that, and began to see the pendulum swing from people always dying to people beginning to do a bit better. And at the same time, my lab was working on the immune modulatory changes that the virus HIV was causing, and began to develop assays to look at killer T-cells in the lab, directed in HIV.

That time the party line most of these did not exist because people weren't looking at them in the right way. A fellow at the time in my lab, Bruce Walker developed a very nice assay that very clearly demonstrated that these cells were both wildly present, HIV present in this chronic infection, probably more than any other viral infection discovered at the time. They played a major role in controlling viral replication in people who were infected and kept people healthy for a prolonged period of time before the virus ultimately overcame their immune response.

This became a focus of vaccine research. And I was kind of working in both areas simultaneously in the late 1980s, and began to see progress with drugs and realized even though the party line was there's going to be a vaccine just around the corner, that there were so many complexities with HIV vaccine development that was going to be years before that came along, and I decided that I would focus more on drugs and got involved, first with developing individual drugs and then later with working with the National Institutes of Health and its AIDS clinical trials group as we develop the principles for antiretroviral therapy.

I ran the group from 1995 through 2002, which was an incredibly exciting period of time, during which time the so-called cocktails developed. And we realized that this disease could be one that was no longer fatal, in fact people would live with it for years and years and go back to doing what they would have done, had this disease not come along.

As we began to get control of disease in the US, I became interested in rather than continuing to study the nuances of antiviral drugs, trying to figure out how to get them to other places. And I and my vice chair of this group at the time, Constance Benson, who became Chair of the group after me, worked with the NIH to develop the first therapeutic research centers in Africa and Latin America and Asia. These research centers run by local people, again, to provide antiretroviral therapy in places where needed most and change the way that NIH did research in those areas.

Instead of having US universities hire people to do the studies, the ACTG gave the grants to African investigators and South Latin American investigators, who ran the studies, ran their units and became part of the scientific community that began to solve this disease in those parts of the world as well.

So HIV is now a disease that we still have ways to go, we still don't have that vaccine. But we do have drugs that can cause people who are able to get access to them and to take them have a life expectancy not that different from people without the disease. We have been able to use the drugs in ways that we can prevent people from coming infected, just like a vaccine would. There now long acting drugs that we learned last month can be injected and work for several months and prevent infection during that period of time very much again, like a vaccine would. So with HIV, we've done with drugs, what people would have liked to have done with vaccines and still have not been able to accomplish and it's been quite a good ... it's been very gratifying to see that disease go from where it was in 1991, to where it is now.

Eric Ries: It's a remarkable turnaround. I really appreciate the work that you have invested in this over a career. As you tell the story, there's some overtones with what we're living through right now that strike me and I wonder if you wouldn't mind telling the story of what you've seen with the COVID pandemic, through that lens. I pick up on when you're talking about the neglect of the authorities and the powers that be not taking it seriously enough, not acting decisively when there might have been a chance to prevent transmission. That certainly has some relevance to today, I think also about the universal belief that only a vaccine could solve the problem and that vaccine is imminent, but the need for complementary therapies and strategies.

That sure does sound familiar and just so you know, we've had some conversations in this series with folks working on repurposing existing drugs, on building an mRNA vaccine, doing drug discovery for possible therapeutics. So we've been through the science of what's possible a little bit here and there. But I think you have a unique perspective and are able to kind of help us understand the big picture of what's this been like from your experience having seen epidemics before. Having had the experience of HIV which of course is a much different and seems like a more complex pathogen in the first place.

But tell us about what the COVID pandemic has been like. What's what struck you as typical of all epidemics and what's unique to the situation?

Robert Schooley: It's very much like deja vu all over again, as they say. This disease was first noted in China. And initially people said, "Well, that's too bad, big problem for China. Not going to happen here." And when HIV was first described in New York and San Francisco, as I said earlier, the reception was this was just a problem for those cities. And what we've seen is this virus spread around the world with remarkable speed held both by its very rapid generation time, but also by this web of travel that is unprecedented and which was certainly how HIV initially got out of its first ... tore holes into humans was as places when the virus in circulating began to be places of interchange in the rest the world, it found its way out.

SARS COVID-2 didn't need to wait, it was already on planes long before we even knew the virus existed. The disease existed and was already circulating in places that we're unaware were circulating, but really feeling pretty smug and safe because it was a problem somewhere else. We've seen repeatedly this concept that if you just stop travel, you can prevent the virus from getting here and therefore we didn't need to worry about it.

You may remember we tried to stop people coming into the US who were HIV infected back in the day in the Reagan administration, and that didn't turn out to work so well. We tried the same thing here. And when we did that we then rather than saying, but we also need to realize it might still get here. And in fact, it's probably already here and look forward, we basically went to sleep. And then waited until the virus was being transmitted within the population widely enough that it was virtually impossible to catch up with by the time people began to acknowledge it as a problem. The only reason it really came to our attention in the US was it finally found its way into a nursing home in Washington State where you had a cluster of people who were susceptible enough to disease as opposed to just infection and transmission to get infected in a rapid succession.

And people suddenly realized the virus had made it to the US. We then turned around and said, "Well, we'll close the door to China" and forgot we had a front door to Europe. And then remembered that and then started this idea that if we just closed that door within 48 hours, we'd be safe. That led to probably the biggest influx of virus into the US from the beginning when people who were infected, Americans who were infected, rushed to get on planes to get back before it was too late. They sat in airports for hours.

Eric Ries: I still remember those images of the people waiting in the holding areas in the airports those days. And after that, it just seemed like if you were once again trying to cook up the perfect vehicle for maximizing transmission, that's how you do it.

Robert Schooley: Right. I turned to my wife sitting on the couch watching that night and said here it is, it couldn't have been better. And that of course, took several weeks to percolate through the northeast and then you had New York and that was all seeded in part by that but also by the people coming back and forth before then. But under the radar, the virus was spreading rapidly in the community and causing what was likely mistaken by more people than not as flu. Because we're in the middle of flu season and a lot of the people who were out and about were young people and weren't getting that ill.

But it wasn't until it began to get into older populations, that the virus began to overwhelm the healthcare system and to take off up and down our northeast corridor. And we're kind of reliving that. As we speak, we know that we were able to take the top off the peak in the country as a whole by robbing the virus of the chance to be spread from person to person by doing by working at home, by wearing masks when we're out, by hand washing, social distancing, decreasing the number of human contacts. And we've got clear evidence that worked.

And we have clear evidence from before we were doing that what the virus was doing epidemiologically it was exploding. Everyone who was infected was infecting three or four more people. And when we go back to what we were doing back to work, back to school, if we do it in the same way we were doing it in March, we'll have that same three to four person rate of spread. And another explosion that we'll have to fight again to get control of with hospitals worried about who's going to get the last respirator and we've already begun to see that happen. Montgomery, Alabama was nearly out of respirators 10 days ago. Things are getting very tight in Arizona now, and Phoenix.

Eric Ries: I think I just read that they are at like 75% ICU utilization, right?

Robert Schooley: Exactly. And when you look at the epidemic curve in Arizona, it's unbelievably steep. These are new cases, you've got the governor saying nonsense like, oh, we're testing more people, less letting us know, we have more infection. We're going to get those tests out there. But what's being countered are cases not ... And people in the hospital, hospitalizations, those are things that happen whether or not you're testing. And what that's telling us is that this virus is having its way with Arizona. And right now there's no end in sight if this current plan that they have continues to be in place.

Eric Ries: So rewind the tape to the start of the pandemic. One of the recurring themes in these conversations is the need to have science-driven policy and leaders who are fluent in the science of the kinds of challenges we're going to face in the 21st century. So what would a science driven policy response to this have looked like? If we could rewind the tape and do it over again?

Robert Schooley: Well, the science driven response would have been to look at what happened in China in late December, early January, where it infected 80,000 people and at least 80,000 people, absolutely cases that were counted in a very rapid fashion. Now, you could argue we didn't know about that, but we actually did, our intelligence agencies knew about it. We would have known more about it if we hadn't pulled all the people from the US CDC who were working in China last June. Up until last June, we pulled all of them out in a spat about tariffs, and we would have had real time intelligence in addition to what the intelligence community was saying.

And we would have said, that virus is highly transmissible, it moved across China, no time flat. And what we need to do is to be ready for it, if it gets here. We need to have our hospitals ready. We need to make sure we have enough respirators, we need to have enough ... We need to develop a test kit quickly, we need to figure out ... so we know who has it. And when you do use that test kit in ways that the test kits we have don't constrain us from finding the disease.

The first community case transmission occurred here in California where a woman who hadn't traveled to China became ill in a local hospital. The doctors taking care of her said this is not a usual pneumonia she must have COVID and wanted to get her tested. When they asked to have her tested, the public health people, the CDC said, "No, no, no, she hadn't been to China, she's not eligible for testing. We don't have enough kits." So she then was transferred to the University of California Davis where the doctors there said, "This sure doesn't look like pneumonia to me, this looks like Coronavirus. Can we test her?" And it took them another two to three days to be willing to test her then. And it was all because they'd set up this concept that it couldn't be Coronavirus if you hadn't had contact with someone from Wuhan China.

And if we'd had widespread test kits available and had used them when people came in, and had done community testing around the nursing home outbreak, we would have known that this virus is here. And it would have redoubled our efforts to make sure that we had the masks and gowns and gloves needed in the hospital. We would have been really much better prepared for this. And we would have talked about it as a severe problem, a serious problem that we need to do something about. We'd have recognized that China stopped having people go home for 10 days, rather than continuing to act like nothing was happening and waiting until people who were watching what was happening to your hospitals realized there were going to be 10s of thousands of deaths and that finally got people's attention.

And that was a missed opportunity for us. It's not ... Can you blame China? Can you blame the WHO? There are things they could have done better. There's evidence now that this virus may have been circulating in China in October, and people either didn't recognize it, or the disease wasn't acknowledged. But we knew about it in December, and we didn't do anything about it.

The Chinese acknowledged it was present in December, and within a week, the sequence of the virus was ... by early January, the sequence of the viruses were already online, we could have started making test kits, then we didn't even have the virus in hand to start developing an assay for it. And when we started trying to make an assay, we should have said to all the scientific community in the US who want to try to develop an assay, "Please do we need to have this." And instead we tried to control it and have the only place that could legally do it be the CDC and they managed not to get it done and to use the FDA to prevent research by researchers in university hospitals from developing an assay that can be used to turn the lights on about where this epidemic was at a time when politicians were saying, not a problem. We don't see it.

So we made a large number of mistakes early on, and we still haven't caught up with that. And unfortunately, we're watching some of those same mistakes be made again.

Eric Ries: It's heartbreaking to think that we're now talking about 100,000 deaths or you're saying the possibility of 200,000 by the end of the summer. I think it's almost too monstrous for us to process that those were preventable deaths. Is that really true?

Robert Schooley: Yeah, I think most of them were preventable. By the time we recognized that, by the time things were really rolling in China, the virus was probably already here. We would have had some deaths but we could have prevented most of them if we'd been prepared to deal with it in a more aggressive way. If you look at the difference in what happened in epidemiology in New York, and in California it's very clear that had we acted a few weeks earlier we would have prevented 10s of thousands of deaths. And New York and California did their shutdowns only three days apart. The difference was that in New York, they were having about 5,000 cases a day and in California, the number of cases a day were less than ... were 200 to 400. And it wasn't the number of cases that was signifying, the difference was that those cases were just a very downstream indicator of all the virus that was already circulating in the community.

And so New York's epidemic, although only the intervention was only three days later, it was much more advanced than California's. And the places that this virus is getting now and the resurgence are beginning to unravel what was going on in New York before the shutdown was put in place.

And it takes a couple of weeks once you decide to do something definitive, to begin to see the peak, occur and go over the other end. And so I really do fear that by ignoring what's happening, we're going to give the virus another run at our population and make it a lot harder to get back to what we want to do.

It was a very, I thought, insightful column by Paul Krugman times earlier this week, the marshmallow game, in which he talked about a game that you play with children in which you put a marshmallow in front of them on a plate. And you say if you wait 15 minutes and don't eat this, I'll give you another. You can have two marshmallows. And New Zealand was smart enough to wait for that second marshmallow, they are waiting until they get control of the epidemic to go back to work. We ate that marshmallow as fast as it was on the plate. And I'm concerned that we are missing the chance to really get this virus under control where we can do contact tracing and look for clusters of cases and get people quarantined when they are sick so they don't infect other people. We're missing that chance by just trying to titrate what we do in a way that the number of deaths is "acceptable".

Well, we're not going to get on top of the epidemic by doing that. And that's ultimately what we want to do. It's not just the peak of the curve, it's the area under the curve. Allowing the area under the curve to continue to evolve by not being willing to take advantage of what would have been a peak going down to the other side of the peak, and just stepping on the virus's neck so it can't come back and cause trouble. We haven't had the political will to do that, and that's bad for us.

Eric Ries: It seems just heartbreaking to me not just the calamity of the deaths and the botched initial response, but then the fact that the time that we all bought with our shared sacrifice of the shutdown and the shelter in place, that that time was squandered. I think that's hard for people to accept.

Robert Schooley: I think it's very hard for people to accept and the counter narrative that you will hear is see we did all that and it didn't matter. We did all that-

Eric Ries: People aren't very good with exponential math. Yeah.

Robert Schooley: Yeah. They aren't very good at exponential math and the message is we did that and we know how that works. We didn't do it long enough. And this talk about well, it's behind us now, and all that wasn't worth it. “It just hurt the economy” is reconstructed history that is really destructive in terms of how to get this epidemic back under control.

Eric Ries: Yeah. So I know in epidemiological circles and public health circles, there's been talk of this kind of pandemic for a long time. Is it your view that a pandemic like this was inevitable, at some point something like this was going to happen?

Robert Schooley: Well, we've seen two of them already. There's the initial SARS outbreak, we were able to get control of that. We had two fortunate events with that one. The first is the biology of that virus is slightly different than this one. This virus, although highly similar, has a unique feature that K Y Yuen and his colleagues at Hong Kong University figured out and that is, rather than stimulating the innate immune response, the first arm in our immune defense, this virus subverts that immune response and it grows in lung tissue about three and a half times as fast as the original SARS virus did.At a time when it's silence their innate immune response, innate immune responses, in fact, how we know we're sick, that's where the what interferon is generated. Interferon is what makes us feel bad when we have the flu. So at the same time, the virus is replicating rapidly by being able to shut that immune response down, it's helping us work and stay in class feeling fine. And the virus then spills over into our nose and throat, on our vocal cords and titers are higher than when you're actually sick and spreads in people who don't have symptoms. That accounts in my view for up to half the spread maybe more.

And SARS, the first SARS outbreak didn't have that feature. So if you isolated sick people, put them in the hospital and got to their contacts quickly, you could stop the epidemic. And luckily for the world that happened in a place where people were willing to do that, China and Hong Kong, they put people in quarantine, who were contacts and they stopped the epidemic.

The same thing happened with MERS, the Middle East Respiratory Syndrome 10 years later that occurred initially in Saudi Arabia and spread to a little offshoot into Korea. But it was also stopped by vigorous isolation and classical public health in places who still had public health priorities and had people in health departments, who could do contact racing. We've left that all atrophy in the US and didn't have that at our disposal.

Eric Ries: Why do you think we've historically neglected these investments?

Robert Schooley: Well, we tend to make investments in things that are in front of us, and we aren't good at preparing for things that we know will occur but aren't there now. And a lot of that is trying to ... we have these short electoral cycles two years at a time. And politicians don't really care what happens in five years, they care what happens in 18 to 24 months. And it's very hard for them to say we need to raise taxes or decrease expenditures in this area to have a reserve of N95 masks because we might need those. It's very hard for them to say, Well, right now we're not having an epidemic, but there's a good chance we will so we need to have health departments, have people who are trained and ready to go out there and find cases and stop them.

So when something subsides, in our rear view mirror, we then invest in something else. And that leaves us always having to catch up when that inevitable thing comes along. This is not going to be the last outbreak of respiratory illness that we see go around the world. If we get control of this, vaccines, drugs, social distancing, I hope we take a careful stock of what we didn't have in place and what could have saved all these lives and made it a lot less devastating to people and families and economies and say, if this comes back again, when it comes back, we're going to be ready this time.

That's the most important long term lesson I think that we as a global society should take home. The other global lesson to be learned is that viruses and infectious pathogens don't have maps that have country borders on them. What they see is people they can infect and we are so heavily intertwined as a global population now, that borders are not going to keep the viruses from spreading when they come along. And we should, as a global community, when we see a problem anywhere, all the rest of us should jump on it and help wherever that is get control of it, because it will be to us later. And it will be much harder to control if it's allowed to continue to expand, evolve, diversify, and deplete resources.

So, I hope in the future that instead of saying, "Boy, that's a problem China's having." We say, "How can we help you control the virus? Do you need some PPE?" And when we need help, they'll say the same to us. We are all in this together. And if anything has shown us that it's this virus, just like HIV showed us 30 years ago.

Eric Ries: I think it's really interesting that so many of the lessons that we need to learn from this virus are not really about health, or science or epidemiology, but rather about the values of our battered liberal democracy and the need for international cooperation, the need for empathy and compassion and truth telling on the part of our leaders. And this really difficult thing to have the right people making the right long term investments even when the problem as you say, it's not right in front of our face.

Robert Schooley: Well, I think the long term investment issue is something that is true for politicians, also true for corporations, and for universities and for societies. We have lost sight of the fact that we're only here for a short period of time on the planet and if we can make changes that benefit people down the road just as much as they benefit us, we're going to be a credit to our species. But if we keep doing things that are easy for us now and you have to pay for later, we should really think hard about why we're here in the first place.

Eric Ries: And what kind of legacy do we want to leave behind?

Robert Schooley: What kind of legacy we want to leave behind in infectious disease legacy, climate legacy, economic, educational legacy. Those are all things that by investing in these areas more than we do and more sustainably than we do, we can make the world exponentially better place than if we continue to try to just get by doing not quite enough damage for it to be cataclysmic, but not really thinking about how to solve a problem.

Eric Ries: I'm glad that you included for profit corporations in your list of institutions that need that way of thinking. We've been talking a lot about this next generation of leaders and the obligations they have to face the challenges of the 21st century in a multi stakeholder long term way. And that epidemic has just driven that home.

Robert Schooley: Well, I think that's right. I think what happens is ... I'm just a country doctor, but I understand shareholder value. And one of the things that has happened is we've changed the horizon for when shareholder value counts, it used to be you'd invest in a company, and watch it evolve over time and watch it develop products and watch it have an impact on society. And you would expect your return to be several years down the road. And now what people want is they want a clinical trial to start in 10 days whether the drug is ready or not, and they want a new bit of software to be out there, whether it's ready to go or not. And the longer term impact of not having stability both causes us to miss a lot of potential opportunities.

A lot of the most exciting fundamental research used to go on within companies. And now what happens is the companies that kind of outsource that to the biotech industry and the biotech industries, in turn, outsource what they used to do to the venture capital, early clusters of small people and each higher layer then tries to gobble up something that looks like it might work. And if it doesn't work in the 10 months, that people are going to give it, then it gets cast away.

In older paradigms in which you had a larger company that could look across platforms, and see where one part of the company had technology might help the other part of the company and where there was a little more patience. Because the CEOs bonus wasn't going to be calculated on the basis of what the stock price was on such and such a date, some of the things would have been really good ideas that actually came to fruition.

And the flip side of that is, of course, if you have too much of that, too many layers of control and caution, you end up stifling out innovation. And we need to find a happy medium point between those two to be able to think longer term than we have.

Eric Ries: And no one could argue that our current capital market structure is optimized for that happy medium. we're way out of whack.

Robert Schooley: Exactly. So I think maybe this will give us a chance to reflect on that as well. But we don't learn from our mistakes and our successes, we're missing great opportunities.

Eric Ries: Well, when I think about the memorial that we will have to build to the preventable deaths that have happened as a result of the pandemic, all I can think about is we just ... it would be a disgrace to let their sacrifice be in vain. And so if we don't take this opportunity, if we don't learn those lessons, then shame on all of us.

Robert Schooley: Couldn't agree with you more.

Eric Ries: Talk a little bit maybe on a more positive note, talk a little bit about what the response has been like in San Diego and at UCSD and the steps that you've taken and as I understand you're also involved in the plan to potentially reopen the campus once you have sufficient testing. Talk a little bit about what that's been like on the ground.

Robert Schooley: Well, we think universities are important obviously, that's why we're here. And we have done the best we could in this last quarter trying to teach our students at home. I think the faculty, I have to give them credit, they within about a 10-day period of time went from all face to face teaching to teaching remotely and delivered a remarkable quarter. But what we don't have when you don't have people go, you just don't have people interacting with their peers, you don't have students engaged actively in research with their professors and learning how to inquire and learning how to question each other. You don't have a research enterprise acting at full potential. And so for us, we think it's very important to be able to have our community back together in the fall, but we all have come back together in a way that we're putting people at risk. So we've tried to put in place three major components.

One is, risk mitigation, which is to try to make it difficult to RSV spread from one person to the other. And by that I mean classroom size, dormitory density, masking, anything we can put on the tennis court, any folding chair to make it hard for the virus to get from one place to the other we want to do.

So we've gotten to a plan using mathematical modeling. I have a brilliant partner named Natasha Martin who doesn't actually use modeling. And she's modeled the impact of larger class sizes, smaller class sizes, double dorm rooms, single rooms, those sorts of things to understand how we can most likely operate.

We then put in place in addition to our risk mitigation component, a component of viral surveillance, and that includes wanting to make sure we know everything we can about anybody who is sick so that we can get them taken care of medically and get them isolated from others. We want to be able to look for virus actively with viral shedding and monitoring. Natasha has done a calculation of how many people we would have to monitor every month with viral shedding tools to be able to have a 90% chance of knowing when we have a cluster of less than 10 cases on campus. So they could really intervene with isolation, and quarantine.

And it turns out that if we were able to do a nasal swab, or an oral swab on everybody on campus once a month, and by that I mean faculty and staff and students, we would achieve that goal. And so we developed a testing plan that will do that. To do that, we knew that we couldn't have it done in the hospital because what that would mean, 60,000 people every month would have to traipse over to the hospital and wait for an hour to be called up to be given a lab slip. And another hour to wait for somebody to take the sample and blow two hours out of your day, and nobody would do that. So we developed a testing format in which we have test boxes kind of all around the campus that have a swab and some transport medium in it and the swab has a QR code on it. People have an app that can read the QR code and assign that swab to their medical record number. So all you have to do is go back pick up a swab, point the app at it, stick the swab in your nose, your mouth and then throw the swab in a box and go on about your work just like you've brushed your teeth. And then we pick them up every few hours and run at the hospital.

Anybody who's got virus that shows is then notified and we make sure they get the health care they need and also find out who they might have been in contact with and look to see if they also need to be tested. And we have room set aside for students where they can have a private bathroom and private bedroom. Meals are brought to them while they're infectious so that we can use the third component of this, which is kind of isolation and contact tracing to prevent ongoing spread of the virus.

And so that three component activity is how we're modeling how we want to operate the campus in the fall. And we hope that we're going to be able to do that a lot but it’ going to depend on what happens to the epidemic over the next couple of months. But if we're at a place where we were at the end of May, then I think we can do this, and keep everybody safe and have the university function in close to the way that it should be functioning with people doing community service and working on research projects and teaching in an integrated, highly efficient way.

Eric Ries: If this plan succeeds, as you hope, could it be a model for how we could reopen other institutions in society?

Robert Schooley: Well hundreds of other institutions and also society as a whole. We're trying to find simple ways to monitor viral activity. We're also, I didn't mention we're going to be looking for virus in wastewater in dormitories and things to identify where the virus is circulating. So all of this about controlling Coronavirus is knowing where the virus is. And to kind of use the Wayne Gretzky model about what made him the greatest hockey player, he said, it's because I don't skate to where the puck is, I skate to where it's going to be. And if you can track where the virus has been moving, you can project where it's going to be and you can put your resources in play to stop that.

And that's what we need to be doing in society. We need to be able to do that with much more watching by testing the public. We need to do that with ways for people who are infected to be protected from their families and others. We need to have a public health effort that helps us identify people who are infected and get them out of harm's way. And we need a very effective hospital system to be able to take care of people efficiently. And in the meantime, we need to be investing vigorously in drug and vaccine development.

Eric Ries: One of the things that strikes me about the UCSD plan is, it's very well thought out, there's a lot of components that the people who are involved in the community would have to know about, you have the testing boxes, you have the app, QR code, the lab capacity, the contact tracing, like it's an integrated plan, it has a coherence to it.

And so if someone is not at UCSD, if they're working in a corporation or in any kind of situation where they're being asked to go back to work, if they're not seeing those signs of preparation around them, would you say that it's not safe, they should demand more from their place of work?

Robert Schooley: Well, ... as you said, what's the one thing that matters the most, the thing that matters the most right now is masking. And I think that it's critical for people who are back at work to be wearing a mask everywhere they go. I think right now we should have companies think carefully about how many people they bring back to work at one time. We're doing that here and not bringing everybody back at once to do research, for example.

I think, thinking about issues like having sanitary wipes and having thoughtful approaches to how we interact socially like in coffee stands, and cafeterias and workplaces. We need to rethink that for now. And if companies aren't doing that then you need to talk to the people in the company about the only way your company is going to be able to continue to function is for your workers to be functional. And that's not going to happen if we don't work together to stop this virus.

Eric Ries: The lack of seriousness on the part of people who are rushing to reopen, I just find totally shocking. And not just federal leaders but local leaders in some places, governors in some places and corporate leaders in some places. When I was talking to this company called Curative, which is an LA based SARS COV-2 testing company, they took over a clear lab and built out this testing capacity to do hundreds of thousands of tests. And they're powering the drive through testing in Los Angeles and in a number of cities around the country.

The thing that just scandalized me, and I just wonder if this is consistent with your experience as well, I think many of us in the public just assume that the reason there's still even today insufficient testing of the virus is simply that we don't have the test. There's not enough testing capacity or the labs aren't ready or the tests aren't ready. There's been a lot of disinformation about that. But what they said to me is they have hundreds of thousands of tests ready to go, they could be setting up drive thru testing in any city in America and the limiting step though, the one thing they really need is more contacts with more mayors to set it up. And the idea that it's a lack of political will, not some kind of technical limitation that's preventing us from doing the testing that would be needed to control the virus and reopen safely, I find it almost unbelievable.

Robert Schooley: Well, I think a lot of places the mayors don't ... in our city, for example, the mayor doesn't have any health component. It's all a county health department. And they're so busy trying to figure out why they don't have the personnel to do what they need to do. It's been very hard for them to set up testing. They work for a board of supervisors that hasn't planned that well for this and that kind of strategic thinking is hard for me to get to.

The other thing that we also need to do is think about the cost of these tests. They don't cost $100 apiece. That's what is charged to do them. But we've allowed some of the large testing companies to get that price because they essentially blackmail the Trump administration into that. When the Trump administration needed to show that they were doing more testing, they threatened to say, "We're not going to do testing at all, if you don't give us that price."

And we need to find a way to move this from a medical platform in which you make a large profit on a small number of tests to a commodity platform, we get the same quality test, but done at a high volume. You can end up having a much bigger impact on health and society and still make money if you move to that. But if a test cost is $100 a test, it's going to be very hard to use those tests to control the virus in the community.

Eric Ries: Given what you know about the reagents involved and the logistics of actually doing the testing, what could it cost?

Robert Schooley: Right now the real cost is probably somewhere around $35 to $40, by the time you pay for reagents that as they're kind of provided by commercial vendors. But the real cost could be as low as $10 or less if people take it to scale, do pooling, use some of the more innovative technologies. And that ought to be where we go with this. We can't have it both ways, which is to try to maintain these high profit margins and at the same time, move it out, to make it available to the millions of people that need to have it available to really understand in the society, what we're doing.

When you think about companies who want to go back to work, by being held hostage by the companies that are keeping the prices of these tests so high, we're essentially letting capitalism kill capitalism by not coming up with a way as a society to figure out how to commoditize these tests, and have them become a public health tool. And really liberate us to go back to work.

Eric Ries: I've been thinking about the saying hindsight is 2020 it, it being 2020 now, but if you think about trying to take advantage of all the hindsight now that we have. So everything that we've seen and learned, all the mistakes that we made all the lessons we should have learned from those mistakes. What do we need to do right now, going forward differently, to beat the virus and to reopen our economy?

Robert Schooley: Well, we need to, first of all, separate the politics from the science. Science says that we can do a lot of things right now that we weren't doing in April safely if we wear masks and pay attention to distancing and density and all that stuff. And we shouldn't have wearing a mask be a signal of where you stand politically. In fact, if I were trying to open the country and put this behind me, the first thing I would do at every time I go to the microphone is I'd be there with a mask on and say, "It's important you wear this so we can get on with our business." Because we know what's going to happen when people go out without masking and do what was going on in March and April.

So the first thing we need to do is to be able to come to agreement that we know where to stop the virus so far, we know we can do it again. But people have to do it and stop making it into some sort of litmus test about where you stand politically about how you feel about masks.

We need to have people who might be sick, have no disincentive to telling their boss or their workplace that they're sick and be sent home with pay, so that they're out of the workplace for the 10 days instead of at the workplace. Because having them there coughing and with a fever and working because they're afraid they're going to lose pay or be fired if they're found to be infected is a short way to keep the virus going. So we need to remove any disincentive to people being tested and to being able to stay home if you're infected.

We need to make it easier for people who are infected, to stay home. Make sure they have ways to get food and make sure that if they're with older people, they get away from those older people. Put your grandmother in a hotel. With a lot of the outbreaks in the ... or go to a hotel yourself. A lot of the outbreaks that have occurred in China and Europe and other places are within families.

So when you know you have a family member who's infected, don't repeat that over and over again with everybody in the family, and certainly not if you have someone who's highly vulnerable to this virus. People who were older and obese and COPD, people with asthma, renal failure, cardiovascular disease, get them out of the way when you know the virus is around and the ... Be patient in terms of trying to get back to large events, we've seen the Memorial Day weekend price we paid, let's not be that place next Memorial Day weekend.

Let's have this ... if you look at New Zealand look where it is now, they can have a Memorial Day weekend, next year.

Eric Ries: The last reported case, as I recall, is done. New Zealand is Coronavirus free, right?.

Robert Schooley: Right. We're a more complex society but there's no reason not to set that as our goal. And we know we have to, to do it and we just need to have the will to do it.

Eric Ries: I feel like I'd be remiss to have you on and not ask you about phage therapy. Do you mind?

Robert Schooley: No.

Eric Ries: Just explain a little bit about what that ... that's a big part of your research so just explain a little bit about phage therapy.

Robert Schooley: Well, we, in addition to dealing with Coronavirus, we're dealing with a kind of a global explosion of bacterial infections that are resistant to most antibiotics, if not all of them that we have. A lot of it is because we've used antibiotics for a long time for good purposes. We also use them to fatten up chickens and bacteria on the planet are Darwinian and they see these antibiotics and they evolve to be able to grow in their presence, develop resistance. And so we're running out of drugs to treat these more severe infections.

Pharma is working on new drugs but their pipeline isn't keeping up with the evolution of the microbiome of the planet. Probably the most efficient Pharma that's been around for 300 million years is the bacteriophage industry. Bacteriophages are viruses that live within bacteria, prey on them, kill them and go on to kill the same bacteria next to them. They are literally eaters of bacteria. And they've been co-evolving with bacteria for 300 million years.

We now know how to isolate them from the environment, to purify them and to use them therapeutically, in people who have some of these multidrug resistant bacterial infections when we don't have antibiotics to use. And I think that as we develop technologically more efficient ways to do this, we will open new avenues of infectious disease, therapeutics that may help us with this MDR pandemic that we're having.

The other thing that these bacteriophages can do is they break through biofilms. Biofilms are films that form on foreign bodies when bacteria grow on them. And one of the reasons why it's very hard to sterilize say, a prosthetic knee or a prosthetic hip if it happens to get infected or a pacemaker. Bacteriophages can break through those biofilms and when used with antibiotics, we think that some of these infections that have to be treated by removing the joint or removing the pacemaker, we may be able to treat with antibiotics and bacteriophage without having to remove the prosthesis which would be a major advance and we think would be very helpful.

So there's a lot of things that I think are on tap that we should think about with bacteriophage research going forward. We've had to back off on some of that in the last couple months because of the COVID outbreak, but the antibiotic resistance challenge hasn't gone away. And I think this is one of the more hopeful ways to get back to business in dealing with these multidrug resistant bacterial pathogens.

Eric Ries: And thinking about the through line of many of the things that you've said, going back to your interest in neglected populations in the public and governmental response to HIV and the lessons that we could learn from that. Obviously, your work on the pandemic itself and preparing our economy to reopen when we can do it safely. And this recurring theme of needing to make the investments that lay the foundation for future prosperity, future progress. What do you really hope will be the lessons that we learn from this in the biggest picture. Of course, we're going to learn ... we've all learned the lesson of funding infectious disease research which we neglected before. I hope we all learn the lesson of science driven policy and, frankly, simple things like washing hands and wearing masks that that's pretty important.

But if you think about the structural changes to our society, our civic culture, the way that we as the public engage with these issues, what do you hope will change as we emerge into the new normal?

Robert Schooley: When we think about who we're kind of wired to care most about as humans. We care about our spouses, and we care about our children. And I think if we think that about everyone on the planet is being in one of those two categories, and what you would want to leave them as your legacy. It helps us make decisions that are sounder in terms of greater good for more people over a longer period of time.

And I wouldn't want to have my children be worried about going out of the house and having someone stop them because of a broken taillight and end up in jail about it. I wouldn't want to have my children get tuberculosis and not have someone in the public health department be able to contact people that my child have been to school with and prevent them from having the same problem. What would you want for the people that matter to you most? And think about that as we make policy for what affects everybody else in the world. Because every decision we make, in varying degrees, has an impact on more than just us.

And I think if we can recast how we think to include that, obviously we’ve got to continue to have individualism. I like things that feel good too, but not have that be the short term satisfactions of things that feel good for a short while be what dominate our thinking as individuals, as corporations, as educational institutions, and think about the longer frame of history.

Eric Ries: We always like to end these conversations with the same question simply. Where do we go from here? How do we get out of the crisis?

Robert Schooley: Well, I think we have a roadmap. We just have to have the patience to follow it. We need to look at states that are having explosions and send people home until the virus spread is quelled. And if they go home and stay home more vigorously than we did the last couple of months ... China didn't stay home for weeks, for months ... They stayed home for two weeks period, and that's because everybody stayed home.

And if we could do that in a really definitive way in these places where the virus is exploding and kind of reset the clock, and then start back, being mindful of what we know about how to stop transmission, we may be out of this, at least the acute crisis and be able to operate our institutions and our companies, and our economy in a way that is sustainable. And work back toward being able to do what we were doing a year ago. Working on vaccines and drugs that will allow us to do that and realize that humanity's been through these infectious crises before with plague and smallpox and influenza, at times when we had many fewer tools and much less insight, than we do now about what we were dealing with. People didn't even know some of these were caused by microbes. And they got out of it. But they got out of it by being attentive to things that worked and didn't work, and being rigorous about taking those lessons to heart.

And I think we should do that with this epidemic as well. And I think we do that we'll get out of this one, just like we have the others.

Eric Ries: Dr. Schooley, I really appreciate you taking the time out, to have this conversation. Thank you for your lifetime of service to the cause of human progress and science driven discovery, and of course, for your leadership during these really difficult times.

Robert Schooley: Thanks. It's been a pleasure talking to you and good luck.

Eric Ries: This has been Out of the Crisis. I'm Eric Ries. Out of the Crisis is produced by Ben Ehrlich, edited by Jacob Tender. Music composed and performed by Cody Martin, hosting is by Breaker. For more information on COVID-19 and ways you can help visit helpwithcovid.com. If you have feedback or you're working on a project related to the pandemic, please reach out to me on Twitter. I'm at E-R-I-C-R-I-E-S. Let's solve this together.

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