 Okay, we're back, we're live, we're doing Corona Watch as we do at noon on Wednesday. And we have a really, really, really special guest today, Dwayne Gubler, he joins us remote from Utah where he has retired the third time. But Dwayne went to Johns Hopkins and studied all kinds of science. And his degree is not an ordinary PhD, it's a PhD in science and it's more demanding than an ordinary PhD. And from there he spent time, G, all over the world with the CDC and the National Institutes of Health and the World Health Organization. He's been through it and it was in his faculty with the John A. Burns School of Medicine and then he left, G must be 10, 15 years ago, to go to Singapore, courtesy Duke University and the National University of Singapore where he had a laboratory, a laboratory he always wanted for infectious diseases, that's his specialty. He's since retired, but he's left his mark on Singapore. In fact, they wanted him to be, he made him an honorary Singapore citizen, which is really something. So, G, you've really been around, Dwayne, and I must say that since I have known you, I have found and treated you as a guy who is 10 feet tall. Our viewers cannot tell from the photograph, from the video, but you are 10 feet tall. You are a world name in infectious diseases and it's an honor, beyond an honor, to have you on our show today. Thanks for coming around, we really appreciate it. Well, thank you, Jay, for inviting me and I only wished I was as tall as you think I am in terms of you. Well, we can disagree on that. Anyway, today, you know, the question before the house is why is COVID-19 so contagious and what we could do, what can we do about it? How much do we really know about it? You have studied all kinds of infectious diseases and you know, what is special? I think there is something special about the coronavirus. You've seen it, you've studied it. What do you think about it? Is it more of a threat than others? Well, that's hard to say because we don't know what the others are. If you look at what's happened in the past 30 or 40 years, we've had a series of major epidemic and pandemic that have swept the world and it's hard to know what the next one is gonna be. We have a problem, Jay, of what I call circular migration. People moving from rural areas into cities and then back to the rural areas to visit family and harvest crops. They're constantly introducing new pathogens that have been infecting people for thousands of years and introducing them into crowded urban centers that have 10 to 20 million people. And every one of those urban centers has a modern airport through which millions of people pass every year and it provides the ideal mechanism to move pathogens around. Now, most of these pathogens, which are usually animal sites of one kind, don't really take in humans. There's not secondary transmission. But once in a while, we see one like the corona, SARS Corona 2 virus that is highly infectious to humans has secondary transmission and moves very rapidly around the world. SARS was another one of those in recent years, in 2003. Others like NEPA encephalitis weren't as infectious and didn't spread, but there are many other viruses. We estimate over 500 viruses in animals out there that have the potential to move into humans. Of those 500, we know that 100 of them will actually infect humans. And so I don't know whether this one is really special in the sense of its pathogenicity and infectivity or not. I think there are probably others out there that are just as bad. You know, one thing I just noticed yesterday was in Japan, which has its own problem about coronavirus, it's pretty serious emergency right now. There are people investigating the notion of micro droplets, micro droplets, not a sneeze or a cough, but breathing and talking. And they use slow motion photography, some kind of infrared photography and to see the droplets, which are very, very small. I don't know what very small is in that context, but it's like 0.01 micrometer or something. And you can see them in the room and they stay in the room. And the people who spray them leave the room, someone else's comes in the room and just kind of explains, and it doesn't take a whole lot of virus. What do you call them, virion? It doesn't take a lot of virus particles to infect you. And so if you walk into that room, you're in trouble. This sounds like it's way more contagious than we originally thought when everybody talked about sneezing and coughing and touching surfaces. It's in the room and there's not too much you can do about that except I suppose open the window, go outdoors or treat the room. I think this makes it very contagious and that's why we're having all these issues about, what do you think about that? Is this new? No, it's not new, but it's certainly true. And we're learning more and more about aerosolization and how pathogens that are transmitted by the respiratory route move. If we look at the pandemics that have occurred, they're generally of two types of transmission. One is the respiratory route and that's of course the most important. The other is by mosquitoes and that's where my specialty lies is in mosquito transmitted diseases. But the respiratory route is the most important and when you cough or you sneeze, you expel respiratory droplets. The bigger ones fall out very rapidly but there are little bubbles that go out and those pop and that aerosolizes the virus and if you talk loud or if you're singing or if you cough or you sneeze, you can push those particles, aerosolized particles out several meters in front of you. And if it's a closed environment and no air movement, no good ventilation and other people that are in the room can be infected. There was an incident in Washington state recently where 75, I think I forget, 60 people I think it was attended acquire practice. And two or three days later, they had people coming down which was turned out to be COVID-19 disease and 75% of that acquire became with SARS-2 virus and then clearly it was all due to aerosolization and respiratory droplets in a confined space. One of the most dangerous places you can go when there's something like COVID-19 spreading as a elevator, you get in there, there's absolutely no movement of air and if someone sneezes or coughs, you can rest assured you're gonna breathe it in. Well, what can you do about it? There's all this talk about masks and we had a, I think a false start in terms of public information. We talked before the show about the intersection of politics and politics and science. And I think we got some bad information about masks and the use of masks and people were led to believe, most people still do believe that the only person who should wear the mask is the person who has the disease. But in fact, if we have a spray going on in the elevator or in a room with no ventilation, I think I'd want a mask. I want a really strong mask. So I didn't breathe that in. It's a mask help. What do you think about this? Well, there's, as you say, it's controversial. A mask will not protect you against most masks. The surgical masks that most people use will not protect you against the aerosolized virus. They will protect you against the larger respiratory droplets, but those are relatively unimportant by comparison. And so one of the reasons why masks were not recommended, and they are recommended now, but have not been recommended, is that the argument is, is that if people are putting masks on, it gives them a false sense of security and they think they're protected and they'll do things that they're not supposed to, i.e. not be conscientious about social distancing and so forth. So without any doubt, masks can reduce some transmission to really prevent infection and it doesn't prevent 100% protection against aerosolized virus. You need what they call N95 masks, which will filter out most of it if it's fitted properly. But most of the masks that you see don't fit properly. They don't filter out the aerosolized virus. And so it probably is maybe, probably doesn't help a whole lot because people take chances they otherwise wouldn't normally do. The other thing a mask does is when you touch your face all the time, it prevents you from touching your mouth and your nose, not so much your eyes, but, so it's controversial that it, used properly, they can decrease the transmission. Let me go to that. So you have entryways, entryways that ultimately go into the respiratory system. And we've been told that it's the nose, obviously you're breathing air into your respiratory system. It's the mouth, I suppose, because from your mouth it goes down and forks into your lungs as opposed to your esophagus. And people have said, well, it's the eyes and they wear these plastic masks in order to prevent the spray into the eyes. And I've even heard the ears because the ears can also drain into the respiratory, into sinus into the respiratory system. But, you know, how true is that about the eyes? That seems to me like that's a bit of a long shot to get from the eyes into the lungs or for that matter from the ears into the lungs. And the really risky part is the nose and the mouth. Am I right about that? No, the eyes are important as well. If you, I don't know what they ever use, eye drops or not. But if you put eye drops in your eye and blink your eyes a few times, you'll taste it in your, it gets into your nose and you'll actually taste it. It goes right down. The reason the eyes, the nose and the mouth are because you've got mucus membranes there, the cells that are highly susceptible to infection by a number of viruses. And so all three areas are susceptible to infection. And it's hard to, yeah, you need to protect them all. Best policy. So now the virus gets into your system. The virus is in your nose and it's going into your lungs. Does this happen in seconds or minutes or hours? Is there anything you can do? The virus infects cells and replicates. It replicates and so it's not instantaneously that it gets into your lungs. No, it has to replicate. And as the virus gets and builds up populations, it'll then migrate to other parts of the body, including the lungs. So unfortunately, we don't have any antiviral or any prophylactic that will prevent that from happening. So when you treat a surface that has this virus, these particles of virus on it, you use a percentage of alcohol and all that. But in fact, some mouthwashers have alcohol in them. And I'm wondering if it helps it all once you think you've been exposed to the gargle with alcohol because the virus particles are in that part of your throat. And presumably that would break the lipid oil on the surface of the particles and make them inert. Does alcohol in the form of something you ingest, does that help? I don't know, Jay. I can't answer that question. I would guess that most of the mouthwash that you would use has a very low concentration of alcohol in it and probably wouldn't be preventive. But if it's alcohol, it might do some good. But I would doubt it. I wouldn't count on that. The best thing to do is decontaminate your surfaces and wash your hands good so you don't transfer it and do practice social distancing so you don't breathe it in. You can't be 100% protected, but you can decrease the probability. So right now there's nothing that stops it. And if we look at the researchers, try to figure out what they're after. And by the way, I've come to believe that there are researchers all over the world working on this, some really good people in the US and elsewhere in many labs and they are collaborating big time on the internet and they're sharing information, including the genome came from China and the like to try to figure out how to stop this thing. And maybe we'll have an early response on some kind of drug that will make the virus inert. But I just wonder if you have any idea what the direction of that research is. So you have the spikes on it. The spikes connect to a healthy cell. The spikes allow it to replicate. If you can diffuse the spikes somehow, then you can stop it from replicating. I mean, what is the theory of slowing this virus down biochemically? Well, there's a lot of different directions of research and you're correct that there are thousands of scientists all over the world working on this, but they're looking at two or three different areas of research. One is that you're talking about is an antiviral that could act either as a prophylactic or as a treatment after a person has been infected. And that antiviral could act in any number of ways, but the ultimate goal is to prevent replication of the virus and kill it before it's to the lungs, to the deep lung and causes severe disease. The spikes that you're talking about, those are, they have receptors that allow the virus to enter the cells. And the other line of research is to try and develop vaccines. One of the things that's been, that's in actually preliminary clinical trials is actually a peptide that blocks that receptor from, and prevents the cell, the virus from entering the cell. So there's a lot of different avenues of research that are being conducted. Probably more working on vaccines than there are on antivirals, but antiviral is a tough nut to crack. They're looking at a lot of old drugs that have been developed for other viruses or tested for other viruses. They've been in many people so that they're considered to be safe. Clarquin is one of these drugs that they've pulled off the shelf. It's an old malaria drug that a lot of physicians are claiming has some effect, but as Fauci points out in his briefings, there haven't been any clinical trials on this, so we really don't know how effective that drug is. It's more anecdotal work reports from physicians who are using it with individual patients or a small number of patients. And so there's no controls to actually show for the fact that it is efficacious. But there are a lot of old drugs out there that have been developed for other viruses and they're testing those. So hopefully some of those will show some promise and actually turn out to be a good antiviral for it. So there's a lot of research going on in that regard but don't hold your breath. We've been trying to develop an antiviral for the flavor viruses for 50 years, 30 years, and we still don't have one. It's not an easy thing to do to develop a... And the problem, part of our problem with both the drugs and the vaccines, Jay, is that we don't have a good animal model for a lot of them. And so it's difficult to measure the efficacy without going into humans and that's unethical in today's world. Well, you know, not that I really know anything about this but it strikes me just to integrate what I've seen on television and read in the papers is that we have the genome and once we have the genome, we can see how the RNA works and the various components and how it's set up. And once we know that, I think we do know that, then we can do gene splicing potentially. And gene splicing, of course, is very frontier and CRISPR is very frontier. But the idea would be to find a way to splice this RNA, to change the genome of the virus and to make it inert using, say, a bacteria which has the power to do that. Is there anything going on about that? What do you think about that as a possible line of investigation? Actually, it's a very, it's relatively new, not really new, but a new line of investigation. People are looking at it for a lot of different pathogens and it shows a lot of promise. I mean, there are ways of doing this but the problem you have with the virus like SARS-CoV-2 is it's new, we have the genome, we know what it is but to actually re-engineer it won't work because the wild virus is out there. It's all over the world now, truly all over the world. And so how will you, you need to develop something to protect against that old virus, not develop a new virus. And so I don't know that gene splicing is a good thing to do for this particular virus. Well, you know, in talking about the epidemiological side of this, yes, it is all over the world and I'm not clear on one thing, maybe you can help me, Duane, is that how many varieties of this are there? Because virus and mutation are almost synonymous, not only that the virus get created by mutation but the virus itself mutates. And if you compare the virus and say the US as a hotspot and Italy or Spain as a hotspot or Japan now as a hotspot, you're gonna find it's different but the virus may be similar, but it's not the same. And so what's happening is the virus is mutating while we watch, while the pandemic goes on. Am I right about that? I think you're right about that. Whether or not that would influence our ability to have a good antiviral or a vaccine against it. I don't know, no one knows at this point, but our experience with other viruses that have multiple subtypes, if you will, of the virus suggests that for flu example, that virus mutates and the vaccine that you develop this year is not truly effective next year. Flu is a rather special bug though because there's something like 144 different combinations of the hemagglutinin on those viruses that can change its genetics. We don't know how coronaviruses relate to that. We know that they probably mutate. We know from our experience with other viruses, those mutations can actually have a tremendous effect on phenotype expression, phenotypic expression, make them more or less virulent, make them attenuated in some cases, give them higher transmissibility, greater epidemic potential, if you will. So we don't know, it's too early in our knowledge of this virus. Give us a few years and we'll have a better idea of how frequently the mutations occur and what impact that those mutations have on the epidemiology and clinical expression of the viral. So there seem to be a couple of possibilities. One is the antibodies from people who have recovered and it reminds me of insulin, which was originally made with fetal pig material and you had to kill a lot of pigs to get the insulin, but then they found a way to make it artificially and all of a sudden we have insulin for everybody. So query, can we take antibodies, which, I mean, I'm not sure that it's actually effective, but can we take antibodies from people who have recovered and then make those antibodies artificial and then spread them around the world to have the same effect on large populations? That there's a very active area of research that's doing that very thing. You're talking about two different things here. You've read about the plasma treatment taking plasma from convalescent patients and using that, infusing that into patients. That's an old, old, old method that's been used for years and years. And in fact, at CDC we always used to keep anti-viral plasma against viruses that we didn't have any vaccines for and that was used for treatment when someone had a laboratory accident and accidentally infected themselves. So that's actually, I think, being tried right now with COVID-2 virus. The other is though to actually manufacture the antibodies that you can actually then use for therapeutic purposes. They're called therapeutic antibodies and these humanized monoclonal antibodies should be, could be very effective if we develop the right ones. Yes, and that's a very active area of research. I think there's one fellow in New Jersey or somewhere that's already developed a monoclonal antibody for COVID-2 and it's going into trials as we speak. And that would be synthetic rather than just taking it out of the plasma of a recovered patient. Yes. One other avenue I wanted to ask you about is, so now the virus gets into your lungs and it creates an inflammation, huge, huge inflammation in your lungs, which is so fragile. Both the oxygen exchange cells and the breathing cells are affected and the inflammation creates all kinds of, let's call it schmutz in your lungs and you drown and you can't breathe very well. So the question is, what can we do about this inflammation? This is the body's own immune system is what's killing the patient. So we have to moderate the body's own immune system. Are there drugs? Can there be drugs? Is there any research going on to minimize the inflammation and thus the immune reaction that is so damaging to the patient? You know, Jay, this is an area that I don't know a lot about, but I do know that cytokine storms that you're talking about that can influence that type of pneumonia. There's a lot of research going on and a lot of other diseases create cytokine storms as well. You know, the hydroxychloroquine that is given, one of the reasons they think it is effective, the ones that are using it, is that it's an anti-inflammatory drug and it reduces the inflammation in the lungs. And so it's an area of research. I have not read much about any progress in the area other than with hydroxychloroquine. Perhaps they're in some of these experimental therapies, they're combining HIV drugs with chloroquine and it seems to be effective, but whether they're anti-inflammatory or not, but the key is to reduce the inflammation, you're correct. We only have a couple of minutes left and I wanted to ask you about vaccines in general. You know, it's like a knee-jerk answer. You ask, how long is it gonna take to get a vaccine? And it's an optimistic thing because we're not sure we can get a vaccine, but let's assume that we have the talent, we have the resources, we have the scientific background to get a vaccine. It seems to me that a good part of the year or 18 months track of that effort is in the trials. And trials are a matter of finding patients or trial subjects who will tolerate it and then making close notes about how it works with them, whether it's efficacious, whether it's them, it's injurious in some way. But it sounds to me actually, and I think Bill Gates would agree, he's been very high profile on this, is that you have to use the best technology you can find and one of the technologies involved in trials is information technology, it's databases. So isn't it true, or my theory anyway, I'll bounce it off you, is that you can move faster on that 18 months. You can move faster on clinical trials if you can use AI or other high speed information technology. Wouldn't that shrink the amount of time it takes to develop a vaccine? I don't want to say no, but my gut feeling is no, it won't increase the time. The problem we have is that if you give an experimental vaccine, give a vaccine to an individual, it will take 30 days minimum for you to usually find out that it's immunogenicity. Does it actually produce the result in producing antibodies, anti-viral antibodies? But that's just the first step. Then the next step is you've got to follow that patient for probably at least a year to find out if the antibodies wane and become undetectable or not protective any longer. And this is all assuming that you've done the safety, phase one safety trials to make sure that it's a safe vaccine. But then you've got to follow that patient or those recipients for ideally for several years to find out if there's any adverse, long-term adverse effects. And if it actually prevents disease against the virus that you've produced it against. So I'm not sure. People say 18 months, yes, FDA can fast-track it and short-ticket it a lot of the, but you're dealing with the unknowns there because you don't know what the long-term effect of that vaccine is going to be. So the safe thing to do is to 18 months is I think if we have a vaccine in 18 months, I'll buy you up and I'll see you J.J. or more. A vaccine, go ahead, go ahead. No, I'm just in today's world with the IRBs and the human trials. You don't have, in the old days, we could do human trials. You could actually put the experimental vaccine or the candidate vaccine in humans and actually measure the effect. Can't do that anymore. We have to use animals and so there are just so many things that delay this process if we're gonna have a safe vaccine. And you know, and I know, you know this area as good as I do J. You're asking me all these questions, you know the answers to them. But you know, as well as I, if we put a vaccine developed in 18 months into people and then six months down the road or a year from now, some of the developed adverse events, whether it's a vaccine related or not, there's gonna be litigation out the Gazoo. And so you just have to, in today's world, we need to be a little more cautious. Yes. And I think back to your point about AI and models. One of the reasons we have the fear and the panic we've had driving this epidemic or a pandemic is the models, the models, you know, they project numbers that are out of this world and it scares people. And they're all magnitude or several magnitudes higher than the actual figures really are. So what we need to do is step back, do some good old basic epidemiology clinical and epidemiolab work and find out what this virus is doing and then start projecting. So, you know, just in the way of, I guess I'll use the word speculating, but speculating on the basis of, you know, all your knowledge of the subject, how do you see this unfolding? How do you see it coming to an end? I mean, because sometimes they correct me, but sometimes viruses, epidemics just come to an end all by themselves. They somehow end. How do you see this unfolding, you know, into the future? Not only in terms of the science, but in terms of the, you know, social and economic effect. Well, again, I will say I don't know, but I will speculate a little, I guess. I think number one, the case fatality rate's gonna be a lot lower than the models projected it would be. That being the case, I talked to Rob Kay here a month ago, I guess, and told him looking at the preliminary data, I would treat it like a severe flu and focus on mitigation in reducing transmission, i.e., social distancing, cough and hand hygiene, et cetera, all of the things that we know reduces exposure. And, you know, I think the impact that it's gonna have, if we lock down this country economically, the implications of light New York, it's gonna have a tremendous economic impact and it's gonna come back to what I projected 10 years ago in 2010 at this policy meeting that it's gonna threaten the economic security, not only in the country, but at the world. So, the public health act of the economic security to be worth the disease itself. So, I think we need to be very cautious about how we proceed. I think all of the evidence from China and from this country definitely suggests that the so-called things that we're doing, quarantine, self-quarantine, actually working and decreasing transmission, that decreases a lot on the healthcare system and we can manage that while maintaining, maybe not business as usual, but some business going on without shutting down the economy. I really think that we need to be cautious about shutting down the whole economy. Now, one thing about the coronavirus is we don't know whether it will just disappear like SARS did or whether it will become endemic like influenza is and come back year after year after year. We still don't know that. It's a highly transmissible, it seems to do well in humans, but keep in mind it's not a human parasite. It's a human disease, it's not a human parasite. It's a humans or unnatural hosts and unnatural hosts tend to get rid of these parasites unless it's really well adapted. So, it's going to take us a year or maybe longer before we know exactly what's going to happen to this. If our containment or our mitigation efforts are good we probably won't build the herd immunity that we need to stop the epidemic. It'll peter out itself. And here again comes back to your comment about mutations. We know that viruses mutate and those mutations sometimes reduce the virulence of the virus so that the viruses can go underground and we know that this virus can already be transmitted in asymptomatic cases. That's one mechanism that allows the virus to develop endomicity. So, bottom line, we don't know yet. Price of liberty is eternal vigilance, isn't it? Yes. Well, no, you know, we've been saying for years, people in my field, that we need to do a better job of surveillance. We need better laboratory-based surveillance. We need to set up pathogen discovery programs. This is what we did in Singapore and what we tried to do in Hawaii. Pathogen discovery programs that will allow us to detect, identify and contain these bugs before they get on airplanes and fly around the world. And that's desperately needed. If we had done that with this virus in February, we'd have had a much smaller problem on our hands today. Well, that takes me to one last question which I think I really need to ask you. And that is, where does testing fit in all of this? Have we done a good job? What can we do better? Is testing still relevant or is it beyond testing? How do you manage an epidemic, a pandemic using testing? You don't manage it using testing. You manage it using mitigation efforts. You use the testing to help you decide where best to apply those mitigation methods. You need good testing. This is what I see with the PCR test that has been to identify this. You know as well as I do, many of these tests will be false negatives or false positives. And the type of sample you take it, who takes that sample, where it's taken from, how it's processed after it's taken. And the technician doing the test all influence the results that you get. And drive-through testing, this is where public opinion is driving decision-making. I wouldn't bet the farm on the results of those drive-through tests. I've not seen any efforts to validate whether the tests are accurate or not. But testing plays a very big role in your surveillance system, Jay. You know that you've got to have reliable tests and you use those tests to know how much transmission is occurring and where it's occurring so that you can target your control efforts appropriately. So testing plays a critical role. But going on testing everybody in the country doesn't help a whole lot. Well, I've become aware that there's two kinds of tests for coronavirus. One is the PCR and the other is the antibody test. And they both give you a different view of what's happening in this patient. And I wonder if it's possible to put them both together and use both of those testing technologies in the same test and get a better handle on what we really have at a given patient? The answer is yes. The answer is yes. And we need to get to know the virus a lot better. But for a lot of viruses, we have combined tests like that where you actually monitor certain antigens that are associated with viremia with the virus. And the other component of it measures the antibody. And primarily IgM antibody because it's an antibody that comes up fairly fast and is protective. And so you have a combined antigen antibody test and you can use it. You can actually use it in point of care. But the problem is, I know that my group in Singapore have developed an antibody test early on. They've been using it now for a month. And I understand CDC and some of the other companies have developed antibody tests too. But my guess is they're focusing on point of care tests and those are usually lateral flow tests which have a very poor sensitivity and asbestosity. I don't know how good they are. The key is to validate these tests before you spend a billion dollars on that basis. The results, same as models, you need to validate them before you make major policy decisions. Ever think about coming back into the fray? You know, you can retire a fourth time when it's over. Well, I get probably two or three invitations a week to get back in the fray. But, you know, I'm 81 years old, Jay. You know, these days you're going to watch out. And my wife thinks I ought to settle down a little bit. Well, thank you, Duane. Duane Goebbler, a researcher par excellence, a global research infectious disease closely connected with Hawaii. Thank you so much. I really appreciate your discussion and all the points that you've helped us with. Aloha. Thank you.