Too early to ease up on lockdowns – Yale microbiologist

SS: But if it were up to you, let's say, you're in charge, you're head of WHO or you are president of one big country. When would you say it's time to sort of ease up on lockdown? 

PT: My preference would be, if we could, to ease up on the lockdown after two to three more months. If we embrace the need to continue to not mix in large groups the way we had become accustomed to in so many years, not to do as much travel around the world as we had done in prior years, we know this is going to help. I mean, it’s fundamental epidemiology. There's no huge mystery that this would help as we continue to grapple with the problem. So the issue is can others afford to be as patient as I seem to be willing to be this patient? And the answer is clearly no. And that's why this is an issue - how quickly can we go forward as well as how prudently can we wait? 

SS: So, WHO earlier said no reason to believe that the pandemic will come to a close in summer but Russia’s health authorities, for instance, they're saying that the virus becomes non-infectious at air temperature over 30 degrees Celsius. What's your view? Do you support the view that hot summer days made COVID-19 lose its grip on us? 

PT: My view based on the evidence that I've seen is that we would probably be fortunate this summer, in any places experiencing warmer climates, we're going to be benefited by this probably with reduced transmission. And it's important that I answered you with a “probably” because of course, we don't know, we are dealing with a new problem. However, I have to say, based on the evidence that I've seen, the experts who I've heard from, the literature that I've read is that we should benefit from this. So the idea of moving forward and opening, reopening prudently with the expectation that we're going to get the benefit of reduced transmission, I think, is a real possibility. And that would be my hope that we navigate that properly. 

SS: But are you on board with those who say that yeah, we'll probably beat it at the end of the summer, but come on, as the temperatures drop, we are going to be bracing the second wave? Do you agree with that, or we could actually not be having the second wave?  

PT: I agree with that because we don't know yet how much of the benefit of herd immunity is going to kick in. I know you've discussed that earlier on your show with experts. So if we do benefit from herd immunity, helping to reduce and cut off the chains of transmission so that people who have never seen the virus before won't be as likely to be infected by it because the chains of transmission will be broken, then in that case, we would benefit from the herd immunity kicking in around the time that we would expect the cold time seasonality to also be problematic. So I try to be an optimist. But I also believe the data and I read as many of the papers as I can, and I'm cautiously optimistic that we're going to get some benefits from herd immunity, that we're going to get some benefits from the summertime seasonality and reduce transmission before the inevitable return in the colder months. 

SS: So the new coronavirus shares 96% of its genome to a bat coronavirus discovered in China in 2013. And this virus was considered low-risk and nobody really thought back then that it could mutate, transmit to humans, cause a pandemic like this. You study the ways viruses adapt and evolve. So tell me, is there no way at all to predict how a virus can mutate? 

PT: I think there are ways to predict how a virus can mutate, there are ways to predict how it can evolve. And it seems like an insurmountable, very difficult problem. But it's more about which of the genes that are most important for that virus as it evolves and sees a new host. That's the thing that we can key in on. And I'm not revealing some mystery, other people think this as well. But what it shows is that evolution is very hard to predict, especially from the point of organismal interactions. So you now have a virus that’s entering a new host of humans. We don't know enough about our own immunity reaction to this virus. We don't know enough about its interactions with immunity and reservoir hosts such as bats. So I think what's emerging now, not to use that term too lightly, but what's emerging is that we need a lot more study of virus host interactions in wild animals to get a greater understanding of how that biology works. I think that would allow us to make a better prediction about how any virus that could emerge in humans would interact with us. 

SS: But then it's not just bats. It's like other animals too, who are potentially, you know, sort of places viruses can spread out too, right? So should we be studying all of the animals that are potential hosts to dangerous, risky viruses to us, humans?  

PT: I love that question because it recognises the scope of the problem. I think you, you may know this, your listeners may know this, essentially we live in a world of viruses, they are the most common thing on this planet. They affect all cellular life, including humans, as well as all the animals that live on the planet. So it's pretty much impossible to do a blanket surveillance in all that biology. We can't figure it all out, but we can key in on the species that seemed to be the most prone for us encountering them in the wild, for us eating them as food, that's out in the wild. So this is what's going to happen in the next few years, for sure, to the next decade, is going to see a lot more basic research on these interactions that humans have with wild animals. what we consume for food. It's a big task, but I think we are up for it. There are a lot of people who study virology of other organisms, not just in humans. And that's really what we're talking about here. How viruses work for their interactions with organisms that are not humans. What can we predict about, what would occur when they jump into humans? 

SS: So I was talking to a very young Russian virologist a couple of days ago, and he was sort of proposing the same idea as you. He was saying, you know, like, out of all the viruses that are out there and potential viruses and they can be hundreds of thousands, we only know about 6000 and then out of those 6000, like, 3 or 4 are plant-based viruses. So if we were to get a database of all the known viruses and study them that would really help us go forward with, you know, coming up with medication and coming up with vaccines and all that. So if that were to happen, how long would that take that you actually study all the potential viruses that, we know, are out there?  

PT: Well, great question. I think unfortunately to study all the viruses that are out there would take centuries potentially, unless our methods for studying them improve radically in terms of the high throughput ability to do it. A better way to go in my opinion is to key in on specific virus families. So we know with сoronavirus it’s been problematic. We were a bit complacent about MERS coronavirus, SARS coronavirus 1, other coronavirus issues that have happened in this century. And we were a little late to that game. We worry a lot about flu and understandably so. But now so much attention is going to be paid to coronavirus. The key is what else is out there. There's certainly other viruses that might have variants, particular species. They're in some family of viruses that we consider to be benign for humans, that we see very easy ones to protect ourselves against. But what if we don't? And this is the problem with studying pandemics, you don't know until you know, it's easier to be reactive and proactive. But I hope that we're entering a new Renaissance here. I don't think we need any more evidence to show us that this is a vitally important problem.  

SS: Okay, so if we talk about coronavirus and because this is the burning question now, and from what we know there are around 30 types of coronavirus known to us, would you say it is more important to work on a universal vaccine that would actually be a vaccine to all of those 30 coronaviruses? Or should we be working for a vaccine that is fitted to each one of them? 

PT: I think currently the goal is probably for those who are chasing the vaccine to work against this coronavirus. And the reason is that we are fortunate in seeing that it's not changing very much at the genetic level over time. It's not like the flu problem when we have to really come up with a new vaccine each flu season because the virus is changing so quickly. And what worries me about a universal vaccine against all coronaviruses is that universal vaccines are just so difficult to establish and prove that they have safety and efficacy across that big group. That's a tall order. I worry about that as the goal and a more realistic goal would be a vaccine targeting this current coronavirus problem that doesn't seem to be changing very quickly. We will face the issue of waning immunity and I'm sure you've heard of that and others have as well as we have no evidence yet that if somebody is infected with this current coronavirus and that they recover from it, that they're protected long-term through immunity. If they were, that would be wonderful. But there's just no evidence to show that in my opinion at this point. So we will be faced with perhaps taking the vaccine and then getting it again just to boost immunity. But I don't think we're at the point right now, where the strategies point to create a universal vaccine against all coronaviruses. Fortunately, the other ones that infect us are very benign. 

SS: Alright, so I'm sure you’ve heard of that TED talk that Bill Gates gave in 2015. Everyone's talking about it right now. It was about how unprepared humanity was for an epidemic following the Ebola outbreak. And he actually proposed dealing with future viruses like we deal with wars - have an anti-germ force on stand-by, train them, have infrastructure in place, constantly train and practice the response, and then none of that happened after Ebola. But would we be able to see something like that after this pandemic? 

PT: Yeah, I think that that's very likely is that the global economic problem resulting from this, I think, unfortunately is as big or a big driver as the health issue. So very many people are unfortunately getting sick and dying, and yet, we don't even know the extent of the global economy problems that have resulted from this pandemic. So what Bill Gates and others might be putting forward, I think it's a prudent idea that should be taken seriously. Prepare ourselves for the future, we know this is going to happen again. We're very population-dense in many areas species, we're highly vulnerable to this from just fundamental basic epidemiology with what one should expect to occur occasionally, and we certainly could be better prepared about it in the future. Working towards that is just a terrific goal. I definitely applaud that effort or that idea. 

SS: Just really quickly, I don't want to go too deep into that, but what do you make of the possible idea of immunity passports that some countries are touting? 

PT: I think that we have probably sufficient technology that we could pull it off. I worry that it's going to contribute to a lot of what we already see in the world as “haves” and “have nots”, who has access to move around the planet. From an economic standpoint, that's clearly the case. Not everybody can travel as easily, either because they can't have the time to move away from their job or just to take a vacation, etc. There's all sorts of restrictions to that. Adding a layer of restriction to it sounds like a pretty daunting and not a very fun way to move forward. And at the same time, I'm a realist. So if there's a shorter period of time when I feel humans may have inconvenience for a good purpose, this seems like one of those times. And if there has to be a reduced ability to just move freely around the planet and if we're better able to track who has been exposed to the virus, who's recovered from it, I can't say that that's a bad idea. 

SS: Alright, back to science. So I've heard that some genes that we find in humans are remnants of viruses of generations and generations ago. So our genome sort of remembers how to fight certain infections, and then we as species grow more resistant over time. And then it got me thinking, how come some people go through chickenpox and then their kids go through chickenpox as well? 

PT: So, this is the interesting thing about interactions between humans and certain pathogens. So you said many things that are very intriguing in your statement. One is that you see in genomes, the ghosts of infection past. So the long, long ago evolution of our predecessors on this planet if they were interacting with viruses and being infected, and if those viruses got into what's called the germline, so if they are passed from generation to generation through gametes, then they become part of our genome. And that's what we can recognise clearly when you do human genome sequencing. Interestingly, some of those genes do us a lot of beneficial good. So part of it, for example, leads to proper formation of placenta and the inability of the mother to reject the child as something that seems like it's a parasite growing within the human body. It's very intriguing that that's a viral gene that allows that interaction to work well in all placental mammals. But now, let's go fast forward to more of the current day. Yes, there are virus genes that might be in our genome that help us in a way express these genes and prevent us from being attacked by other viruses as vigorously. So I take your questions to mean, if we fast forward ahead to many hundreds of years or thousands of years into the future, the viruses of today are shaping the evolution of the future. Definitely the case. And the ways that happens, very unclear. I don't think we have a great roadmap to see how that happens. We're still trying to decipher how it occurred in the past and is undoubtedly happening in the current day. 

SS: I guess also, what I was trying to ask is that have our immune systems evolved too well over time and become too good so that viruses now have to develop new mutations to get inside us? 

PT: Oh, I see. Yes, that's that's an intriguing question. So the immune system to me is fascinating. And I should say, very transparently, I'm not an immunologist. But I try to read up on the topic as much as I can and talk to other immunologists. So the interesting thing of immunology, it's one of the few things that to me reflects increased complexity over time and evolution. So evolution doesn't always have this path and increasing complexity. And there's plenty of single celled organisms around today that were around billions of years ago, for example, and they're doing quite well, thank you. But the point is that an increasingly complex system is prone to break down and breaks in the armor. So the thing about immune response to some pathogens in ways that we don't entirely know, they could be too vigorous, right? You're seeing this in the current pandemic, some individuals are being infected and their immune systems are, in a way seemingly overreacting to the problem, creating a worst problem, maybe hastening it becoming a mortality issue. And I don't think that this is very well understood, but it's certainly very real. So what I'm getting at is the unfortunate consequence of an increasingly complex immune system is that yes, it creates vulnerabilities because it is a complex immune system. It works very well to protect this and I'm very happy I have it. But at the same time, this is the root cause of autoimmunity. The misfiring the immune system to solve problems can actually turn the immune system on you and even cause worse problems as a result. I think that's what you were getting at. But please let me know that's not the case. 

SS: Yeah, I know that you've also said that viruses are immensely diverse and plentiful on our planet, so we could be infected with a ton of different viruses and serve as a host to them and never even be aware of it, and that we also see with coronavirus. I mean, some people are asymptomatic. They don't even know they have Corona, COVID-19. So, put aside COVID-19, are most viruses harmless to humans? 

PT: They're either harmless to humans, or we amount enough of what's called an innate immune barrier to them, that we don't even have to wait for antibodies to kick in. We just have barriers against the infection and there's lots of ways that that's built in to the genome. So the kind of a 30,000-foot level way for me to answer your question is it is a bit like swimming in a sea of viruses on this planet. They're in the air we breathe the water, we drink the food we eat. And by and large, a lot of them are incapable of infecting ourselves. But interestingly, some of them will pass right through you. So they could be infecting plant matter and you eat salad, and you ingest the plant virus and it exits the other end, and it could go on and infect a plant after that. So fortunately, we never know when some viruses enter and leave our body because they do absolutely no harm or we fight them off successfully. And the ones we do care about are at the so-called top of what's been referred to as a pathogen pyramid. At the base of the pyramid are very many microbes, including pathogens that you see every day, as you march upwards. You know, as you traverse the top of this pyramid, you eventually get to those that are of epidemic potential or pandemic potential and they get the most attention, deservedly so, and the unfortunate consequences that we pay so much attention to them. For all we know, coronaviruses might be interacting with other viruses that are already in some people in some way, either directly or indirectly, and this might be a clue to why the coronavirus might be especially deadly in that person. So that's in the realm of what you call polymicrobial disease. That's a big phrase just to say multiple microbes contributing to disease. And I would have to say that that's a very understudied problem, because it's a difficult problem to study. It's not as if scientists have ignored it. It's just a difficult one to grapple with. Because you just have a variety of data to sift through there. What's making him sick versus her sick could be due to some virus that's lurking in there that has not been described at all in science. So I think we need to march forward in those efforts as well. The secondary infections that come in with coronavirus, even non-viral bacterial infections that seem to be contributing to secondary pneumonias and death in some individuals, this really has to be examined from a polymicrobial effort. 

SS: Do we know of any essential viruses that live in us that are important and actually good for our well-being kind of like “good bacteria - bad bacteria”? 

Well, maybe. So the residents of our microbiome are diverse, and it includes viruses. And that's sometimes referred to as the virome. So just like the microbiome, and most people have heard about it and are familiar with it, different parts of your body, you have different types of viruses that are characteristics or residing in that part of your body. And exactly what they're doing there is not quite clear. Are they so-called free-riders? Are they just there and we don't have any benefit or detriment to having them there? Are they interacting in some circumstances with the residents of our microbiome to synergistically keep us healthy? I think that's plausible. I don't know of any very strong direct evidence for it, but I like your question, because that's also a great one for future effort. The virome has not been as well characterized from person to person in interaction with things that we do every day, like our diet. How much does a vegetarian diet versus a non-vegetarian diet contribute to your virome? I mean, it might just because anything seems to be plausible these days with microbiomes. So I think I don't have a strong, definitive answer for you yet, because I don't believe science has found a definitive answer for you yet. The positive versus negative consequences of interacting with these viruses that are with us every single day is a great possibility for future work. 

SS: So when a virus makes it into the body it sort of hijacks cells to replicate and you've been experimenting with luring the virus into the wrong type of cells that wouldn't sustain the virus to the extent that it would eventually die out before doing substantial harm. Could this technology work with COVID-19? 

PT: Interesting question. Yes, we looked into this with HIV infection and could you develop cheaper in a way HIV approaches to... So let me back up. Somebody who is infected with HIV is typically never cured. They are simply, at best, we can create antiviral combinations that keep the load of virus down in their body for them to live a long life without the viral load increasing to a point that they become an AIDS patient. So the point is, yes, we looked into this idea if you could take some cell type in the body that is less precious than your immune cells, such as your blood cells, could you decorate with something that would attract HIV to infect those cells instead? In the case of HIV, that might be a good strategy because there's no nucleus in red blood cells. So therefore, there's no way for HIV to enter that cell and actually replicate. There's no machinery to hijack, because there's no DNA in the nucleus. So that was a fun project to work on. We moved it along, we didn't advance that research very much. But I think that you’re raising this issue... The time that we're living in right now, I believe, is a special time. We look back on it when it seemed as if far out there leftfield, so to speak, ideas were a little too much for biomedicine. But now that we're scrambling to find ways to solve the pandemic. In a way, I wonder if we're going to enter into a time when there's a little more openness within the realms of safety, to examine ideas that are pretty atypical ones for biomedicine. Can we bridge into engineering principles, other realms of science biology to come up with? You know, is this really an idea that might be a game changer? And if we put a little bit of effort towards doing it over several months or a year, we might just develop something that is so new to the world and to biomedicine that there will be a major transition. And to me, that is my hope, is that once we deal with this problem and we get to the other side of it, whatever the other side may be, is that will really tread safely, mind you with some very out-of-the-box thinking with what we might do to solve human biomedical problems. 

SS: Oh Paul,I hope we humans get the chance to see this out-of-the-box things that could be so new but amazing for the whole humanity. Thank you very much for this wonderful interview, for this insight. I wish you all the best. Stay safe and hopefully we'll talk soon again, when times are better, when the pandemic is over. 

PT: Thank you for having me. I appreciate it. 

SS: Thank you so much. Bye