Dmitry Korkin: Computational Biology of Coronavirus | Lex Fridman Podcast #90

The following is a conversation with Dmitry Korkin. He's a professor of bioinformatics and computational biology at WPI Worcester Polytechnic Institute, where he specializes in bioinformatics of complex diseases, computational genomics, systems biology, and biomedical data analytics. I came across Dmitri's work when, in February, his group used the viral genome of the COVID 19 to reconstruct the 3D structure of its major viral proteins and their interaction with the human proteins, in effect creating a structural genomics map of the coronavirus and making this data open and available to researchers everywhere. We talked about the biology of COVID 19, SARS, and viruses in general, and how computational methods can help us understand their structure and function in order to develop antiviral drugs and vaccines. This conversation was recorded recently in the time of the coronavirus pandemic. For everyone feeling the medical, psychological, and financial burden of this crisis, I'm sending love your way. Stay strong. We're in this together. We'll beat this thing. This is the Artificial Intelligence Podcast. If you enjoy it, subscribe on YouTube, review it with five stars on Apple Podcast, support it on Patreon, or simply connect with me on Twitter lexfriedman spelled F R I D M A n this show is presented by Cash App, the number one finance app in the App Store. When you get it, use code Lex Podcast Cash App lets you send money to friends, buy Bitcoin, and invest in the stock market with as little as $1. Since Cash App allows you to buy Bitcoin, let me mention that cryptocurrency in the context of the history of money is fascinating. I recommend Ascent of Money as a great book on this history. Debits and credits on ledgers started around 30,000 years ago, the US dollar created over 200 years ago, and Bitcoin and the first decentralized cryptocurrency released just over 10 years ago. So given that history, cryptocurrency is still very much in its early days of development, but is still aiming to and just might redefine the nature of money. So again, if you get Cash App from the App Store, Google Play and use the code LEXPodcast, you get $10. And Cash App will also donate $10 to first, an organization that is helping to advance robotics and STEM education for young people around the world. And now, here's my conversation with Dimitri Korkin. Do you find viruses terrifying or fascinating?

When I think about viruses, I think about them. I mean, I imagine them as those villains that do their work so perfectly. Well. That's that is impossible. Not to be fascinated with them.

So what do you imagine when you think about a virus? Do you imagine the individual sort of these hundred nanometer particle things, or do you imagine the whole pandemic, like society level, when you say the efficiency at which they do their work, do you think of viruses as the millions that occupy a human body or a living organism, society level, like spreading as a pandemic, or do you think of the individual little guy?

Yes, this is, I think this is a unique, a unique concept that allows you to move from micro scale to the macro scale. Right. So the virus itself, I mean, it's not a living organism, it's a machine. To me, it's a machine, but it is perfected to the way that it essentially has a limited number of functions. It needs to do necessary functions and essentially has enough information just to do those functions, as well as the ability to modify itself. So, you know, it's a machine, it's an intelligent machine.

So, yeah, maybe on that point you're in danger of reducing the power of this thing by calling it a machine. Right. But you now mentioned that it's also possibly intelligent. It seems that there is these elements of brilliance that a virus has of intelligence, of maximizing so many things about its behavior and to ensure its survival and it's, and its success. So do you see it as intelligent?

So, you know, I think the, it's a different, I understand it differently than, you know, I think about, you know, intelligence over humankind or intelligence of, of the, of the, you know, of the artificial intelligence mechanisms. I think the intelligence of a virus is in its simplicity, the ability to do so much with so little material and information. But also, I think it's interesting, it keeps me thinking, it keeps me wondering whether or not. But it's also an example of the basic swarm intelligence where essentially the viruses act as the whole and they're extremely efficient in that.

So what do you attribute the incredible simplicity and the efficiency to? Is it the evolutionary process? So maybe another way to ask that. If you look at the next hundred years, are you more worried about the natural pandemics or the engineered pandemics? So how hard is it to build a virus?

Yes, it's, it's a very, very interesting question because obviously there's a lot of conversations about the, you know, whether we are capable of engineering an even worse virus. I personally expect and am mostly concerned with the naturally occurring viruses simply because we keep seeing that. We keep seeing new strains of influenza emerging, some of them becoming pandemic. We keep seeing new Strains of coronaviruses emerging. This is a natural process and I think this is why it's so powerful. You know, if you ask me, you know, did. I've read papers about scientists trying to study the capacity of the modern, you know, biotechnology to alter the viruses. But I hope that it won't be our main concern in the near future.

What do you mean by hope?

Well, if you look back and look at the history of the most dangerous viruses, right, so the first thing that comes into mind is smallpox. So right now there is perhaps a handful of places where the strains of this virus are stored. Right. So this is essentially the effort of the whole society to limit the access to those viruses.

You mean in the lab, in the controlled environment in order to study. And then smallpox is one of the viruses for which should be stated there's a vaccine is developed.

Yes, yes. And it's, you know, it's until 70s. It, I mean in my opinion it was perhaps the most dangerous thing that was there.

Is that a very different virus than, than the influenza and the coronaviruses?

It is, it is different in several aspects. Biologically it's, you know, so called double stranded DNA virus, but also in the way that it is much more contagious. So the R naught for. So this is, this is the.

What's R naught?

R naught is essentially an average number as person infected by the virus can spread to other people. So then the average number of people that he or she can spread it to. And there is still some discussion about the estimates of the current virus. The estimations vary between 1.5 and 3. In case of smallpox it was 5 to 7. And we're talking about the exponential growth. Right. So, so that's, that's a very big difference. It's not the most contagious one. Measles for example, It's I think 15 and up. So, so it's, it's, you know, but it's definitely, definitely more contagious that the seasonal flu than the current coronavirus or SARS for that matter.

What makes the virus more contagious? I'm sure there's a lot of variables that come into play, but is it that whole discussion of aerosol and the size of droplets if it's airborne or is there some other stuff that's more biology?

I mean there are a lot of components and there are biological components that there are also, you know, social components. The ability of the virus to, you know, so the ways in which the virus is spread is definitely one. The ability to virus to stay on the surfaces, to survive, the ability of the virus to replicate fast or so.

You know, once it's in the cell.

Or whatever, once it's inside the host. And interestingly enough, something that I think we didn't pay that much attention to is the incubation period, the where, you know, hosts are symptomatic. And now it turns out that another thing that we one really needs to take into account the percentage of the asymptomatic population because those people still shed this virus and still are, you know, they still are contagious.

I saw there's an. The Iceland study, which I think is probably the most impressive size wise, shows 50% asymptomatic for this virus. I also recently learned the. The swine flu is like the. Just the number of people who got infected was in the billions. It was some crazy number. It was like, it was like, like 20% of the pop, 30 of the population, something crazy like that. So the lucky thing there is the fatality rate is low. But the fact that a virus can just take over an entire population so quickly.

Yes, it's terrifying, I think. I mean, this is, you know, that's perhaps my favorite example of a butterfly effect because it's really, I mean, it's even tinier than a butterfly. And look at, you know, and with, you know, if you think about it, right, so it used to be in those bat species and perhaps because of a couple of small changes in the viral genome, it first had become capable of jumping from bats to human, and then it became capable of jumping from human to human. So this is, I mean, it's not even the size of a virus. It's the size of several, you know, several atoms or a few atoms. And all of a sudden this change has such a major impact.

So is that a mutation like on a single virus? Is that like. So if we talk about those, the flap of a butterfly wing, like what's the first flap?

Well, I think this is the mutations that make that made this virus capable of jumping from bad species to human. Of course, the scientists are still trying to find, I mean, they're still even trying to find who was the first infected, right? The patient zero, the first human. The first human infected. Right. I mean, the fact that there are coronaviruses, different strains of coronaviruses in various bat species, I mean, we know that. So we, you know, virologists observe them, they study them, they look at their genomic sequences. They are trying, of course, to understand what make these viruses to jump from bats to Human there was, you know, similar to that in influenza. There was, I think a few years ago there was this, you know, interesting story where several groups of scientists studying influenza virus essentially, you know, made experiments to show that this virus can jump from one species to another, you know, by changing, I think just a couple of residues. And, and, and of course it was very controversial. I think there was a moratorium on this study for a while, but then the study was released, it was published.

So that why was there a moratorium is because it shows through engineering it, through modifying it, you can make a jump.

Yes, yes, I, I personally think it is important to study this. I mean we should be informed, we should try to understand as much as possible in order to prevent it.

But so then the engineering aspect there is. Can't you then just start searching because there's so many strands of viruses out there. Can't you just search for the ones in bats that are the deadliest from the virologist perspective and then just try to engineer, try to see how to. But see that's there's a nice aspect to it. The really nice thing about engineering viruses, it has the same problem as nuclear weapons is it's hard for it to not delete to mutual self destruction. So you can't control a virus, it can't be used as a weapon. Right.

Yeah, that's why I, you know, in the beginning I said, you know, I, I'm hopeful because that definitely there definitely regulations to be needed to be introduced and I mean as the scientific society is, we are in charge of, you know, making the right actions, making the right decisions. But I think we will benefit tremendously by understanding the mechanisms by which the virus can jump, by which the virus can become more dangerous to humans. Because all these answers would eventually lead to designing better vaccines, hopefully universal vaccines and that would be triumph of the, of science.

So what's the universal vaccine? So is that something that, well, how universal is universal?

Well, I mean, you know, so what's the dream?

I guess because you kind of mentioned the dream of this, I would be.

Extremely happy if you know, we designed the vaccine that is able. I mean, I'll give you an example. Right. So. So every year we do a seasonal flu shot. The reason we do it is because we are in the arms race. Our vaccines are in the arms race with constantly changing virus. Now if the next influenza pandemic will occur, most likely this vaccine would not save us. Right. Although it's the same virus, might be different strain. So if we're able to essentially Design a vaccine against influenza A virus, no matter what's the strain, no matter which species did it jump from. That would be, I think that would be a huge, huge progress and advancement.

You mentioned smallpox until the 70s. Might have been something that you would be worried the most about. What about these days? Well, we're sitting here in the middle of a COVID 19 pandemic, but these days, nevertheless, what is your biggest worry, virus wise? What are you keeping your eye out on?

It looks like. And you know, based on the past several years of the, of the new viruses emerging, I think we're still dealing with different types of influence. I mean, so, so the H7 and 9 avian flu that was, that emerged I think a couple of years ago in China, I think the mortality rate was incredible. I mean it was, you know, I think above 30%. You know, so this is, this is huge. I mean, luckily for us, this strain was not pandemic, right? So it was jumping from birds to human, but I don't think it was actually transmittable between the humans. And this is actually a very interesting question which scientists try to understand, right? So the balance, the delicate balance between the virus being very contagious, right? So efficient in spreading and virus to be very pathogenic, you know, causing, you know, harms, you know, and deaths to, to the horse. So it looks like that the more pathogenic the virus is, the less contagious it is.

Is that a property of biology or what is it? What is?

I, I don't have an answer to that. And I, I think this is, this is still an open question. But you know, if you look at, you know, with the coronavirus, for example, if you look at, you know, the, the deadlier relative mers. MERS was never a pandemic virus.

Right?

But the, you know, the, again, the, the mortality rate from MERS is far above, you know, I think 20 or 30%. So.

So whatever is making this all happen doesn't want us dead because it's balancing out nicely. I mean, how do you explain that we're not dead yet? Because there's so many viruses and they're so good at what they do. Why do they keep us alive?

I mean, we also have a lot of protection, right? So with the immune system. And so, I mean, we do have, you know, ways to fight against those viruses. And I think with the now we're much better equipped, right? So with the discoveries of vaccines and you know, there are vaccines against the viruses that maybe 200 years ago would wipe us out completely. But because of these vaccines, we are actually, we are capable of eradicating pretty much fully, as is the case with smallpox.

So if we could, can we go to the basics, a little bit of the biology of the virus? How does a virus infect the body?

So I think there are some key steps that the virus needs to perform. And of course, the first one, the viral particle needs to get attached to the host cell. In the case of coronavirus, there is a lot of evidence that it actually interacts in the same way as the SARS coronavirus. So it gets attached to AC2, human receptor. And so there is, I mean, as we speak, there is a growing number of papers suggesting it. Moreover, most recent, I think most recent results suggest that this virus attaches more efficiently to this human receptor than sars.

So just to sort of back off. So there is a family of viruses, the coronaviruses and sars, whatever the heck forgot this respiratory, whatever that stands for.

So SARS actually stands for the disease that you get is the syndrome of acute respiratory syndrome.