Yale researcher studies viruses ‘For the good they can do’
Paul Turner thinks viruses are cool. That’s not the common opinion, of course, at least not right now.
But his work at Yale is about finding ways to put viruses to work for us using phage therapy, an alternative to traditional antibiotic treatment.
In his Turner Lab, researchers study how, and where, viruses live in the wild, and how they make the jump from animals to people, as the current coronavirus has.
Turner talked to me as part of a series of conversations about understanding coronavirus for the CT Mirror podcast, “Steady Habits.”
Here is an edited excerpt of that conversation about how viruses work for, and against, humans.
Dr. Paul Turner: A lot of my interests are in “how do viruses overcome environmental challenges to evolve and adapt?” And so my interests have definitely included the emergence problem that we’re seeing right now. How is it that viruses can be in one host and then jump successfully into another host, especially humans? A lot of my work in that area has been done more generally through laboratory research, using models of viruses that could be harmful.
In other words, doing very safe research in the lab and not dabbling in emergence itself, but trying to understand how mutationally this happens, what environmental drivers caused it to happen. And that’s one aspect of my work that relates to the current pandemic.
The other work that I do that relates to what’s going on now is that we look at viruses for the good that they can do. And hang with me for a moment, because this is not a time to be talking about viruses doing good work and have people believe it. But there’s some viruses out there that are specific to bacteria. And when those bacteria infect humans, often we have antibiotics that simply don’t work anymore. So I’ve been working on something called phage therapy, where we take these viruses called bacteriophages or phages for short and we actually put them into emergency cases of lung infections of people who have antibiotic resistant bacteria chronically infecting the lung, especially in cystic fibrosis patients. And we’ve been doing this very effectively.
The way that relates to the current crisis is that some of these Covid-19 patients have viral pneumonia, understandably, but they may suffer mortality from a secondary bacterial pneumonia that comes in and infects the lung tissue because they’re so vulnerable. In those circumstances, we just started working on how could you find viruses that kill those bacteria that come in and eradicate them from the lungs of Covid-19 patients so that they don’t end up succumbing to the secondary bacterial pneumonia, which could be deadly to them, especially in those who are immune compromised or have other lung problems like cystic fibrosis, like chronic obstructive pulmonary disease, bronchiectasis, etc.
John Dankosky: So a viral therapy for a bacterial infection that may be related to a different type of viral infection?
PT: That’s correct.
JD: Do you and your colleagues think about some potential unintended consequences about the way in which we are attacking coronavirus? Something that may result through the evolution of this virus over time?
PT: It’s so hard to gain this perspective of the long view when we’re dealing with the crisis at the moment. Right? That’s just a hard thing for humans to grapple with.
I just don’t know of another comparable problem this large at all for what we’re seeing with the asymptomatic side. So the problem with a virus that’s spreading and emerging is your inability to know who’s already infected – I don’t think we’ve been challenged with anything similar to that. If you get the flu, you know it … because it is very debilitating and you can’t really get out of bed. And there’s very classic symptoms that are associated with it. And SARS-2 (Covid-19 or SARS-CoV-2) is just not that. I mean, you can have that in people or you can have those walking around not even knowing they’re infected.
It’s so hard to gain this perspective of the long view when we’re dealing with the crisis at the moment. Right? That’s just a hard thing for humans to grapple with.”
So it’s just very, very difficult. And the challenge that we’re seeing that I wish we could wave the magic wand is we figure out very quickly through an immediate, reliable test who’s actually infected and then sequester away those who should be put in quarantine.
The question is what, if any, response would there be in the virus to the lengthening of time between transmission events? In other words, if you’re preventing the virus from jumping into the next host by separating people and lengthening that transmission time, what is the consequence? Classically, the thought is that it should help select for that virus to evolve, to be less virulent because its current host will matter more. It doesn’t have the luxury of jumping into the next host and sort of burning through its current host, perhaps killing that current host and moving on to the next individual.
There will be a natural tendency for selection to push the virus to be less debilitating to its current host because we’ve broken this easy chain of transmission.
JD: I’m wondering if you could go back and talk a bit about the work that you’ve done about viruses jumping from one host to another, especially from animals into people.
PT: Yes. So my lab and my interests have centered for a long time on something that is talked about in ecology and evolution as, “what is it that makes an organism specialized versus generalized?” And in the sense of a virus, there are lots of viruses out there that are just highly specialized to their host and they’re not very predisposed to move to a new host.
As a prime example, there is the smallpox virus, Variola virus. So this was eradicated from humans with a worldwide vaccine campaign quite a while ago now. And what we benefited from is that there was no order for the virus to hide. It wasn’t as if it was going to move back into some reservoir species living in the wild and then spill back into humans. As soon as we – with a lot of effort – moved it out of the human host, it had nowhere to go.
I’m wondering if you could go back and talk a bit about the work that you’ve done about viruses jumping from one host to another, especially from animals into people.”
And this is not what we’re dealing with with coronavirus. (There) is a very poor understanding of where they reside out there in the wild to spill back into the human population. But more to your question, if one understands that a generalized virus that is already existing in other species like a bat or wild fowl, waterfowl, et cetera, there’s probably something that predisposes it to do that. And humans are just one more host, unfortunately, on the menu.
And if they get into our species, then it might be very easy for them to continue to infect more humans. So the goal in that kind of research is to find the generalities that allow a virus to do this.
I’ve had some success in working with our fabulous immunologists here at Yale. We talk a lot about vaccines, the ability for developing a vaccine to withstand a virus that’s spreading in humans. Vaccines mimic what’s called “adaptive immunity.” So you create these antibodies and it protects you from future infection because you’ve seen something that primed immunity the right way. Before that ever kicks in is something called innate immunity. That’s the ability of cells just to withstand being infected by some virus that comes in.
So my point is that if you understand how viruses that are out there in the wild, existing in multiple species where those species have different aspects of their innate immunity, there’s got to be something that the virus is doing successfully to find those nodes in an immune network and overcome them.
And if you know that, then we should have better insight into the viruses that are predisposed to jump into humans, maybe do some better surveillance for them in particular, because the expectation I have is that they’ve come in and they can overcome our innate immunity barriers immediately. Those are the ones we need to be more worried about. And it’s just very difficult to do the surveillance that we need to do in the natural world. It’s expensive and it’s very hard to find the right species to do the surveillance within.
Humans are just one more host, unfortunately, on the menu.”
JD: Are there any conditions that you see in society, in the world right now, any conditions that we’ve created environmentally that you believe will allow viruses that act in this way to thrive? Or is this just an unusual case of something that has taken us a bit off guard?
PT: Well, I think we are at a point where humans are dense enough and encroaching enough on natural systems … that these kinds of contact situations happen more readily.
We need to remember, not everybody has kind of centralized agriculture like we do in the United States, where there are some places with just huge herds of beef cattle, for example. And they they process it there. And then the food goes out and the network from very few nodes in the network.
In many places, people are harvesting from the ocean or from forest systems to feed themselves and the people in their homes. And they have to. So I do take some issue with, “oh, you know, just stop the bushmeat hunting and stop the wet markets where people are bringing live animals in to be purchased for food.”
I think we can’t be naive – this is what’s driving people’s health and protein intake in a lot of places in the world. So this is a challenging thing. How do you make sure people have food security without having to go into the forest and hunt their own food, where if it’s undercooked or just interacting with those systems, they’re going to be more likely to have this kind of emergence event occur in them and then spread regionally and perhaps globally and something that’s as dire as a pandemic.
So the question is what do we do to prevent something like this from happening in the future?
Viruses, like all biological entities, can mutate, and it’s very difficult to understand the precursor mutation that would happen in some virus that’s infecting a bat. The point there is not all of those virus genotypes in that bat could spill over into humans. It’s particular mutants that are in that bat that could immediately grow and overcome our innate immunity, etc. and take hold in an infection. So this is in the realm of the kind of predictability of evolution.
Every single scientist I’ve ever talked to who has been studying something for a very long period of time thinks that the thing that they study is super, super cool. And so I’m just wondering if you could maybe make a case for viruses. Like, why are they so cool?”
Now, of course, the problem is how are you going to know what those mutants are inside of an entire roost of bats in some arbitrary jungle in the middle of nowhere? And I say that this is important knowledge and I think it helps us, but it gets back to the surveillance issue. It’s even hard to know what is out there to make the accurate prediction.
JD: I just want to ask you one last thing. Every single scientist I’ve ever talked to who has been studying something for a very long period of time thinks that the thing that they study is super, super cool. And so I’m just wondering if you could maybe make a case for viruses. Like, why are they so cool?
PT: Ok. I like this. Well, backing up what drives me to be a biologist at all. I feel like since childhood I was impressed with species biodiversity on the planet. I grew up in the time of “Wild Kingdom.” It was a TV show that I loved to watch and this sort of event glimpses into.
JD: I remember it well.
PT: You remember “Wild Kingdom?” But the point there is watching Jacques Cousteau’s undersea world and all this kind of stuff as a kid really jazzed my interest in wow, it’s a big biodiverse world out there.
And then suddenly I become a microbiologist. And I’m especially impressed with viruses. They are the most abundant thing on this planet. And they’re extremely tiny. And people don’t always appreciate them unless they’re making them sick. But they are the most biodiverse thing that we’ve got. And that is special in biology.
So the thing that impresses me about viruses is how they can outnumber all of the things on earth at least ten fold and harbor this amazing biodiversity where some of it is completely neutral. They are coming in and out of a host like us and you never know you’re infected.
So the thing that impresses me about viruses is how they can outnumber all of the things on earth at least ten fold and harbor this amazing biodiversity where some of it is completely neutral. They are coming in and out of a host like us and you never know you’re infected.”
Some of it is actually beneficial. You don’t hear as much about (the fact that) there are plenty of viruses that do some good for their hosts, but the ones that get attention are the ones that we’re dealing with now and the current pandemic.
So they run the gamut. They’re neutral to their hosts. They’re beneficial to their hosts. And we pay a lot of attention to them when they’re deleterious. So to me, that just will always capture my imagination. What allows them to be biodiverse?
I think an appreciation also for which ones are able to exist in multiple host types, like coronaviruses, versus what makes them highly confined to only a specific host. And you could push them out of an ecosystem entirely like smallpox virus.
So I will never run out of interest in how they make a living on this planet. But maybe to more succinctly answer your question, it’s the biodiversity that viruses present, the easy ability for me and my students and colleagues, when we go out and look in nature, and we find viruses, we will find new ones. Humans are not at all close to us understanding the peak of biodiversity of viruses. We’re only at a little bit of the tip of the iceberg.
There’s an amazing biodiversity out there. Some of it can do some good. Some of it can do some harm. So there’s a strong need to understand how the biodiversity, biodiversity of viruses evolve on this planet.
Dr. Paul Turner is the Rachel Carson Professor of Ecology and Evolutionary Biology at Yale University. John Dankosky is host of the Connecticut Mirror podcast, “Steady Habits.”
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