The Evolution of Infectious Diseases

Penn State undergrad Emma Sieminski  interviews Biology and Entomology professor, former Director of the Huck Institutes of the Life Sciences, and current Senior VP of Research, Andrew Read about his research on the ecology and evolution of infectious disease. 

Emma Sieminski 
Undergraduate student at Penn State majoring in Forensic Science

Andrew Read
Evan Pugh Professor of Biology and Entomology, Senior Vice President of Research at Penn State

Transcript

Mark Shriver:

From the Center for Human Evolution and Diversity at Penn State, this is Tracking Traits

[THEME MUSIC]

Cole Hons:

Greetings fellow Homo sapiens, this is Cole Hons from The Huck Institutes of the Life Sciences. Welcome back to the podcast. 

For episode four of our third season, we bring you Penn State Forensic Science undergrad Emma Sieminski interviewing evolutionary biologist Andrew Read, Evan Pugh professor of biology and entomology at Penn State.

Dr. Read was directing the Huck Institutes of the Life Sciences at the time of this interview and has since been appointed Senior Vice President of Research at Penn State. His research focuses on the evolution of infectious diseases, particularly those that rapidly evolve in hospital settings, profoundly impacting human health. 

In this podcast conversation with Emma, Read emphasizes the importance of understanding how medical treatments, such as drugs and vaccines, can drive the evolution of pathogens. As he explains, when pathogens evolve fast enough to outsmart these treatments, the consequences can be deadly. 

Read also shares some personal insights he’s gained at critical moments in his career, shares advice for students entering the field of science, and chimes in on the impact of COVID-19 on his field, the benefits of interdisciplinary research, and the quest to design of evolution-proof drugs and vaccines. 

Here's Emma Sieminski interviewing Andrew Read about “The Evolution of Infectious Diseases.”

[MUSICAL INTERLUDE]

Emma Sieminski:

Hi Dr. Read. Thank you so much for joining me today. So I'm going to have you start off by introducing yourself and giving me a brief summary of your research.

Andrew Read:

I'm Andrew Read. I'm an evolutionary microbiologist. I work on the evolution of pathogens, mostly my career, malaria and various hospital bacteria and some viruses.

Emma Sieminski:

So did you always know that you wanted to become an evolutionary biologist?

Andrew Read:

For most of my schooling and university time, I didn't actually realize there were such things as evolutionary biologists. Yeah, as you can tell from my accent, I come from New Zealand. And so I spent all of my life up until I went to do my PhD, in New Zealand. And New Zealand has these really incredibly interesting animals, because they've evolved in isolation through Kiwis and things. And that got me very interested in the evolution. So I used to read a lot of books and articles about evolution, think about it a lot. And while I was at university, there were no courses on evolutionary biology. So I didn't realize it was actually a specialization. But I worked on offshore islands on conservation problems. And one of the problems we worked on was kākāpō, which are flightless parrots that breed on the ground. And they have all sorts of crazy behaviors and breeding behaviors.

And the females and the males only come together once every four years, only for sex. There's a whole lot of strange things they do. And I was asking the questions of the scientists on that program, "Why are these birds so crazy? What's going on?" And they started sending me papers and books of theories, not about kākāpō, but about related birds. And that's when I realized there were people in the world making a living by thinking about the sort of things I was thinking about. There were actually theories and people doing experiments and studies, and I thought, "Wow, it is actually possible to be a professional evolutionary biologist. You can make money doing this stuff."

And so it was really an eye-opener and that hit me. And I remember being on one of the offshore islands in a tent, rain lashing away, trying to study this bird's breeding system and reading one of these books and thinking, "Why don't I write a book like this? Why don't I do this?" It really hit me that, "Wow, I could actually become not somebody who's trying to save birds, but somebody who's actually studying the evolution." And that's where it was a big moment for me, and that led to PhD and beyond, where I am now.

Emma Sieminski:

Love that. That's a really cool story.  How did you get into your work in infectious diseases?

Andrew Read:

During my PhD I realized that most people who were studying infectious diseases in those days were not studying the evolution of those infectious diseases. Even though things like the evolution of drug resistance in malaria or drug resistant bacteria in hospitals was clearly highly relevant and it was killing people. And it happened in super fast time as well. So compared to the evolution of birds or the evolution of plants, evolution of infectious diseases takes place as COVID has shown us in weeks, days, months. And so you can study it and it matters. So I got drawn out of things I had been working on and into infectious diseases, both because I thought it was going to be good to study evolution in real time and because it's evolution that matters.

Emma Sieminski:

Oh, that's really interesting. So something you touched on in your introduction was your work with malaria carrying parasites. How has your work with them given you insight into how viruses evolve?

Andrew Read:

Yeah, malaria parasites are a single-celled organism, so they're related to an amoeba, so full eukaryotic single-cell organisms. And those are obviously very different from viruses in terms of how they replicate the structures and so forth. Completely different ends of the spectrum. But from an evolutionary biology point of view, malaria parasites turn out to have a lot of great features. They are, for example, relatively stable, so they don't mutate at crazy rates. They have very discreet transmission stages and they go to mosquitoes, so you can measure transmission. The genetics are pretty stable and well understood. And so there was a whole lot of things that allowed me in malaria to make progress on the evolutionary questions we were interested in, and make what I still think of as very good experimental progress.

And then I got interested in various viruses because of some of the work that we'd done. It seemed to have played out some of the evolution that we were seeing in the lab and malaria, this evolution of particular parasite traits was relevant to some of the viruses we ended up studying. So for example, one of the questions we worked on a lot was, the virus or the parasite, how sick does it make you? And work that we'd done on the malaria parasites about the nature of the evolution of disease severity was parallel to what had been going on with myxoma virus, which is a virus of rabbits that's been well studied as a biocontrol agent in which has evolved in real time. And so conceptually one thing links to another very easily. In my eyes, there's obviously very big differences in the actual underlying biology, but from the point of view of the evolutionary biology, a lot of analogies, a lot of similarities.

Emma Sieminski:

Definitely. So it seems like a lot of your research has focused on the effect that treating diseases or trying to prevent them, especially through vaccines has on the virulence or the severity of the pathogens. Could you talk a little bit about how that works?

Andrew Read:

Yeah, I got really interested in the fact that a lot of what we do in medicine is aimed at destroying these organisms. So destroying the malaria parasites, destroying the viruses. So drugs are aimed at killing these bugs. Vaccines are aimed at preventing them infecting in the first place, or if they do infect, killing them as fast as possible. So most of the things we do in medicine targeted at these living organisms the result will kill them. And so there's very, very strong selection for those organisms to overcome these treatments. And so one of the strongest driving pressures for the evolution of many of these pathogens is in fact the medical treatments that we throw at them. And so I got very interested in that, because that's something we control, so experimentally it's something we can do ourselves. And also it's something where when the virus or the parasite finds a way around these things, if it can become drug resistant, then people get sick, because the drugs start don't work as well.

So that's why I got very interested in it, because it's very strong selection pressures that we control and the outcome of the evolution that they prompt, matters from the human health point of view. Now, the issue about disease severity is the question of if you have, let's say two different strains of COVID, where one strain is causing more severe disease than another, let's say the Delta variant compared to some of the earlier ones like Alpha. So we have there, we know that there are genetic differences encoded in the virus that cause differences in disease severity. And the question that I got really interested in, was were any medical procedures selecting for more virulent strains or less virulent strains? And I got very interested in whether drugs could do that and there are ways they can, antimicrobial drugs and then whether vaccines could. And vaccines are aimed at preventing the transmission of viruses. And so the real question there, was whether or not you could have some circumstances where vaccines might select for more or less virulent strains. And that's where that came from.

Emma Sieminski:

Okay. Now going along with that topic, one of your papers on this topic has received a significant amount of attention despite being made years earlier. The paper absolutely skyrocketed to popularity in the height of the COVID-19 pandemic. And it's actually been discussed in a YouTube video that has received 3.2 million views, where the creator concluded from your paper that COVID vaccines could be doing harm and increasing the severity of COVID-19 in the long run. Can you explain first of all, the experience of having a paper become so popular? And specifically, your thoughts on the conclusions made in that video?

Andrew Read:

Yeah, okay. Well, so the paper was published in 2015 and it got a reasonable amount of attention in the scientific literature. And I certainly had good reactions from it, or at least a lot of engagement in the scientific conferences before COVID. And then in COVID times it started getting some attention and eventually got picked up by Joe Rogan and he made a show around the paper. The paper shows in a virus of chickens that the vaccines that were used in that chicken disease, where birds are being vaccinated, created the conditions that allow very virulent strains to persist in the environment. And so the strains that exist of this particular virus on poultry farms in America today, are so virulent that they kill the birds if they're not vaccinated, they kill the birds so fast that the virus can't transmit. And the vaccination keeps the birds alive and allows the virus transmission. So strains that were too virulent to persist in the pre-vaccine era can now persist in the vaccine era.

And Joe and I, and the experiments and all the controversy that this generated, nobody's questioned our data or the experimental conclusions. So that seems to be unambiguously well-supported. What the issue was, that Joe Rogan concluded from that, or at least he implied very strongly on the show, that that was a reason not to use COVID vaccines. I first heard about this when Penn State's strategic communication phoned me up on a Saturday morning to say there was a journalist wanting to talk about what I thought about Joe Rogan's show. And I have to say my first reaction was, "Who's Joe Rogan?" Yeah, I know that seems uncredible now, but allow me, I'm a scientist, okay? And then I talked to the journalist, Forbes it was, and they came up with a headline, Joe Rogan Wrong Says Scientist.

In the cold light of Dawn, actually Joe Rogan did a pretty good job of summarizing our paper and the science in it. The bit that I really disagreed with and the bit that caused all the controversy, was the extension that from evolution of a virus in chickens, one should then choose not to vaccinate against COVID. And that is a hell of a step. And weirdly, if you think about it, you are asking that for some hypothetical evolutionary possibility about the future, which is played out in the chicken virus, but not very many other places, you should therefore not take lifesaving vaccines. And that's just such a radical conclusion. After the Rogan show, it went crazy on Twitter. It is now one of the most tweeted papers of all time. And I got physicians from all over the world reaching out to me saying, "You have to write something so that I can show my patients that just because what happened in a chicken is not what's going to happen in the human case."

And so we wrote an article summarizing the paper, the reaction and the logical fallacy and the risks associated with concluding from our paper that you should avoid lifesaving vaccines. The paper itself has been viewed over half a million times on The Scientific Journal now. So by far the most viewed paper in that journal. It's been still being tweeted several times a night, it's being tweeted out. It is by far the most Tweeted paper in Penn State's history I believe. I found the whole thing pretty unsettling, because the science is quite complicated. It's not easy soundbite stuff. And it's all about risks and balances and the current risks versus hypothetical future risks. And that's all stuff that humanity doesn't cope well with at the best of times. And in the middle of a pandemic where people were dying, it was pretty emotional I thought. Yeah, yeah.

Emma Sieminski:

So we've touched on COVID a number of times in this conversation already, but how has COVID-19, being such a worldwide phenomenon, affected your field and your work?

Andrew Read:

Well, it was obviously the disruptions that came to all the lab work, just because of the pandemic disruptions. But it meant everybody in infectious disease really was pivoting on a dime to focus on COVID. A lot of people that were not at all interested in viral evolution became very rapidly interested in it when we started going through the different variants. Early on, there was a lot of discussion that there wasn't going to be any evolution of any interest. Now the whole thing is dominated by new variants and the evolution of the variants that'll come after that. So it's completely transformed the way in which microbiologists, virologists think about the importance of evolution in their work.

A huge amount of work is going on now in COVID, it's by far the best studied virus of all time, and it's now perhaps becoming the textbook for almost every aspect of things. So the science has been radically changed and we've learned a huge amount from it. I think the field maybe has learned a bit of humility. There's a lot of things that we didn't know at the time that we felt more confident about than we were. And for me personally, the biggest thing has been that I used to have trouble explaining what I did and now I just say Omicron, Alpha Delta and everybody understands.

Emma Sieminski:

So one of your research papers talks about this idea of infection blocking vaccines, which might not have the same negative consequences that other vaccines such as the Marek's disease vaccine that we were just talking about has. So can you talk a little bit about what infection blocking vaccines are and how they work?

 Andrew Read:

Yeah. So infection blocking vaccines, these are ones we define that they prevent a person becoming infected in the first place, or they prevent an infected person becoming infectious. So if it's working perfectly, then the vaccine means that the vaccinated person, is a dead end for the virus. It's not going to transmit on. And that stops the evolution. So if you have no one with transmission, you have no evolution. And so from an evolutionary biologist's perspective, infection blocking is key. And then the question becomes, "okay, how much inflection blocking is going on?" And if you take something like the measles vaccine, for example, which if you get vaccinated against measles, you have lifelong immunity. And as far as we know, almost nobody who's vaccinated becomes infected and passes the infection onto anybody else. And so measles is what we call a childhood disease, because it only exists in people who have not seen measles or the measles vaccine before. It can only infect fully susceptible people.

The issue becomes interesting when you start to have leakage where there is some transmission, and in the case of the Marek's disease virus, the chicken virus that we worked on, they don't prevent transmission at all. They stop the birds getting sick, but they don't prevent transmission in the slightest. And so there's a lot of evolution that can go on in the vaccinated population as much or even more than went on in the unvaccinated population. COVID vaccines, the mRNA vaccines fell somewhere between those two extremes. So they're better than Marek's disease vaccines at reducing transmission, but they're not as good as measles vaccines.

And that I think is why we've had substantial amounts of evolution going on. It's certainly been a contributor to that. If we could get COVID vaccines that fully blocked infection, then not only would the thing have very little evolution going on, and so probably we'd get the variants down, it could even die out. Even if it didn't die out, it would be circulating only in the unvaccinated and those that have not seen the infection. So infection blocking vaccines need to be the gold standard to which we should all aspire. We were lucky with the mRNA vaccines that they were so good at preventing severe disease, but we've got a ways to go before they block transmission.

Emma Sieminski:

Okay. Wow, that's very interesting. Now all of this begs the question in my mind at least, is it possible to make widespread evolution proof drugs, vaccines, treatments, et cetera?

Andrew Read:

Right. So the question is whether or not we can have these medical interventions, antibiotics, antimicrobial drugs, vaccines where evolution of the virus or the parasite or whatever doesn't happen. So that's like asking if we could find an antibiotic where we wouldn't get the evolution of antibiotic resistance. Yeah, I do think that's possible. There are some examples already. For instance, HIV treatment now is multi-drug treatments and when those are adhered to, the virus does not evolve drug resistance and does not transmit onwards and so forth. So adherence to the HIV therapies, the modern ones, those are evolution proof drugs.

TB drugs, some combinations of TB drugs do the same things, they're evolution proof. And that's because these contain many different drugs. And so if the bug becomes resistant to one drug, one of the other drugs will kill it. And so that makes it extremely hard for a virus or a bacteria to find its way around three or four drugs simultaneously. We can use that lesson in vaccinology I think, that if we can find vaccines that stimulate immune responses against many different parts of the target organism, we should be able to get the same effect. So if you can get, for example, a vaccine that targets the several parts of the spike protein on the COVID virus and maybe some other targets on the virus as well, it's going to be very challenging for that virus to find a solution simultaneously to all those different killing sites.

So I think there are ways of doing that, and I think we probably don't have as many evolution proof drugs and vaccines as we do should do, simply because usually medics are interested in treating the patient not concerning themselves with the downstream evolutionary effects. And so single drugs that very effectively treat most patients can in the long run generate the evolution of drug resistance, but it's a medium term problem, not a short term problem. And that's why we are typically focused on the short term patient health issue rather than making evolution proof drugs. But next generation biotech is definitely going to be towards evolution proof drugs and vaccines.

Emma Sieminski:

Right. That's good to hear. So how overall do you want your research to impact the world?

Andrew Read:

Oh, I'd like lives to be saved from my research before I retire, or at least that we're well on the way to lives being saved. And for me, that would mean these evolution proof drugs or vaccines strategies to use existing drugs or vaccines, that will mean we won't get the evolution that harms patients down the line. What's next for the research? Well, right now we are working on what are in effect, anti-evolution drugs. These are compounds that we imagine you would take alongside your antibiotics and they would interfere with any antibiotic that got into a place where it's selecting for resistance but not needed for clinical use. To give you a specific example of that, many of the bugs that you can get in a hospital that are multi-drug resistant, you get treated with intravenous antibiotics to get those out of the blood system.

And that's critical because they are very lethal. A third of people can die with a bloodstream bacteria infection. So you get the intravenous antibiotic and that kills the bugs in your blood. But some of the antibiotics gets into the gut where it selects for resistance in the gut. And there's no need to have it in the gut, but it leaks in there because of the way in which the drugs are excreted. So we are building compounds that will work in the gut to absorb any antibiotics that got there. So that would remove the selection for resistance and it would stop the onward transmission of drug resistant bugs. So that would be an anti-evolution drug if you like. And we call them anti-antibiotics. And we've got some very promising mouse results and very promising novel compounds that we're working with. And I'd be very, very pleased if we have this into humans and preventing antibiotic resistance before I retire.

Emma:

Wow, that sounds so exciting. I can't wait to see that come to fruition. 

So you're the director of the Huck Institutes, which is a supporter of CHED that sponsors this podcast. How does CHED factor into the Huck and what is the Huck doing more broadly at Penn State?

Andrew Read:

Yeah, CHED's a very good example of the Huck mission. So the Center for Human Evolution and Diversity is focused on a very interdisciplinary group of faculty that are using a whole variety of different approaches to look at human evolution and the existing diversity in humans we see today. Huck's job is to make that interdisciplinarity happen in very a large number of areas in the life sciences across Penn State. 

So Penn State, like most universities, has a very strong vertical structure. It has colleges and departments. And those are often the traditional department structures that existed in the 1950s, chemistry, mathematics, and so forth. And of course, the science doesn't follow the 1950s boundaries anymore. It's very cross-cutting. And even something like anthropology, it's got bits of genetics, it's got bits of microbiology, it's got all sorts, bones, it's got everything.

And CHED is an exemplar of that. And so we support enterprises on campus that are trying to break down the silos of science to make life science horizontal, if you like, across the university. And we do that in a variety of different areas. So CHED is one of them, but we've got here we are doing things in plant science and biotechnology, in infectious disease, all sorts of areas where the work itself is not necessarily focused in any one department. And we do our very best to join things up and link things across campus. And CHED is a particularly good example of that, and that's why Huck has been a supporter of CHED long before I became director.

Emma Sieminski:

Great. Now lastly, I just wanted to ask what would be your advice to the next generation of scientists?

Andrew Read:

Yeah, okay. Andy Stevenson, who was a plant scientist at Penn State recently retired. And somebody asked him exactly that question at his final seminar and he said after a moment's thought, "Have ideas, pursue vigorously." So, "Have ideas, pursue vigorously." And that is really what it's about. Having ideas is actually quite hard. And a lot of the training that goes into PhD students and beyond is about trying to get people good at asking questions of the right sort, that are well-defined, that are important and potentially answerable. So that's quite a hard knack to get. And then the pursue vigorously, that is about a lot of hard work. But I think Andy also meant go for the jugular on it.

So when you've got an idea, do the experiment that's going to disprove it and keep pushing hard on that push, push, push, don't ease up. And if it's a good idea, it'll fly and it will survive the beating you give it. If you don't pursue vigorously, the idea just sits there and it's not progressed at all. Most ideas are wrong and the sooner it's wrong the better. Yeah, so that'd be my advice, have ideas, pursue vigorously. Everything else is secondary to that. It does matter that you give a good talk. It does matter that you network. It does matter that you have collaborative skills, et cetera. It does matter that you have good techniques, that you learn modern science and facts and stuff. But really it boils down to have good ideas, pursue vigorously.

Emma Sieminski:

I think that's a wonderful piece of advice. Thank you so much for joining me today. It was an absolute pleasure to talk with you about your work. 

 Andrew Read:

My pleasure.