Episode 58: Tracing Ancient History with Modern Science

Episode 58: David Engelthaler, Ph.D.

Karie Dozer [00:00:03] I'm Karie Dozer, and this is TGen Talks. Valley Fever, formerly known as coccidioidomycosis or “cocci” for short, is an illness caused by a fungus that lives in the soil here in the Southwest, because it isn't widely known in areas where the fungus does not grow, it can be misdiagnosed and hard to treat. The fungus typically only found in desert areas has recently spread, and some scientists have said climate change is to blame. But what if the fungus showing up someplace other than the desert isn't a new phenomenon at all? Rather a very old one. In this episode of TGen Talks, we meet again with Dr. David Engelthaler, the director of the Pathogen Genomics Division at TGen North. Dave, thanks for coming down to talk with us once again about Valley Fever.

Dr. Engelthaler [00:00:52] You bet. Hi, Karie. As you know, we do spend a lot of time on valley fever. It is Arizona's disease and it is starting to pop up in some different places, certainly in the western part of the United States. One of those places is up in Washington state, which didn't make any sense because we know this is a desert fungus. It gets in the air, in the desert and blows around and we breathe it in. Why is it up in Washington? And so naturally, a lot of people are concerned that, well, maybe it's because of global warming, climate change, the environment's changing enough that now this fungus is spreading. And in fact, that's become part of the kind of the popular mythology about this now. And so I really want to dive deep into that and see if that's what's happening with this fungus.

Karie Dozer [00:01:32] And is that because in part a television show?

Dr. Engelthaler [00:01:35] Yeah, I think it's a show on HBO called The Last of US, which is a kind of end of the world zombie apocalypse, but it's from a fungal pathogen that is spreading and potentially spreading because the environment changed. So people are thinking about the actual fungal diseases we have like valley fever. And is that changing or is the environment changing enough that the disease is spreading?

Karie Dozer [00:01:59] So is the popular culture or the coverage on the news. The reason you decided to ask the question or were other people asking at the same time?

Dr. Engelthaler [00:02:07] You know, this is something we've been looking at for four years. And in a hypothesis that I've been working on is that we know that Valley Fever is or has been found in places like archeological digs where archeology students have, you know, been going through a site and then they end up getting exposed to valley fever, completely unexpected. They've never had it before. And then you get an outbreak.

Karie Dozer [00:02:30] And that could be anywhere.

Dr. Engelthaler [00:02:31] Yeah. And that's been in a number of places. Northern California, in Arizona, it's occurred it's occurred up in northern Utah as well. And the thought is, okay, well, they're uncovering or the thought is, is that the fungus was there in these archeological sites and they're getting exposed. So archeology students get lessons on how to be careful and not get exposed to valley fever Now. But the point is, is the Valley fever fungus was there at those sites. How did it get there in was it has it been just recently spreading because of climate change or is it been there all along? And we're just kind of uncovering it as we're doing these archeological investigations.

Karie Dozer [00:03:08] All right. So you've got a question, but you've got a lot of questions. When do you start deciding to devote a good portion of your time to answering this one? And how do you go about it?

Dr. Engelthaler [00:03:15] Yeah, well, what we got to do is look at all the different types of data and evidence that's available out there to understand what's the most likely reason this happened. So it's my contention that Valley Fever is now up in Washington State. It has been up there for a very long time, we think thousands of years. We know this fungus is really, really old. It's millions of years old in the southwest, but up there, probably only thousands of years. And we can do that because we can look at the genome and we can look at the mutations that kind of put it what we call a molecular clock on it and try to figure out how old the strains are in the local region. And really the data is telling us that those strains up there in Washington state are really a few thousand years old.

Karie Dozer [00:03:56] So people read about carbon dating of Bones. Is that what you're doing with the virus?

Dr. Engelthaler [00:04:00] It's a very similar thing. In this case with the fungus, we're actually able to look at the number of mutations and how fast those mutations occur, and then we can kind of use some math and statistics to go backwards to get a pretty good estimate of how old something is.

Karie Dozer [00:04:17] And you said only thousands of years old, which means only thousands is a fairly young. It's young for a fungus. Is that true?

Dr. Engelthaler [00:04:25] It's young for a fungus, but it hasn't been occurring in, say, the last 50 to 100 years where we might link it to more modern climate change. We think that in certainly thousands of years would be before, you know, the Europeans came over to the Western Hemisphere. So this was likely back when indigenous populations were here and potentially they may have been moving the fungus around. And we think that might have been what happened.

Karie Dozer [00:04:54] So you don't write this paper yourself and you don't do the research yourself. Who joined you in this mission to answer the question?

Dr. Engelthaler [00:05:00] Yeah, well, I had a couple. Full of great coauthors. Dr. Arturo Casadevall, who's a world-renowned immunologist and fungal expert at Johns Hopkins University, and I've written with him in the past, and he's just a tremendous thinker, and it's been a lot of fun to kind of explore these ideas with him. And then we also brought in Dr. Jim Chatters, who is a paleontologist, archeologist and actually a paleo climatologist, and he spent a lot of time up there in and still operates up in the Washington region. And I invited him to join into this investigation. And we just kind of went through what is all the data that's available to us and what makes the most sense.

Karie Dozer [00:05:40] I giggled a little bit and you said Paleo climatologist, because that's a combination of disciplines that I've never heard before. Are there many of him or is he the only one?

Dr. Engelthaler [00:05:50] No, I'm sure that there are many of him, but you can probably count him on your fingers around the world really trying to decipher based off what we understand about plant life. And we can see how waters rose and decreased and where rainfall was occurring, etc., thousands to hundreds of thousands of years ago. And that can give us a pretty good picture of what was happening well before people were around to document it.

Karie Dozer [00:06:16] All right. So you gather your evidence and you present a paper. Where do you present it? Who listens and who finally decides whether or not you've convinced the body of science that that you in fact, your hypothesis is correct?

Dr. Engelthaler [00:06:30] That's a great question. So this really is a hypothesis piece where we then we provide a lot of evidence. Then we look at alternate hypotheses and provide the available evidence for those. And it really does look like the most likely scenario is that the Valley fever fungus moved up there probably with an infected person from the San Joaquin Valley area. That's what the strains are most closely related to. In fact, San Joaquin Valley is what the valley fevers named after.

Karie Dozer [00:06:58] Not us.

Dr. Engelthaler [00:06:59] Not the Valley of the Sun, but it is highly endemic in both places. And it looks like those strains somehow got up there. Most likely an individual was infected, perhaps a dog was infected and was moved up to the Washington state area. And that happened through trade and travel, which was happening thousands of years ago with the different indigenous populations that were in the western United States.

Karie Dozer [00:07:25] So what's the result of the paper? You present the paper and then do other researchers pick it up where you left it off and try to decide to either prove or disprove your hypothesis? What happens next?

Dr. Engelthaler [00:07:36] Yeah, maybe to better answer the question is we really can't prove this is exactly what happened. We don't have empirical data. We can't go back in time. But what we can do is continue to look at the available data. And if we don't see that this is spreading in outlying regions of Washington or elsewhere in the Pacific Northwest is pretty good evidence that we still have this likely a single introduction event thousands of years ago. We try to look for other evidence that would help negate this hypothesis. And if that happens, then, then, yeah, we can start to maybe generate new hypotheses. But for now, we wanted to put something out there that made sense biologically. It made sense with the genomic timeline. It made sense with the epidemiology of this fungus. And I think that's what we've done.

Karie Dozer [00:08:27] Regardless the reasons why Valley Fever has spread to places like Washington. What do we do about the actual Valley fever?

Dr. Engelthaler [00:08:33] Yeah, well, here's one thing that might be useful for others, is if we can understand that, you know, things like climate change don't automatically make everything worse. And in that, you know, we frequently do use climate change as either the reason or the excuse for a lot of bad things that happen in in this particular case, there's been a fair amount of news coverage and others thinking that this fungus is spreading and we can't do anything about it because of climate change. It's just going to get worse and we're going to have more cases all over. I don't think that that's what's happening, and I do think that that's useful for people to know that it's that not everybody's at risk and we can better pinpoint where Cox actually is and spend resources there educating health care professionals, educating the public, and what you can do to maybe limit your exposure and then the health care providers and what they can do and what they should be on the lookout for.

Karie Dozer [00:09:31] You don't treat people with valley fever, but you know more about it than most physicians. Is it true that in regions like Arizona and the San Joaquin Valley that, you know, local providers, which is actually where people are getting their health care, know more about it, and that some physicians in other parts of the country have never seen it, know very little about it and therefore aren't fit to treat it.

Dr. Engelthaler [00:09:52] Yeah, you know, you would think that we would have all the world's experts, or at least all the doctors here would be experts in Valley Fever because it is so prevalent in. In Arizona, especially in the southern part of the state. And it turns out every time we do a study, there is a lot of misinformation and a lack of testing for suspect patients. People walking around with community acquired pneumonia and doctors not testing for it. And they're trying to treated with antibiotics and it's not working. So we still see that a very large percentage of these patients never get tested. And the right ones then oftentimes don't get treated until it gets maybe more serious. So there's still a lot of physician education to happen even in an endemic area. But we also know that Cocci shows up all over the country in patients, and that's because they come out to the West for travel, to go to the Grand Canyon or to California. They get exposed and then go back. And doctors certainly aren't looking for it in Minnesota, in Michigan and in New York and a lot of places that they should because they have people that travel and they should know where their patients have gone to. And if they've been to the southwest and they have kind of a walking pneumonia, they should be testing for Cox.

Karie Dozer [00:11:06] What is the work that you do day to day do to help add to the body of knowledge about how to treat valley fever? I mean, at the end of the day, we want to treat it better, not just find out where it's going. Yeah.

Dr. Engelthaler [00:11:18] We have at t Jen really been focused on Valley Fever for 15 plus years. We see it as, as I mentioned, Arizona's disease. So we've got to really throw everything we can at it. So we have developed the only molecular test that's been approved by the FDA for Valley Fever, and we're going to have that in our clear lab so we can test patients soon and hopefully others can use it as well. We have a team that's been working on trying to find better targets for possible vaccines because this is really a disease we should be vaccinating for because people are continually being exposed. If you're coming to the southwest, you're going to be exposed. Most of us won't have a bad bout of it, but we still should have vaccine for. And teaching is using its next generation tools and technology to help find targets there. And we're just helping to better understand where exactly people are at risk. So we're doing air filter monitoring all over the metropolitan Phenix area and trying to understand which places are hotspots and what part of the year is really important to be looking for this.

Karie Dozer [00:12:21] As a guy who's made a life out of studying microbiomes and fungus and strange bugs that infect us. Do you find it difficult that mainstream media or now the millions of different choices of things that people can watch at home and be frightened by has grown so that it seems that we can't watch much of anything without seeing the end of the world. Does that make your job harder?

Dr. Engelthaler [00:12:45] Well, possibly it may be at least the messaging about this. I mean, I do believe, you know, because a lot of, you know, media wants something exciting, but it ends up ends up turning us all into catastrophes like this is the worst thing. And you remember when m pox or what was called monkey pox came out. Lots of people thought that was a, you know, the next big thing. And it was never really a risk to the general public. We didn't know that because we weren't getting great information out. So it is becoming more difficult. Some people are more in tune in looking out for the next pandemic and other people are less in tune and less likely to believe that they got to worry about a new public health problem. So, yeah, we've got a lot of work ahead of us.

Karie Dozer [00:13:26] So as someone who knows more about these diseases and these fungi than the director or the creator of the cereal is special, whatever it is, do you often watch them with a sense of humor? Do you often watch them and think this is irresponsible?

Dr. Engelthaler [00:13:41] Yeah. Well, just a quick note on the show, The Last of US, that is about a type of fungus that's called cordyceps fungus, which are actually is really devastating fungi. If you're an insect, they don't really infect mammals. They can't it's just it's just not capable. They just don't have the right genomic material to do something like that. And we don't see it evolving that way. But it is it is something that we've talked about. You know, if there was ever a zombie apocalypse, that would be a really nasty one. And they've made a pretty interesting TV show about it. But that's all it is. It's still just a TV show.

Karie Dozer [00:14:18] Anything that you watch that is in that genre or that realm that you find entertaining or particularly correct, scientifically accurate.

Dr. Engelthaler [00:14:28] Yeah. I mean, it's actually was hard to find anything correct just about the pandemic, which was real life happening. I do find it entertaining. I do I do find these shows interesting because it helps us sometimes. I'm not sure if it did during the pandemic, helps us think through these kind of emergencies. I'd like to think about the epidemiology and how these diseases can move around, but also how do people respond. We know now firsthand how people respond to contagions, and they're either there absolute fear them or complete lack of fear of them. And that makes it. Very difficult to have a really good policy that works across the society and is most effective in our communities because we realize as humans we're all very different and we respond to things very differently.

Karie Dozer [00:15:14] Yeah, for sure. Anything else? Anything I missed? Anything else you want to share about your hypothesis or where you hope this goes?

Dr. Engelthaler [00:15:20] Well, I'm hoping that we can actually spend a little more time looking at those spots where we know the soil conditions and the climate conditions are good for Cox to grow. And maybe there are archeological sites and those are going to be potentially areas where we can look for high risk. I think we can stop worrying that this is just going to spread like a wave across the western United States. I don't see any evidence for that. It doesn't mean it's not important. It doesn't mean that we're not going to still spend a lot of time on this particular disease and in others to see where we could use genomics to, again, improve diagnostics, therapies and vaccines.

Karie Dozer [00:16:03] It seems like whatever the effects are causes of climate change. One thing that has happened is that soil is eroding in places that it wasn't eroding before. There are no lakes where there were lakes. So there are, simply put, a lot more places for archeologists to start digging who might be closer to finding what they're looking for. So if you can pinpoint where it might be more dangerous, at least those people can be on alert.

Dr. Engelthaler [00:16:28] Yeah, One of the things and we point this out too, in the study is that while climate change may not be pushing some of these pathogens into new areas, they might be starting to reveal where they were because of the changing environmental conditions.

Karie Dozer [00:16:44] Pretty interesting. Good luck.

Dr. Engelthaler [00:16:45] Thanks, Karie.

Karie Dozer [00:16:47] For more on TGen’s research, go to TGen dot org slash news. The Translational Genomics Research Institute, part of City of Hope, is an Arizona based nonprofit medical research institution dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at TGen dot org slash TGen Talks, Apple and Spotify and most podcast platforms. For TGen Talks. I'm Karie Dozer.