[00:00:00] “Decompose” Theme Music

[00:00:05] Anne Chappelle: We’ve been doing Adverse Reactions, and this is what our 

[00:00:08] David Faulkner: Fourth

[00:00:09] Anne Chappelle: Fourth

[00:00:09] David Faulkner: Season

[00:00:10] Anne Chappelle: Season

[00:00:11] David Faulkner: Amazing. 

[00:00:11] Anne Chappelle: So, David, do we have a theme? 

[00:00:13] David Faulkner: Everything is so much more complicated and interesting and more interconnected than we ever think it’s going to be. 

[00:00:22] Anne Chappelle: We’ve really kind of strayed from traditional toxicology in this season.

[00:00:28] David Faulkner: It’s true. We have been expanding the reach of what most people think of as toxicology because one of the things I love about this discipline is that it is a necessarily applied science and that means it touches basically everything—all the other sciences.

[00:00:44] Anne Chappelle: Have a listen.

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[00:00:52] David Faulkner: “Tox in Your Backyard,” with Dr. Julie Miller of the Commonwealth of Pennsylvania.

[00:00:58] Julie Miller: Our emergency response system in our body, our cytokines—so, they’re the ambulance coming, and the siren saying, “Okay, something’s happening.” So, you have, whether it’s related to a physical stressor or a physical injury heat, cold, all those kinds of things. When you’re someone that has been chronically stressed, for example, maybe your body can’t respond as quickly or as well to those types of exposures, too.

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[00:01:26] Anne Chappelle: We are really excited to welcome Julie Miller to the show today. Hello, Julie!

[00:01:32] Julie Miller: Hello.

[00:01:33] Anne Chappelle: Julie is a public health toxicologist at the Pennsylvania Department of Health. She is board certified, and prior to this, she worked as a consultant providing toxin analytical chemistry expertise to various industries, including chemical, pharma, consumer products. So, you consider yourself a toxicologist, not an epidemiologist.

[00:01:55] Julie Miller: Correct. I would say I am privileged to work in a department that has over 100 epidemiologists and I am the lone toxicologist. 

[00:02:05] Anne Chappelle: What?

[00:02:06] Julie Miller: Yeah.

[00:02:07] Anne Chappelle: They have a hundred epidemiologists working for the state?

[00:02:10] Julie Miller: Yeah. So, our Bureau of Epidemiology is pretty large. I would say it probably increased in size during COVID. So, that’s epidemiologists from PhD level all the way down to maybe a bachelor’s and master’s level. We have the whole gamut.

[00:02:23] Anne Chappelle: I would say so.

[00:02:25] Julie Miller: We’re pretty big. I think Pennsylvania is pretty unique from a lot of other states in that—for Ohio, for example, they’re broken down into all their different health districts for different counties and things like that—whereas in Pennsylvania, we do have county and municipal health departments, but there’s not very many of them.

So, as the Department of Health for Pennsylvania, we’re responsible for everyone but also for municipalities or counties that have their own health department. They take care of certain things, but environmental epidemiology and toxicology, which is where I’m housed, we are pretty much for the whole state.

[00:02:57] Anne Chappelle: So, you call yourself a toxicologist. You have the DABT, but you’re one of those sneaky chemists.

[00:03:05] Julie Miller: I always say in a former life I was an analytical chemist, but yeah, I think a lot of people don’t realize that toxicology is a pretty small field. I didn’t know what toxicology was until I went to graduate school, and my advisor, luckily for me, was housed in the analytical chemistry department. But he was a toxicologist by training. So, all of our research and coursework that I took and things like that, all framed my toxicology training.

[00:03:28] Anne Chappelle: What made you decide to go into a state government position?

[00:03:33] Julie Miller: This might be a little bit of a long-winded answer. So born and raised in Pennsylvania. I love Pennsylvania so much, or PA as most of us say. And so, when you go to public school and you want to graduate, you have to do a senior project. So, I did my senior project on black lung disease because my grandfather actually had passed away from black lung. And I always thought the intersection of your environment and in your workplace, you know, how does it affect your health? But at the same time, I didn’t know what that was. It was just something I was interested in. I went to undergrad for chemistry because I was really interested in chemistry. My mom was a medical technologist, and so, she was always in the lab and doing things. But also, providing, not necessarily patient-facing, but providing a service that’s really important to patients that are at a hospital or whatever.

And also, my mom’s family is from a little town called Palmerton, Pennsylvania. It’s near a pretty large Superfund site, but I just always remember being in my grandparents’ kitchen, looking out the window at a mountain that was completely devoid of greenery. It was just rocks. And I thought, “Well, that’s really strange for Pennsylvania.” Little did I know, it was because of the former zinc smelting plant that was there for decades and decades, which is now a Superfund site. So again, always interested in that connection between the environment and human health. 

Then, I went to graduate school as most people in undergrad that were graduating during the great recession, and I thought, “I want to give this a shot.” So, I went and studied at WVU for analytical chemistry, and my advisor was just super passionate about toxicology and really incorporating many different fields in order to answer a question. So, he had grants from DARPA, from other government agencies.

I always wanted to work for government, and I always wanted to do something that had a purpose. That’s mostly why I ended up where I did. And then, of course, I had to go to NIOSH; it’s in Morgantown, West Virginia. It’s also where the health effects laboratory branch is located and their toxicology department where you do basic science research. And so again, that was also marrying my inspiration of occupational health and all of those things and also learning a lot more animal models and things like that.

Because then, in graduate school, I was doing in vitro. I was also doing some human subject research, but I really thought to be a well-rounded toxicologist I wouldn’t know it unless I did it. In that respect, we did a lot of animal work, a lot of animal modeling for Gulf War illness, which was really an exciting project and also something that was really fulfilling for me. 

From there, I really like being in the lab, but I think I’m ready to step out of the lab. And so, I then went into consulting because what I told my graduate school advisor was, “I want to be a practicing toxicologist. I want to be someone that looks at things and to understand what’s safe and what’s not, or how do I protect people at the end of the day.” So, I think I really got to sink my teeth into a lot of that in consulting from many different types of projects ultimately to try and understand, again, environmental or exposures and then human health.

But I was ready for a change. And when I saw this pop up, I’m like, “Who would be better than me? I love Pennsylvania so much.” I thought I had to take that leap, and it was a little bit daunting and I was a little bit nervous because it’s so much responsibility. I also didn’t know at the time that I applied that I would be the only toxicologist employed by the state of Pennsylvania or commonwealth, as we say. That was a little nerve-wracking, but once I got here, it’s been really worthwhile. 

[00:06:53] David Faulkner: That’s phenomenal. I wanted to dig into something a little bit in your switch from chemistry to toxicology. I really am fascinated by that because I think about my own journey and I think the journey of a lot of people is from either biology or biochemistry into toxicology. Do you think that you have certain skills that are special to the fact that you did analytical chemistry? 

[00:07:17] Julie Miller: My mantra was always, “You can’t manage what you can’t measure.” And so, in analytical chemistry, it really gave you the insight and tools to be creative, but also that analytical mind of, “If I don’t know what something is, how can I better protect people?” I think understanding how molecules move in your body. You know, everything goes back down to the chemistry level. 

[00:07:37] Anne Chappelle: Could you tell us what Gulf War syndrome is? How do you define that?

[00:07:42] Julie Miller: Gulf War illness is a multi-symptom disorder that is classified with many different symptoms. So, you can have generalized fatigue, malaise. Could be similar to chronic fatigue illness, things like that. But it’s unique to the population of soldiers that had been deployed during the Gulf War in the early nineties. And I believe, at some point, there was a statistic where about a third of the Gulf War soldiers or people that deployed ended up getting some form of Gulf War illness. And it’s a spectrum, but I think it’s also something where we don’t know how it happened or why it happened. And it’s also difficult to put all these different symptoms together. It’s a really interesting topic.

[00:08:23] Anne Chappelle: Have you met people with Gulf War illness?

[00:08:25] Julie Miller: Yeah. So, our grant that was funded when I was at NIOSH was funded by the Congressionally directed Medical Research Program, so it’s money that’s earmarked by Congress to specifically study Gulf War illness—at the time, anyways. And we had the privilege to work with these people that had Gulf War illness or people that were representing veterans that were concerned about their health and didn’t really know how to get the appropriate medical treatment or medical attention that they needed.

A lot of times, I think people will go to the doctor and you say what you have, and either you’re getting dismissed or they just don’t know what it is. And I think it was number one, “We see you,” and validating those symptoms and their experience, but then also, ultimately, trying to figure out what had happened. What is this from? Is it from some combination of your stress when you’re deployed, and it’s that intersection of your body’s innate stress response but then also different chemical exposures. And I think of it as the ultimate mixture.

Mixtures are difficult in of themselves, you know. We’re constantly exposed to mixtures every day, but what about just stress response is also a component to that. And when you’re stressed, your body reacts differently to any type of insult, whether it’s some type of injury, wound healing, exposure to a certain chemical, or things like that.

So, I was really excited by the concepts and the research that we were doing at the time. 

[00:09:47] Anne Chappelle: So, you have this target population. What kind of research did you do to try and help them?

[00:09:53] Julie Miller: In our laboratory, we had an animal model for Gulf War illness, which was giving intermittent waves of cortisol that we give to animals, which would be corticosterone, and then, also, they would have a single insult to some type of organophosphate, whether it be certain type of cholinergic-acting chemicals, irreversible or reversible. And then, they would be stressed at the time, and then, we would monitor them. So, they would have that one exposure to a chemical insult, and then, every other week, they would be getting waves of corticosterone or exogenous stress. From that, we saw that there was a neuroinflammatory relationship that was unique related to the stress exposure plus the initial chemical exposure.

So, essentially, trying to either mimic some type of chemical warfare agent, but then also a lot of the pesticides or things that were used on soldiers uniforms at the times, things like that that were cholinergic acting. It was really just trying to figure out what type of chemical or soup of chemicals may have been implicated in doing this. And using an animal model, that’s something that we could reproduce and then be able to test not only how to get that appropriate paradigm or that appropriate animal model but then ultimately being able to try and have some type of treatment options that we could figure out what would maybe lessen neuroinflammation or reduce some type of response.

[00:11:20] David Faulkner: I think with something like Gulf War illness, there’s this sort of cluster of symptoms, right? As you described. But there’s been a lot of mystery around the physiology of it. What I’m really interested in is the way that your analytical chemistry background gives you a different way of looking at this problem because so far this is the sort of thing where, how do we measure this? What are we measuring? How do you anatomize that problem to figure out how do we establish causality here?

[00:11:48] Julie Miller: Exactly. And what is that disruption and brain chemistry that’s really going on? If it’s something that is affecting the brain, or neuroinflammation as we know it, a lot of these chemicals we know are potentially acting on the brain. There’s a lot of important processes that are occurring, and how does just a one snapshot in time exposure causing something many years later? And something that’s kind of phasic, right? So, it’ll happen intermittently. Maybe it happens when you get sick, you get really sick, whereas someone else if you have just a run-of-the-mill cold, they’ll be fine and be able to recuperate. But maybe when you get sick, it takes many weeks, and you just feel down and out. So I think that was really trying to understand not only the symptoms that people were experiencing but then tying that back to something that we can reproduce in the lab and try and understand.

[00:12:37] David Faulkner: You’re looking at Gulf War illness, and you’re tying in these really high-stress situations, these acute high-stress situations, plus exposures. And then I’m thinking like, “Okay, there have been other large-scale, high-stress situations that have emerged since.” You can look at the experience of the United States after 9/11, the great recession 2007/2008. You had the pandemic is pretty stressful. You think that there is a chance that we could see other types of illness emerging as a result of these really super high-stress events that affect a lot of people.

[00:13:12] Julie Miller: Yeah, absolutely. You know, it also speaks to the fact that it needs to be recognized, especially when it comes to emergency response or things like that, our public health officials and public health staff, the pandemic was probably the pinnacle of stress for that type of response and that field in general. And so, really just being able to reflect and get back to, “Oh, you know what, maybe I do need to talk to someone about this.” Or also, putting at the forefront how important mental health is. Mental health is health. And it’s something that I think we all need to recognize that our own stress response is another exposure that we’re providing an insult to our body. And I think that’s just something that it’s the ultimate mixture of trying to figure out how stress or a lack of stress is impacting our response to many different things.

[00:14:00] David Faulkner: This idea of chronic stress or really high-level acute stress is something that we see reflected in other parts of the literature, right? Where different types of minority populations show worse adverse health outcomes across a variety of different exposures?

[00:14:15] Julie Miller: There’s been a big emphasis, and rightfully so, in the last probably 5 to 10 years of really trying to get environmental justice calculations put into so much of what we do. When we’re looking at a contaminated site and the community nearby, environmental justice metrics absolutely influence how that community is going to have that exposure affect them. It’s not just that maybe they live near a plant that’s emitting a lot of particulate matter or something like that for generations, but also, there’s the components of the added stress: Are they connected to health care? Do they have access issues? How does socioeconomics affect that? And I think a lot of that framework and those calculations are an attempt to recognize that it’s not just, “I live here, and this plant is here. This is my exposure.” It’s really, “Wait a second, these are all the other things going on in this community, and they have that added. This plant is polluting my community situation.” So, I think they’re great first steps, and I think it’s important that it’s included when we’re trying to evaluate hazardous waste sites or different locations. 

[00:15:26] David Faulkner: So, is this perhaps, maybe coming up with different ways of measuring the physiological burden of stress? Could there be a way of measuring physiological stress that would allow us to actually apply these measurement techniques to say, “Actually, we can quantify what effects poverty and racism have done to these bodies”?

[00:15:48] Julie Miller: Ultimately, that would be the goal. I think we’re in the infancy stages of even being able to try and incorporate that. We’re already struggling with just having chemical Y plus chemical X together. But I think, ultimately, that would be the dream: to be able to tie in physiological stress, whatever that stress might be to you. And everyone doesn’t feel stressed equally, right? Being able to include that would be amazing. But, right now, I think we’re at the ground level but trying to get there.

[00:16:15] David Faulkner: So, is it just cortisol, or is that the only game in town? Or are there other things that you could measure?

[00:16:21] Julie Miller: So, your cortisol is essentially your flight-or-fight response or stress response. And I know when I’m in stressful meetings, whether that’s a public meeting to talk about an air quality study or whatever, my watch will tell me not only relax. It’ll start saying, “Oh, you’re actually in a HIIT class, a high-intensity interval training.” It thinks I’m vigorously exercising. And so, as a scientist, we’re all obsessed with data. I’m obsessed with looking at things like that, too. And I think just trying to understand those inflection points, but then, how are they sustained and things like that is really interesting. But yeah, cortisol would be main one.

[00:16:56] David Faulkner: What about secondary measures or things like that, thinking about long-term cortisol effects on the body. Do other things get shifted? If you’re just constantly pressing the gas, that’s got to do something to other body systems. There should be biomarkers, right?

[00:17:09] Julie Miller: Yeah, I think a lot of times our—how do I put it?—our emergency response system in our body, our cytokines, so they’re the ambulance coming and the siren saying, “Okay, something’s happening.” So, you have, whether it’s related to a physical stressor or a physical injury heat, cold, all those kinds of things. When you’re someone that has been chronically stressed, for example, maybe your body can’t respond as quickly or as well to those types of exposures, too. So, I think those types of things are absolutely something you can look at and trying to understand because they, especially cytokines, they can fluctuate so quickly. So, I think that’s something you can look at, too.

[00:17:48] David Faulkner: Yeah, they’re meant to be really fast. Makes sense. 

I’m intrigued by this study that you worked on., “The Salivary Cytokines as a Biomarker of Social Stress and a Mock Rescue Mission.” Can you tell us a little bit about that because that sounds really intriguing? 

[00:18:02] Julie Miller: Yeah, wow. The story behind that one. That was a project that I started when I was in, I think, my third year of graduate school, and it was a project for DARPA. And it was trying to understand how to better construct special operator teams. So, you think of Bud’s training or Navy SEALs, and you get all these high-operating individuals together, but how do you make the best and most cohesive team? ’Cause it’s not necessarily all the straight-A students or maybe the people that can run the fastest mile together, but it’s how can they strategically work together and be the best team? And we’re trying to understand if there was anything that you could measure. To put a quantity or to quantify that as opposed to using psychological metrics for these personalities usually would get together or would usually get along well. And so, it was trying to understand cytokines and then also looking at like heart rate variability, things like that. 

So, we had a bunch of ROTC members at WVU connected to different wearables—this was before everyone had a watch—that had different metrics on them. So, we had these chest straps that had different things that they could measure. And then, we would collect blood and saliva samples before and after they would do maybe some type of mock stressful situation. I don’t know how stressful it might have been. I think a lot of things are stressful just because of the competitive nature of people. 

[00:19:25] David Faulkner: Could be just like, “Do a bunch of math homework,” or it could be, “Climb this pole.” 

[00:19:29] Julie Miller: Yeah, and especially when you’re on a team, you want to work together well and do it best. Are you someone that would assume the role of leader, or are you someone that would rather be, “I just need someone to tell me what to do, and I’m going to go do it”? And so, it’s trying to understand those dynamics of what makes a good team and if there’s someone that would maybe physiologically or chemically be a leader or physiologically or chemically be a great follower for things like that. It was a weird project. 

[00:19:54] Anne Chappelle: I was thinking, “Oh, these grants you had, oh, those were back when maybe you were at Stantec or graduate school,” but no, you’ve got one with ATSDR right now, “Promoting local efforts to reduce environmental exposure. Tell me more.

[00:20:08] Julie Miller: Yes. Thank you for reading that out because we all say, “APPLETREE.” And then, that’s when I follow up with it’s a very long acronym for a title of a grant, but no, it’s funded by ATSDR and it’s a cooperative agreement grant. There are, I believe, 32 states right now that are funded for it. It’s a competitive grant and it’s mostly to evaluate hazardous waste sites, Superfund sites, things like that within your state.

And Pennsylvania, we have the third most NPL or Superfund sites. I think we have 91 or 92 now. We just got a new one this spring, but Contaminated Site is our health assessment program. So, trying to understand at the end of the day is maybe it’s a active industry. So, are they actively polluting or emitting certain things into the air that could be affecting a nearby community, or is it a Superfund site that we’re trying to understand? Is there still risk to the community, whether it be kids trespassing on a facility that doesn’t have a fence, or is it something that has contaminated groundwater and now there’s an underground plume that is potentially impacting a nearby community?

So, it’s the whole gamut of vapor intrusion groundwater impacts. Pennsylvania, we have, I think, up to a third of the residents are on private well water. And so not regulated, but also in Pennsylvania, the well installation construction and then testing is also not regulated. So, we are one of two states that have that.

There’s many different types of threats within Pennsylvania. And so, we try and understand what data is available, and how can we say is a community safe or maybe at risk for detrimental health effects?

[00:21:47] Anne Chappelle: How do you prioritize?

[00:21:49] Julie Miller: So, for prioritization, I think, I have a whiteboard that has a very long list of things that I need to do, but for our health assessment program, we have certain sites that are priority based upon the size of the potential population being impacted, or is it something where there’s a potential risk for acute exposure potential or hazards and things like that? And in terms of prioritizing sites, we try to make sure that we are paying attention to all sites, of course, but there’s ones where, is the community more at risk? Maybe there’s a groundwater plume and everyone in the area is on public water, so we’re not necessarily concerned as much with the drinking water implications as we would if the whole community was on well water. Is this something where we need to step in and get someone to install point-of-entry systems or things like that so that they’re drinking safe water? And so, I think those types of prioritizations are important. 

I have our APPLETREE grant. We have three staff that is working on that grant. So, we have health assessors that are responsible for several sites. They write the reports, they review the data, and then, I’ll review the report to make sure for technical accuracy and things like that.

But then, emergency response can always throw a wrench into all of your plans because an emergency can happen at any time: Friday evening, after hours, Saturday morning, all those times. In those instances, things that usually then jump to the front of the line because I have to protect human health in the next five minutes or five hours, whatever it is.

So, I think that’s part of it. And then, there’s always some projects where maybe I only need to devote a little bit of time to it per month or per quarter, things like that. But yeah, wear many hats. I’m involved with our health assessment program. We have harmful algal bloom program, trying to understand a lot of the lakes within Pennsylvania. You know, are there cyanobacteria events going on, and is there a consideration for needing to close a beach? Things like that because maybe the levels are at a place where it wouldn’t be safe for someone to be swimming, for example. We have our Fish Consumption Advisory Board assistance to our DEP, which is the Department of Environmental Protection. So, they’re the ones that will collect all the data. We don’t collect any environmental data for the Department of Health. We rely on our state and federal agencies to do a lot of that. Emerging contaminants of concern. We also have an environmental health complaint line. So, if you’re a resident of Pennsylvania and you’re saying, “I’m having health effects. Maybe I’m having asthma. Maybe I’m having more asthma attacks than normal, and I’ve noticed that there’s a lot of bad days with air quality.” Maybe someone will call in and want to talk to someone about that, or maybe someone is on private well water and they had it tested and they’re like, “There’s a lot of arsenic in my water. What do I do?” And then, we’ll try and answer those questions for them, within a health context and health lens. And so, the phrase “tox on cal” is essentially like anything and everything related to human health toxicology can essentially come to my desk. 

[00:24:45] David Faulkner: So, I’m guessing you drink a lot of coffee then.

[00:24:47] Julie Miller: Lots of coffee. I love coffee. 

[00:24:51] David Faulkner: So, we’re coming up towards the end of our time together today.

We have a couple of questions that we like to ask everybody, and my favorite question is what would you be doing if you were not doing what you were currently doing for a living. What would you be doing in an alternate universe?

[00:25:04] Julie Miller: Oh, gosh. That’s a great question. I think at the end of the day, I always love teaching. So, I think I probably would have liked to mold young minds to be excited about chemistry and science as much as I am. So, anytime we have community events where I get to talk to a little kid about soil lead or things like that, that’s when I’m the happiest. So, I think, ultimately, being a, probably being a teacher would be a dream job for me.

[00:25:29] David Faulkner: Noble, very noble.

We want to be respectful of your time. So, we’ve come up on the end part of the interview, but thank you so much for talking with us today. This has been absolutely wonderful.

[00:25:39] Julie Miller: Thank you so much. 

[00:25:40] Anne Chappelle: Thank you.

[00:25:41] “Decompose” Theme Music

[00:25:47] David Faulkner: On the next Adverse Reactions,

“Cardiovascular Risks from Low-Level Metal Mixtures” with Nivetha Subramaniam, a student at McGill University.

[00:25:57] Nivetha Subramaniam: So, arsenic on its own can generate ROS. So, we studied that in a dish where we have the cells of interest, we add arsenic, and we look at their effects. Do they increase ROS? Do they increase lipid uptake? So, all these, yes, same thing with cadmium. It has been done. Really, it’s the early on proatherogenic mechanisms where they can have an effect and that could eventually lead to your atherosclerosis. And we’ve actually characterized the plaque size and the plaque phenotype in these mice. So, we’ve done the early proatherogenic mechanisms in a dish.

[00:26:25] “Decompose” Theme Music

[00:26:29] Anne Chappelle: Thank you, all, for joining us for this episode of Adverse Reactions presented by the Society of Toxicology.

[00:26:36] David Faulkner: And thank you to Dave Leve at Ma3stro Studios,

[00:26:39] Anne Chappelle: that’s Ma3stro, with a three, not an E,

[00:26:42] David Faulkner: who created and produced all the music for Adverse Reactions, including the theme song, “Decompose.”

[00:26:48] Anne Chappelle: The viewpoints and information presented in Adverse Reactions represent those of the participating individuals. Although the Society of Toxicology holds the copyright to this production, it has,

[00:26:59] David Faulkner: definitely, 

[00:27:01] Anne Chappelle: not vetted or reviewed the information presented herein,

[00:27:05] David Faulkner: nor does presenting and distributing this podcast represent any proposal or endorsement of any position by the Society.

[00:27:11] Anne Chappelle: You can find out more information about the show at adversereactionspodcast.com 

[00:27:17] David Faulkner: and more information about the Society of Toxicology on Facebook, Instagram, LinkedIn, and Twitter.

[00:27:23] Anne Chappelle: I’m Anne Chappelle, 

[00:27:24] David Faulkner: and I’m David Faulkner. 

[00:27:25] Anne Chappelle: This podcast was approved by Anne’s mom.

[00:27:29] “Decompose” Theme Music

[00:27:31] Episode Ends