Studying the effects of metals in whales and alligators, among other species, can offer immense insight into human health, John P. Wise Sr. tells Adverse Reactions co-hosts Anne Chappelle and David Faulkner. Dr. Wise also discusses research on chromosome instability and how you can help people everywhere make connections to the importance of environmental health.
About the Guest
John P. Wise Sr., PhD, is head of the Wise Laboratory of Environmental and Genetic Toxicology and Professor of Pharmacology and Toxicology, Distinguished University Scholar, and Chair of the Center for Environmental and Occupational Health in the University of Louisville School of Medicine. His formal education includes a bachelor's degree in biology with high distinction and recognition from George Mason University and a PhD in pharmacology from the George Washington University.
Dr. Wise’s postdoctoral training focused on molecular epidemiology under Curtis Harris at the National Cancer Institute, followed by experience with occupational health and risk assessment as a Senior Toxicologist at Jonathan Borak and Company. He served on the faculty of the Yale University School of Medicine and the University of Southern Maine School of Public Health before joining the faculty at the University of Louisville.
Dr. Wise’s research focuses on understanding how environmental toxicants affect health and cause cancer from a “One Environmental Health” perspective, considering cellular and molecular mechanisms in both humans and wildlife. He has earned over $14 million in extramural support and published over 130 peer-reviewed research papers. His work has been featured in numerous articles in local, national, and international press and social media sites, including short documentaries with Alexandra Cousteau and Miles O’Brien.
Dr. Wise has mentored and trained over 200 faculty, postdoctoral fellows, and students in biomedical and environmental health research. He fosters a diverse, supportive, multi-layered mentoring environment and is supported by an engaging and active team of faculty, staff, and students from a diverse array of backgrounds, cultures, and perspectives. For his mentoring efforts, he was awarded the 2022 SOT Toxicologist Mentoring Award. His students have won numerous local, national, and international awards and grants and have gone onto successful careers in academia, government, industry, and nongovernmental organizations.
Dr. Wise also has earned the Metals Career Achievement Award from the SOT Metals Specialty Section and education awards from both SOT and the Environmental Mutagenesis and Genomics Society (EMGS).
[00:00:00] Adverse Reactions “Decompose” Theme Music
[00:00:05] David Faulkner: Hello, and welcome to Adverse Reactions Season 2. My name is David Faulkner, and this is my co-host,
[00:00:11] Anne Chappelle: Anne Chappelle.
[00:00:12] David Faulkner: As much fun as the first season of Adverse Reactions was, I think Season 2 is better.
[00:00:16] Anne Chappelle: Hidden.
[00:00:17] David Faulkner: Secretive.
[00:00:18] Anne Chappelle: Exactly.
[00:00:19] David Faulkner: The toxicology that happens when you’re not looking,
[00:00:22] Anne Chappelle: or toxicology that you forgot about.
[00:00:24] David Faulkner: It’s still important, and we’re here to talk about it. Welcome to Season 2 of Adverse Reactions:
[00:00:28] Anne Chappelle: “Hidden Toxicology.”
[00:00:31] Adverse Reactions “Decompose” Theme Music
[00:00:37] Anne Chappelle: “Toxicology Is a Wise Choice.”
[00:00:40] John Wise: Great whales are known to have low rates of cancer. And so, what is it about that that’s helping them avoid cancer despite living 200 years?
[00:00:48] Anne Chappelle: Or, “One Health, Many Ecosystems”: environmental toxicology with John Wise.
[00:00:55] John Wise: And we really wanted to create a space for toxicology environmental stressors, so we coined the phrase “One Environmental Health” as a subset of the One Health to draw more attention to those. There’s always been an interplay between animals and human health.
[00:01:13] David Faulkner: Welcome to Adverse Reactions. Very glad to be here today with Dr. John Wise, Sr.—very important—from the University of Louisville Department of Pharmacology and Toxicology School of Medicine.
Thank you so much for joining us.
[00:01:27] John Wise: Thanks for having me. And I will comment that actually the “Senior” has become quite important because John Wise Jr. is a Society of Toxicology member and starting his own lab next month.
[00:01:37] David Faulkner: Very cool. Wow. So, this interest in toxicology runs in the family.
[00:01:40] John Wise: Yeah. It’s quite a family business actually for us, ’cause all three of my children have PhDs in toxicology or related to toxicology.
[00:01:49] Anne Chappelle: So, did you wed outside of toxicology? Does your partner have anything to talk with you about at the kitchen table? Or is it—
[00:01:59] John Wise: It gets richer than that. So, my ex-wife has been working with me for 20-plus years. Got her PhD with her research focused on toxicology.
My fiancé just recently completed her PhD in toxicology, and my daughter’s significant other, he has his PhD in toxicology, so there’s a lot of tox.
[00:02:19] Anne Chappelle: So, all I can imagine is, thank goodness you went into toxicology and not law. Otherwise, it would’ve been Wise, Wise, Wise, Wise, Wise, Wise, and Wise.
[00:02:29] John Wise: Yep. There are a few papers like that. We have written papers, a number of papers. I didn’t expect them all to go into toxicology. I actually didn’t expect any of them to go into toxicology. I think they went into it, one part because being a professor is a pretty good life. But also because I work on whales and sea turtles and alligators, and they went with me when they were little and I would go to Aquaria and SeaWorld and places like that, behind-the-scenes access to get samples and see things. They got to experience that. So, I think some of that is what inspired them pursue toxicology.
[00:03:03] Anne Chappelle: When I think of some of the things you’ve described about your alligator work and whale work and turtles, I usually think of that reserved as marine biology. So, you still consider yourself a toxicologist?
[00:03:16] John Wise: Oh, no, without a doubt. The core of our work is trying to understand how chromium in particular, but metals in general, turn normal cells into tumor cells to cause lung cancer. We’ve been intensely studying human disease, and we got into the marine organisms and some of the other things from the context of trying to understand human disease at first. And then once in it, realized that there were a lot of marine toxicology questions that it lent itself to that needed addressing.
And then, once there, realized that led to a bunch of ecosystem type–level questions that need addressing. And so, we were playing and working in that arena and that sphere for a long time. And then we learned about this national or international movement of One Health to try to understand interaction of ecosystem health and human health and wildlife health or animal health—studying that interconnectedness as a focal point. So, it was kind of cool that we’ve been doing it for a long time and then realized there was a label for what we did. And we really wanted to create a space for toxicology environmental stressors, so we coined the phrase “One Environmental Health” as a subset of the One Health to draw more attention to those. There’s always been an interplay between animals and human health. So, yes, very much a toxicologist.
[00:04:36] Anne Chappelle: But it’s usually in a more manageable and less lethal species, right? I mean, sea turtles, I get that. But usually, I wouldn’t have expected it in a species that seems quite so hearty, that’s back through prehistoric times.
[00:04:52] John Wise: Yeah, so some of that goes back to pioneering work done by Lou Gillette, who passed away a few years ago. But Lou really was one of the pioneers of the endocrine-disruption field, using alligators as a model. And he really showed that pesticides in the environment were interfering with alligator reproduction, causing endocrine disruption. And he introduced me, as a collaboration, into studying alligators.
[00:05:16] Anne Chappelle: So, this kind of leads me to, can you tell me a little bit more about what is the core of your research and what you’re trying to show using these different models?
[00:05:26] John Wise: So, it’s a two-prong core. At the highest level, we study One Environmental Health, which is the idea that all health is interrelated. And then at a more specific level, we study chromosomes and chromosome instability. And so in human cancer, we’re concerned about chromosome instability causing a normal cell to become a tumor cell. In a wildlife species, we’re concerned about chromosome instability interfering with reproduction and development, so consequently, you get endangered species that don’t survive as well. And then in an ecosystem setting, we’re using chromosome instability and DNA damage as a tool to see if there are consequences of climate change that are emerging over time.
[00:06:06] Anne Chappelle: What kind of tools do you need to do this kind of work? And when I say that, I think of chromosome, instability, DNA damage—those, to me, are classic toxicology. How do you need to innovate to stay competitive for your grant research versus it may be that you just have a ton of actual questions that you can ask with this classical tox tools?
[00:06:30] John Wise: The real cutting-edge, innovative stuff with chromosome instability, aside from understanding the mechanisms for how chemicals cause it, which are not well understood, we’re pretty familiar with translocations in chromosomes and aneuploidy and too many chromosomes, but how exactly you go from a robust cell to those outcomes is not very well understood. We’ve been finding that chromium’s targeting the homologous recombination repair pathway, so it’s inducing the breaks and targeting the repair pathway, which is leading to the structural changes. On the numerical side, we’re finding it’s disrupting central zones, both areas of which are not well studied in toxicology.
But then the really cutting-edge stuff is to start thinking about how you go from a double-strand break in a simple DNA helix, how that affects the various folding levels that gets you to the metaphase chromosome and getting in and learning about things like topologically associating domains, which are into the chromosome structure and folding that really affects gene expression. And then the organization of the chromosomes within the nucleus into what are called chromosome territories, because chromosomes aren’t just randomly in the nucleus; they actually have neighborhoods that they live in. And that’s why some of the translocations occur, because they’re positioned in the nucleus near each other, but that’s also affecting gene expression. And all of that hasn’t been studied in toxicology. So, those are some of the really bleeding-edge things that we’re getting involved in.
[00:07:58] David Faulkner: People think of cells as just “a bag of enzymes,” is the phrase, but they’re these highly ordered structures. And that’s something that I’ve always thought was very interesting, was these questions around how does the three-dimensional structure and arrangement affect all the things that we see? Because we very often just think in terms of almost like a number line in terms of a sequence—this happens to this, this happens to this—but these things are happening in space. So, if we take this One Environmental Health, maybe One Cellular Health, all of these things matter, all of those relative positioning and relationships, these all matter.
[00:08:31] John Wise: Exactly. What I was just telling you about chromium inhibiting homologous recombination repair, it’s not doing that in whale cells. So, what is it about a whale cell that avoids that? So, we treat whale cells and human cells with chromium, we get the exact same amount of DNA double-strand breaks. But in the human cells, chromium can inhibit the repair; whale cells, it cannot. And so, we see chromosome instability in the human cells; we don’t see them in whale cells. The great whales are known to have low rates of cancer. And so, what is it about that that’s helping them avoid cancer despite living 200 years?
[00:09:02] Anne Chappelle: You seem to have a lot of water-based activities for being based in a town that is not waterfront.
[00:09:10] John Wise: Louisville’s on the Ohio River.
[00:09:14] Anne Chappelle: It’s not oceanfront, where you find some of these—
[00:09:18] John Wise: It’s true. So, there’s a couple of things behind that. One is that the University of Louisville sees the future of One Environmental Health and the importance of it in medicine and wanted to have that presence on their faculty. So, they specifically recruited me there.
One of the things that impressed me actually was when they interviewed me, the department chair said to me that people had asked him that question and he had gone up and looked it up and realized that I always flew to the boat, so it didn’t matter where I lived, because I could still get to the boat. And he knew where all the boats were that I used. So, I was pretty impressed with that during the interview.
But I would say that people in the Midwest care about the ocean, and we need people in the Midwest caring about the ocean. So, it’s important to have that message and that presence in the Midwest. The landlocked states need to care about the ocean because it’s such an important thing on the earth, but they like whales and sea turtles—and alligators is a more specialized taste. And so, it’s important to have that presence in the middle of the country as well.
[00:10:17] David Faulkner: That’s something that I think about, too, is you do this work on these incredible habitats with these amazing animals. I personally have this tremendous reverence for nature, and I would imagine that part of that plays into your work as well. Do you find it emotionally challenging at times to see all these oil-covered animals? How does that affect you to do that work?
[00:10:38] John Wise: That’s not easy. We always make a point of spending time with the whales to remind ourselves that—because you know how it is in science, you can just get caught up in your assays and your endpoints and kind of forget about the bigger picture in a way. So, we always take some time to just sit on the boat and listen to the whales, just to hear their sounds and just realize how massive and impressive these animals are.
[00:11:01] Anne Chappelle: So, in terms of thinking about hidden toxicology, when I think of metals and I think of exposures, the ocean’s so big, we’ve dumped stuff in there for so long. Using chromium, where is that coming from? Is it e-waste? Is it this necessary element that just happens to get in the water? I don’t know much about metals. ’Cause when I think of metals toxicity, I think of lead in water.
[00:11:27] John Wise: I think when you think about hidden tox, it’s not limited to metals. I think when we think about chemicals in the environment, it’s hidden, and it’s hidden because the water is not yellow and the air is not necessarily smoggy. In fact, one of fascinating things that we encountered was when we started measuring chromium levels in the whales, we were surprised to find whales that had levels that resembled levels found in the lungs of occupationally exposed people who had worked with chromium for 20 or more years and died of lung cancer. So basically, an individual who worked in the chromate industry, died of lung cancer, and then they measured chromium levels in that person’s lung, the whales had skin levels that were in that range.
But chromium is not like mercury. It doesn’t move up the food chain. It really is an individual issue. And so everybody we talked to is like, oh, there must be a lot of chromium pollution in the water. We said, no, actually, we think the whales are inhaling it. Everybody’s like, no, the air’s pristine, we’re offshore. We look at the ocean, we think it’s clean and pristine. We look at ocean air, we think it’s clean and pristine. And then you realize, no, it’s all full of chemicals and we’re poisoning ourselves as well.
[00:12:34] David Faulkner: It seems like all of these issues really do come back to perception and the things that are right in front of people and making it about people. If you want people to care about the work that you do, you have to talk about it in this toxicology context and say, this affects you, too.
I was talking with somebody, and they said, well, I don’t care about the environment. And I thought, well, where, where do you live? Like, what? Are you in a void somewhere? Like, how is this working? And you’ve done a fair bit of science communication; how do you center these things for people? How do you try to convey that and make it personal?
[00:13:11] John Wise: You have to kind of work with people to dispel the labeling of “environmental this,” or “green this,” and “green that,” and really talk about the world we live in and how this affects all of us. I don’t know anybody that doesn’t want clean air and clean water and healthy parks and healthy forests. I don’t know anybody that says that’s a bad idea. They’re just, their perception is they look around and it all looks fine.
There’s a scaling to this people don’t always think about, too. I had a conversation with my stepdaughters, who are 10-year-old twins. There was a pond that we were walking around up here that’s a source of drinking water for people, for the local towns. So, you’re not allowed to swim in it. And they were hot, and they were like, can’t we just put our feet in it? I said, well, if you put your feet in it, probably no big deal. But look at all these people here; what if everybody puts their feet in it? And they’re like, oh, that’d be really gross. I said, that’s the point. That one water bottle that you don’t throw away may be no big deal, but if a million people take the same freedom and a million people throw away one water bottle into the ocean, now you have million water bottles in the ocean.
[00:14:12] David Faulkner: Right.
[00:14:12] John Wise: And people don’t think like that too often, until you actually discuss it with them. And then they start to go and get it. That was one of the things that struck us, was just how much trash is floating around the ocean. So we were off the Atlantic coast, nothing in sight, nothing. But yet, we were picking up trash every day because it just blows off of boats and blows here and blows there. Balloons in particular. We’ve picked up thousands of balloons as we go on. We’re in the remotest parts of the Sea of Cortez, and there’s balloons floating in the water.
[00:14:39] David Faulkner: Jeez.
[00:14:40] John Wise: That’s why we’ve got to have better and more science communication and, and making science more relatable. I think historically scientists have been too much in an ivory tower on a mountain saying, we’ll tell you how it is. That’s opposed to increasing the scientific literacy of everybody, so people know how to think about it.
[00:14:57] David Faulkner: Like accessibility.
[00:14:58] John Wise: Yeah. I think it’s critical.
[00:15:00] Anne Chappelle: Along those lines, too, a couple of thoughts was, one is teaching people what is a good source of information and what is not. That’s really difficult nowadays with the electronic communication, with Facebook, with everything else, teaching people that scientists are not always right—except don’t tell my children.
[00:15:20] John Wise: Well, scientists are not always right, but mothers are.
[00:15:24] Anne Chappelle: Yes, that’s true. But around really saying, this is the information I knew at the time. And I’ve got new information. The whole process of systemic improvement. But how do you train your students to be good public communicators?
[00:15:38] John Wise: Well, for us, it’s a specific point of emphasis. I mean, we work on it all the way through a student’s career. We work on it collectively and individually, and it’s just a specific point of emphasis. And a lot of it is understanding your audience and what are you talking about? I always tell them, explain it so your mother can understand it, and you won’t offend any of your colleagues. Most of the people you’re talking to don’t remember what chromosome instability is. It doesn’t matter if they have maybe a PhD and an MD; if they haven’t been working on it, they haven’t thinking about it. They just need a reminder. So, if you’re speaking at a level that your mother can understand, anybody can understand it.
[00:16:14] Anne Chappelle: In your field, what’s the next new thing you think that’s going to come out? What’s the next thing we’re going to hear about from the Wise Lab that we’re going to go, that’s cool?
[00:16:25] John Wise: The challenge of toxicology and aging in what we’re referring to as sort of two sides of a toxic coin, if you will. On the one side, in nine years, 20%, 25%, something like that, of the US population is going to be over 65, which is considered geriatric. In the next 19 years, by 2030, I believe it’s 2030, we’re expecting to have 300- to 500,000 people who are a hundred years old. So, that’s 300- to 500,000 people who’ve lived 35 years or so in a geriatric state. And if you think about how the body is changing when you’re geriatric, and then you think about risk assessment, and risk assessment’s concerned about the most susceptible populations, most susceptible part of our population. And we think a lot about unborn children or developing children. What about the age? The age that individuals are going to be exposed to chemicals for 30-plus years in a body that’s breaking down? So, what’s happening from a toxicology perspective to the aged?
And then there’s the other side of the toxic coin, which is the idea that chemicals in the environment are prematurely aging your organs. So, you may look like you’re 40, but your organs may be 65. It’s a term called “gerontogen,” which was coined in the ’80s, ’84 or ’87. There’s only a handful of papers out there about your gerontogens, but I think those are both big areas are going to grow because our aging populations is growing. We need to think about, what’s the susceptibility of the aged population, but also how are chemicals making us age internally faster than we are externally?
[00:18:00] David Faulkner: Fascinating. A gerontogen. This is the first time I’ve ever heard that term. And that is really interesting, really interesting stuff.
[00:18:06] John Wise: Yeah. We’re up here developing this small fish model to answer some of those questions. So, we’re going to look at, should we call it young, middle-aged, and old fish and see how susceptibility changes and see whether the organs are aging. And just to bring it back around, one of the hallmarks of aging and gerontogens is chromosome instability.
[00:18:24] Anne Chappelle: Bringing it back around. In the same way that children are not little adults and geriatrics are not just continuation, older, you know, they’re just not adults. I think it is true, especially when you have more of the legislators in that other demographic, it’s suddenly going to be very interesting to people.
[00:18:46] David Faulkner: We’re getting down to the last few minutes here. What is the most significant adverse reaction that you’ve experienced in your life?
[00:18:53] John Wise: The most significant adverse reaction was the enormous anti–environmental health during the Deepwater Horizon crisis.
[00:19:04] David Faulkner: Really?
[00:19:05] John Wise: Yeah, we had some remarkable experiences with planes following us around. And you had a whole ecosystem in turmoil, and then you had all the communities dependent on it in turmoil, and very little ability of scientists to talk to them because of the legal matters surrounding it. And there’s some crazy things that happened, and I was just surprised because you think we’re all in this together trying to understand what’s going on and what the problem is and how to mitigate that. And that’s not the case.
[00:19:34] Anne Chappelle: Keeping with the theme of “hidden toxicology,” could you share any of your hidden talents?
[00:19:41] John Wise: A hidden talent? When I was younger, I did a lot of community theater. That’s kind of unusual.
[00:19:45] Anne Chappelle: That’s a good one.
[00:19:46] David Faulkner: We haven’t talked to anybody who has done that sort of thing, really.
[00:19:48] John Wise: I think the biggest thing I take from that experience into my science communication is that it’s about the audience. It’s not about the speaker. That’s what I try to convey to the students. And I had directors, or that was what they conveyed, was your voice has to be loud enough so the person in the furthest corner can hear you. And I remember, somebody changes a scene and there’s a prop left behind—don’t ignore it. Pick it up and integrate into what you’re doing, because the audience will worry about that prop. So, you have to worry about what the audience is thinking. That’s the biggest thing.
And I think that’s the biggest thing in science communication, because the things that I’m constantly reinforcing for my students is don’t make your graphs so small that people can’t see them and don’t speak in jargon. Rather than putting four, five, six graphs on a slide, just make it one or two and use three slides. The audience matters because if you lose the audience, then they’re just sitting there and they’re not paying attention.
[00:20:43] Anne Chappelle: I think those pretty much left most of our questions. Is there anything else you wanted talk about or ask us?
[00:20:48] John Wise: I think one thing we didn’t really touch on is our work in Vieques, Puerto Rico. But—
[00:20:52] Anne Chappelle: I looked at that and your research down there, and I was like, wow, you get to really go to some cool places.
[00:20:59] John Wise: Yeah, we do. I mean, there’s a lot of hard work that goes into it.
[00:21:01] Anne Chappelle: Oh, yeah, I mean it’s not all glory, I know that.
[00:21:03] John Wise: Oh, no. And there’s an element, in all the situations, you have to build local trust. Places have experienced a lot of scientists that come in, get what they need, and leave, and then, kind of exploit the situation.
Vieques was a place that, we were looking for a land-based field lab because so much was on boats. And I got introduced to it from my high school debate coach, who I had not seen since high school. So, like 20 years went by, and then Dale emailed me and said he’d spoken to somebody about grant writing. And they said, well, you should talk to John. So, here was 20 years post–high school, maybe more—it might’ve been 30 years post–high school. And he was talking about how he worked for this small nonprofit in Vieques.
And of course, Vieques was used as a bombing target by the Navy for decades, so a significant metals issue. But Vieques is a small community; there’s no university, there’s no college there. People there tend to stay there. And so, we wanted to work on the local issue of what’s happening with the metal pollution, but also do a lot of K–12 outreach. So, we partnered with the Vieques Conservation and Historical Trust, and it’s been over 10 years we’ve been working with them. Published a couple papers.
[00:22:13] Anne Chappelle: I’ve had a really good time.
[00:22:14] David Faulkner: It’s been great. Thank you so much for talking with us. This has been so fun.
[00:22:16] John Wise: Anytime. I'm always happy to talk.
[00:22:20] Adverse Reactions “Decompose” Theme Music
[00:22:25] Anne Chappelle: Next time, on Adverse Reactions.
[00:22:28] David Faulkner: “A Legacy of Looking at the Life-Giving Properties of Lactose,” or
[00:22:33] Anne Chappelle: “Banking on Milk: Liquid Gold,” with Christina Chambers.
[00:22:38] Christina Chambers: It’s just an amazing thing in the scientific world that we have a tissue that is recommended to be the only source of nutrition—and certainly the primary source of nutrition—for every child in the universe, and yet, we don’t know enough about the components of it, how it functions, and so on. And it’s been a neglected area of research.
[00:22:58] Adverse Reactions “Decompose” Theme Music
[00:23:04] Anne Chappelle: Thank you, all, for joining us for this episode of Adverse Reactions, presented by the Society of Toxicology.
[00:23:10] David Faulkner: And thank you to Dave Leve at Ma3stro Studios.
[00:23:13] Anne Chappelle: That’s Ma3stro with a three, not an E.
[00:23:16] David Faulkner: Who created and produced all the music for Adverse Reactions, including the theme song, “Decompose.”
[00:23:23] 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,
[00:23:34] David Faulkner: definitely,
[00:23:35] Anne Chappelle: not vetted or reviewed the information presented herein,
[00:23:39] David Faulkner: nor does presenting and distributing this podcast represent any proposal or endorsement of any position by the Society.
[00:23:45] Anne Chappelle: You can find out more information about the show at AdverseReactionsPodcast.com,
[00:23:51] David Faulkner: and more information about the Society of Toxicology on Facebook, Instagram, LinkedIn, and Twitter.
[00:23:57] Anne Chappelle: I’m Anne Chappelle.
[00:23:58] David Faulkner: And I’m David Faulkner.
[00:24:00] Anne Chappelle: This podcast was approved by Anne’s mom.
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[00:24:06] End of Episode