Heart diseases are the most prevalent medical conditions in the country, and drugs like statins and beta blockers are widely prescribed to help treat them. But new research reveals that those drugs are now showing up in local waterways and fish. Reporter Chris Schulz spoke with Prof. Kyle Hartman and doctoral student Joseph Kingsbury about their research into this issue.
This interview was edited for length and clarity.
Schulz: When we’re talking about heart medications, what exactly is it that we’re talking about? I know personally, I took my statin blockers this morning. But for those that are unaware, what are we talking about when we’re talking about heart medications?
Kingsbury: In terms of the scope of the study, that kind of falls under statins and beta blockers. There are additional heart medicines out there obviously, there are probably several dozen at minimum in circulation right now. But we primarily focused on the statins and the beta blockers.
Schulz: What led you all to first of all even be looking for these medications in our waterways?
Hartman: For a long time, I’ve been kind of interested in this. Some of these drugs, I’ll let Joe talk about the beta blockers, but the statin drugs, for us, we’re trying to control cholesterol and fat and things like that in our bodies. You hit 40 years old, and they prescribe you these things, whether you need it or not, so they’re very prevalent out there.
But for fish in particular, it’s important for them to be able to store lipids in order to get through lean times, to make it through the winter. In terms of reproduction, lipids are what fuels that egg in a fish in order to be able to hatch and survive and make the next generation. For them, lipids are really important to have in their bodies and so anything that would reduce lipids in their eggs, that reduces an already low chance of survival for that egg, that it will even hatch. They don’t have enough energy reserves to make it until it can start feeding on its own, it uses up the yolk sac, just like a chicken egg. That’s its fuel. So anything that would reduce that for them might be affecting reproduction of fish. But it’s probably not lethal, not something that we can observe because it’s probably just eroding population. So I was interested from the perspective of “This could be sort of a silent, negative thing happening to our fish populations,” where we might see those that are exposed to these lipid drugs, their populations declining. And we don’t know why because we can’t see the smoking gun that in this case, would potentially be the statin drugs.
Schulz: Joe, what about for you? What led you to this line of research?
Kingsbury: I started my master’s in 2019 and I didn’t really have a project set. I have a water quality background from previous work, as well as an interest in overall fish physiology and toxicology and stuff like that because I’ve worked with more traditional contaminants like acid mine drainage, whatnot. I tried to pitch a project involving water quality impacts to fish health. I approached Kyle, and Kyle’s like “We should go talk to the USGS Co Op unit leader” who had this idea since 2017-2018. She turned me on to [it] and so I did a bunch of digging, and I realized “Oh, there actually might be something here.” We haven’t really tapped into this type of research super heavily yet. And this might be a fun and actually quite important project for us considering the widespread use of pharmaceuticals and pretty much everyday life across the globe.
Schulz: These are very prevalent medications, statin and beta blockers. Heart disease is the number one illness that people live with in the country if I’m not mistaken. Can you explain to me where you all theorize this is coming from? Is it pass through in humans into wastewater? Or is it improper disposal of excess medication?
Hartman: It’s purely going through wastewater. Joe could give you more details about the processes there because actually, part of his study was collecting water samples, and some of that was done at the sewage treatment plants, both in-stream and also in the plant.
Kingsbury: We’ve seen a lot of different work regarding wastewater treatment facilities, and that, for the most part, when we ingest these types of pharmaceuticals, our bodies are not perfect, they’re never going to get to ingest and process 100 percent of the drug. Oftentimes, we’ll process a given proportion, it varies from pharmaceutical to pharmaceutical, every drug is a little different. But basically, we will end up excreting, usually through our urine or feces, some quantity of this pharmaceutical. And because they are very resistant to actual degradation, because they’re meant to be shelf stable, they’re meant to be processed in a very specific way within our bodies, they hit our wastewater facilities, which actually don’t recreate those same processes. And so they don’t always break down and basically remove these pharmaceuticals as waste. What ends up happening is we treat all this water and stuff and we go, “Okay, it’s clean, it’s safe to return back to our surface waters,” and we just discharge it, but we never actually specifically treat it for the pharmaceuticals per se.
Recently, we’ve seen it’s detected globally at this point. Usually, the sewage treatment facilities are a primary source of the pharmaceuticals themselves into our surface waters. We do occasionally get it from landfills, which is just the conglomeration of runoff from landfills. Other drugs can come from agriculture, if we’re using, say, antibiotics or other pharmaceuticals on livestock, we can also get it from there. But for the most part, it’s coming out of our sewage treatment facilities, which just aren’t equipped to really treat for these pharmaceuticals and these more complex compounds.
Schulz: What did you see in the field, when you detected these medications, in the fish that you studied?
Hartman: I would say, sort of a point of clarification, is part of the reason why we’re so concerned about how pharmaceuticals might affect wildlife is because usually if they do a study at all, it’s with some obscure species, like fat head minnows or something. And their end point is death. Well, the concentrations that they’re going to find in a river, they’re not going to kill the fish outright, but they might reduce the lipids so that they don’t have enough lipids to make it through the winter. Whereas previously, if they weren’t exposed to them, they would be fine.
Maybe now we’re seeing a higher mortality rate. What we see when we’re out sampling fishes, we see the ones that are surviving, not the ones that passed away. So it’s difficult to detect it, and it’s certainly not anything that a company is required to do. But we know these drugs are necessary, it’s more of, let’s find out what impact they are having. We tested four different medications: two statins and two beta blockers, and some of them are less influential on the fish. So it might be more of a “Let’s steer doctors towards prescribing this drug as opposed to that drug.”
Schulz: Oftentimes, if there’s a big die off, that’s what concerns people. So what’s the actual impact that you saw in your study in the field? What was the indicator to you that this was actually an issue?
Kingsbury: We sampled a bunch of different species in the field. And we grouped them by genus, because in terms of an individual genus they’re very similar to one another, like species to species pretty much. For the data analysis, we had to do that to make it really run. But what we saw was we used something called relative condition, or relative weight, I should say, to see how overall condition of a fish changed based upon concentration of the drugs. We’re able to measure drug concentrations upstream of a given wastewater facility and downstream. Then using a little bit of chemistry, we can estimate the concentration near the discharge point. From there, we were able to capture the fish and assess relative weight as an index of health. Basically how thick is that fish, and the bigger the fish, the better, compared to its average.
What we saw was that different genuses responded differently to different drugs. We kind of expected because you know, species do alter, and they have slightly different pathways and like different body shapes and different characteristics. We definitely saw a mixture of negative and positive, we saw some fish responded positively to exposure, whereas other fish responded negatively as exposure increased. And when I say exposure, I’m talking trace amounts, we’re talking nanograms per liter, which is incredibly small. To even see that that effect size, with some confidence, was surprising to us, at least. I was kind of hoping “Well, maybe we won’t see anything, maybe we will.” But when we saw the model produce those results, when we saw specific genus have actual decreases, over even minute increases of exposure, that was a little bit concerning.
That kind of played into the fact that while these pharmaceuticals are not going to probably kill those fish outright, they’re going to add additional stress and reduce their survival chances moving forward as they’re consistently exposed. And the difference between what we did versus a traditional study is, I wasn’t looking for, “I need to give them this much drug to kill them,” versus “I wanted to see how their condition changed over relative to exposure,” which is a little different than traditional toxicology, which often relies on like controlled endpoints, where it’s we looked at fish to have an exposed presumably for their entire lifetime because of the system they came from, which was the Tygart Valley, and the West Fork Rivers here in West Virginia.
Schulz: So what’s the next step for your study?
Kingsbury: Traditionally, this study is done in more urbanized environments, like say Pittsburgh, for example versus we typically ignore rural areas because of low population densities. The next step, really, would be to basically create more accurate estimates of the pharmaceuticals entering the waterways over time, and that is hard to do. But it’s not impossible. Part of that involves more rigorous water quality testing, to get a better feel for how that fluctuates over time, because there’s going to be seasonality to it, because temperature and other types of parameters will alter the concentration within the water column.
Hartman: Just seasonally in terms of discharge in the river, the old “Dilution is the solution to pollution” genre there. So when we’ve got higher flows, we still probably got the same amount of drugs going in. It’s just more dilute.
Kinsbury: That was part of my study, as well as looking at how the demographics of West Virginia could potentially contribute to pharmaceuticals, based upon the National Health Institute’s, this age group and this demographic are prescribed at this rate. We can take that and apply that to local demographics as well, instead of trying using prescription sales, which is very, very hard to do because of the way prescription sales work. But instead of actually looking at demographics, and trying to estimate our loadings going into our treatment facilities to help us prioritize “Well, this is what we should probably be looking at based upon this demographic” like this demographic is older, and more likely to prescribe these drugs versus, say, a younger demographic or more transient demographic, that’s not going to experience that same type of pharmaceutical level.
That’s kind of the next big step is, you know, getting a better feel for what areas need to be prioritized for further research. To even see it in rural areas tells us that this is not just a city based problem, this is an everywhere problem, most likely, other than places that have no human influence whatsoever, which are pretty rare far between at this point. So that’s probably our next step would be getting better at estimating our pharmaceutical loadings within a given system based upon surrounding demographics and who is contributing to those treatment facilities. And in conjunction, every facility is a little different. Some facilities are very basic, others are very complex that will have third and fourth stage treatments like UV treatment, activated sludge, aeration, stuff like that, and the more treatments they have, the better it is. But being able to basically see that pattern and map that pattern relative to our demographic loadings is kind of the next big step. But that’s definitely more of a civil engineering type of thing. So that’s why this is very interdisciplinary, very collaborative, where we have to talk to chemists and engineers and kind of figure out well, where do we, where do we prioritize? Because we don’t have unlimited money, we have to pick and choose where to pick our battles.
Schulz: What is the desired outcome for this?
Hartman: I think ultimately, it’s like, we’re still trying to understand, where these drugs are, where they’re affecting things. Joe said some species responded, they were in higher condition, when they were exposed to higher concentrations, others were lower. We’re still trying to figure that out. We probably should give a shout out to Dr. Sanchez, who Joe worked with up at Pittsburgh on the methods to actually be able to detect this in water and fish. I want to make sure we at least give him some props there since we worked together to achieve that.
But I think until we know a little bit more about what’s involved in and then breaking it down, like, can we actually show that we have reduced recruitment, reduced reproduction in the laboratory, where we have more controlled conditions? I don’t think we’re looking to change anything until we have more information. But ultimately, if we have information that shows these drugs are way worse for the fish in the environment, then there are plenty of alternative medications that maybe aren’t.
Kinsbury: Our current long term goal is looking at more chronic toxicity, long term exposure regimes, just to get more information on what’s really going on, because again, we just don’t have unlimited resources. This is part of the process of informed decision making, in terms of what drugs are you more concerned about? Oftentimes we talk about risk and risk mitigation, and just highlighting which drugs even require risk mitigation is part of our current problem of understanding what is actually happening. And unfortunately, all pharmaceuticals are pretty unique.
They’re probably, I would argue, one of the most challenging contaminants of our time, because they’re all so unique in the way they’re designed to target biological pathways, both in us and in fish, because we share a lot of the same pathways. I think for us right now, we’re still in the information gathering stage to begin recommending changes to certain industries, whether it’s the pharmaceutical companies, wastewater management or even doctors in terms of what they prescribe. I still think we’re a ways out from that because we just don’t fully understand the full picture yet. Right now we’re still trying to untangle this huge ball of yarn that is pharmaceutical contamination.
That’s also another area we’re still working on is how to more effectively and cost effectively detect these things within fish, because that’s, you know, it can be in the water. But if we don’t know what’s in the fish, it’s really tough for us to understand how these different exposure levels alter and like, what are those exposure levels realistically. So we’re still trying to figure out how to even look at the picture right now. We can give recommendations on what needs to be changed.
