Recently I gained a cube-mate at work. His name is Turqi (short for Turquoise), and frankly, he isn’t the smartest fellow I know, but he is beautiful. He is the first Betta splendens I have ever kept, and I wanted to learn more about him (and see if I could find anything interesting to blog about in the process). So I searched the literature, and I found many papers, including this 1957 paper on Betta splendens color genetics by Wall brunn et al. One of the coolest papers though was written by Sharon Lynn and colleagues detailing an undergraduate laboratory exercise using Betta splendens as a model organism in a laboratory to investigate mechanisms of aggressive behavior. Using bettas in labs to observe aggressive behavior is nothing new, but this paper had a twist. It was an actual physiology laboratory, titled “Fish on Prozac”, and the laboratory, in which students expose bettas to water containing fluoxetine (the active component of Prozac™), serves to illustrate several concepts including: interrelationships of physiology and behavior, the mechanism of action of SSRIs, experimental design and statistical analysis, and the interplay of environmental contaminants and animal physiology in regulating the expression of behavior. It was that last objective that interested me. SSRIs in our water? At concentrations high enough to affect animal behavior?
I know antibiotic contamination of water supplies is a problem. I know that you are never, ever supposed to flush old drugs down the toilet, wash them down the sink, or toss them into the trash. I am fortunate to live in a community where the local police department has a 24/7 drop box for expired/unused pharmaceuticals, and I use it. But I never realized the extent of the environmental problem or really stopped to consider the consequences of having compounds that muck about with neurotransmitters as contaminants in our water supply.
It turns out that I am a little behind the curve on this topic. A fair amount of work has been done looking at pharmaceutical products and by products that end up in sewage treatment plant influx and efflux, surface waters (lakes, rivers, etc), and ground water, and some work (though significantly less) has been done to see if these same compounds are making it into drinking water (Mompleat et al. 2008; Synder and Benotti, 2010). The problem isn’t limited to fluoxetine or antibiotics, but includes pharmaceuticals like ibuprofen, codeine, steroid hormones, lipid regulators, warfarin, and others. However, to keep this blog post to a reasonable length, I’ll stick to fluoxetine.
In a 2012 paper Winder and colleagues, studied spontaneous swimming in the sheepshead minnow (Cyprinodon variegatus). In this study they treat the fish in water containing varying concentrations of fluoxetine and found that at the highest concentration that they tested, which was well below the lethal dosage for the minnow but above the reported concentrations in surface waters for the United States or United Kingdom, spontaneous swimming behavior was affected.
Other studies have described reproductive effects of fluoxetine found in water and sediment on freshwater snails and midges whose life cycles that involve sediment-borne larval stages (Sánchez-Argüello et al. 2009). An earlier article described effects on growth and reproduction in Daphnia, the freshwater amphipod, H. azteca, and a freshwater shrimp, but no effect on the midge (Pery, et al. 2008). In 2010, a nice study by Guler and Ford garnered some attention. They showed that shrimp exposed to the same concentrations of fluoxetine that are found in waste water efflux are five times more likely to move toward light, rather than seek dark spaces. This makes them more vulnerable to predators, and could ultimately affect the aquatic food chain (Guler and Ford 2010). Granted these species are probably more affected by the relatively low concentrations of these drugs in the water than you and I are, but what happens as the concentrations increase? And just how much do you need before you start seeing drug interactions between things in drinking water and prescriptions you are taking? And how sensitive is a human fetus in utero to these contaminants?
The problem with pharmaceutical compounds in the water is a daunting one. Detection is not simple. The biological assays that are based on indicator organisms like Daphnia or snails are time consuming and laborious. Analytical detection tests are not simple and usually involve rather complicated chemistry and equipment, and considering the budgets within which most municipal water treatment plants must function, performing lots of liquid or gas chromatography or mass spectrometry analysis may not be an option. Furthermore there are almost an infinite number of pharmaceutical and personal care contaminants that must be detected not only in their unaltered but also in their metabolized and partially metabolized forms. And, after these contaminants are detected, somehow they must be safely neutralized. The chemists among us have a lot of work to do.
The easiest solution is to prevent the contamination in the first place, but pharmaceuticals and personal care products do a great deal of good and alleviate much pain and suffering in the world, so eliminating the source really isn’t an option. However, we can significantly reduce the source of contamination by using drugs at the minimal effective dose and only when required to treat a specific condition (both in agriculture and medicine), discarding unused pharmaceuticals properly, and working to improve drug design to include an environmental evaluation step for both the manufacture and the physiology of the drug.
So as I look at Turqi, I think we really do need to do some education about this problem of water contamination and its ramifications. I love the Lynn et al. laboratory “Fish on Prozac”, because it uses a real-world problem to teach science, a lot of science (neuroscience, environmental science, experimental design and data analysis). You can even teach a little ethics by having your students write the proposal for the laboratory for the IRB. Students would gain a lot from seeing first hand how these contaminants, which they only know as two-dimensional, stick chemical structures on a page in their textbooks, can have real-world consequences. My only problem with the lab is that I can’t figure out what you do with the treatment water—surely you don’t just pour it down the drain.
Turqi might not be the sharpest fish, but he’s sure taught me a lot.
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