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SUMMER 2005
Casting Prozac Upon the Waters
by Kelli Whitlock

Marsha Black has learned that sometimes the best way to see the big picture is to study the small details. The University of Georgia ecotoxicologist has examined water-quality issues for decades, spending most of that time trying to better understand the biological impact that pollutants can have on even the tiniest of aquatic organisms. Recently, she has turned her attention to a new concern — the steady deposit of antidepressant drugs such as Prozac into wastewater, their ultimate presence in creeks, streams, and other surface waters, and the consequent effects of these chemicals on wildlife.

Ironically, when Black’s collaborator, Mississippi State University scientist Kevin Armbrust, was younger, his father used to joke that “the world would be a better place if its drinking water supply had a little bit of Prozac in it.” But while Prozac and related medications offer hope to millions of people who experience a range of mental-health problems, such drugs have properties similar to other pollutants when they wind up in unintended places. And the damage they wreak on aquatic species there could be just as great. Black and Armbrust are discovering, for example, that when certain types of fish and frogs are exposed to “a little bit” of these medications, they experience problems that include slowed rates of development and a sluggish state that leaves them vulnerable to predators.

The intricate relationships among animals and plants that make up an ecosystem depend upon a certain balance. Therefore the question that haunts Black, Armbrust and others is: What happens to those organisms — and to us — if that balance is upset? “We used to think that only compounds in the water would harm humans, and only through direct exposure,” Black said. But scientists have come to realize that the harm may occur indirectly by disrupting ecological biodiversity.

Chemicals Out of Place
Up to 90 percent of many prescription drugs that humans consume ultimately find their way to sewage-treatment plants. While treatment plants that process drinking water remove these chemicals and their metabolic byproducts, these compounds pass through sewage-treatment facilities, which are designed to remove solids and bacteria but are not equipped to screen for pharmaceuticals. Armbrust, who is also the state chemist for Mississippi, was particularly taken aback by a 1999 paper in the journal Environmental Health Perspectives that documented a steady stream of pharmaceuticals — including Prozac and other selective serotonin re-uptake inhibitors, or SSRIs — being passed into the nation’s waters. SSRIs are among the 200 most-prescribed medications in the United States; the number of adults taking antidepressants has nearly tripled since Prozac was first introduced to the market in 1987, according to the Centers for Disease Control and Prevention.

In some people who have depression, the brain doesn’t produce enough of the neurotransmitter serotonin — a natural chemical that helps transport electrical impulses by shuttling back and forth across the spaces between neurons. So SSRIs are deployed to keep the chemical’s concentration high. In animals, serotonin also performs a critical role of “regulating a broad spectrum of behaviors, ranging from mating to feeding,” said Christian Daughton, chief of the Environmental Chemistry Branch of EPA’s National Exposure Research Laboratory and a co-author of the 1999 paper that first piqued Armbrust’s and Black’s interest.

Black, who came to UGA in 1995, first examined water-quality issues as a graduate student at the University of Tennessee. Her focus on the biological aspects of contamination — the impacts of pollutants on aquatic life — neatly complements Armbrust’s interest in the chemistry of contaminants. While Black (who serves as principal investigator on the EPA grant) and her group observe the effects of SSRIs on aquatic invertebrates, fish and frogs, Armbrust’s team analyzes the chemical behavior of the drugs — what’s getting through the wastewater-treatment facilities, how quickly the SSRIs biodegrade once they’re in the environment, what they break down into and how long all these chemicals persist. Basically, said Armbrust, “we’re measuring exposure and they’re measuring effects.”

Provacative Results
When Black and Armbrust first conducted an extensive review of the scientific literature to see what was already known, they found evidence to suggest that Prozac affected the reproductive systems of clams. Was it possible that other forms of aquatic life were affected as well?

Early results in Black’s lab suggested that SSRIs may indeed cause problems for a range of organisms. For one thing, fish and frogs exposed to SSRIs were lethargic, which could leave them easy targets for predators. But on a deeper biological level, Black and UGA post-doctoral fellow Theodore Henry, now on the faculty at the University of Tennessee, observed that relatively low concentrations of Prozac in mosquito fish led to developmental delays, particularly in the formation of reproductive tissue. Because reproductive success in fish depends heavily on timing, even modest delays could leave them unable to generate new broods and ultimately lead to population declines. Henry also found increased mortality and lower reproductive rates in daphnids, tiny crustaceans commonly used to evaluate a compound’s toxicity in aquatic environments.

The group’s most provocative results so far have involved amphibians. Serotonin is believed to affect thyroid function, which is particularly important in frogs because thyroid hormones are thought to trigger their metamorphosis. In one set of experiments, Black and doctoral student Emily Rogers discovered that exposure to Prozac slowed this essential process. “The delay’s biggest problem is that it can leave frogs totally vulnerable for much longer periods,” said Black, and not only with respect to predation. Many tadpoles undergo metamorphosis while nestled in small pools of ephemeral waters on land. If their developmental timing is off, the water could dry up before the immature frogs complete this stage.

Studies by Armbrust and post-doctoral fellow Jeong Wook Kwon also are yielding interesting findings, particularly on Prozac’s environmental persistence in water and sediment. “If it’s in water,” Armbrust said, “it’s not going to break down quickly – the half-life there is about four months. And in sediment, it doesn’t seem to biodegrade at all.”

Despite their early results, Black and Armbrust are not yet prepared to sound any alarms on SSRIs in the environment. They suspect that the degree of impact depends not so much on short-term concentrations, even if relatively intense, but on long-term exposures to constant environmental levels of the drugs. The latter occurrence is likely, given that people who take SSRIs usually do so for long periods of time. But because that cumulative effect on populations of aquatic life has not been demonstrated, it is what the researchers plan to explore next.

“From an ecological standpoint, the preservation of biodiversity is so important,” Black said. “The loss of one species may not seem that critical, but could be very critical if it was the sole food source for another species.”

In the past, a lack of technology and information may have limited scientists’ ability to see the big picture on water quality, but research advances over the past few decades may be changing the situation, Black suggested. “Perhaps now that we’re looking more holistically at watersheds,” she said, “we’ll see things we missed before.”

For more information, contact Marsha Black at mblack@uga.edu or access www.uga.edu/publichealth/ehs/dept/people/mblack.html

Kelli Whitlock is a freelance science writer based in Ohio.