Drugs in the water: Behold the power of synergy

funky MathES&T Online News: Can drugs found in water harm humans?

Researchers agree that aquatic species face the greatest risk from exposure to low levels of pharmaceuticals, such as synthetic hormones, which can act as endocrine disrupters at environmental levels. However, little is known about the potential human health effects arising from complex drug mixtures.

Well, it is often more difficult to analyze complex mixtures because Experimental Design 101 makes you want to isolate the effects. And when you do compounds one by one in series, the tendency is to always add them up from the individual experiments. Unfortunately, body chemistry is not like that. I’ve always wanted to design a study that started complex and then tried to isolate later.

To his surprise, Pomati observed that this mixture of drugs at environmental levels inhibited the growth of human embryonic kidney cells. After 48 hours of exposure, cell proliferation was reduced by 10–30% compared with controls. However, no inhibition was observed when cells were exposed to only the toxic cancer drug at environmental levels.

Well, that seems conclusive enough, but here comes the “Experimental Design 101” Scold:

The results show that the growth inhibition is not due to the single most cytotoxic compound alone. But that does not conclusively prove that synergistic or additive effects exist between drugs in the mixture, cautions Thomas Heberer of the Institute of Food Chemistry at the Technical University of Berlin. To show that the individual drugs behave additively, Heberer suggests that researchers should analyze the effects of compounds with a common mode of action, such as antibiotics, alone and in various mixtures.

No, No, and No. Doing this presupposes that you know that mechanism of action, meaning you’ve half answered your question. The question Heberer is trying to answer is “do individual drugs with the same mode of action behave additively”. The question Pomati is trying to answer is “Can we demonstrate cytotoxic effects of a cocktail of drugs at ambient levels in a laboratory setting”? These are two completely different questions and Pomati’s question is more valuable at this point in time. Heberer’s strategy, on the other hand, will keep a lab well funded for years to come! But, it is very much the final step.

It is more important at this point in time to demonstrate other effects such as endocrine disruption, mutagenicity, etc in the lab at environmentally relevant levels of mixtures. Then we can get a better handle on which  effects are relevant and which ones to ignore.

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