When you put yeast on Prozac, do you observe any side effects? Off-target effects of psychiatric drugs are a big problem, and researchers have been eager to identify the cellular processes that are responsible for these side effects. Often the cellular process involved in the drug's the main effect is known, but what causes the side effects is not well known. To get at this issue, a group of researchers at the University of Toronto tested the effects of 214 psychoactive drugs on yeast. Why yeast? When it comes to the most basic cellular processes, yeast have the same ones we do, and in yeast it is easier to identify what parts of the cellular machinery are being affected by the drug. Even better, yeast don't have any of the sophisticated neurological machinery we have. That neurological machinery is the main target of these drugs; since that main target is absent in yeast, scientists can focus purely on the off-target drug effects. Without neurons to modulate, only a subset of the drugs actually had any effect in yeast - 81 out of the 214 drugs the researchers tested (including Prozac). With those 81 drugs in hand, the scientists applied a set of formidable genome-scale tools to figure out what basic cell functions are affected by these drugs. The researchers tested each drug on a set of mutant yeast - actually thousands of mutant strains, one mutant per gene. The logic goes like this: if you knock out gene X, and a drug is more potent when gene X is gone, then gene X may have something to do with the cellular pathway impacted by the drug. For example, if we know gene X is involved in reshaping large-scale DNA structure, then we suspect our drug is having an effect on reshaping DNA structure. Studying mutants in this way gives us a clue about what the drug is doing, a clue that we can then follow up with more detailed experiments. In this study, the Toronto researchers found a variety of basic cellular functions that were affected by the drugs. Many of the drugs had an impact on what's called the secretory pathway, the pathway by which a cell moves stuff outside of its membrane (hormones, or waste products such as the remains of the metabolized drug). When you mess up this system, all sorts of harmful products start to accumulate in the cell, and the scientists speculated that inhibited drug detoxification could be a significant source of side effects. Yeast aren't quite human, so it is possible that there are some cellular processes specific to animals that are involved in drug side effects, and those processes wouldn't be picked up in this study. But the researchers took a good shot at finding very core, fundamental cell functions that are disrupted by psychoactive drugs, functions whose disruption could very well be responsible for some major side effects. And by the way, if you're looking to impress somebody at an Olympics party this week, note that this kind of research is known as pharmacogenetics (or pharmacogenomics, when it involves all of the genes in a genome) - basically using the tools of genetics to study drugs.