Bees on cocaine

A few years ago researchers published a study in the Journal of Experimental Biology investigating the effects of cocaine on bees.  In all honesty this research article caught my attention because of an amusing “Shouts & Murmurs” in The New Yorker clearly inspired by the seemingly wacky set of experiments outlined in the paper.    So what exactly was the logical basis behind this article?  What were these researchers setting out to understand?    What does this have to do with chemical ecology?  And then the obvious question:  Do bees abuse cocaine?  

This “bees on cocaine” study, in a roundabout way, gets at a central question in the field of chemical ecology:  What are the natural roles of chemicals produced in the environment?  As humans we have an understandably anthropocentric take on why certain molecules are useful.  Lovastatin, for example, is a natural product produced by the fungus Aspergillus terreus.  This molecule, which inhibits a human enzyme involved in cholesterol biosynthesis, ultimately paved the way for the development of the statin class of drugs (Lipitor), which have become a major treatment for heart disease.  Yet, while we know quite a bit about the biology of lovastatin in the human body, we have very little understanding of what this molecule is actually doing for the fungus that produces it.   Is it essential for the survival of the fungus?  Does it target another organism involved in a symbiosis with Aspergillus?   Most likely this natural function has nothing to do with chronic heart disease in humans.

Cocaine, which is produced by the plant Erythroxylon coca, is an oddly similar example.  It has had some success in the clinic, but has been remarkably popular for more recreational purposes.  Yet, much like the production of lovastatin byAspergillus, the production of cocaine is not naturally intended for human use.  In 1993, Nathanson et al. published a study showing that cocaine may serve as an insecticide – a way for the coca plant to deter its insect predators.  Researchers measured “leaf protection” by placing insect larvae on tomato leaves (which obviously do not produce cocaine) and then treating them with increasing doses of cocaine.  These experiments revealed that larvae exhibited impaired motor function, decreased time spent on the leaf, and with further increased concentrations, would ultimately die.  For understandable reasons, these physiological effects minimized the larvae’s desire, or ability, to chow down.  This study revealed a potential natural role for cocaine as a defense mechanism for the coca plant – and ultimately raised a lot of questions about the difference between insect and human responsiveness to this drug.

So this is where the bees come in.  In a further exploration of the effects of cocaine on insects, Barron et al. administered cocaine to bees and observed its effects on a number of behaviors.  Most notably, these researchers made the thrilling observation that cocaine had a profound effect on the bees’ dancing. Upon the discovery of an exciting resource (pollen, for example), forager honeybees return to the hive and perform a “waggle dance” that indicates to their hive mates the location of this desirable resources.  Treatment with cocaine increased the rate and likelihood of dancing after foraging without obviously affecting other behaviors or general motor function.  Further, after multiple treatments with the drug, the bees exhibited signs of withdrawal if the drug was removed.   So, to answer the question posed at the beginning of this post, apparently bees would abuse cocaine…? If given the opportunity of course.

These two studies taken together seem sort of contradictory.  One asserts that cocaine is basically toxic to insects while the other suggests that cocaine not only triggers reward processing in insects, but is also addicting.   The difference in findings between these two papers is highly interesting for a number of reasons.  One is that the dosage of cocaine (which is not clearly consistent between these two studies) likely has a pretty significant effect on how it affects invertebrates.  More interestingly, it perfectly exemplifies the “paradox of drug reward” - in other words, the question of why an organism, like the coca plant, would evolve to produce an insecticide that has a potentially self-defeating side effect, like addictiveness (nicotine is another example).  This question remains wide open.  Ultimately, studying the effects of cocaine on bees gained widespread attention – in part because of its novelty (clearly the motivation for the “Shouts & Murmurs” piece), but also because the similarities between bee responsiveness to cocaine and the well-documented effects of cocaine on mammals suggested the potential for using insects as a model system for understanding the convoluted neurological effects of cocaine and perhaps even untangling the perplexing biology behind drug addiction.

Chemical ecology is amazingly complex but can be far-reaching in its implications.  Acknowledging the difference in how we, as humans, use natural products, versus how these molecules are actually used by the organisms that produce them, can increase our understanding of the world around us and cause us to wonder how, or why, these organisms evolved to produce such diverse molecules.   Pursuing such studies can ultimately lead to the discovery of new molecules with diverse biological activity, and the development of model systems for understanding human biology and treating disease.