In preparation for the debut of our collaborative wasp yeast beer at the World Beer Festival in Raleigh on April 5, 2014, I revived the Science Miniseries: The Big Story of Alcohol, Civilization and a Little Fungus that I wrote in 2012. We started with “He Is a Wise Man Who Invented Beer,” and then followed up last week with “A Sip for the Ancestors: The True Story of Civilization’s Stumbling Debt to Beer and Fungus.” Today I offer you Chapter 2, a story of self-medicating fruit flies:

Sometimes scientists are asked if they have hobbies. What follows is an awkward pause. It is not as if scientists don’t have hobbies, it is just that their hobbies tend to involve doing exactly the same thing they do at work, just at home. For example, my friend Jim Rice is a fish biologist. He studies fish all day every day. And when he has some spare time, well, he goes fishing. The emotions a scientist feels for his or her quarry do not just disappear upon heading home.

When the fruit fly biologist Todd Schlenke (now at Reed College) picked up a hobby in graduate school it was catching fruit flies in his backyard. Fly catching is easy. While one might, with some real luck, catch a hundred fish in a day, Todd could catch hundreds of fruit flies in a single jar, sometimes of many different species. It is a good hobby. He genuinely loves it. It is a delight to see all the flies. You never know exactly what you will see. Any jar might hold a rare species or reveal a new behavior. No matter how bad your day is, if you come home to a new fly, it is a good day. The down side is fruit flies follow Todd Schlenke wherever he goes


ToddAspiratingWaspsTodd Schlenke searching his neighbor’s compost and delightedly sucking out flies.

One day when checking on his flies Todd saw something odd. It would change his life. A wasp was crawling from one fly larva to the next, stepping over them as they lay alive, but prone. The wasp was tiny, delicate, and was, as he would later figure out, using its needle like ovipositor to inject its eggs inside the larvae of the fruit flies. The wasp eggs would then hatch, consume the fly from the inside and, once metamorphosed, break out of their borrowed skin, winged and reborn. Todd became fascinated with the story of the flies and the wasps. It was a kind of war going on everywhere, or at least everywhere within rotten bananas, which in his life were really, truly, everywhere [2].

Wasp-laying-egg-inside-fly1A wasp sinking an egg into the body of a larval fly.

More species of these wasps, called parasitoids, live on Earth than species of birds or mammals, many more [3]. Theirs is among the most often repeated dramas, a Shakespearean tragedy playing out on a billion small stages. All around you, animals are being born out of the bodies of other animals. Listen carefully and you can almost hear the sound of thoraxes cracking open and fairy-winged wasps being born. Once they’ve mated, these wasps are good mothers, better than average anyway. Like their own mums, they take care to put their children where they will have food and protection, inside other animals. To do so, the wasps must find their hosts, fly expertly in order to lay their eggs inside them as they flee and evade, have an egg-needle just the right length and width to put an egg deep enough but not too deep, and elude the host’s immune system with chemicals and other subterfuge so the hosts immune system does not kill her precious children. For these reasons, wasps often lay their eggs in just one or a few host species, those species with which they have evolved, hosts for which their sinister tools of motherhood are honed.

The wasp Todd has come to study is one species of these multitudes, a species engaged in a protracted evolutionary battle with fruit flies, or rather with a specific species of fruit fly, Drosophila melanogaster. Each generation, the wasp evolves to be better and better at finding flies, sinking its eggs in those flies and having the eggs mature into wasps. Each generation, the fruit flies, in turn, evolve counter responses. It is this evolutionary drama on which Todd has focused much of his professional life, that and booze.

Todd studies these wasps and flies out of raw fascination. They are at war. If the fly wants anything, it is to survive and mate. The wasp wants the same. Their goals at are at odds. But, like most of the many thousands of people who study fruit flies, he also sees their bodies as miniature versions of our own bodies. The flies are toy soldiers with which he can reenact particular battles again and again and understand the circumstances that lead the one or the other side to lose. He gets to revisit the history of wasps and flies, but, in doing so, he also hopes to understand the story of humans and the species living in our bodies, if not wasps then bacteria, viruses, worms, and more. In this context, Todd began to wonder whether the flies could do more than use their immune systems to fight their wars with the wasps. He wondered if flies used, however accidentally, alcohol as a kind of weapon. He wondered if they could drink themselves to life and, a bit more remotely, he could not help but wonder if we could too.

Todd envisioned a contest between two individuals (the fly and the wasp), in which the one who is least affected by alcohol wins. Todd thought the flies might be able to hold their alcohol better than the wasps. His idea was speculative and yet plausible.  Fruit flies feed on all sorts of toxic things, including alcohol, and it was already known that in some cases the flies tolerate more of the toxins than the species that feed on the flies. Species evolve to tolerate the toxins to which they are most frequently exposed, or they suffer, fail to reproduce and, ultimately, go extinct [4].

Wasps-about-to-Hatch-out-of-Flies1Wasps ready to hatch out of the “skins” of their fly larvae.

Todd’s idea was not the sort of thing his fruit fly colleagues often study, but Todd did not yet have to convince his colleagues that his idea was interesting. He just had to convince excitable young students, which he did. Neil Milan, a graduate student working with Todd and Balint Kacsoh, an ambitious undergrad, decided to test Todd’s idea. They began with simple tests of the kind a high school lab could do. They put flies and wasps in different levels of alcohol to see when they died. It was a little more complex than that, but not much [5]. Voila! Todd’s predictions held. Fruit flies could deal with the highest concentration of alcohol, followed by the specialist wasps and then the generalist wasp (which was presumably less adapted to dealing with the flies’ tricks). When they performed a follow up experiment, things got more interesting. Neil and Balint went back to the lab and tested whether the wasps tended to lay fewer eggs in the larvae of flies that had been drinking high proof alcohol. It would only make sense for the wasps to avoid toxic flies.  Oh clever wasps, they did.

It was when the students looked at the older flies (and within them the older wasps) that they saw something curious. Flies who had not been drinking alcohol and were then infected could kill their wasps by drinking AFTER being infected by a wasp (They did this in a particularly gruesome way; the alcohol in the flies caused the innards of the wasps to dissolve and spill out their anuses). This simple observation raised the crazy possibility, a possibility only a man who loves flies and marvels at their ingenuity would consider. Perhaps, the flies might be able to use the alcohol as a kind of medicine, to kill the wasps once they were infected. This would require the flies to be able to know when they were infected and to respond by drinking more alcohol when they were, even though high levels of alcohol could make them sick too. It was crazy, but possible. Crazy ideas are what give scientists the delighted shivers. Suddenly the two students and Todd found themselves moving further out, shimming a little, onto a speculative limb. From there they reached and then, when there was little left to hold them up, jumped.

Much of what modern scientists do, in studying fruit flies, is akin to a sort of sophisticated flea circus. Flies are made to do things, scientific tricks, which simultaneously amuse scientists and educate them. In each new study, the tricks are made more elaborate. “Spectators, can this fly jump through the hoop?” becomes “Spectators can this wingless fly, jump through the flaming hoop?” In the thousands, yes literally thousands, of labs with fruit flies, these tricks are being performed daily, typically set to the theme of whatever music is popular among the students of the time.

The hoop Todd and his students wanted the flies to jump through was the one marked “use tools to medicate themselves when they are sick.” It was an outlandish hoop, and yet easy to test and so they made the flies jump. In the experiment, some flies were infected by wasps. The others were not. The flies were then allowed to choose where to feed. For Todd and his students this was a nerve-wracking experiment. If the infected flies self-medicated, it would be exciting. It would be a “Yaaah, science is great, I can’t believe what wild things can do. OHHHH, I wonder if this applies to humans moment.” But if they did not, well, it would be clear evidence of what flies can’t do which, needless to say, no one actually cares about.

Other species medicate themselves. The flies would not be the first. Some ants gather resin to kill bacteria. Some monkeys eat millipedes. But what was different was that the question of the fly seemed to have to do with humans. Here was more than metaphor. If the flies could drink alcohol to kill their parasites, it would suggest that maybe the same thing might apply to humans. Solomon Katz, an anthropologist at the University of Pennsylvania, had already suggested that perhaps humans had begun to drink alcohol to kill their parasites. Without quite knowing it, Todd was conducting one of the most direct tests of Katz’s hypothesis. Todd waited and tried not to hope, but who are we kidding. He wanted for the flies to choose the booze.

Time passed. Some flies died. Some wasps emerged. Choices were made. And then and only then were the data analyzed and the data revealed that, yes, yes, yes, the flies chose to imbibe more alcohol when they were infected. Not only do flies who drink more alcohol deter their parasitic wasps, they kill them. Not only do they kill them, but when they are infected with wasps, they tend to seek out alcohol, in order to kill them. These flies, who drink for a living, drink more in order to stay parasite free, even if it makes them a little sick. They drink more when parasites are more of a problem. They drink more, in other words, in situations like those encountered by the first settlements of humans, situations in which parasites are common. They drink more when they are infected even though drinking more actually makes them more likely to die from the alcohol too, just less likely than from the wasps. Todd and the students were elated. Their idea held up. The sensation of having an idea bear out is a kind of exalted and lucky grace. It is joyful and fleeting and, did I mention fleeting?

From the perspective of a naturalist, one wonders how many other species self-medicate by drinking alcohol. From the perspective of humanity, one wonders whether the same sort of thing might be going on inside our own bodies. Of course, we do not get infected by wasps who lay their eggs in our flesh only to have those eggs turn into larvae that eat us from the inside out (although see Mark Moffett’s body). Bless their hearts, such is the fate of insect hosts not vertebrates. But, we do suffer from parasites and pathogens. Is it possible we could also drink them to death?

It would not be that hard to repeat versions of Schlenke’s experiments with pathogens of humans. You could not do it in the same way, of course. Even college students object to being put in petri dishes over the weekend, even if they get to drink. But it could be done. Actually, parts of it already had been, by a student named Janet in Inverness, Scotland. Like Schlenke and his students, once she started thinking about the benefits of alcohol, she was addicted. She could not stop. (Stay tuned for the next installment in the series…)

Header photo credit: Drosophila melanogaster, Mr.checker | Wikimedia Commons

In-text photo credits: Todd Schlenke

[1] It is not a downside for Todd, who loves the flies. It is only a downside for the people who know Todd.

[3] I will speculate, though don’t know, that there are even more species of hyperparasitoids (parasitoids that lay their eggs inside of parasitoids which are, in turn, inside of other hosts), than there are birds or mammals. The world is full of animals living inside other animals.

[4] This may well be why pigeons, fish and rats go uneaten even in cities where people are starving. They have both evolved the ability to survive despite consuming high levels of toxins. If we eat them, we have no such resistance. Success, sort of, success always being relative in evolution.

[5] Perhaps the one additional detail worth mentioning is that the two students compared the flies’ tolerance to that of two different species of wasps, one that is a specialist on fruit flies and one that is not. The prediction, at least as it came to them when they were planning the project, was that the wasp that had not evolved to depend on the fruit flies would be less able to deal with their heavy intake of alcohol.