Rx on the Wing
by David Raney
Imagine you’re on a quiz show, and the category is monarch butterflies. Unless you happen to be competing against an entomologist, you’ll probably do OK. You know they have beautiful black and orange stained-glass wings, delicate antennae and legs. Maybe you’ve seen photos of them congregating by the millions in Mexico, draping trees like Spanish moss after migrating there from Canada. You might even dredge up the fact that they’re partial to milkweed—or that a different butterfly (extra points for “viceroy”) looks enough like the poisonous monarch to get some sneaky protection from predators.
An expert would be able to supply the insect’s scientific name (Danaus plexippus), and much else besides. But until about a year ago, both of you would have gotten the next question wrong: “Can monarchs use medicine?”
It turns out they can. And Emory’s own Jaap De Roode, assistant professor of biology, is the first to prove it.
The idea, which has received plenty of media attention and prompted Popular Science to name De Roode one of its “Brilliant 10” top scientists under forty, seems odd enough to the layman. It suggests New Yorker-cartoon images of bleary butterflies standing at medicine cabinets. But it may be even odder to scientists. The ability to selectively eat or drink natural substances in order to treat some disease or condition was long thought to be the exclusive province of a few animals with very high cognitive skills: basically, elephants, apes and us.
But the work of De Roode and his colleagues, published in Ecology Letters in December 2010, has upset that particular apple cart. His experiments show that adult female monarchs prefer to lay their eggs on a certain kind of milkweed that confers protection from a parasite called Ophryocystis elektroscirrha.
“It’s a really cool parasite,” De Roode said recently. This may well be the first and last time you’ll hear that sentence, unless you’re one of his lucky students, but it was the parasite that drew De Roode to the butterfly, not the other way around. In a conversation in his sunlit Emory office last December he described how he came to this surprising result, and why it matters.
“I was really interested in parasite evolution,” says De Roode, a native of the Netherlands. “I had worked with malaria in mice, but got frustrated with the artificial laboratory system and wanted to study such systems in the wild.” So in 2005 he began working with monarchs. And after a while he became bored.
“Monarchs are very picky,” he explains. The caterpillars refuse to eat anything but milkweed, and they have prodigious appetites, growing to more than 2500 times their original size in just two weeks. “That first year I spent so much time raising the plants, and making sure they were pest-free, and watering and fertilizing, that finally I wanted to do something else. Just for fun I decided to raise a different species of milkweed, to see if that affected the parasites.”
It did. The monarchs reared on tropical instead of swamp milkweed (there are some 140 varieties) had fewer parasites, and they also “lived longer, could fly better, had a longer egg-laying span, lots of good things. I immediately thought Wow, what if monarchs can use this?” So De Roode posed that question in the discussion section of his first paper on the topic: Do monarchs lay their eggs preferentially on medicinal milkweed?
“I had to take it out,” he says. “The editors said absolutely not, that’s impossible.” Then he adds, smiling, “There’s nothing as motivating as a disagreeing scientist. And we proved them wrong. Which is fun.”
It’s easy to see why even scientists in the field might resist the notion that insects medicate themselves. “Absolutely,” De Roode agrees. “It’s long been argued that animals need to show higher learning to do that. You’re sick, you see another chimp eat a particular fruit or leaf…. But we’ve shown that’s not the case. You can have a fairly simple organism, one without the mental capabilities we and chimps and elephants have, and they can use medication to fend off their parasites. That was really the main breakthrough.”
That, and the trans-generational aspect. Strictly speaking the monarchs don’t even medicate themselves but rather their offspring (as yet unborn), which, if anything, is even harder to wrap your mind around. “It’s clear they do, though,” says De Roode. “The nice thing is, it’s what we call a plastic response. When the females are infected they choose the medicinal plant, and when they’re not they don’t.” He also tested infected caterpillars to see if they chose one milkweed over another, but they showed no preference. It’s only the mothers who visit this natural pharmacy, and only when they need to.
“That makes a kind of sense,” De Roode points out. “Even when we humans use medicine, we use it only when we need it. Lots of medicines have side effects, things we don’t want to do to our healthy bodies, but these are outweighed by the positive effects on a parasite or virus or whatever is ailing us. And this is what monarchs do too. The medicinal milkweed can actually have negative effects on healthy caterpillars, so they use it only when they have to.”
Asked if he thinks this is going to turn out to be true for lots of other species, De Roode answers, “I think so. There’s a lot of research on ants, for instance. Some of them incorporate little bits of tree resin into their nests. They don’t feed on it, it doesn’t have any structural function—but it turns out you can put that resin on a bacterial plate and you’ll find it has antimicrobial properties. So basically they’re using it to keep down bacterial growth in their nests.
“And there are lots of other studies where people are looking at insects, especially those that feed on plants, because we know that while plants offer nutrition they also have all these biologically active compounds, including ones that we extract for our own drugs. I’m absolutely convinced research will show that a lot of other species exhibit these sorts of behaviors. I think it’s starting.”
So what’s next? “What we’re doing now is looking at populations in south Florida, where the parasite risk is very high—up to 90% of monarchs are infected—to find out if this changes how the insects behave. There’s a chance that under higher parasite pressure they use plants prophylactically, to avoid getting sick, rather than just therapeutically.
Left: A healthy monarch butterfly about to emerge from its chrysalis. Center: When monarch butterflies are heavily infected with the protozoan parasite Ophryocystis elektroscirrha, they can sometimes get stuck to their chrysalis. This means death for both monarch and parasite. Right: In the lab, monarchs are reared in plastic tubes with milkweed plants
“The other thing we’d really like to do is find out what makes these plants medicinal in the first place. Because the parasite we’re studying is quite close to one that causes malaria, as well as the toxoplasma parasite, and cryptosporidium, which causes lots of disease in immune-weakened patients, including HIV patients. Evolutionarily speaking they’re very closely related, so we’re interested in identifying the chemicals in these plants, and the way insects use them, and possibly applying them to human health down the line.
“Let’s look at another thousand insect species and what they use for medicines, and see if we can’t identify compounds that would be good for humans as well.”
Remarkable findings like this make it fun to teach evolution, De Roode says. “Everyone finds it interesting. These nature programs, with David Attenborough and so forth, are extremely popular. People want to know how things work. Because you always have to ask the question: OK, something crazy is happening here, but why? It’s one thing to describe it, but to try to explain how it came to be, that’s exciting.
“Nature is very cool. I do this because it’s just interesting. But I would be happy if it resulted in something beyond that.”