In the summer of 1986, Thomas Kaufman was waiting in the lunch line at a research conference devoted to Drosophila—more commonly known as fruit flies. A fellow biologist informed him that the California Institute of Technology was interested in getting rid of its huge inventory of flies—insects that are used in scientific studies and distributed to researchers upon request.
“I said, ‘maybe we could move the stock to Indiana,’” says Kaufman, a biologist at Indiana University. When he returned to Bloomington a few days later, he asked a post-doc in his lab if she’d be interested in running a fly-stock center. She said she would.
Back at Caltech, the flies were ushered into tiny glass vials, placed in generously padded boxes, and sent on their way to the Hoosier state, courtesy of the U.S. Postal System.
“There were about 1,600 pure breeding lines at the time, different mutant strains, flies with different eye colors, bristles, wing shape, body color, and that sort of thing,” Kaufman tells me. There are now more than 50,000 mutant lines in the stock collection. The center sends out thousands of fly stocks each week to scientists all over the world.
It’s from that venerable and varied stock that Ellie Heckscher acquires her flies, or, more precisely, her maggots. Heckscher, an assistant professor of molecular genetics and cell biology at the University of Chicago, breeds flies and uses their larvae as models to study the neuronal basis of movement. It offers a gateway to understanding specific diseases in humans such as Lou Gehrig’s disease.
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Heckscher became involved with maggots while a graduate student. She has a high regard for the wee organisms, despite their icky reputation among the general populous.
“We work on very young maggots,” Heckscher explains. “They’re tiny. They’re actually kind of cute. I think the big ones are the ones that are gross to people. I think people associate maggots with flesh or trash, but they’re also really tough. They’re little tanks.”
It’s true: Maggots are associated with flesh, trash, and of course disease. The larvae of botflies insinuate themselves beneath the flesh of cattle make the animals miserable and their hides worthless. Maggots that infest sheep or humans are not only unsightly, but painful, even debilitating to the host.
As far as the average maggot is concerned, whether medicinal or not, its main purpose in life is to eat, grow, and reproduce. However, there are maggots whose destiny is to help both animals and humans. They are bred for the task.
Take, for example, maggot-debridement therapy for horses with laminitis, an inflammation of the tissues that bond the hoof wall to the bottommost bone in the equine leg. For this therapeutic procedure to succeed, not just any maggots will do, particularly not maggots found in un-emptied trash bins protruding from alleyways behind downtown eating establishments. No, this case calls for medicinal maggots. They must be freshly emerged—germ-free, and their mothers and fathers should be green blow flies, Lucilia sericata.
After a sufficient supply of L. sericata is secured from a safe source, a veterinarian or another brave soul tucks the maggots in and around the wound. A nylon retention net quickly corrals the larvae. The larvae then celebrate their good fortune by eating dead tissue and destroying noxious bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug-resistant Pseudomonas aeruginosa, and Escherichia coli. Maggots are used in much the same way to treat gangrene of foot ulcers in people with diabetes.
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Researchers like Heckscher are interested in how neural circuits develop and enable organisms to move. “The maggot model gives me a powerful way to ask these questions,” says Heckscher, who was trained as a developmental biologist.
That’s because the “maggot model” is of intermediate size. The creature provides researchers with roughly 10,000 neurons to work with, far more than the classic Caenorhabditis elegans, a roundworm, which offers a mere 300 neurons for scientists to explore, but far fewer than humans’ 100 billion neurons. “An intermediate complexity model, I think, is super powerful for asking questions that people haven’t been able to answer,” says Heckscher. “We think maggots really are the sweet spot now.”
Heckscher says scientists now have a detailed map of all the connections of a maggot brain, a complete picture of all its neurons. That means researchers can see individual synapses, which are the sights of communication between nerve cells. This in turn gives them a snapshot of which neurons could be “talking” to each other.
But for now, scientists don’t truly understand the neural basis of movement, according to Heckscher. It’s known that neurons make muscles contract, but the organization of the circuitry is still poorly understood.
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Maggots can help—in particular, the creation of a tiny maggot highway. As it turns out, maggots crawl in a “really erratic way,” as Heckscher puts it. She places them in tiny channels, essentially little roadways, carved into agar, a gelatinous substance derived from sea algae, so they can move in only one direction.
“We are really just simplifying their behavioral repertoire so we can get that link between behavior and neurons,” says Heckscher. “One of the great things about maggots as a research tool is that they’re clear, at least in the early stages.” Clear as in transparent. That means Heckscher’s team can put florescent proteins into the maggots to track how they move.
Among other things, Heckscher is trying to see how the maggots’ neurons develop from neural stem cells, undifferentiated cells that can differentiate into specialized cell types, to create networks of neurons that control movement.
“If you can understand that then you can imagine making stem-cell therapies,” Heckscher tells me. She thinks a set of relatively simple rules might evolve time. “There’s this idea that the control of movement is generated through sequential means. I think this component of time and development is going to be really important for sorting out how you get something so complex. You don’t just build it overnight.”
Fly research got its start more than a century ago. The first fly paper was published in 1910 by Thomas H. Morgan at Columbia University, who received the 1933 Nobel Prize in physiology or medicine for his discoveries of the role of the chromosome in heredity.
Now, flies and maggots have become workhorses for understanding diseases and opening the door to mitigating them. Are they gross? Sometimes, yes, when a gaggle of them slurp atop trash or flesh. But when it comes to studying diseases, maggots, as Heckscher says, are “exquisitely built machines”—and refreshingly ideal scientific collaborators.
This article appears courtesy of Object Lessons.
This post appears courtesy of Object Lessons.
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