Could a spring-loaded fly swatter save NFL football players and Iraq war veterans from the effects of concussions and traumatic brain injuries?
Before you shrug off that question, geneticist Barry Ganetzky at the University of Wisconsin-Madison medical school suggests you consider that fruit fly brains have already proved their worth in figuring out far more complex human neurological problems.
“They have been used for study of learning and memory; they have been used to study models of epilepsy; they have been used to study circadian rhythm; they have been used to study sleep, and they have been used to study addiction,” Ganetzky said. “At a fundamental level, a brain cell is a brain cell. If there’s some damage to it, it shouldn’t make any difference if that damage is occurring because it’s inside the head of a fly or inside the head of a human.”
Fruit flies can be raised by the thousands and altered genetically. They also live brief lives. So figuring out what happens “later in life” amounts to days or a weeks. (Try doing concussion work with rodents, which can amount to dropping weights on the heads of mice. Those look like “medieval torture,” by comparison, Ganetzky offered.)
By slapping spring-loaded vials of Drosophila melanogaster against a foam pad and knocking the flies senseless, Ganetzky and his colleagues believe they have found leads toward a biological marker for concussions and a path toward blocking degeneration of neurons that can cause symptoms of dementia. Their results were published online Monday in the journal Proceedings of the National Academy of Sciences.
Ganetzky, who has studied the nerve cells of fruit flies for more than three decades, said he was inspired to look at concussions after the suicide of retired San Diego Chargers linebacker Junior Seau, whose brain tissue showed signs of a chronic traumatic encephalopathy, a degenerative brain condition related to repetitive head injuries.
It occurred to Ganetzky that there wasn’t a very good medical definition of concussion -- doctors on the sidelines of Monday Night Football could look at a player’s pupils, ask a few questions and use their best judgment. “It’s symptomatic,” said Ganetzky. “It’s not like you measure something. It’s not like diabetes or high blood pressure.”
Then Ganetzky remembered his post-doctorate days at Caltech, with genetics pioneer Seymour Benzer. Ganetzky had slapped a vial of flies against his palm, then watched the groggy flies slowly recover. “I thought, this was an interesting curiosity, but I didn’t invest much in it,” he said. “But years later, I’m thinking: that’s exactly the definition of a concussion.”
Ganetzky was wary that people would think he was nuts. So he brought up the idea with his colleague David Wassarman. “His jaw just dropped,” Ganetzky said. “He said, if you’re not going to study that, then I want to. That’s when I knew we were onto something.”
Wassarman insisted they forgo the palm slapping and build a machine. After all, laboratory science is about doing things that can be reproduced reliably and be measured. Wassarman constructed a device that hurled a vial of flies at 6.7 mph, delivering 2 newtons of force. That’s about the grip of a nurse taking your pulse, but it wacks the heck out of flies.
Besides finding that age at the time of injury and the number of injuries correlate with the risk of neurodegeneration, researchers discovered that concussion activated innate immune responses similar to those in humans. Those responses have been linked to degenerative disorders in the brain.
By looking at 47 genetic lines of flies, the researchers also found that both the threshold for death and the longevity of swatted flies was linked to certain genes that have an equivalent in human cells.
“If we can really validate this as an appropriate model for humans, we can now start to screen for drugs” that might block damage, said Ganetzky. “We can begin to look for diagnostic markers, where you can actually measure something and not just say: Who’s the president and when were you born?”