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Thomas Schwarz, PhD, is passionate about his fruit flies, or Drosophila melanogaster, as he affectionately calls them. In his research laboratory in Children’s Hospital Boston’s Neurobiology Center, Schwarz and his team of a dozen researchers experiment on millions of fruit flies to study genes important for nerve cells’ synaptic function—or how neurons talk to each other. For him, it’s a dream come true, partly because it allows him to marry his dual loves of neurobiology and genetics, but also because he’s able to indulge his curiosity about this most unique breed of fly. "I love my flies," he says, grinning. "They’re pretty smart little guys. They have intricate courtship rituals in which they sing to each other by vibrating their wings, very stylized ways of fighting over mates and food—and a really incredible sense of smell."
Schwarz’s demeanor is gentle, modest and congenial, but when he’s extolling the virtues of his favorite insect, his tone becomes almost reverential. Listening to him wax poetic about Drosophila, which sounds like an exotic woman’s name when it rolls off his tongue, it’s clear why fruit flies have been so valuable to researchers for the past century. Their genomes are remarkably similar to those of humans, they breed quickly (thereby creating many new research subjects) and, most interesting to Schwarz, have quite sophisticated nervous systems. "They can fly—which humans can’t," he enthuses. "They can steer themselves toward a specific object in the face of wind currents and avoid the swat of your hand, which requires a huge amount of darting. And they coordinate walking with six legs. They may not publish scientific articles or compose operas, but the calculations their brains have to do are amazing."
Stacked on shelves in Schwarz’s lab are thousands of vials, many containing mutant breeds of flies that his team has genetically manipulated. They will live about two months depending, according to Schwarz, on how happy they are and if their environment is temperate. Most flies find room temperature to be satisfactory, but the more sensitive stocks get incubators. "We pamper them," Schwarz smiles.
Schwarz became interested in fruit fly genetics when he was an undergraduate at Harvard during what he calls "the dawn of molecular biology," when it was just becoming possible to start with a mutated fly and work backward to see what gene could be responsible for the mutation. "It reminded me of when TVs had tubes in them, you could take a tube out and figure out how the TV worked by seeing what went wrong," he says. "The logic of genetics was beautiful and appealing in the same way."
Now that he has a lab of his own, Schwarz’s team conducts much of their research using this approach, called a mutant screen. "Basically, we mutate flies at random, trashing genes left and right, find the interesting ones and ask, ëWhat was it we screwed up in this fly?’" he says. The odder the fly the more potential it has: Those with physical abnormalities, who have trouble hatching or flying, have unusual reproductive habits or hold their wings strangely, are prime research subjects.
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For Schwarz, some of the appeal of this method is its inherent element of surprise. "There’s a joke in the fly world that with a mutant screen, you always find what you’re looking for—you just didn’t know what you were looking for," he says. One study yielded especially shocking results. He started with a mutant screening of about a million flies whose photoreceptors were genetically manipulated, making them blind. Then he zeroed in on a few hundred whose eyes looked normal and whose eye cells responded to light but somehow couldn’t transmit vision signals to the rest of their brains.
Puzzling this out took several years, even after Schwarz identified the gene that was responsible. As it turned out, the problem wasn’t how cells’ synapses formed, as he’d supposed. Instead, the synapses weren’t working properly because the mitochondria that powered the cells were trapped and unable to supply them with energy. "We had no idea we were looking for things that controlled how mitochondria moved around," Schwarz says. "I hadn’t thought about mitochondria in 20 years and there they were."
That discovery led Schwarz out of genetics and into research on a completely different disease. "We ended up studying how mitochondria move around inside cells which, as it is turning out, may be a crucial part of the pathology of Parkinson’s disease."
Despite these kinds of advances, Schwarz sometimes finds himself in the position of defending his research subject of choice to those who question the value of studying such seemingly insignificant creatures—and the dig Sarah Palin made about public money being wasted on fruit fly research during the Presidential election still stings. "She was actually making fun of the species that damages olives, but still, it was a cheap shot," he says. But it didn’t diminish his enthusiasm. "We tend to think of fruit flies as being a lower organism and humans a higher one. I’m not sure the flies would agree with us."
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