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Science File

Fly Trials of 1950s Evolve

Research: The notion that genes shape behavior was discounted. Scientists are taking another look.


Back in the 1950s, a biologist named Jerry Hirsch embarked on an odd but trailblazing endeavor: He coaxed flies to crawl and fly through elaborate mazes so as to separate ones that prefer to move up from ones that prefer to move down.

In those days, psychologists pooh-poohed the notion that genes could help shape behavior, believing instead that all behaviors were learned. Hirsch's lovingly selected lines of high- and low-seeking fruit flies forced them to think again.

Hirsch is long retired; descendants of his original flies languished in a few bottles filled with yeasty food. Now, at last, they are back in the limelight--and blazing trails again.

Today, scientists are probing Hirsch's strange flies with modern molecular tools to try to answer what could never be answered before: Why do some of Hirsch's flies fly up? And why do the others fly down? What kinds of genetic changes was Hirsch selecting for all those years?

Writing today in the journal Nature Genetics, a team of researchers say they've pinpointed several of the genes involved in this trait--and have strong clues about some others.

And that is important for more than just fans of fruit fly behavior. While some genes studied by scientists have large, in-your-face influences, many more have small and subtle contributions. Hirsch's flies are a prime example of the kind of trait that involves the action of many genes.

Studying the flies, therefore, stands to teach scientists lessons about the genetic nuts and bolts of evolution as well as the ancient art of plant and animal breeding.

For eons--long before recorded history--people have domesticated animals, deliberately selecting for traits such as docility, disease-resistance, milk production and more.

Studies such as the one of Hirsch's flies "finally give us a way to see what the genes are that are contributing to the selection," said Tim Tully, professor of genetics at Cold Spring Harbor Laboratory in Long Island, N.Y., and a former graduate student of Hirsch's.

The studies demonstrate how scientists can more easily get their hands on agriculturally important genes--ones that often are hard to find because dozens, even hundreds, are involved in a trait, each one contributing just a little.

Central to these new lines of investigation is the development of high-tech DNA computer chips, which are loaded with samples of thousands of genes, allowing scientists to quickly probe huge chunks of a genome.

The chips could potentially allow agricultural researchers to ferret out specific genes more readily, easing the quest to breed beefier cattle or fungus-resistant lettuce.

Such studies already are underway for a variety of crops and livestock, said Max Rothschild, the Curtiss distinguished professor of agriculture, animal breeding and genetics at Iowa State University in Ames. The experiments with Hirsch's flies are an important demonstration that the approach works.

"It's inventive, revealing, really innovative stuff," Rothschild said.

Hirsch started his project while in graduate school in the 1950s, working with a scientist who was breeding smart and dumb lines of rats. Hirsch also wanted to study behavior--but decided that fruit flies were handier to use. The flies were small, well-studied and fast breeding: Flat out, they could manage a generation every 10 days.

What's more, flies do exhibit behaviors--including "geotaxis," or the preference to move in relation to the pull of gravity.

When the flies are in their larval stage, for instance, they like to move downward. That way they'll burrow ever deeper into the pungent, moldy fruit they adore.

When the time comes to pupate, they change their tune--heading up out of their food to a nice, dry place where the fly can emerge safely when it's time to hatch.

And, as anyone who's opened a smelly garbage can or tried to swat a fly knows, flies like to fly up to safety when startled.

"Other than that, who knows?" said Ralph Greenspan, Cullman Fellow in Experimental Neurobiology at the Neurosciences Institute in San Diego, and senior author of the paper published today. "You'd have to put yourself into their heads and think like them."

Hirsch, in any case, didn't need to probe the fly's psyche: He just needed a way to gauge its preferences. And so he constructed a cunning maze shaped like a candelabrum turned on its side. Into one end, he loaded a fine mix of flies. Then he waited as they slowly moved through it.

At numerous points in the maze, each fly had a choice: Go up or go down. Valve-like cones discouraged any backtracking. At the far end of the maze, each fly ended up in one of a series of tubes, each at a different height.

Generally, flies chose pretty randomly: Most ended up in the middle set of tubes.

But after every run through the maze, Hirsch enriched his population of outliers: flies that ended up highest and flies that ended up lowest. He'd use these outliers as the parents for the next generation.

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