Lab abuzz with genetics project

SUN JOURNAL

Genome: Rockville scientists aim to draft the first genetic blueprint of the fruit fly, using a strategy they hope to apply to the study of humans.

May 10, 1999|By Douglas Birch | Douglas Birch,SUN STAFF

ROCKVILLE -- One of the great scientific quests of this century began in 1907, when a student of the naturalist Thomas Hunt Morgan put a ripe banana on a Manhattan windowsill and recruited fruit flies for a simple experiment. The final chapter of that saga opened at a biotech company here Wednesday, as humming machines used lasers to zap the insect's DNA.

"OK, we're started," said scientist J. Craig Venter.

With that telegraphic benediction, Venter and his partner, Nobel Prize winner Hamilton Smith, set out to finish the work begun by Morgan, whose study of the asterisk-sized fly, Drosophila melanogaster, laid the foundation for 20th-century genetics.

By this fall, Venter, Smith and others at Celera Genomics Corp. hope to draft the first genetic blueprint of Drosophila -- to record all, or almost all, of the 165 million chemicals, called nucleotide bases, that form its DNA.

No one thinks the task will be easy. "We're trying to do in six months what the biggest government-funded labs couldn't do in a decade," Venter says.

In part, Venter and Smith are using the fly to test their shortcut strategy for creating the first human genetic blueprint. They hope to complete that work by the end of 2001, and beat the U.S.-led Human Genome Project to its goal.

Recording the sequence of the 3 billion bases in human DNA could mark a turning point in human civilization. The human genome is likely to become the foundation of biology and medicine for the next century, leading to the eradication or control of scores of diseases.

But some scientists are as eager to have a complete catalog of fly DNA as of human. "If you believe in science, then you have to believe in this project," says William G. "Chip" Quinn, a fly researcher at the Massachusetts Institute of Technology.

Even for an insect, the fruit fly is unimpressive. Its chief characteristics are its two-week life cycle, its weakness for the fermenting juices of plants and its talent for procreation.

But in the field of genetics, Drosophila is a star. And the scientist most responsible for its prominence is Thomas Hunt Morgan.

Born in Lexington, Ky., Morgan was the nephew of a storied Confederate army general, and great-grandson of Francis Scott Key. After earning his doctorate at the Johns Hopkins University, he became a professor of zoology at Columbia University, where he studied embryology.

In 1907, one of Morgan's students wanted to breed animals in the dark, to see if they would lose the instinct to seek light. Morgan suggested that the student use fruit flies, which wouldn't take up much room in the crowded lab. When the breeding experiment worked, Morgan began large-scale fly husbandry, keeping them in milk bottles stolen from the school cafeteria.

Morgan's team chilled the flies, heated them and doused them with acids, bases and alcohol. They peered at thousands of bugs under the microscope, hoping to find mutants.

It took two years, but in May 1910, Morgan spotted his first mutant, a fly with white eyes instead of the standard red. He had found his life's work.

By tracking mutations through hundreds of generations, Morgan discovered that genes -- the inherited units that determine eye color, body size and other traits -- are located on threadlike structures called chromosomes. He and his students were even able to determine where specific genes were located on chromosomes, creating the first rough gene maps.

Where Morgan led, thousands of scientists followed. And they found that flies have more in common with people than most of us would like to think. About half the fly's 12,000 genes have counterparts in human DNA.

"Fruit flies are the closest to humans, in terms of biochemistry and behavior, that you can do detailed genetic analysis and detailed experimentation on," says Gerald M. Rubin of the University of California at Berkeley, leader of the publicly funded Fruit Fly Genome Project. Rubin is collaborating with Venter and Smith on their work.

By the 1990s, scientists had identified 4,000 mutant fly genes. Morgan liked to give these rogue genes simple, descriptive names -- calling the white-eyed gene "white," and another gene "beaded," after the dysfunctional shape it gave the fly's wing. Fly scientists still use these names, and compete to outdo each other in coming up with clever new ones.

Today, a breed of fly that is easily stunned carries a gene called "TKO," from the boxing term "technical knockout." A gene that causes a rapid and catastrophic deterioration of the fly's nervous system is called "drop dead"; one that interferes with mating is called "coitus interruptus."

Seymour Benzer of the California Institute of Technology used flies to pioneer the study of the genetics of behavior. One day, research by Benzer and his students may help settle the sometimes rancorous debate over how deeply genes influence what humans think and how we act.

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