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Gonna Fly Now 

Trading with the enemy helps a Berkeley geneticist divine the secrets of the fruit fly

Wednesday, Jan 27 1999
Gerald Rubin is an unpretentious man with an open face behind his glasses, a patch of gray in his brown beard. On occasion, a hint of Boston slides into his speech, betraying his eastern roots.

A genetics professor at UC Berkeley, Rubin has spent the past seven of his 48 years toiling to isolate and map the 15,000 genes that make up Drosophila melanogaster -- the fruit fly, to you and me. One thousand fruit flies, each just one-eighth of an inch long, could fit easily in-side the drink tumbler on Rubin's desk, with room to spare.

What interests Rubin about these tiny pests is that, stripped down to their biological essence, they are remarkably similar to human beings. Roughly 60 percent of all the genes found in humans can also be found in fruit flies.

The flies are part of an odd scientific trinity: Together with brewer's yeast and roundworms, they are so-called "model organisms" that scientists often study for insights into the genetic workings of people. Fruit flies and human beings are so closely related in evolutionary terms that we share "the same nuts and bolts," as Rubin puts it.

Scientists can probe the yeast, worms, and flies for clues about cancer, circadian rhythms, alcoholism, and neurological disorders in humans, without running into the ethical and practical limits that go along with experimenting on people.

For most of the four decades since researchers discovered DNA -- the building blocks of genetics -- isolating specific genes like, for instance, those that determine eye color or a proclivity for certain diseases has been an arduous task. Researchers have been able to pinpoint some key human genes -- such as the one responsible for cystic fibrosis -- but hunting for each one within the entire human genetic structure can take a decade, cost millions of dollars, and still involve a dose of luck.

Harder still has been the effort to map out genomes -- complete blueprints of every gene found in a particular organism.

The genome of brewer's yeast, the smallest and easiest of the trinity, was finished just three years ago. The roundworm's blueprint was finished in December, after eight years of research.

The fly genome has yet to be finished. And the human genome, the grandest prize of all, is even further down the road.

In the early 1980s, scientists' best guesstimate was that a complete blueprint of the roughly 100,000 genes that make up a human would be beyond their grasp until deep into the 21st century.

But everything changed in 1990, when the U.S. government committed itself to the most ambitious undertaking in the history of genetic research -- a $3 billion program to completely decode the human blueprint by 2005. The National Institutes of Health and the Department of Energy are now doling out the money to researchers who, using new technology, are assembling the human genome.

The quest began as pure science. But lately, big money has come into play. Multinational medical, research, and pharmaceutical companies figured out that there is gold in the human blueprint.

The government is interested solely in the science of the thing. It plans to draw up the map and give it away to anyone who wants a copy. But private companies are seeing profits, in the form of patents on specific portions of the blueprint. Imagine, for instance, a company that owns the rights to the genetic data that helps determine whether a woman will come down with breast cancer. Everyone wanting that genetic information to conduct research, devise diagnostic tests, or come up with treatments will have to pay royalties to that company.

But only if that company can isolate the critical genetic information and patent it before government researchers give it to the world for free. Speed is now of the essence.

And, suddenly, the fruit flies Rubin has been crushing and analyzing at his Berkeley lab have become quite important. Through an odd confluence of forces, finishing the fruit fly genome is now seen as a significant intermediate step in the quest for the ultimate goal -- mapping out the human blueprint.

Once something of a lone prophet within the small community of fruit fly researchers, Rubin is suddenly receiving generous offers of help in finishing his fly blueprint as quickly as possible.

But the help is coming from one of the most notorious opportunists in genetics, a fellow scientist named J. Craig Venter. This has placed Rubin in a curious position. Although he prides himself on his devotion to pure science, speeding up his work -- indeed, achieving the goal he has pursued for most of his professional life -- has compelled Rubin to throw in with a man mistrusted and reviled the world over.

The government's decision to bankroll the Human Genome Project, as the quest for the human blueprint is called, launched a scientific undertaking no less ambitious than the Manhattan Project. Just as the work on nuclear fission at Los Alamos, N.M., in the 1940s changed physics, the genome project will change all the life sciences.

In theory, the HGP will usher in a new age of biotechnology and medicine, one that will enable mankind to pick the lock on inherited disorders such as heart disease, cancer, and mental illness. The decoding -- sequencing, in scientific parlance -- of the human genome will generate the basic information scientists need to diagnose disorders and treat them with gene therapies that carry no side effects.

Back in the mid-1980s, three decades after James Watson and Francis Crick discovered DNA's structure, scientists still despaired of advancing genetic research beyond a technological Bronze Age.

They were saddled with cumbersome tools -- often involving radioactive dyes -- and were restricted to analyzing but a few genes at a time. Yet all the research told them that genetic disorders most often involve layer upon layer of genes. They truly couldn't see the forest for the trees.

About The Author

Philip Dawdy


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