Gonna Fly Now

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

After being broken into minute "pieces," the DNA -- just molecules, really -- is cloned and placed in a petri dish with a strain of E. coli. Ironically, DNA grows quite well in a soup of the bacteria. In the petri dish, the DNA becomes barely visible, cloning itself hundreds of times until it resembles coarse sea salt on a wafer.

A specially designed machine is used to pick 96 pieces of DNA out of the petri dish, and put them on a plate.

The DNA is prepped with chemical primers and fluorescent dyes, and fed into a sequencing machine that is able to read its smallest particles. The result is a series of codes that identify the genes and where they fit into the larger blueprint. The work is tedious, and even with the best equipment Rubin's lab is only identifying about 1 percent of the fruit fly genome each month.

At that pace, Rubin had felt somewhat bedeviled by the progress of his project. As of last spring, he could only hope that he would finish sometime in 2001, a disheartening wait for the 5,000 scientists around the world who use Drosophila as a tool for genetic research.

But last May, Rubin and his project were struck by a thunderbolt: the offer of a scientific collaboration that would allow completion 18 months faster and $9 million cheaper than Rubin's earlier projections.

The offer came from J. Craig Venter.

Molecular biologists and geneticists around the world view J. Craig Venter as "the enemy." His critics, and there are many, are convinced that Venter and his corporate allies are out to seize control of vital genetic information by creating a company that will be the Microsoft of biotechnology.

Last May, a private corporation named Celera was formed by Venter and scientific instrumentation giant Perkin-Elmer. Celera's goal, simply, is to beat out all those scientists the government is funding, and finish the human genome first.

Venter is a biochemist from Maryland who worked for the Human Genome Project until 1992, and the announcement of Celera's formation rocked the scientific world. Venter claimed that Celera would beat the HGP by four years, and do the job $2.75 billion more cheaply.

The payoff for Celera, of course, would be the ability to decide which of the estimated 100,000 human genes it would like to patent before others find them. Many human genes are of little value or interest, beyond academic research. But great riches will come to whoever patents the really important ones. Whoever winds up with the patent on the genetic information underlying leukemia or manic-depression, for example, stands to make billions by licensing that information to medical researchers and pharmaceutical companies, which would develop diagnostic tests, drugs, and gene therapies.

The government intended the genetic code to be public information, unpatentable and available to all. But Venter and Celera want to own the pieces that contain commercial value -- and under U.S. law there is nothing to stop them. Patenting genetic data is perfectly legal.

So, like the Oklahoma Sooners of the 1880s, huge corporations and upstart companies alike are scrambling to stake out claims on the new scientific landscape.

To jump ahead of the government's project, Venter and Celera have decided to bet on new, relatively untested technology. They are using a different, faster method of gene sequencing, one critics say is so error-prone that its scientific integrity is open to doubt.

The difference is best explained by likening genetic research to regular old map-making.

The government's HGP is working slowly and deliberately, piecing the human genome together as if it were a road map, carefully plotting each block, each street, each city, and so on.

Venter's method, on the other hand, is more like parachuting into a foreign country, mapping one portion of it, and then racing off somewhere else. He winds up with a lot of small maps, but no coherent way to connect them all together.

It is possible that Venter's method will never produce a complete and accurate human genome. But, for profit's sake, that may not matter. Celera will be able to sequence more DNA in a day than all of the government's researchers do in a month, and cherry-pick the richest finds for itself.

That in and of itself should have been enough to enrage most of Venter's fellow scientists. But, in announcing Celera's formation, Venter engaged in an act of self-adulation that rankled his colleagues even more.

With Celera established, Venter said, there was really no need for the government's HGP anymore. He suggested that the HGP scientists leave the human genome to him. Maybe they could spend their time working on something else, like the mouse genome.

Such talk led Science magazine to headline an article on Venter and Celera "Hubris and the Human Genome," and prompted a congressional hearing last June to determine if the HGP itself needed to be revisited. (The answer was no.)

Even Gerald Rubin admits that Venter is "not the most lovable character to many people."

But Venter isn't seeking the love of his peers. He's out to win a race. Last May, Venter realized that he needed some way to test his methods, to ensure that his fast-track sequencing procedure is not as flawed as his critics suggest. Otherwise Perkin-Elmer might be investing $250 million in a scientific boondoggle.

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