Monday, May. 22, 2000

A New DNA Twist from DoubleTwist

By MICHAEL D. LEMONICK

The race to sequence the human genome is almost over. Within a few weeks at most, the private company Celera Genomics will be announcing its successful completion of this monumental project, and the publicly funded Human Genome Project won't be far behind.

But the somewhat artificial nature of this much anticipated milestone was underscored in two separate announcements last week. Writing in the journal Nature, a team of scientists working on the public project reported that they had finished decoding chromosome 21, the strand of DNA responsible for, among other things, Down syndrome. And a California company, DoubleTwist, Inc., said it had used data from the public genome project to pinpoint 65,000 individual genes, out of the 100,000 or so in each human cell.

DoubleTwist's achievement reminds us that sequencing the human genome isn't the same as understanding it. What Celera and the federal project have been doing is figuring out the order of the DNA's chemical constituents--some 3 billion molecular "letters" that spell out the instructions for constructing a functioning human being.

But an estimated 95% of those letters fall into the category of "junk DNA"--molecular gobbledygook that spells nothing at all. Discovering where the actual genes begin and end, therefore, is key to understanding their functions--and DoubleTwist has taken a step in that direction. Using a Sun Microsystems supercomputer, the company has taken raw data downloaded from the public project's growing online database and put them through a computational wringer.

The result: a kind of road map to the genome, showing where along its long spirals of DNA the genes are located--65,000 of them with reasonable confidence, an additional 40,000 tagged more tentatively. For $10,000 a year, subscribers to DoubleTwist's website can read portions of the map; for $650,000 they can download the whole thing. And while the information is less detailed and thus less useful than what the gene sequencers will ultimately provide, DoubleTwist managed to get there first.

If DoubleTwist's coup shows that the genome project could generate profits even before it's finished, the mapping of chromosome 21 illustrates the converse: completion of the project won't mean scientists understand genetic diseases.

In Down syndrome, for example, victims somehow acquire a third copy of the chromosome, whereas most people have just two. But exactly which of the 225 or so genes on chromosome 21 trigger the scores of physical and cognitive symptoms typical of the syndrome--or whether it's simply DNA overload from having an extra chromosome--isn't clear, nor will it be without lots of additional research.

The same is true of the rest of the chromosomes. Sequencing all 23 will mean the crossing of a finish line of sorts. But it will be just the start of a long, difficult process to turn the information into practical treatments that can cure or prevent human suffering.

--By Michael D. Lemonick. Reported by Dan Cray/Los Angeles

With reporting by Dan Cray/Los Angeles