Originally created 02/14/01

Genome findings lay groundwork for decades of research



WASHINGTON - Now that scientists have published their first examinations of nearly all the human genetic code - the genome - the job of figuring it out and reaping benefits is just beginning.

Imagine trying to figure out how a large corporation works by scrutinizing its telephone directory. You've got lots of names and locations. But what does each of these people do? How do they work together to get things done? If something goes wrong, what employees or teams are at fault?

That's one way to look at how decades of research will proceed from the new data.

Both teams that largely decoded the genome say their results have already helped others find dozens of disease-promoting genes. That's a step toward understanding the biological roots of disease, which could someday pay off in better treatments.

But that's just one payoff scientists are hoping for from the genome work.

Researchers also want to find ways to use a patient's particular genetic makeup to choose therapies that will work best and with fewest side effects, for example. Better understanding of human biology should also help scientists evaluate environmental hazards as well, researchers say.

And on the scientific side, scientists hope to learn more about evolution, ancient migrations of human populations and puzzles about the genome's own history and structure.

"We have peered for the first time at the ancient text," said Eric Lander, director of the Whitehead Institute Center for Genome Research in Cambridge, Mass., and a co-author of one of the new analyses. "We find a few answers and dozens of new mysteries."

Both versions of the genome being published this week in the journals Nature and Science are still being worked on. One, presented by a consortium of federal and institutional scientists in the United States with colleagues in five other countries, is a draft with a couple more years' work scheduled. And Celera Genomics of Rockville, Md., will continue to improve its version, says Celera president J. Craig Venter.

The two groups determined most of the 3 billion "letters" of the human DNA code, a long chemical sequence that contains the basic instructions for building and running a human body. Both agreed that they found surprisingly few genes, some 26,000 to 39,000 according to Celera, and about 30,000 to 40,000, according to the consortium.

The findings reaffirmed that all humans were almost genetically identical, Roger-Gerard Schwartzenberg, France's minister of research, said at a Paris news conference. "Today, the 12th of February is a bad day for supporters of racism and xenophobia."

It's not easy to accurately identify genes in the human genome, and nailing down a more precise count will be one task for the future.

Then there's the immense job of figuring out what newly found genes do. Venter said 40 percent of the minimum 26,000 genes in his group's count are mysteries, with no known function.

And the real biological understanding will come not only from learning what individual genes do, but also tackling more complex questions: how genes work together, how their activity is regulated and how the proteins they give rise to interact, scientists say.

The genome data can help scientists find disease-promoting genes in several ways. One is by pointing out millions of subtle variations in the DNA code between people. Each variation can be used as a landmark in the chromosomes, the microscopic structures that carry genes, and the landmarks can be used to find genes through studies of inheritance patterns.

Once a chromosome region is implicated in this way, the DNA code for that region can be quickly searched on a computer database, yielding a list of genes for further testing. That's far faster than years of seeking these genes by analyzing the DNA itself.

Such computer searches are also a speedy way to find unknown genes that are structurally similar to known disease genes. Such similar genes might also be involved in disease. The consortium's paper reports it found 286 such matches.

Dr. Francis Collins, a co-author of the consortium paper and director of the National Human Genome Research Institute, recalls it took two scientific teams 10 years to isolate the gene that causes cystic fibrosis when defective. Now a comparable search could be finished by a single graduate student in about two weeks, Collins said.

In Germany, Research Minister Edelgard Bulmahn said scientists will concentrate on five common health problems: heart problems, cancer, diseases afflicting the nervous system, environmentally linked illnesses and infections.

Venter warned against thinking that all of a person's traits are hard-wired by the genome, or that the DNA code itself will ever explain things like how personality and intellect arise.

But he said he expects many discoveries over the next 50 to 100 years about subtle and intricate mechanisms that regulate gene activity, and their importance for how organisms function.

And when scientists that far in the future look back on the two papers published this week, he said, they will see "the documented ignorance of how little we know in 2001."