BY NELL BOYCE

At the White House ceremony for the completion of the Human Genome Project two years ago, President Clinton noted that "one of the great truths to emerge from this triumphant expedition inside the human genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 percent the same." Last week, however, scientists announced the start of a new genetic map, one that puts the spotlight not on genetic similarity but on the small differences that remain.

The genetic code of DNA contains 3 billion chemical "letters," and while almost all of the sequence is identical in every human being, tiny spelling differences turn up every few hundred letters or so. Just a single letter's difference can raise a person's risk of disease. But because the total number of spelling variants could be as high as 10 million, screening people for all of them to identify ones linked to diseases would be a daunting task.

Just over a year ago, researchers got a break. They learned that each individual doesn't inherit a different, mix-and-match set of variants. Instead, those that are neighbors on the long DNA molecules get inherited together, in blocks 10,000 letters or more in length. If scientists had a map of these inherited blocks and the patterns of genetic variation found within them, they wouldn't need to sort through millions of possibilities. Instead, they could screen just enough to zero in on blocks linked to diseases and start the gene hunt there.

Francis Collins, head of the National Human Genome Research Institute, expects this shortcut to have "a profound impact on the future of medicine." Nine groups in five countries will work on the HapMap, hoping to complete it in three years at a cost of $100 million.

Global view. People who are even distantly related may have similar blocks, called haplotypes. To identify the widest possible range of blocks, the investigators plan to study 200 to 400 people whose ancestors separated long ago during humanity's prehistoric migrations. They'll begin by looking at Americans with ancestry from Northern and Western Europe, a group called the Yoruba in Nigeria, and people from Japan and China.

And that's where the 800-pound gorilla enters the room. Ethicists worry that the HapMap could easily be misunderstood as a catalog of racial differences. In fact, most gene variants will show up in all groups because of their shared ancestry, although a given variant might be more common in one group than another. "Being a member of a group doesn't tell you much, because the overlapping is so great," says David Altshuler of the Whitehead Institute, whose work helped lead to the HapMap.

HapMap organizers are still hotly debating whether they should bury the race issue by putting all their samples in one big group rather than labeling them by geographic origin. But some scientists would like to keep the labels because they think they'll prove useful for gene hunting. It's not just the subtle variations but also the typical size of the blocks that could differ between populations. Researchers would like to start their gene hunts in a population with large blocks, for example, and then move to groups with smaller ones.

Still, a preview of how findings about genes and race can get oversimplified came last month. In the New England Journal of Medicine, researchers reported the discovery of genetic variants found in both whites and blacks with heart failure. Yet headlines widely described the finding as "genes influencing chronic heart failure in blacks," notes Altshuler. The genes do appear to be more common in blacks, but most blacks–even those with heart failure–don't have these variants. And nongenetic factors like diet and access to healthcare loom large in this disease.

The HapMap will confront scientists and the public with many more examples of what our genetic differences do–and don't–mean, says Ellen Wright Clayton of Vanderbilt University, cochair of the project's ethics board. The project, she believes, "is really going to force us to face up to how we can talk about this."