The Race to Map Our Genes

By Christine Gorman

Biologists, unlike physicists, are unaccustomed to gargantuan, gazillion- dollar research projects. So when American geneticists embarked on a $3 billion effort to map out all the hereditary information found on the 23 pairs of human chromosomes, they decided, like the proverbial tortoise, to take the slow and careful route. Plotting out a 12-year game plan, the geneticists subdivided the work among nine different laboratories so that eventually the scientists could pool their results in one highly detailed chart. Along the way, they have been trying to patent their discoveries, even before knowing precisely what their importance was.

But they did not count on the harelike speed -- and less mercenary mind-set -- of Daniel Cohen. An ambitious French geneticist, he has jumped ahead of his American rivals and is close to completing the first map of the human genome.

Cohen and his colleagues at the Center for the Study of Human Polymorphism in Paris will soon unveil their pioneering cartography. Thanks to a series of clever shortcuts, the French team's map will be available two years ahead of the schedule U.S. scientists set for themselves. Though somewhat rudimentary, Cohen's charts will make it easier for researchers to track down and isolate single genes scattered along the length of human chromosomes. "We don't want to say that we have beaten the Americans," the 41-year-old geneticist protests. "We like to compete, but not on a nationalistic basis." And yet he notes, "On this map, 90% of the work will have been done in France."

The U.S. government has tacitly acknowledged the French achievement by awarding researchers at M.I.T. $24 million to adopt Cohen's techniques. But the American effort has yet to emulate the most admirable aspect of the French effort: Cohen intends to donate his gene map to the United Nations as a gift to the world, thereby ensuring all scientists unrestricted access to the vital data. Cohen feels he owes this to the public because his work has been largely funded by public donations to a muscular-dystrophy telethon.

The federally funded U.S. project, led by the National Institutes of Health, has mounted a campaign to patent each DNA fragment that its researchers can reproduce, even before its usefulness is determined. The policy has been heavily criticized within scientific circles and figured in the abrupt resignation last spring of Nobel-prizewinning geneticist James Watson as head of the Genome Project. Cohen speaks for many critics when he names the two big problems with the NIH approach: "The first is moral. You can't patent something that belongs to everyone. It's like trying to patent the stars. The second is economic. By patenting something without knowing the use of it, you inhibit industry. This could be a catastrophe."

The initial maps under construction on both sides of the Atlantic will not identify every gene on every chromosome. Instead, the maps describe fragments of DNA arranged in the proper order as they would appear on the chromosomes. So far, researchers have identified a few genetic markers on each fragment: for example, the gene for Huntington's disease on a fragment of chromosome 4. In a later phase, they hope to crack the code of each gene -- a code that is written in chemical constituents called base pairs. The great challenge is the sheer size of the task. The human genome contains 3.5 billion base pairs.

To decipher so much material, researchers must first chop the genetic material into smaller, more manageable fragments. Most U.S. scientists have been working with fragments that are about 50,000 base pairs long. Unfortunately, since there are 70,000 fragments to analyze, the work is extraordinarily tedious. Cohen had a better idea: use fewer but much bigger fragments. He was able to create large chunks of human DNA by genetically manipulating yeast cells to produce them. "It's a big breakthrough," says David Botstein, chairman of Stanford's genetics department. "It's terrific for getting the order of things, even though it won't give you the fine detail."

Cohen's scheme worked so well that his lab was able to divide the entire human genome into just 500 pieces -- each about 7 million base pairs long. Some of these fragments have since been further divided for more precise analysis. Researchers are using computers to examine the pieces and arrange them in the proper order. But such fast progress comes at a price. The huge fragments often contain bits of yeast DNA and omit some of the human stuff. Cohen's team can catch only the most glaring errors.

Even a slightly faulty map will speed the search for the specific genes of disease. Cohen hopes to deliver it as soon as this spring. But it may be another 10 years before scientists can consult the ultimate genetic recipe book: a printout of the base-pair sequences for all 100,000 human genes. But whether they will be able to consult it for free or for a fee is being decided now. If Cohen follows through on his intention to donate his research, the NIH may have to abandon its attempts to profit from the genome. Heredity will belong to all of humanity.

With reporting by Dick Thompson/Washington and Frederick Ungeheuer/Paris