Mapping genome just start of decades of research, experts say

WASHINGTON - An essentially completed map of the human genes, to be announced jointly on Monday by two competing groups, is just the beginning of a genetic revolution in medicine that may take a century to complete, experts say.

President Clinton, speaking in anticipation of the announcement, said ''the whole landscape of health care'' will be changed forever by decoding the human genetic pattern.

But that change won't come easily or quickly, the experts said. It may take another two years to completely finish and double check the genome map, and even that will be only a beginning - just as learning to read simple words is only the beginning of an education. Whole libraries of new knowledge await medical researchers.

Ultimately, understanding the human genome will lead to new drugs, advanced treatment of genetically related diseases such as cancer and heart disease, and better techniques for diagnosing disease.

Some experts believe that people someday will have their unique genetic code on smart cards that will enable doctors to prescribe drugs and treatments tailor-made for each patient's gene pattern.

The human genome project - started 10 years ago by publicly financed agencies in four countries and more recently by a private Maryland firm - has been described by experts as the ''Apollo moon landing program of biology.''

''It will be like man on the moon, like the start of the industrial revolution,'' said Richard Gibbs, head of the gene sequencing center at the Baylor College of Medicine in Houston. ''The impact eventually will be enormous in medicine.''

Leaders of both a publically-funded project and a competing private company issued statements Friday that they jointly would announce the status of their work on Monday.

The international public project, led by an agency of the National Institutes of Health, said that it would announced completion of a ''working draft'', which officials said means the mapping is about 90 percent complete.

The private effort by Celera Genomics of Rockville, Md. may be farther along. A company statement said it would announce ''the first assembly of the human genome.''

For both projects, the goal is to sequence correctly the 3.1 billion DNA subunits that make up the human genome and put those sequences into the correct order within the 23 pairs of human chromosomes.

The publicly financed human genome project has already cost about $300 million and officials said it has identified about 50,000 genes with several thousand more still expected to be found. Computers reading DNA are sending more than 10,000 sequences an hour into a public data bank.

Gibbs said the ''working draft'' of the genome has been on the brink of completion for several weeks and was being ''tuned up'' in preparation for the announcement.

He and others admitted, however, that the final genome map, checked and rechecked repeatedly, will not be completed for at least two more years and even then gaps may remain that cannot be filled with present technology

Celera started its project later, but is using a faster method powered by the world's largest private assemblage of supercomputers. The firm announced earlier this year that it had sequenced all of the genes from one human being, an unidentified male, and that it expected in June to have those gene reassembled into the correct order and location on the 23 pairs of human chromosomes.

Gene sequences produced by Celera are not being made immediately available to other researchers, but company officials said the data eventually will be posted on a Web site and available to subscribing universities and pharmaceutical companies.

For months, the parallel public and private efforts were seen as competing and contentious, with bitter criticism and harsh words exchanged in public. But leaders of the two groups publicly shook hands and exchanged compliments last month. Later, sources said, they agreed to the joint announcement.

The public gene sequencing program is a joint effort of the Human Genome Research Institute at the National Institutes of Health, the Department of Energy, the Wellcome Trust in Britain, the Whitehead Institute in Cambridge, Mass., the Washington University School of Medicine in St. Louis, Baylor College of Medicine in Houston, along with contributions from researchers in Germany and Japan.

J. Craig Venter, Celera's chief scientist and co-founder, said that after mapping the genome, science will be confronted with an immensely complex job of identifying, characterizing and understanding thousands of proteins that are made by the genes.

''That may take a century,'' he said.

Genes do their work of directing the formation and functioning of cells by causing proteins to be made.

Dr. Francis Collins, head of the Human Genome Research Institute, agreed that a complete understanding of proteins produced by the genes may take 100 years. ''Where we may have 50,000 genes, we may have as many as a million proteins to keep track of,'' he explained.

The most immediate goal, he said, is identifying the differences between genes that are normal and genes that cause disease.

Collins said researchers must study about 10 million DNA variations, called single nucleotide polymorphisms (SNPs, pronounced ''snips''), that give each person a unique gene structure.

''Most of those SNPs will not alter function in a medically relevant way,'' Collins said. ''There are probably only a few thousand responsible for medical conditions. But we've got to find those and that is the hard part.''

Once disease-causing SNPs are found, researchers will be able to find drugs or other therapies that neutralize the effects of these flawed genes.

It may also be possible, said Collins, to find SNPs that eventually will cause disease. This would enable patients to make changes in diet or lifestyle to head off disease in the future, or to start taking medicine to prevent illness instead of drugs to cure it.

All of that is possible, said Collins, with the new understanding of the human genes.

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On the Net: NIH site: http://www.ornl.gov/hgmis/project/progress.html