Genome Project Turning Out To Be A Bargain Program To Map Human Dna Going Faster, Costing Less Than Expected

Here’s a pleasant surprise: A huge federal science program that’s turning out to be both faster and cheaper than planned.

The Human Genome Project, which aims to decipher the complete genetic code of life by 2005, will celebrate its fifth birthday next month.

So far the enterprise has cost $871 million - less than the $1 billion projected - and completed its first map of human DNA more than a year ahead of schedule.

At least 50 disease-causing genes have been identified. Tests for a dozen genetic disorders have been developed. And a start has been made toward the Holy Grail of medical science - the ability to prevent or cure cancer, birth defects, Alzheimer’s and other diseases by fixing damaged genes.

“We can no longer say tracking down a specific disease gene is made difficult by lack of a good map,” said Dr. Francis Collins, discoverer of the first human disease gene and the project’s director. “We have a good map.”

Collins acknowledged, however, that practical applications are still a long way off. And researchers are just beginning to deal with the emotional and privacy implications that arise when science is able to determine that a person has a defective gene, but no treatment for the disease is available.

But the results have been impressive enough that even the penny-pinching Republican Congress voted an 11.2 percent budget increase for genome research in 1996 - $170 million, up from $154 million last year and even more than President Clinton requested.

“I am happy to report that the project is running ahead of schedule and under budget,” Collins told a House Appropriations subcommittee. Despite great initial skepticism, he said, “the end goal is in sight.”

When scientists started talking about unscrambling the genome a decade ago. it seemed like an impossible dream.

“The eventual isolation of most disease genes still seemed in the mid-1980s beyond human capability,” said James Watson, who shared the Nobel Prize for discovering the double helix shape of the DNA molecule 40 years ago.

But in time, the pessimists were overcome, and Congress approved a 15-year Human Genome Project starting officially on Oct. 1, 1990.

Since then, thousands of scientists - some in government research centers but mostly at universities and private laboratories - have been toiling at the immense task. Their work has been speeded by recent advances in computing and automation.

Eric Lander of the Whitehead Institute in Cambridge, Mass. for example, has developed a robot he calls the “Genomatron” that can spit out hundreds of strings of DNA in a few hours. University of Michigan geneticist David Burke is designing a computer chip that can analyze DNA.

Human DNA, the master molecule in every cell, is made up of 3 billion tiny chemical units - known as “bases.” There are four kinds of bases, known by their first initial as A, C, G and T. (The initials stand for the chemical compounds adenine, cytosine, guanine and thymine.)

Long strings of bases form genes, which govern the function of each cell, determining whether it is part of an eye or a toe, male or female, healthy or cancerous. All 100,000 genes together are known as the genome.

Originally, the cost of the genome project was estimated at $200 million a year, for a total of $3 billion, or one dollar per base. The cost is now down to 50 cents a base, and some scientists think the job can be completed for 10 cents a base.

Already, several significant milestones have been passed:

A rough map of human DNA, consisting of nearly 6,000 “markers” spaced from 500,000 to 1 million bases apart, was completed last October. The map is four times more accurate than the goal set in 1990.

A much more detailed “physical map,” consisting of 30,000 markers spaced about 100,000 bases apart, is halfway finished.

A start has been made toward the most ambitious goal of the genome project - identifying the precise sequence of each of the 3 billion bases in human DNA.

Once the entire sequence has been spelled out, much work will remain. The meaning of the genetic code must be deciphered and the function of each gene determined. Otherwise, sequencing the genome would be like buying an encyclopedia written in Sanskrit.

And even then, knowing the sequence is not the same as having a treatment or cure - the project’s ultimate goal.

Another concern is privacy. Genome researchers fear that employers or insurance companies will discriminate against persons known to be at risk for genetic disease, even though they are still healthy.

Dr. Kathy Hudson, assistant director of the National Center for Human Genome Research, said 22 percent of families diagnosed with a genetic flaw have been denied health insurance.

A federal task force on the ethical implications of genome research has recommended legislation prohibiting such discrimination.

Genome project officials also worry about emotional harm to persons who learn they have a defective gene before a treatment is available.

Danilo Tagle, a scientist at the National Center for Human Genome Research, said people ask: “What good would this knowledge do to me if there is no cure?”

But Collins insisted that, on balance, it is better to know than not to know.

He told Congress about a woman, identified only as Beth M., who was about to undergo a hysterectomy to reduce the risk of an inherited form of cancer that killed her father and two brothers.

Thanks to a test made possible by the genome project, he said, Beth learned she did not have the defective gene and was spared unnecessary surgery and fear.

Despite the concerns, deciphering the genetic code continues at an accelerating rate.

Scientists and politicians are delighted at the progress to date. Patients need more patience.