Human genetic map: worth the effort?

Human genetic map: Worth the effort?

When researchers last week in Chicagoannounced their success in constructing the rough map of a bacterium's entire genetic code, the new information added another line to the expanding book on deciphering the complete human genome. But because an organism's genome includes all of its genetic material, the current federal program to map the highly complex human genome is having some technical and political difficulties.

Charles R. Cantor of Columbia Universitysaid at the annual meeting of the American Association for the Advancement of Science that he and his coworkers had divided the genome of the common bacterium Escherichia coli into 23 pieces and had used a new method to prepare the DNA for study. He emphasized that the data are "sketches' of the E. coli genome, not a complete sequence of all its components.

Although the project took several researchersmore than a year to complete, Cantor says current technology could shorten the time required to two or three weeks. The Columbia research was one of several pilot studies being conducted to see if such sketches can be used to map entire genomes, and its success was welcome news to those anxious to systematically map the genetic code.

But the E. coli genome is only aboutone-tenth the size of the smallest human chromosome. In turning to the human system, Cantor's group and another from Yale University currently are trying to map pieces of chromosome 6 (important in transplant compatibility) and chromosome 4 (involved in Huntington's disease) by using similar techniques.

Whether these latest efforts are successfulor not, they have already yielded some unexpected results, according to Cantor. "The major surprise is . . . the human genome is mosaic,' he says. "What this means is that genes for related functions appear to be clustered together in the chromosomes more than originally thought.' As a result, segments of the chromosomes located near specific disease-causing genes may be used to a greater extent in diagnosis.

The promise of improved diagnosisand treatment for the more than 3,000 known genetic diseases is enticing, but at the same time frustrating. If it were uncoiled from the nucleus of a cell, human genetic material would stretch 2.7 meters. If the information stored there were printed out on paper, it would fill 200 Manhattan telephone books, or three years worth of daily newspapers, say scientists. And only 0.2 percent of the human genome has been decoded.

Just to process the data produced bymapping the entire human genome would require "an extraordinarily rich' computer base, possibly using artificial intelligence capability, says Mark W. Bitensky from Los Alamos National Laboratory in New Mexico. The Los Alamos lab and its so-called GenBank (a repository for genetic sequencing data) join Lawrence Livermore National Laboratory in California and Columbia University as the primary centers for the Department of Energy's (DOE) Human Genome Initiative (HGI).

All the nonscientific elements of modernscience also can be found in the government's human genome project-- international cooperation/competition, ethical questions about working with human genetic material, controversy ovre the high price for a fairly narrow area of research, basic science giving way to technology, and much more.

According to Charles P. DeLisi, from theDOE's Office of Health and Environmental Research and a principal supporter of HGI, if mapping of the human genome proceeds at its present-day pace, it will take, 7,000 years to decipher the entire sequence. But with adequate financial and human resources, he claims that the HGI could supply the entire genome by the year 2000; DeLisi adds that the Japanese are building a robot capable of decoding DNA 1000-fold faster than methods currently used in the United States. DeLisi predicts that X-ray lasers or new types of scanning electron microscopes may be used in the U.S. effort.

Despite the technological dazzle, thereare those biologists who ask about the economic and scientific costs of such a project, wondering whether it is, in Bitensky's words, "technological determinism rather than good science.' The questions are similar to those being asked by physicists critical of the high-cost superconductor project. Reagan's proposed budget for fiscal year 1988 includes a $12 million request for the genome project (up from $2 million the previous year). A DOE advisory committee projected expenditures of $20 million to $40 million per year during the initial technology-development phase of the project; the second phase of actual sequencing may cost as much as $3 billion a year, says DeLisi, who is quick to point out that this estimate is based on current technology that would be replaced by less expensive methods.

Walter Gilbert, a Nobel laureate atHarvard University, calls decoding the human genome "the biology of the 21st century.' And Bitensky says that "the insights that lurk in the genome are very exciting . . . comparable to the information that awaits us in outer space, or at the heart of particle physics.' Whether that information is worth the cost is still being debated.