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To effect a cure, doctors would remove bone-marrow cells from a patient and expose them to a retrovirus* engineered to carry correctly functioning versions of the patient's faulty gene. When the retrovirus invaded a marrow cell, it would insert itself into the cellular DNA, as retroviruses are wont to do, carrying the good gene with it. Reimplanted in the marrow, the altered marrow cells would take hold and multiply, churning out the previously lacking protein and curing the thalassemia patient.
Easier said than done. Scientists have had trouble getting such implanted genes to "turn on" in their new environment, and they worry about unforeseen consequences if the gene is inserted in the wrong place in a chromosome. Should the gene be slipped into the middle of another vital gene, for example, it might disrupt the functioning of that gene, with disastrous consequences. Also, says M.I.T. biologist Richard Mulligan, there are limitations to the viral insertion of genes. "Most genes," he explains, "are too big to fit into a retrovirus."
Undaunted, researchers are refining their techniques in experiments with mice, and Mulligan believes that the first human-gene-therapy experiments could occur in the next three years. Looking further ahead, other scientists are experimenting with a kind of genetic microsurgery that bypasses the retrovirus, mechanically inserting genes directly into the cell nucleus.
Not only those with rare genetic disorders could benefit from the new technology. Says John Brunzell, a University of Washington medicine professor: "Ten years ago, it was thought that only 10% of premature coronary heart disease came from inherited abnormalities. Now that proportion is approaching 80% to 90%."
Harvard geneticist Philip Leder cites many common diseases -- hyper-tension, allergies, diabetes, heart disease, mental illness and some (perhaps all) cancers -- that have a genetic component. Unlike Huntington's and Tay-Sachs diseases, which are caused by a single defective gene, many of these disorders have their roots in several errant genes and would require genetic therapy far more sophisticated than any now even being contemplated. Still, says Leder, "in the end, genetic mapping is going to have its greatest impact on these major diseases."
Of all the enthusiasm that the genome project has generated among scientists and their supporters in Washington, however, none matches that of James Watson as he gears up for the monumental task ahead. "It excites me enormously," he says, and he remains confident that it can be accomplished despite the naysayers both within and outside the scientific community. "How can we not do it?" he demands. "We used to think our fate was in our stars. Now we know, in large measure, our fate is in our genes."
FOOTNOTE: *Except red blood cells, which have no nucleus.
FOOTNOTE: *A virus consisting largely of RNA, a single-stranded chain of bases similar to the DNA double helix.