Medicine: AIDS Research Spurs New Interest in Some Ancient Enemies

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And medical researchers hope soon to have a powerful ally in their campaign against viruses: vaccines made from genetically engineered viruses. At the NIH, Dr. Bernard Moss is using recombinant DNA techniques to convert vaccinia, a large virus that causes cowpox, into a one-shot, multidisease vaccine. He plans to insert only the antigen-coding genes of eight to ten kinds of dangerous viruses into the DNA of live but weakened vaccinia viruses. The re- engineered vaccinia would then sport the antigens of the harmful viruses, but not their ability to cause disease. Once inoculated, it would stimulate the immune system into producing cells that could later act against infection by any of the harmful viruses.

In an even more dramatic development, a dozen teams of scientists are working on techniques to use viruses for "gene therapy" on humans with genetic disorders. Using recombinant DNA techniques, they plan to make retroviruses harmless by removing key genes, and to endow the viruses with other genes -- the ones lacking or inoperative in people with genetic diseases. These re-engineered retroviruses would be employed as vectors that would invade the appropriate human cells and insert the healthy genes correctly into the cells' DNA.

The first candidates for this therapy would be people with life-threatening hereditary disorders that are caused by a single, known defective gene. Among the illnesses being considered for gene therapy: beta-thalassemia, a severe form of anemia, and three rare disorders caused in each case by a defect in a gene that orders the production of a single, vital protein.

Although experimental work on mammals is proceeding slowly, Richard Mulligan, who has been practicing gene therapy on mice at the Whitehead Institute, is optimistic. "We are pretty damn close," he says. "We have retrovirus vectors that transfer efficiently. It looks like we can infect the ( appropriate types of cells reasonably safely." But, he concedes, he has not yet been able to induce the genes to "turn on" and order the cells to produce the missing proteins.

The solution, Mulligan hopes, is to attach the protein's gene to a section of DNA that acts as an on-switch, or promoter, before implanting it in the retrovirus. In his experiments to date, he says, the strategy is "working fantastically," and he expects encouraging results within two or three months.

Still, despite the viruses' apparent potential for good, their much greater capacity for evil has been amply demonstrated. Smallpox. Yellow fever. Rabies. Polio. And now the cruel AIDS epidemic. Concludes David Baltimore: "You could get rid of all the viruses from the world and the world would not be the worse for it."