How does gene therapy work?

Arthur Nienhuis, a hematologist at St. Jude Children's Research Hospital in Memphis, Tenn., and outgoing president of the American Society of Gene Therapy, responds:

Gene therapy is the addition of new genes to a patient's cells to replace missing or malfunctioning genes. Researchers typically use a virus to carry the genetic cargo into cells, because that is what viruses evolved to do with their own genetic material.

Doctors can perform the treatment, first tested in humans in 1990, inside or outside the body. In the former case, they may inject the gene-carrying virus directly into the region that has defective cells. This approach is useful in therapies for Parkinson's disease, for instance, in which only part of the brain must be targeted.

Early in-the-body gene therapies used an adenovirus—the variety behind the common cold—but such an agent can trigger an immune reaction from the body. Today researchers use so-called adeno-associated virus, which is not known to cause any disease in humans.

In out-of-the-body gene therapy, researchers take blood or bone marrow from a patient and separate out immature cells. They add a gene to those cells and inject them into the bloodstream of the patient; the cells travel to the bone marrow, mature and multiply rapidly, eventually replacing the defective cells. Investigators are working on the ability to thus replace all of a patient's bone marrow or the entire blood system—as would be useful in treating sickle cell anemia, in which crescent-shaped red cells block blood flow.

Out-of-the-body gene therapy has already been used as a remedy for severe combined immunodeficiency (SCID), sometimes known as boy-in-the-bubble syndrome. SCID patients are unable to fight off routine infections and usually die in childhood. For this treatment, scientists use retroviruses, of which HIV is an example. These agents are extremely adept at inserting their genes into host cells' DNA. Some 30 children have been treated for SCID, and more than 90 percent have been cured—an improvement over the 50 percent chance of recovery offered by bone marrow transplants.

One risk associated with retroviruses is that they may stitch their genes anywhere into the host's DNA, disrupting other genes and causing leukemia. This complication has affected five of the SCID patients treated thus far; four of them, however, have beaten the cancer. Researchers are now working to lower the risk of bringing on leukemia.

Although no gene therapy products currently exist on the U.S. market, recent studies in both Parkinson's disease and Leber congenital amaurosis, a rare form of blindness, have returned very promising results. If this potential is borne out, hundreds of diseases could be eligible for treatment.

Why does bread go stale?

—H. Yang, Stafford, Tex.

James BeMiller, emeritus professor of food science at Purdue University, offers an answer:

Although the process has not been fully explained, the crystallization of starch polymer molecules is the most widely accepted, but not the only, contributing factor. Staling begins as soon as the loaf leaves the oven and begins to cool. How quickly bread hardens depends on its ingredients, how it was baked and its storage conditions.

Bread is a foamlike network made of starch molecules and molecules of a wheat flour protein called gluten. Inside this scaffolding are pockets of carbon dioxide gas produced by yeast during fermentation.

As time goes by, the starch molecules tend to crystallize. (Starch crystals are not like those of sugar or salt but are microcrystals formed in small regions of the starch polymer macromolecules.) Water is necessary for these crystallites to form, and the starch may take the required water molecules from the gluten. The removal of water from gluten changes it from a rubbery state to a rigid, so-called glassy state, firming the bread. Heating stale bread, however, will soften the glass, thereby freshening the bread.

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