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In a somewhat subtler series of experiments, Baltimore and his colleagues are studying how genes for disease-fighting antibodies are coordinated to respond to thousands of different invading microbes. They tailor-made a mouse gene for producing antibodies and inserted it into the DNA of a normal mouse. Although the antibody gene was bequeathed to every cell of the transgenic mouse, it was turned on (expressed) only where antibody genes normally operate: in the white blood cells. Now the scientists can determine just what gives the gene a preference for one tissue type over another, a crucial step in determining how cells diversify.
To understand better the genetic basis of cancer, Philip Leder, a molecular geneticist at the Harvard Medical School and his colleague Timothy Stewart, have bred a line of transgenic mice that may someday serve as a model for human breast malignancy. He designed a DNA hybrid consisting of a gene called c-myc, which has been implicated in animal and human cancer, linked to a regulatory segment of another gene that is expressed in developing and lactating breast tissue. Soon after female mice with the injected gene give birth and begin nursing, they grow sizable tumors in their breasts. Perhaps more remarkable still, when these transgenic mice are interbred, their offspring occasionally have a startling sort of limb deformity, fused leg bones, for example, and three digits instead of five. The reason is that some of the descendant's own genes have been disrupted by the inherited but foreign c-myc DNA. "This approach will certainly help us understand limb development and what can go wrong with it," says Leder. "Why, for example, did Anne Boleyn have six fingers?"
Although transgenic technology is still in its infancy, some scientists hope that they can use it soon to reap medical benefits. If cancer genes can be so readily turned on, for example, the new technique may reveal ways to turn them off. And what is learned about gene expression could be applied to human gene therapy, in which people born with defective genes will have a "good" gene introduced into their bone marrow to produce the missing proteins. If all goes well, such therapy will begin on victims of blood disorders and enzyme deficiencies within five years. --By Natalie Angier. Reported by David Bjerklie/New York