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Genetically Altered Mice Offer Clues to Cancer

By Inserting Genes, Philip Leder '56 Uses Patented Animals to Study Causes of the Disease

"These animals, since they spontaneously develop cancer, are good models for regiments, or testing procedures to prevent incidence of malignancy," Leder says.

"Using recombinant DNA technology, we can isolate genes which we think may be involved in cancer, we can alter them in accordance to a hypothesis we have about the development of that cancer, and then we can test the hypothesis by introducing the gene into the fertilized egg of a mouse," he continues.

The offspring of this mouse will have the gene which has been altered, he adds, and if the gene is involved in the development of that malignancy, then it would be expected that the offspring will develop the cancer.

For example, the mice could be used to test the theory that a high fat diet is a factor in the development of tumors. Another theory, that pregnancy at a young age in humans prevents cancer, can be easily tested.

"You can make any model system you want," says Leder, including mice to study colon cancer, leukemia, lung cancer or any other form of the disease.

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The model system, he adds, is a good one to test agents which might be useful in the treatment of tumors because these are, in a sense, naturally occurring tumors in their native context.

The strains are kept breeding, Leder says, and can even be bred to one another so that one animal's genetic code includes two factors for the causation or prevention of cancer.

"Transgenic mice are used all over the world now in research," says Leder.

Initial Research

Leder says that studies done may years ago on concer known as Burkitt's lymphoma paved the way for his transgenic research.

The disease causes lymphomas, or tumors of the blood, in children. Leder says that upon characterization of the cancer, the genetic background of its development produced some interesting results.

"Invariably, it occurs as a particular kind of genetic damage called a translocation," he says. A translocation occurs when a piece of a chromosome is broken off and joined to a different chromosome abnormally.

"The reason we arrived at Burkitt's lymphoma was that the research was directed at the genetic basis for formation of antibodies," says Leder.

He says that researchers were asking where the genetic information necessary to create the body's millions of antibodies came from.

When the DNA locus of the encoding of these antibody producers was identified, he says, it was found that this locus was always involved in the same region as Burkitt's lymphoma. The insertion of the lymphoma abnormality, a gene known as c-myc, was responsible for the rise of the tumor.

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