Medicine: Moving Toward Designer Genes

DNA research steps up from the cell to the animal

Since scientists first began manipulating genes, they have been envisioning a brave new world in which diseases from Huntington's chorea to sickle-cell anemia to possibly diabetes could be cured simply by inserting the correct strip of DNA into the body's cells. So far, though, most of the genetic tinkering has been limited to transplanting genes into isolated cells in laboratory dishes or into bacteria.

But the dawn of designer genes is slowly moving closer. Researchers are now extending their experiments to living animals. In April, scientists at the University of California in Los Angeles reported they had inserted into intact adult mice a gene that makes cells resistant to a specific drug. Last week a team of Yale University scientists announced they had altered an animal's hereditary makeup at a more basic level: by injecting foreign genes into a mouse at its earliest stage of development, a fertilized egg.

In the Yale experiment, described by Biologist Francis Ruddle at an international conference on cell biology in West Berlin, he and Colleagues Jon Gordon and George Scangos isolated genes from two viruses and manufactured them in large quantities. Then, guided by a high-powered microscope and using tubes thinner than hairs, they delicately microinjected 1,000 to 20,000 copies of the genetic material directly into the nuclei of newly fertilized mouse eggs kept alive in laboratory dishes. The eggs were then carefully transferred to the wombs of female mice and eventually the foster mothers gave birth to 150 infants. The newborns were promptly killed, and the DNA was extracted from their tissues for study. Portions of the viral genes were found in two of the mice. Presumably the genes had been present in every cell of those animals.

While the experiment offers the possibility that by changing the genetic material in the human egg, doctors may one day be able to eliminate a host of inherited diseases—including hemophilia, Tay-Sachs disease and phenylketonuria, a metabolic disorder that may result in brain damage—many basic questions must first be answered. For example, will the transplanted genes actually work as they are supposed to or will they be modified or inactivated by the animal's own genetic machinery? Will the foreign genes free-float in the cells or will they latch on to the other genes arranged along the chromosomes? Will genes that normally are switched on only in specific types of cells function in the same way when they have been introduced into other types of cells through genetic engineering? Finally, will transplanted genes be inherited by the animal's descendants?