Scientists Create Smarter Mice
Jeff Barnard,
Associated Press Writer

2:02 PM EST; September 1, 1999 -- Scientists have genetically engineered smarter mice, pointing the way to a brave new world in which parents could -- in theory, at least -- create baby Einsteins. The breakthrough could also lead someday to drugs for treating Alzheimer's or stroke. By inserting an extra gene, researchers produced a strain of mice that excelled in a range of tasks, such as recognizing a Lego piece they had encountered before, learning the location of a hidden underwater platform, and recognizing signs that they were about to receive a mild shock.

The mice -- nicknamed "Doogie" after the boy genius in the TV show "Doogie Howser, M.D." -- carried their enhanced intelligence into adulthood, when learning ability and memory naturally taper off, and passed it on to their offspring. "This points to the possibility that enhancement of learning and memory or even IQ is feasible through genetic means, through genetic engineering," said Joseph Z. Tsien, the Professor of Molecular Biology at Princeton University who led the research team. The findings were published in Thursday's issue of the journal Nature.

"To jump from this very elegant molecular work in a mouse model to humans is a very, very big jump," said Dr. Robert Malenka, a psychiatrist and behavioral sciences specialist at Stanford University School of Medicine. "Nevertheless, it is a jump we can make and will make eventually. When we jump to humans, it will probably be a lot more complicated." The improved learning and memory came from increased production of a brain protein called NR2B. The research indicates that a common mechanism lies at the root of all learning, and identifies NR2B as a key player, Tsien said. "The work could lead to a drug to treat memory disorders, such as Alzheimer's, by increasing NR2B levels," Tsien said. "Production of NR2B normally decreases with age, corresponding to the loss of memory and learning ability commonly experienced by older people," he said. Drug companies are already looking into the manipulation of NR2B levels to treat strokes, according to Dr. Ron McKay of the National Institute of Neurological Disorders and Stroke.

The prospect of genetically engineering smarter babies raises big ethical questions. "What we are looking at is the baby steps toward a world in which we can design our descendants," said Arthur Caplan, Director of the Center for Bioethics at the University of Pennsylvania Health System. "I don't think that is necessarily bad. Finding ways to repair autism or mental retardation associated with Down Syndrome or Alzheimer's Disease or other disabling neurological diseases is a very good thing." "But just as parents strive to improve their children by sending them to better schools or giving them piano lessons, some will want to create smart children by way of genetic engineering," Caplan said. As in other areas of life, the rich would have an advantage. "We already have a brain gap in this society when some children go to kindergartens that cost $15,000 a year and other children go to kindergartens that don't have adequate plumbing," he said.

Using a tiny glass needle, the scientists injected a gene carrying a blueprint for NR2B into the nucleus of a fertilized mouse egg, then implanted the resulting embryo into the uterus of a surrogate mother mouse. Mice born with the extra gene made more NR2B than usual in their brains. That boosted mental abilities by enhancing the function of brain-cell switches called NMDA receptors. The results confirm the idea, proposed in 1949, that these switches play a key role in learning. The NMDA switches require two signals to open, which fits in with the idea that learning involves associating pairs of events or facts, like a tone and an electrical shock. Boosting levels of NR2B kept the switches open longer than usual. "If you associated food with a bell, a voice with a face, a face with a name, these are all associative learning, the major forms of learning in humans," Tsien said. "To associate those things you require some kind of cellular machinery. It is so nice to convince ourselves that we are working with the right machinery."