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Scientists can now make mice smarter
Genetic modification raises 'some thorny issues'
Thursday, September 2, 1999
By RICHARD SALTUS
Scientists say they have genetically modified mice to make them smarter, and the feat raises anew provocative questions of when or if such genetic enhancement of normal abilities should ever be attempted in humans.
After using gene implants to create a strain of mice having double the normal amount of a memory protein in their brains, the researchers found that the animals learned significantly faster and remembered longer than their normal counterparts.
Moreover, the added gene prevented the normal decline in memory and learning that occurs with advancing age in both mouse and man.
The finding, being reported in the journal Nature today, is certain to attract wide interest and stimulate debates over how society should use the growing power of genetics.
"This is the first evidence for manipulation of genes producing improvement in a higher function" in animals, said Dr. Larry Squire, a leading memory researcher, at the University of California in San Diego.
The gene-altered mice outshone unmodified rodents in a series 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 carried their enhanced intelligence into adulthood, when learning ability and memory naturally taper off, and passed it on to their offspring.
However, specialists pointed out, creating improved memory and learning ability is not the same as boosting intelligence, the complex and hard-to-define ability measured by IQ tests.
Daniel Schacter, chair of psychology at Harvard, said the paper does not assert that the mice had superior reasoning or analytical skills -- elements of what would be called intelligence in humans. Nevertheless, Schacter said, the report "raises a host of thorny issues."
If the research led to a safe and reliable memory drug that helped people with dementia or other memory disorders, said Schacter, "there would be the question of who should be using this among the normal population, and are you penalized if you don't use these drugs? These are questions we've never had to face before."
Besides drugs, this line of research could theoretically lead to genetic modification of human embryos to include a human version of the gene that created the "smart" mice.
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's syndrome or Alzheimer's 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 genetical engineering, Caplan said. As in other areas of life, the rich would have an advantage.
The report in the current Nature came from the laboratory of Joe Tsien at Princeton University and collaborators at the Massachusetts Institute of Technology and Washington University. Ya-Ping Tang of Princeton is lead author.
The researchers came up with the name Doogie for the strain of brainy mice, a nod to the TV series "Doogie Howser, M.D.," which was about a precocious boy who is only 10 when he graduates from college.
The discovery might be applicable to humans because the mechanism that the scientists tinkered with in the mice is fundamentally the same one that creates memory in humans as well as in animals as lowly as the sea slug. Memories -- representations of thoughts -- are stored in networks of brain cells in many places in the brain but are indexed in a structure called the hippocampus.
Information is transmitted through the brain as electrical impulses that flow through one brain cell, or neuron, and then hurdle the gap, or synapse, between one neuron and the next. Chemical messengers carry the impulse across the synapse.
When the same information (a sight, a sound, a thought) repeatedly crosses the same synapse, chemical changes make the synapse easier for the message to cross. When this happens, the information becomes more strongly etched into the neuron pathways as a memory that can later be retrieved.
Controlling the flow of impulses across the synapse is a protein called the NMDA receptor, which acts as a switch for memory formation. When it is stimulated by two adjacent nerve cells -- which would happen if two pieces of information were coming together in an association to be remembered -- the NMDA receptor opens for a fraction of a second, allowing the impulses to jump the synapse easily and create a stored memory.
When humans (or mice) are young, the NMDA gateway stays open slightly longer, providing more time for the mental association to be made and remembered. As people age, that time window narrows, and people store information less easily.
The Tsien group at Princeton created the smarter mice by adding extra copies of a gene called NR2B (which makes a protein for the NMDA receptor) to normal mouse embryos. The resulting newborn mice had about twice as much NR2B activity as normal mice, and this extra dose meant their brains were more open to new information in a shorter time.
As a result, the genetically modified animals were able to remember associations, such as whether an object in their cage was new or had been there previously, for several more days than the normal mice.
This report contains information from The Associated Press.
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