Gene manipulation creates a smarter strain of mice; Research implications could counter memory loss in humans, raise IQ levels


In a major test of how learning works at the level of nerve cells, a scientist has created a smarter strain of mice by manipulating a gene involved in memory formation.

He believes his work lays the basis for eventually doing the same in people, whether in helping patients with memory deficits, counteracting the loss of memory in older people, and even in making healthy individuals smarter.

Other experts, while praising the technical quality of the work, see its first application as lying in treating patients with memory deficits rather than in enhancing intelligence.

Also, they say, although there are reasons to believe mice and humans are similar in this respect, the applicability of the work to people remains to be established.

The mice were created in an experiment designed to assess how memories are formed in the mammalian brain. The animals performed better than normal mice in six different tests, a strong indication that the altered gene is indeed involved in learning and memory formation.

The finding, reported in today's issue of Nature, also explains why young animals learn better than older ones, because the manipulated gene is one whose activity is known to fade with age in mice, monkeys and probably people, too.

The smarter mice were created by a team of researchers led by Dr. Joe Z. Tsien, a neurobiologist at Princeton University. Dr. Eric R. Kandel, a leading brain expert at Columbia University, praised the quality of Tsien's work, saying his new research "seems really reliable and is very nicely done."

For scientists, the importance of Tsien's paper is that it goes a considerable way toward proving a long-standing idea, known as Hebbs rule, about how the brain forms the neural associations that are the basis of memory.

"This paper takes a big step forward to showing people had been on the right track," said Dr. Charles Stevens, a neurobiologist at the Salk Institute.

For others, the interest of Tsien's work lies in its possible application to people.

Though no one yet knows whether the same manipulation would make people smarter, Tsien said, the DNA sequence of the gene he manipulated is 98 percent identical in mice and humans, suggesting that altering it by drugs or gene therapy might also make people smarter.

"It is not a hypothetical question. It is time for people and the public to begin to discuss these issues," he said.

In all tests, the genetically engineered mice performed consistently better than normal mice, giving Tsien his basis for believing the animals have enhanced intelligence as well as better memory.

Kandel notes that Tsien was not restoring the learning ability of old mice but doing something even more interesting, that of enhancing the natural abilities of young mice.

The experiment thus raises the question of "whether intelligence is optimized by the brain or could you push it even further? That you can improve a young animal's performance is interesting," Kandel said.

Tsien's experiment brings home the fact that the blueprint for the brain is written in the genes and that, probably well before society is ready to assess the full implications, biologists now stand on the threshold of being able to change fundamental aspects of the brain's architecture.

"Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible," Tsien and colleagues declare in their Nature article.

Other experts do not disagree with this assessment but put greater emphasis on the complications that lie ahead.

"One has to move with great caution and the realization that these are very complicated processes," Kandel said. "Our understanding of memory processes is quite shallow -- this is the beginning of the beginning.

"What the bad consequences or limitations are we don't really understand. But by and large the thinking is probably on the right track."

Pub Date: 9/02/99

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