COVER STORY: SEPTEMBER 13, 1999 VOL. 154 NO. 10

Smart Genes?
A new study sheds light on how memory works and raises questions about whether we should use genetics to make people brainier
By MICHAEL D. LEMONICK

The small, brown, furry creature inside a cage in Princeton University's molecular-biology department looks for all the world like an ordinary mouse. It sniffs around, climbs the bars, burrows into wood shavings on the floor, eats, eliminates, sleeps.

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But put the animal through its paces in a testing lab, and it quickly becomes evident that this mouse is anything but ordinary. One after another, it knocks off a variety of tasks designed to test a rodent's mental capacities--and almost invariably learns more quickly, remembers what it learns for a longer time and adapts to changes in its environment more flexibly than a normal mouse.

This is a supermouse, no doubt about it, though it didn't get its better brain by coming from another world. It was engineered by scientists at Princeton, M.I.T. and Washington University, who cleverly altered its DNA--or, more precisely, that of its genetic forebears--in ways that changed the reactions between neurons deep within its tiny cranium. The result, say its creators, is a strain of mouse (which they nicknamed "Doogie," after the precocious lead character of the old TV show Doogie Howser, M.D.) that is smarter than his dim-witted cousins. Not only that, the scientists wrote in last week's issue of the journal Nature, "our results suggest that the genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible."

Their audacious use of the I word triggered an avalanche of criticism from many of their colleagues, who called their conclusions unwarranted and farfetched. And it's easy to understand why. The idea that intelligence is rooted in the genes has long been an inflammatory notion--witness the charges of racism put to Richard Herrnstein and Charles Murray, authors of The Bell Curve, their controversial study of IQ and race. Beyond that, the very concept of intelligence is slippery. It involves many qualities--some of them elusive, like creativity, others more clear-cut like the ability to solve problems. "This is a very important study," says Eric Kandel, of the Howard Hughes Medical Institute at Columbia University, but he goes on to sound a polite note of caution. "Intelligence involves many genes, many features," he adds. "There are many things that go into it."

Yet even if Doogie isn't the Einstein of the order Rodentia, as some headline writers have portrayed him, most psychologists and neurobiologists are convinced that its memory and learning ability have indeed been enhanced. That has important implications. It suggests that even though the gulf between mice and men is continent-wide, this sort of research may eventually lead to practical medical results for humans, such as therapies to treat learning and memory disorders, including Alzheimer's disease, a condition likely to afflict more and more people in an increasingly aging population. In fact, the Princeton scientists are talking to drug companies about commercializing their work.

And the research inevitably raises the possibility that healthy people will try to boost their performance or, even more likely, that of their children--a prospect that has bioethicists ruminating feverishly. (See following story.)

Therapeutic promise is only one key implication of the new research. More immediate, and for now more important, is that the work gives neurobiologists further evidence about what memory is and how it works--a mystery whose secrets have been slowly unfolding for decades.

One thing has become clear to scientists: memory is absolutely crucial to our consciousness. Says Janellen Huttenlocher, a professor of psychology at the University of Chicago: "There's almost nothing you do, from perception to thinking, that doesn't draw continuously on your memory."

It can't be otherwise, since there's really no such thing as the present. As you read this sentence, the sentence that went before is already a second or two in the past; the first line of this story went by minutes ago. Yet without a memory of what's been said, none of what you are now reading makes the slightest sense. The same is true for our lives as a whole. Memory provides personal context, a sense of self and a sense of familiarity with people and surroundings, a past and present and a frame for the future.

But even as psychologists and brain researchers have learned to appreciate memory's central role in our mental lives, they have come to realize that memory is not a single phenomenon. "We do not have a memory system in the brain," says James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine. "We have memory systems, each playing a different role."

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