Building a better brain?

Scientists alter mice genetics to increase intelligence, raising

In a breakthrough with important implications for science and ethics, a team of researchers announced yesterday they have produced more intelligent mice by altering the animals' genetics.

The mice, named after the precocious TV doctor Doogie Howser, exhibited superior learning and memory skills after scientists altered a gene for a crucial protein in their brains.

The research marks the first time that scientists have genetically manipulated mammals to augment basic skills that are the building blocks of intelligence.

What's more, these results were achieved by adding a single gene to the DNA of mice embryos. This simplicity implies that big shifts in biology can be wrought through relatively small changes in a complex organism's genetics.

The research may provide key clues to ameliorating disorders such as dementia or Alzheimer's, researchers say. But it also represents a new threshold in the ethics of genetics, as scientists move closer to being able to alter core human capabilities.

"It's unlikely that we can find a gene that we can alter and turn the average person into the next Einstein," says Michael Shapiro, a law professor and expert in bioethics at the University of Southern California in Los Angeles. "But it is, in principle, possible to make a statistically significant difference in certain abilities in humans."

Unlocking the key gene

The gene that makes "Doogie" different is named NR2B. Found in mice, monkeys, and humans, as well as in other mammals, NR2B is believed to be a key part of memory because it helps the brain forge a connection between two distinct neurological stimuli. For example, it helps humans associate the sensation of cold and the image of an ice cube, scientists say.

"This receptor is a molecular coincidence detector, an essential feature to implement learning and memory in the brain," says Joe Tsien, a Princeton University neurologist and the lead researcher on the project.

In their research, Dr. Tsien and his colleagues inserted an extra gene that produces NR2B into the DNA of mice embryos. Throughout their test, the Doogie mice handily outperformed the unchanged control group, often learning a task or making an association between two separate stimuli in half the time. They could recognize a Lego block they'd seen before, for instance.

The neurological mechanisms and genes involving NR2B in mice are nearly identical to their counterpart genes and mechanisms in humans and other mammals, Tsien says. But his research provides a small sample of the vast store of genetic knowledge that will be unlocked in the next few years when scientists complete their quest to map the entire human genome.

Between Doogie mice and gene maps, however, science appears to be heading for a clash with some of basic popular American beliefs about the human condition. At the heart of the matter are questions of who might get to use these new genetic techniques.

"The American way is that everyone has an equal opportunity to go out and exercise their abilities," says Dr. Shapiro. "But if scientists can stack the deck in the womb, exercising these abilities won't be enough. If there is unequal access to this technology, there is a substantial risk of ... making irreversible social stratification."

To some degree, the prospect of genetic manipulation might undermine universal precepts of human freedom. "When you talk about cloning a human for example or altering the intellect of a human or adding a gene to an embryo, this violates a very basic philosophy about human freedom," says Steven Collins, a professor who studies bioethics and innovation at the University of Washington at Bothell. "There is a natural tendency among Americans to be very cautious about taking that step."

But discoveries like Tsien's may not necessarily be used for such controversial ends. If they led to a drug that could deal with diseases associated with the brain, people might be more open to such research, says Hank Greely, a law professor at Stanford University in California.

Also, the degree to which gene manipulation will affect the basic human traits remains unclear. There are other factors that are perhaps of equal or even greater importance than genetic makeup, such as education, nutrition, and environment.

The importance of genetics

Indeed, the media may be focusing too much attention on genetics. "Popular understandings tend to move in overbroad swings," says Professor Greely. "Now, we tend to overestimate how important genes are. Thirty years ago, we may have underestimated how important genes are. But somehow genes seem sexier."

Furthermore, the intricate interplay of DNA and other factors that affect human development may prove difficult to unravel. "Humans are complicated and there are few things for which we are susceptible to quick fixes," adds Greely.

While smarter humans through genetics might be decades off, everyone agrees that the issue needs to be examined thoroughly. But so far, consensus seems elusive and much of the general public has yet to think deeply about such issues.

"My experience with students discussing these questions suggests that the average citizenry has really not yet begun to digest the significance of this research," says Collins. "When they are presented with it, they are surprised at how far we have come."

(c) Copyright 1999. The Christian Science Publishing Society