Viagra for the Brain Robert Langreth, Forbes Magazine, 02.04.02 Biotech firms are tantalizingly close to unraveling the mysteries of memory. On the way are drugs to help fading minds remember and let haunted ones forget. Inside a small lab in an anonymous office park off the Garden State Parkway in northern New Jersey, researchers probe the molecular intricacies of memory. Tiny metal electrodes zap minute jolts of electricity at precise intervals into slices of rat brain suspended in nutrient broth in plastic lab dishes. This simulates the electrochemical changes that occur in brain cells when a new memory is created. A robotic pump drips experimental drugs through plastic tubes onto the brain cells, while other electrodes measure how each drug alters their activity. Six such setups chart the mind-altering effects of dozens of compounds a month. Most have little effect, but a few drugs fit a cherished profile: helping the disembodied neurons form stronger, longer-lasting connections. Memory Pharmaceuticals, the closely held biotech firm doing this work, is at the forefront of an intense scientific race to devise the first effective memory-enhancing drug. The idea has long been the stuff of science fiction, but now researchers are decoding the molecular details of how memories are formed and how they are lost. They have taken a crucial first step: identifying the genes and proteins inside brain cells that regulate memory formation. They are tantalizingly close to creating a kind of Viagra for the brain: a chemical that reinvigorates an organ that has faded with age. This new generation of drugs could mend memory loss in the seriously ill or the merely absentminded. "My friends keep asking when the little red pill is coming," says Eric Kandel, 72, the elder statesman of the field, a Columbia University researcher who founded Memory Pharmaceuticals in 1998 and won the Nobel Prize in 2000. He began his work in the 1950s, when most researchers viewed it as futile. "If we continue making the kind of progress we are now, we will have drugs for age-related memory loss in five or ten years," he says. At his lab chemists have concocted prototypes that counteract age-related memory loss, making grizzled mice race through mazes as quickly as younger ones. Human trials could begin next year. Kandel's archrival in this race is 25 years younger and a bit more brazen: Timothy Tully, 47, a researcher at Cold Spring Harbor Laboratory and a founder of privately held Helicon Therapeutics in Farmingdale, N.Y. He hopes to begin human trials in two years. Other small biotechs and big drug firms, including Merck, Johnson & Johnson and GlaxoSmithKline, also are in pursuit. The prize is a stake in what will be one of the next huge global drug markets.