Gary Lynch: The Memory Doctor

In a few months, results will be in on an unprecedented experiment: the first human trials of a memory-boosting compound designed from the synapses up. The drug, called Ampalex, was hand-crafted to tweak the brain's molecular wiring. It's the creation of one of the world's leading authorities on memory, neuroscientist Gary S. Lynch of the University of California at Irvine, and his colleagues at a UC spin-off, Cortex Pharmaceuticals Inc.

Lynch has already proven that Ampalex lets middle-aged rodents race through learned mazes with the alacrity of animals half their age. And the drug sailed through human safety trials at the Free University of Berlin last fall. In May, fresh data should clarify if the drug can help its primary target: patients in early stages of age-related dementia. "I'm convinced this is going to work," says Lynch. Then he flinches: "But that's the moment the gods step in."

MANY FLOPS. Lynch's caution is understandable. Other drugs have worked miracles in animals, only to flop in humans. And the brain, with 10 billion neurons, is orders of magnitude more complex than other organs.

On the other hand, no one is better equipped to crack the mysteries. Earning a PhD in psychology from Princeton in 1969, Lynch became, at 31, the youngest tenured full professor at the University of California. He spent the next two decades exploring how the brain learns and remembers--pausing only to co-found a chip company called Synaptics Inc. with Federico Faggin and Carver Meade aimed at mimicking the brain's wiring in silicon.

His main work focused on a class of glutamate protein clusters in the brain called AMPA receptors. These interact with neurotransmitters to carve the billions of electrical pathways that make up memories. Analyzing the mechanism, Lynch and his cohorts built molecules that hold communication channels open an eye-blink longer--turning fleeting impressions to long-term memories.

In 1987, Lynch and two colleagues founded Cortex to commercialize their ideas. Despite heavy research bills and no hope of a quick blockbuster, the trio attracted powerful backers, including George Soros' Quantum Fund, which purchased almost a fifth of the company in November, 1993.

JUST COFFEE? Now, Cortex is burning through its limited investment capital, and some scientists are pessimistic. Damage to synapses in Alzheimer's patients' brains is probably irreversible. What's more, says Salk Institute for Biological Studies professor Charles F. Stevens, "Gary's drugs aren't making the rats much smarter." Translated to humans, he figures, "they're not much different from a cup of coffee." Still, by bolstering undamaged synapses, Ampalex could make life happier for millions in the early stage of memory loss.

Besides, say Lynch's many supporters, Ampalex is just the beginning. Although final results aren't in, "there's a huge need for drugs of this type," says Leon N. Cooper, head of Brown University's neural systems and brain institute. Cooper, who shared a Nobel prize in 1972 for his work in superconductivity, calls Lynch "a remarkably creative scientist who has made major contributions." In the future, both men predict, most drugs will be designed from knowledge, not trial and error. "We may miss this time," Lynch admits. "But we won't miss the next."

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