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Chasing Memory | Second of four parts

Trials, and a series of errors, in the brain lab

Gary Lynch's UC Irvine research team struggles to understand how memories are made. It is crucial to treating age-related declines.

August 20, 2007|Terry McDermott | Times staff writer

The myth of modern science, that it proceeds carefully, rationally, incrementally, building bit by bit from rock-solid foundations to impregnable fortresses of fact, comes unraveled in contemporary neuroscience. Fortresses, entire kingdoms of neuroscience have been built on what turn out to be frail premises that get swept away entirely when the next new thing comes along.

A few years ago, a huge amount of effort was spent researching the then-thought marvelous qualities of a humble molecule called nitric oxide. This molecule, better-known in the broader world as the key element in laughing gas, was celebrated as a vital actor in human memory and cognition.

Science Magazine, as if honoring a rock star or president, put the thing on its cover and declared it Molecule of the Year.

By the end of the next year, nitric oxide had fallen off the end of the Earth. Little of what had been claimed on its behalf turned out to be true. This was but one example in a long, sad tradition of a science, as if gripped by mass hysteria, going off the deep end and pretending it knew how to swim.

For The Record
Los Angeles Times Tuesday, August 21, 2007 Home Edition Main News Part Page News Desk 3 inches; 118 words Type of Material: Correction
Chasing memory: An article in Monday's Section A about UC Irvine neuroscientist Gary Lynch's research into memory said nitric oxide was a key element in laughing gas. It is not; nitrous oxide is what makes up laughing gas. Also, the glossary accompanying the memory articles in Sunday and Monday's Section A defined genes as "strings of amino acids that make up an organism's genome, a sort of blueprint from which the organism is built. Individual genes are strings of amino acids; each string contains instructions for building a particular protein." The definition should have said: "Genes: strings of DNA that form a blueprint from which the organism is built. Each gene contains instructions for building a particular protein."

There was no guarantee, neuroscientist Gary Lynch liked to say, that something was important just because you happened to study it.

"You always imagine those animals out in a herd, the wildebeests -- they're running along, and a lion jumps up and takes out this guy named Clyde," Lynch said. And the world proceeds as if Clyde never happened. "They don't talk about Clyde anymore. It's just not good form to talk about him."

Lynch, who runs a lab at UC Irvine, has spent three decades studying a phenomenon known within neuroscience as long-term potentiation, or LTP, which can be very loosely defined as a process in which electrical stimulation strengthens connections between brain cells. Lynch had taken up the study of LTP because it had characteristics strikingly similar to human learning and memory. It seemed to take place in parts of the brain where memory was thought to occur, and like memory, it occurred in an instant and could last a lifetime.

The practical reality of memory -- that human beings, from very young ages on, learn and store information -- had been established and studied for millenniums. How it happened, however, remained a dark continent yet to be mapped.

When people, even scientists, talked about memory, they likened it to objects or concepts in everyday life. They talked about filing cabinets, and photographs, and videotape replays. They almost never talked about what memories really, physically were. Why? They didn't know. LTP seemed an excellent candidate to be that physical, molecular underpinning of memory.

Beyond the pure scientific intrigue of it, memory research has grown more important as medical advances allow more people to live into old age. With longevity has come an epidemic of memory failure among the aged. Alzheimer's disease and other forms of crippling dementia threaten to make living longer less a blessing than a curse.

Things can go radically wrong inside an old brain, and unless you understood how the physical processes of memory worked, Lynch thought, you'd never be able to fix it when it broke.

Brain scientists generally agreed that networks of neurons somehow wired together in the brain were fundamental elements of memory. LTP was hypothesized as the means by which that wiring occurred.

Lynch had bet his career that he could work out the details of LTP, and that what he found would matter -- that it would turn out to be something beyond "an interesting little bit of biology." There were too many similarities between LTP and memory, he thought. The gods were unpredictable, he said, but seldom that cruel.

LTP had been discovered in 1973 not as a naturally occurring phenomenon, but in the artificial and arbitrary conditions of a laboratory experiment. Because of this, not everyone was convinced LTP had significance outside the lab. As one of Lynch's rivals, Nobel laureate Eric Kandel of Columbia University, said: "You know what LTP is? It's an artificial way of stimulating your brain. Who knows if this is what happens in learning and memory?"

That no one had figured out LTP was due largely to the inherent complexity of brain biology. Seth Grant, a neuroscientist at the Sanger Institute outside London, has counted more than 1,000 proteins thought to be involved in memory. If even half of that number actually were involved, isolating and understanding the behavior of each would be a Herculean undertaking.

Lynch was more prosaic. "It's a bitch and two-thirds," he said. "And stupid too."

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