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Chasing Memory / Final of four parts

Success, with a big dose of rejection

Gary Lynch expects his lab's work to bring 'all the tribes of neuroscience to the same campfire.' But he meets resistance.

August 22, 2007|Terry McDermott | Times Staff Writer

Reflecting in the spring of 2005 on his lab's recent successes, which he regarded as a culmination of decades of work, UC Irvine neuroscientist Gary Lynch said: "This will be a moment when all the tribes of neuroscience come to the same campfire."

He was wrong. There was no reaction. Nothing. Initially, he couldn't even get a short paper on a crucial visualization experiment published. Lynch envisioned the experiment as a grand confirmation of his notion that a change in the physical structure of brain cells at the connections between them was responsible for the encoding and persistence of memory.

It had taken 20 years to acquire the tools to execute, and when Eniko Kramar, a senior scientist in Lynch's lab, produced a series of spectacular microscopic photographs depicting where and how the change occurred, Lynch awaited the triumphal acclamation of the lab's success.

The tribes were not at the same campfire. Many apparently hadn't yet learned that fire had been discovered.

When a paper is submitted to a scientific journal, the journal editors send it for review to panels of scientists. Peer review is the backbone of contemporary scientific legitimacy and lauded by everyone involved. It is also an opportunity for mischief and misunderstanding.

Lynch's history of antagonizing his peers sometimes made peer review more a gantlet than a critique. Richard Thompson of USC, a renowned neuropsychologist, said he had more than once nominated Lynch to membership in the prestigious National Academy of Sciences, but was told by other members Lynch would not be elected so long as they lived.

"There's a reason for his paranoia. There are a lot of people out there who don't like him. Gary doesn't suffer fools gladly," Thompson said, then paused for a moment. He chuckled and said: "And there are a lot of fools in the world."

The reviews on Kramar's paper seemed not to even acknowledge its main point -- that the lab had for the first time demonstrated the physical reorganization of cells that occurred in the final stage of long-term potentiation, or LTP, which Lynch believed was the biochemical process underlying memory.

One reviewer, in recommending against publication, complained that the scientists had only looked at a specific set of synapses, which was inexplicable as criticism. They looked there because that's where they were doing the experiment, that was where the condition they were examining existed. It was as if a traffic engineer, having proposed adding carpool lanes to the San Diego Freeway, was asked why he hadn't examined four-way stop signs in Barstow.

Lynch was irate, and for a couple of days everybody avoided him. Then one morning, he was at his desk, smirking like a boy with the key to the cookie jar.

What happened? I asked.

"I can't tell you," he said, his grin growing.

But, of course, it was Lynch; he had to tell. He pointed at his computer monitor on which was displayed information on a company called Memory Pharmaceuticals, founded by Nobel laureate Eric Kandel, and a competitor of Lynch's biotech company, Cortex Pharmaceuticals.

"I'm shorting Eric's stock," Lynch said and cackled.

Kandel was the god king of contemporary neuroscience. He won the Nobel Prize in 2000 for investigations of synaptic activity that occurred during reflex learning in sea snails. He had also almost single-handedly made the study of protein synthesis a major focus of neuroscience.

Lynch thought the emphasis was wrongheaded, but there was little he could do. Kandel, for his part, had nothing but nice things to say about Lynch. He barely acknowledged they were competitors, despite the fact that the two had led opposing armies in a 1990s war over where at the synapse the crucial actions of LTP occurred.

Lynch turned out to be right and won that battle, but he lost the war. Kandel received the Nobel Prize; Lynch went to ground.

For reasons not entirely clear even to Lynch, he retreated to his Irvine lab. He focused on his research, continued to publish voluminously, but largely absented himself from the numerous academic conferences and symposiums at which neuroscience findings were presented and debated and, not insignificantly, reputations made and maintained. He declined to meet with visiting researchers and fought with administrators and colleagues.

"It got to be very hard for me to keep playing with the boys," he said.

Few things are more punishing to an ambitious man than to be right and unappreciated. The latest fight over the Kramar paper was but one more slight. In the end, Lynch reacted as he had before: He complained bitterly then went back to work.

One of the things he devoted time to was the development of a family of drugs, called ampakines, intended to enhance LTP.

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