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Chasing Memory : Third of four parts

Breakthroughs, and new crises, in the lab

As Gary Lynch's team starts piecing together the story of memory, his health prompts him to look into his own brain.

August 21, 2007|Terry McDermott | Times Staff Writer

The mundane nature of the molecules involved made the findings more convincing, Lynch thought. No divine intervention, no magic gene -- "just another lift from the parts bin," as he termed it.

"You give up grandeur, but in return you get confidence," he said.

One morning, not long after, Lynch woke up and could barely get out of bed. He had no balance. He couldn't walk down the hall. Within the week, he developed an acute respiratory infection. He had an attack of gout. Another unrelated ancient ailment -- caused by a chronic spinal condition -- recurred. It was like a perverse illustration of his constant complaint that you never knew what was about to go wrong.

The lack of balance was thought to be the result of a viral infection of the inner ear; his doctor sent him to get an MRI to rule out problems deeper inside.

Each image of a typical MRI shows a very thin slice of whatever body part is being examined. A brain MRI produces in digital form what you would get if you were able to take a very large kitchen mandoline and work your way down, slice by slice, from the top of a skull to the bottom. The resulting stack presents a digital photo album of the inside of the head. After the exam, Lynch asked for copies of the images.

He left the clinic that day with a CD-ROM containing the interior images of his head in the pocket of his black cotton jacket. He hopped in his brand-new cobalt-blue 400-horse Chevrolet Corvette convertible and headed toward Irvine.

Lynch is a torque man. He drives very fast, especially in the lower gears, where the experience of speed is visceral. Unless he's on the freeway, he seldom gets out of third gear. Of course, in the Corvette, third gear can mean flying 100 mph down a blind alley, giggling like a schoolgirl.

Lynch took the CD-ROM back to his lab, where he fed the images into a computer program that allowed him to scroll from top to bottom -- like riding the Magic School Bus with Ms. Frizzle -- through his brain. Upon first sight of his own brain, Lynch began to make some not altogether happy noises. There were low whistles, smacked lips and much muttering. He shook his head a couple of times. He grew uncharacteristically somber.

MRIs, as useful as they can be, remain crude tools. They allow one to see larger structures inside the body. Unfortunately, the work of the brain occurs mainly at the micro scale. The MRI would give Lynch a flyover from 35,000 feet; what he really wanted was to blow down through the anatomical weeds, low to the ground in first gear in the Vette.

Even so, the MRI revealed cause for concern. The human brain contains in each hemisphere large cavities -- literal holes in the head -- called ventricles, where cerebrospinal fluid is produced. The ventricles in Lynch's brain were enlarged. This in itself came as no great surprise. Ventricle enlargement often accompanies aging. The crucial questions were how much expansion and from what cause.

As he sat in his office, looking at his brain blown up to quadruple scale on his giant Mac monitor, he exhaled, shook his head, pointed, and said, "Boy howdy. That doesn't look very good."

Lynch and a company he co-founded were that very month trying to get Federal Drug Administration approval to begin testing the drugs he had invented, called ampakines, in humans. The ampakines were intended to help alleviate a wide variety of brain malfunctions.

He slumped back in his chair and said, "You better hope we come up with something on them ampakines. Normal or not, you don't want this."

Despite the siege of illnesses, Lynch continued going to the lab every day. One Friday, he realized he had forgotten to submit to the National Institutes of Health crucial data supporting his request for renewed funding. The data were long past due. Lynch was stricken.

That afternoon, everybody in the lab gathered to celebrate the incredible run of good fortune. Somebody dug out three bottles of Sierra Nevada Pale Ale and divided it up among a dozen or so people. With no drinking glasses at hand, they poured the beer into test tubes and tiny chemical beakers.

Lynch, standing in the middle of the celebration, raised his beaker:

"We do adenosine, Eni's integrin experiments. We ran the table. We ran the table. Then I realize: I forgot my grant. I forgot to send the supplemental material. I'm a chronic screw-up. I promise you, I'm the only neuroscientist in history who forgot his grant. This is a screw-up of biblical proportions. Even I have to say it -- that's a screw-up. This grant is cursed."

Lynch stood there, swaying back and forth. His face, expressive even when becalmed, now seemed about to stretch beyond the bones beneath it. His jaw worked slowly from side to side, his grin shifting with it. He leaned on a lab bench for support, to keep standing.

He stood with his little beaker of beer and grinned. He stood there like that, grinning and quiet and swaying, for a long time.

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