The Brazilian brooded.
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He ought to finish what he started, he decided, no matter how futile the effort.
His wife lent a hand.
Marchetto — red tank top, blue jeans and yellow hair — was a splash of primary colors against the laboratory's gray concrete walls. She knew little about neural anatomy. Her doctorate was in skin cancer biology. But she was more meticulous than her husband.
As her eyes learned the microscopic maze of synapses and support cells, she could see a glow inside the translucent spheres of brain cells.
"It was, like, crazy green," she recalled. First one cell, then five, 10, a dozen.
She found the fireflies in the brain.
In the black light of the microscopy room, her brilliant smile was like the moon emerging from the clouds.
"Please," she said, calling her husband to the microscope. "This is a neuron."
They caught it in the act.
To their wonder, the L1 sequence had left its distinctive mark wherever they looked in the mouse brains — throughout areas devoted to memory, learning, emotion, motor control and the senses.
They discovered that the sequence affected only developing brain cells. It also seemed to home in on neural genes, arbitrarily changing their behavior. Every time it affected a gene, it set that neuron apart from its neighbors in the brain and from all other cells in the body.
In the mouse experiment, the sequence jumped into one of every 100 brain cells.
Unpublished data from follow-up experiments by colleagues suggest that in human cells, the sequence jumps into 80 of every 100 neurons.
"Every neuron may have a different genetic profile," Muotri said. "Almost all the cells have at least one L1 insertion."
The researchers were elated but puzzled.
From the standpoint of conventional evolutionary theory, any independent genetic change in a neuron was a dead end. The random changes caused by L1 inside a brain cell could never be passed on directly through the genetic shuffle of sex.
At this point, Muotri and Gage had an audacious thought.
Perhaps the sequence, striving for its own survival inside the growing neuron, made the brain more responsive to changing circumstances. Had natural selection seized on the one rogue sequence most useful for crafting an infinitely adaptable human brain?
"There are subtle differences in everything we do throughout our lives," Gage said. "Maybe this is how we generate a deeper adaptability to deal with the unexpected.
"We believe the sequence is generating this diversity to fine-tune the brain."
MAPPING THE MIND
One in a series of occasional articles about scientists' efforts to explore the creation of beliefs and behavior in the synapses of the brain. To read previous articles in this series, go to latimes.com/mind. For an archive of Column One articles, visit latimes.com/columnone.