Gage had recruited him to study brain diseases, drawn by his intellectual energy and persistent curiosity. When that project failed to materialize as expected, Muotri was open to a new question, even one outside his immediate field.
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In a gray T-shirt, shorts and flip-flops, Muotri had the look of someone who came to La Jolla for the surf, not the science. He wore a carving of a hammerhead shark on a chain around his neck and a watch with three dials on his right wrist.
"I felt like an odd fish in the aquarium," Muotri would say later. "I decided to look with the cancer mind-set. Maybe I [would] learn something."
Gage invested more than $1 million in private funds, time and laboratory resources in the experiment.
No federal agency would fund it.
"They probably think I'd gone off the deep end," Gage said later. "It was too wild."
Muotri and Gage wanted to know whether the L1 sequence was actually moving around in developing brain cells.
Normally, the sequence copied itself into reproductive cells in the testes and ovaries, where a randomly remodeled gene might be passed to succeeding generations. The sequence did not seem active in any other type of cell in the body.
They could not experiment on people, so they inserted the human DNA into a custom-made brood of mice.
To make the L1 sequence visible under a microscope, Muotri and his colleagues added to it a molecular tracer — a green fluorescent protein — that would light up whenever the DNA intruder entered a growing cell.
With a splinter of hollow glass, Muotri injected the sequence into mouse eggs, then transferred them into female mice, where he hoped the new DNA would take hold in growing embryos.
Of seven brown mice in the litter, two contained the altered human DNA.
He bred those with wild mice to create a family in which the L1 sequence was poised to jump into any cell of the body. He ended up with 20 transgenic mice.
To search for evidence of brain activity, he sliced each mouse into wafers 40 microns thick and mounted tissue from every organ on slides.
If the sequence had jumped anywhere, it should reveal itself, like a firefly at midnight, with a fluorescent glow.
Searching the slides under ultraviolet black light was such an eyestrain that Muotri could only keep it up for about four hours a day. At the same time, the fluorescence was depleted by exposure to ultraviolet. So the longer he looked, the fainter the light became.
During a break halfway through one scanning session, Muotri browsed research articles in the Proceedings of the National Academy of Sciences. He stiffened.
At the University of Pennsylvania, a rival research team had already conducted his experiment and published the results: They examined the entire animal for signs that the sequence was jumping from cell to cell outside reproductive organs but failed to find any evidence of the brain activity that Muotri sought.