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Paralysis research requires a barrel of monkeys

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At the Miller Laboratory of Limb Motor Control, “monkey business” is a misnomer.

The lab, located at the Feinberg School of Medicine, is hoping to one day treat paralysis due to spinal cord injury by sidestepping the spinal cord and letting the brain indirectly control muscles through electrical stimulation.

For this reason, the lab’s research is geared toward understanding the relationship between the brain and arm movement. Researchers first map the neurons associated with a particular pattern of muscle activity in a rhesus monkey, then temporarily paralyze its arm with a local anesthetic. Researchers then directly stimulate the monkey’s arm muscles, simulating voluntary movement according to the intention of the brain.

Just as in any lab, the mission statement is only shorthand for the many factors involved in research. On top of the difficulties of training and using monkeys, the lab also needs to secure funding, student workers and a source for publication.

Emily Oby, for example, spends several hours a day carefully monitoring her research monkey, Thelonious, as part of her project within the lab. As a third-year Feinberg student, Oby no longer takes classes or serves as a teaching assistant but instead spends all her time doing research.

Before any data can be collected, researchers in Miller Lab must spend months training their monkeys how to perform the tasks that will be used in data collection, an incremental process that includes training the monkey how to sit properly, Oby said.

“One of the hardest things to train is the connection between what they’re doing and what’s happening on the computer screen,” Oby said.

Oby focuses her research on wrist Flexion, or movement to the left, and wrist Extension, or movement to the right. In the experiment, Thelonious is seated with a joystick in his left hand in front of a computer screen. He is trained to move the smiley-face cursor into a red square, which appears on either the left or right of the smiley face. For every correct movement, he is rewarded with a drop of juice.

“He’s a high-maintenance monkey,” Oby said.

Anil Cherian is training a new monkey to collect data. Promising findings from a previous monkey, Fashizzle, have led the seventh-year Feinberg student to attempt to replicate them in Arthur. Cherian estimates he spends about a third of his day working with Arthur, and the rest on data analysis.

Still, unexpected difficulties can arise at any point during the research process. Flexibility is important in case of equipment failure and unexpected experimental results, which may require a retooling of the experiment’s design, Cherian said.

Oby and Cherian work independently, but their experiments fit under the umbrella of Miller Lab. The laboratory is the standard organizational unit of research at Feinberg. Labs are largely headed by tenure-track professors, who serve as the principle investigators for the work done in those labs.

Miller Lab came into being when Lee Miller was promoted to assistant professor in 1993. The lab’s mission is an extension of Miller’s own graduate thesis work. The staff currently consists of Miller, the principle investigator, five graduate students, one post-doctoral fellow and three technicians.

Neuroscience graduate students spend their first year rotating through three labs and then in their second year choose one lab that interests them to devote their research to for the rest of their graduate career, Oby said.

Recruiting students to work in the lab begins with prospective students who are still considering NU and then continues once those students have arrived on campus, Miller said.

Of course, monkeys and staff cost a lot of money, so the lab must consistently secure additional funding to keep its projects going. The university will give newly hired faculty a several-hundred-thousand dollar startup package to purchase equipment and begin hiring staff members, but labs quickly have to find external support, Miller said.

Typically, this support comes in the form of grants. Miller acquires most of his lab’s funding from the National Institutes of Health, which has an extensive application process to secure funding for projects lasting up to 5 years, Miller said. This money is then channelled to the students’ projects.

“The students and the post-docs are the ones really doing the work, and the lab chief is the one who’s running the business, essentially,” Miller said.

And like any business, the lab has a product. For the Miller Lab, the immediate result of their work is an article for publication.

After enough data from any one project has been collected to make a conclusion, the publication of those findings brings that conclusion to the scientific community and the public at large. The publication of findings on monkey research adheres to a unique set of standards, Miller said, and can take years from start to finish.

“If there’s a really compelling result early on from one monkey, you can write a preliminary paper describing that, but generally a good substantial publication requires results from several monkeys, and that draws the process out quite a bit,” Miller said.

The lab’s mission lasts far beyond the doctoral students doing the research, however. As Oby, Cherian and the other researchers finish their degrees and move on, new graduate students and post-doctorate fellows will take their place. Each student’s time in the lab contributes toward its larger mission, further defining and exposing the challenges to be tackled by incoming lab members.

“Generally, you end up at the end of the project with more questions than you went in, hopefully having answered a few along the way,” Miller said.

By: Steven Berger

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