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See Also Of cells and wires, Neuroprosthetics and FES, Priority Setting at the NIH

Of Cells and Wires

The man skis down sharp inclines at tremendous speeds, sees wind frolic through a woman's hair as the French countryside passes outside of the car window, checks out a nurse's cleavage. These are the visions and memories of the protagonist in The Diving Bell and the Butterfly, a film by Julian Shnabel about a man with locked-in-syndrome whose vibrant mind can only control the movement of his left eye. The audience experiences locked-in syndrome through the thoughts of the witty and irreverent Jean-Dominique Bauby, the former journalist and editor of the fashion magazine Elle, as he learns to communicate, and in fact dictate a bestselling memoir, with only the blink of his eye. Bauby became "locked-in" in 1995 and died in 1997 from pneumonia, seven years before the first man with locked-in syndrome was implanted with an electrode that might one day allow him to control a voice synthesizer with his thoughts.

While eagerly awaited by people who cannot walk, neuroprosthetics such as implantable electrodes have also captured the imagination of those who fantasize about carrying out actions with their minds alone. Imagine walking into your classroom and turning on the lights, then flicking through your Powerpoint slides with a thought. For a brain neuroprosthetic to work, surgeons implant an electrode into brain tissue which records signals. "It's like sticking knives in the brain. They're just very little knives," says Robert Kirsch director of technology at the Functional Electrical Stimulation (FES) Center in Cleveland, a consortium that researches electrical shock in stimulating the nervous system. Wires from the electrodes pass through the skull and a skullcap, transmitting the signals to devices such as a computer or electric limb outside the body which carry out the brain's command. For researchers working on developing neuroprosthetics, brain implants have always been the holy grail: the signal is cleaner and more precise, the connection is direct.

But the fantastic sci-fi world of controlling things with your thoughts alone—while becoming less and less of a fiction and more of a science—is still stumbling on the first step: recording a clean signal from the brain over an extended period.

"It's like sticking knives in the brain. They're just very little knives." —Robert Kirsch

To date, only seven people have received implanted electrodes in the brain; and the movements they can achieve remain rudimentary at best. For instance, one patient with locked-in syndrome who received the implanted electrode has learned to control his brain signals enough to emit three vowel sounds. While this is a great achievement in demonstrating the possibility of controlling language, vowel sounds are still a far cry from language. Other experiments have enabled paralyzed patients to move a cursor on a computer screen, as well as produce simple movements using a mechanical arm.

One issue that many in the field struggle with is that, while it's not difficult to record stimulation from individual neurons (neuroscientists have been voltage-clamping nerve cells since the 1940s), it is more difficult to do it continuously in vivo. Over a long period of time the signal from the implanted electrode degrades and the connection is lost. John Donoghue at Department of Neuroscience Brown University, whose implanted electrodes let quadriplegic patients move a computer cursor and robotic arm, says that he's recorded signals from patients for as much as 1,000 consecutive days. But for other researchers, between two weeks and a month is the longest time for continual electrode recording, and they still aren't entirely sure why.

Priority Setting at the NIH

Nearly 10 years after stepping down as director, Harold Varmus reflects on his life at the agency, and some of the delicate negotiations that often precede funding decisions. By Harold Varmus

Editor 's note : The following is an excerpt from Harold Varmus's upcoming memoir, The Art and Politics of Science, (Norton Books, Feb. 2009). In his book, Varmus recounts his days at the forefront of cancer research at the University of California, San Francisco, and shares his perspective from the trenches of politicized battlegrounds ranging from budget fights to stem cell research, global health to science publishing. Varmus served as the director of the National Institutes of Health director from 1993 to 1999, and is now president of Memorial Sloan-Kettering Cancer Center.

One of the most difficult aspects of the job of running the NIH, or of directing any individual institute, is the designation of research priorities. This is an emotionally and politically sensitive part of the job because it is closely watched by some of NIH's strongest supporters, who often advocate for the NIH because of a passionate interest in a small fraction of what the NIH does. That fraction is almost always a specific disease or even a subset or facet of that disease.

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