Nobelists Leaven Science with Laughter
By Rich McManus
On the Front Page...
One of the great secrets of modern biomedical science is that it can't be prosecuted successfully in the absence of cartoons; virtually no serious NIH lecture fails to include colorful artwork, which can range from stick-figure crude to animated PowerPoint savvy. Most often only incidentally comic, cartoons carry the heavy freight of complex thinking, and can represent matters either hopelessly small or abstract. From a limited vocabulary of arrows, circles and dots, a skilled speaker, say Nobel laureate Dr. Paul Greengard, who opened the Florence S. Mahoney Lecture on Aging June 12 in Masur Auditorium, can compress years of arduous investigation, illuminating pathways governing everything from movement to emotion.
Greengard, head of the Laboratory of Molecular and Cellular Neuroscience at the Rockefeller University and winner of the 2000 Nobel Prize in Physiology or Medicine, filled his hour of the double-bill (with co-Nobelist Dr. Eric Kandel) with pulsating arrows linking circles of varying diameter, each indicating how an abundance of this leads to a dearth of that, with the end result being either human happiness or the desolation of disease.
It proved a good idea to stay with simple tools given that his talk, on the neurobiology of slow synaptic transmission, dealt with the brain, with its billions of cells, and its 1,000 contacts between individual nerve cells residing only next door to one another. He was just in, he explained, from a 5-week trip to China, and was about to embark on a discussion of Alzheimer's disease, how neurotransmitter release is regulated, and how these transmitters affect their target cells. Facing a hall jammed with scientists, he began with a joke that had gone over well in Asia: The mayor of a town convenes all the men in the town square and asks, "All of you who are obedient to your wives, please stand over to the right." All but one of the men shift to the right. The mayor asks the loner, "Aren't you obedient to your wife?" The man replies, "She told me to stay away from crowds."
The Masur crowd now in his hands, Greengard commenced relying on cartoons as he explained fast (less than a thousandth of a second) and slow synaptic transmission, excitatory and inhibitory interactions, sodium and chloride ion channels. Nothing will do but a cartoon to represent how protein kinases cascade toward ion pumps and channels, neurotransmitter receptors and transcription factors. Most of the colors in the M&M bag were required, and the artwork wasn't trivial; this research is perhaps the world's best hope for understanding and combatting Parkinson's disease, schizophrenia, drug abuse and Alzheimer's.
But as sheer labor, a barefoot climb up Everest looked less burdensome. Just when the talk would become staggeringly complex, Greengard would back off and say something like, "Why did God put all these arrows here? Well, the reason He told me to was..."
The molecule that gave him most of his insights, a form of dopamine called DARPP32, he called a "Rosetta stone" yielding a trove of information on neurotransmitter action. "It plays an essential role in mediating the actions of numerous neurotransmitters, therapeutic agents and drugs of abuse."
Mice whose DARPP32 has been knocked out exhibit a variety of characteristics, Greengard explained, among them being changes in "female responsiveness."
As his talk wound to a close, it was perhaps unnecessary for Greengard to say, "This is an incredibly complex story...(illuminating) the exquisite nature of the human brain. Certainly we are uncovering lots of new targets for the pharmaceutical industry."
After a 15-second pause to accommodate the producers of the event's videocast, the program continued with Eric Kandel of Columbia University, who began with a tribute to NIH: "The opportunity to do science I owe completely to my experience here," said the Vienna, Austria native, who came to the United States in 1939. "I arrived motivated but completely incompetent, and I left here after 3 years a professional scientist...Why is NIH such a remarkable place? Because it offers educational opportunities for people to move up the academic and social ladder...[NIH is] really a paradigm of American values." He said he had enjoyed lunch that day with summer students visiting here "from New Zealand to Uruguay," and added, "I would not be here today if not for the chance to have had an American experience at NIH."
But it was not long before he, too, went comic. His science has asked, "Where in the brain is memory stored?" and "How is memory stored at each site?" Answering himself in a sort of solo Socrates-meets-Woody Allen dialogue, undertaken while pacing the stage, Kandel said there are two major forms of long-term memory: "explicit, or declarative, memory, and implicit, or procedural memory, which is unconscious. I function most of the time on this level."
A few moments later, taking note of a Masur usher upright in the aisle and mistaking him for a seatless attendee, Kandel stopped to direct the man to an open chair. "I used to work as an usher," he said, "so you'll have to excuse me."
As his talk ventured past the hour mark (he had joked often that memories of his lecture would soon vanish from listeners' minds), he explained that repetition is crucial in converting short- to long-term memory, and said he was currently obsessed with how memory is perpetuated. Both speakers, by leaving their audience laughing, guaranteed some sort of fond recall.
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