Three Neuroscientists Share Nobel In Medicine - C&EN Global

and Eric R. Kandel, 70, director of the Center for Neurobiology & Behavior at Columbia University and a Howard Hughes Medical Institute senior inv...
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is created. As the cascade continues, the positive charge can migrate down the conjugated chain. Thefirstconducting polymers were unprocessible and difficult to work with. Doped polyacetylene itself is unstable in air and sensitive to humidity. But over the years, as the fledgling field went through its ups and downs, scientists developed ingenious methods to convert some of these polymers into stable, processible materials suitable for commercial applications. Some of that crucial work was carried out in industrial labs such as at Uniax Corp., a Santa Barbara-based company that Heeger cofounded in 1990 to develop commercial electronic devices based on conducting polymers. Uniax was purchased earlier this year by DuPont (C&EN, June 26, page 20). Despite much progress in R&D, no conducting polymer has yet been reported to conduct electricity as well as copper, Epstein points out. If some conducting polymers could be prepared with a more highly ordered molecular arrangement, he says, it's possible that their conductivity would exceed copper's—but that hasn't been demonstrated yet. Nevertheless, Holmes remarks, "this is definitely the age of plastic electronics." And this year's Nobel Prize provides "fantastic recognition" for the pioneers of this field, he says. Epstein, a long-time collaborator of MacDiarmid's, points out that the Chemistry Nobel reflects interdisciplinary cooperation among chemists, physicists, and materials scientists. "I think it's terrific—a wonderful choice. I'm absolutely delighted." Ron Dagani

Three Neuroscientists Share Nobel In Medicine Arvid Carlsson, 77, emeritus professor of pharmacology at the University of Goteborg, Sweden; Paul Greengard, 74, head of the Laboratory of Molecular & Cellular Neuroscience at Rockefeller University, New York City; and Eric R. Kandel, 70, director of the Center for Neurobiology & Behavior at Columbia University and a Howard Hughes Medical Institute senior investigator, will share this year's Nobel Prize in Physiology or Medicine. The award, worth more than $900,000, honors their collective contributions to the neurochemistry of synaptic transmission, the mechanism by which nerve cells in the

brain communicate with each other through chemical transmitters. The award winners' achievements "have been crucial for an understanding of the normal function of the brain and how disturbances in [synaptic transmission] can give rise to neurological and psychiatric diseases," states the Nobel Assembly at Sweden's Karolinska Institute, which selects the winners of the Physiology or Medicine Prize. Throughout their careers, the three scientists independently studied mechanisms of neurotransmission, delivering interconnecting discoveries that shed light on the neurochemical roots of mood, memory, mental illness, and neurodegenerative disorders. In the 1950s, Carlsson showed that dopamine is a neurotransmitter (rather than just a precursor of the neurotransmitter norepinephrine) that normally exists in high concentrations in the basal ganglia, an area of the brain that controls movement. In animal studies, he determined that a dopamine-depleting drug produced symptoms like those of Parkinson's disease that were reversed by administering the dopamine precursor 3-hydroxy-L-tyrosine (L-DOPA). This work led to a resolution of the neurochemical basis for Parkinson's disease and to the therapeutic drug L-DOPA, which is still the major treatment for the disease. Carlsson also showed that antipsychotic drugs used to treat schizophrenia act by blocking dopamine receptors. This discovery proved important in developing drugs to treat depression, including selective serotonin reuptake inhibitors such as Prozac. Greengard is cited for studies on norepinephrine, dopamine, and serotonin that revealed the cascade of reactions evoked when such neurotransmitters transmit their signals at the synapse. He showed, for example, that when dopamine binds to its receptor, the intracellular concentration of cyclic adenosine monophosphate (cAMP) in the postsynaptic neuron increases. Subsequently, cAMP activates protein kinases that phosphory-

Clockwise from top left: Carlsson, Greengard, and Kandel

late target proteins, which proceed through one or more steps to elicit the intended physiological response. Greengard and his group also have identified a large number of phosphorylated proteins that occur only in the brain, some in all types of nerve cells and others in one or two types only. Such differences among nerve cells could lead to highly specific drugs for treating various disorders. Kandel is recognized for his research on the molecular basis of memory and learning. Studying the simple nervous system of the sea slug Aplysia, Kandel monitored synaptic changes associated with stimuli that amplify the slug's protective reflex. Strengthening of this reflex is considered a form of learning. Weak stimuli give rise to short-term memory, which involves phosphorylation of ion-channel proteins and the release of increased amounts of neurotransmitter. Stronger and more lasting stimuli are needed to create long-term memory, which requires a cascade of intracellular reactions that ultimately result in the synthesis of new proteins and a reshaping of the synapse. Commenting on the award winners, Solomon H. Snyder, director of the department of neuroscience at Johns Hopkins University, says, "The Nobel committee clearly decided to honor the greatest neuroscientists in the world who broadly work in the area of neurotransmission [under] a broad connecting theme. And that's very, very nice because these are not only my heroes, but the heroes of other brain researchers." Mairin Brennan OCTOBER 16, 2000 C&EN

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