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Historical Perspective Neuroscience at Johns Hopkins

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Historical Perspective Neuroscience at Johns Hopkins CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - PublisherNeuron, Connector Vol. 48, 201–211, October 20, 2005, Copyright ª2005 by Elsevier Inc. DOI 10.1016/j.neuron.2005.10.005 Neuroscience at Historical Perspective Johns Hopkins Solomon H. Snyder* ing these talents and himself making major contribu- Department of Neuroscience tions to pathology. William Osler defined the field of in- Johns Hopkins University School of Medicine ternal medicine, and William Halstead inaugurated 725 North Wolfe Street modern surgery. There was no Neurology Department Baltimore, Maryland 21205 nor even a neurology division of Medicine. Neurosurgery remained a subdivision of the surgery department for al- most 70 years till Donlin Long was appointed the direc- In 1979, Joshua Lederburg, recently appointed presi- tor of a new Neurosurgery Department. dent of Rockefeller University, was in recruiting mode. Based on his long-term interest in the brain and psychi- Neurosurgery and Systems Neuroscience atry, Josh approached me with an attractive offer for In 1906, Harvey Cushing was appointed the first head of myself and my colleagues Joe Coyle and Mike Kuhar. neurosurgery at Hopkins (Figure 1). He revolutionized pi- I visited our Dean, Richard Ross, to say goodbye, as tuitary surgery and, by carefully monitoring symptoms I knew that Hopkins could never provide us Rockefeller- following removal of pituitary tumors, he was able to elu- like resources. While Ross couldn’t match the Rockefel- cidate the role of excess or deficient secretion of the an- ler offer for a professor, he had an alternative proposal. terior pituitary and to confirm his clinical observations Years earlier, an advisory committee had recommended with studies in animals (Cushing, 1909). He showed that Hopkins establish a Department of Neuroscience. that hormonally active tumors arising in young people Dr. Ross suggested a mini-department comprised lead to gigantism and, in adults, to acromegaly. solely of myself, Coyle, and Kuhar, which might integrate Walter Dandy succeeded Cushing as head of the neu- Hopkins neuroscience. In contrast to the tens of millions rosurgery division. In 1913, he elucidated the circulation of dollars provided nowadays as dowries for new de- of cerebrospinal fluid (CSF), showing how selective partmental directors, the Dean offered only a modest blockade leads to hydrocephalus (Dandy and Blackfan, annual budget that could be ‘‘saved’’ for the three years 1913). In dogs, obstructing the Sylvian Aqueduct caused till a single floor would become available for our depart- dilation of the third and lateral ventricles, while blocking ment. Dan Nathans, Director of Microbiology and a val- the Foramen of Monro elicited a similar ballooning of the ued confidant, advised that a new department must be lateral ventricle. In the same study, he provided the first done ‘‘right’’ so I should ask for triple the offered space. definitive evidence that the choroid plexus elaborates The Dean agreed, and on July 1, 1980, our department CSF, as its removal prevented hydrocephalus. He dis- commenced operations. Today, Neuroscience is the covered how CSF is absorbed into subarachnoid blood largest basic science department at Hopkins. Our fac- vessels. He extended this basic research into patients, ulty has done well. Among present and emeritus mem- observing that every case of ‘‘idiopathic hydrocephalus’’ bers, three of our primary faculty have been elected to was associated with obstruction of the Sylvian Aque- the National Academy of Sciences, four are fellows of duct or one of the critical foramina. the Academy of Arts and Sciences, two of the American Even more important was Dandy’s development Philosophical Society, two have received the Lasker in 1918 of pneumoencephalography, conceptualized Award, two the National Medal of Science, and various when he noticed in the chest X-ray of a patient with a per- faculty members have accumulated more than 13 hon- forated intestine, free air outlining the structure of vari- orary doctorates. Science citation analysis indicates ous abdominal viscera. Might injected air outline the ce- that of the eight most highly cited Johns Hopkins medi- rebral ventricles? In short-order he injected gas into the cal scientists, five are appointed in our department. For cerebral ventricles, inaugurating pneumoencephalogra- the decade 1989–1998, four of the world’s 16 most phy, which, until the advent of CAT scans, remained the highly cited neuroscientists were from Hopkins, with most powerful means of identifying brain tumors and no other institution having more than one. other abnormalities (Dandy, 1918). But neuroscience at Hopkins did not begin in 1980. Systems neuroscience began with operative ablation Johns Hopkins has a long tradition of contributions in of various brain regions to mimic abnormalities associ- the field. More than most other institutions, Hopkins’ ef- ated with brain tumors or surgical removal of brain tis- forts in the neurosciences encompass clinical as well as sue to cope with injuries or epilepsy. Phillip Bard, the basic science. Let me relate some of these in a brief pan- fourth Director of Physiology at Hopkins, arrived in Bal- orama that is not meant to be exhaustive but merely to timore in 1933 following training at Harvard with Walter illustrate a few major themes, especially the breadth of Cannon. Work in Cannon’s laboratory had revealed research and the uniquely collegial relationships of Hop- that disconnecting the cerebral cortex from the brain- kins neuroscientists. stem of cats elicited rage responses. As these responses were not associated with ‘‘real’’ anger and were not di- Early Days rected toward the triggering stimulus, they were desig- The founding fathers of Hopkins were giants in American nated ‘‘sham rage.’’ At Hopkins, Bard attempted to local- medicine, with William Welch, the first Dean, orchestrat- ize the specific brain regions responsible for sham rage. After decorticating cats to elicit rage, he made various transactions through the brain stem. Successive trans- *Correspondence: [email protected] actions in a caudal direction failed to alter sham rage Neuron 202 recordings would be critical. In 1933, Ralph Gerard, working at the University of Chicago, had identified cere- bral action potentials, and, with Wade Marshall, he em- ployed this approach to characterize sensory activity in the cerebral cortex. In the late 1930s, Marshall moved to Hopkins, and, with Bard and Clinton Woolsey, he de- veloped technology for measuring evoked cortical po- tentials and mapped the sites for cutaneous touch sensation on the primate postcentral gyrus (Marshall et al., 1937). Vernon Mountcastle, Bard’s successor in 1964 as Di- rector of Physiology, took up the challenge of mapping the somatic sensory system with greater refinement. In the mid-1950s, utilizing newly developed microelectro- des that permitted single-cell recoding, Mountcastle discovered that submodalities of touch and pressure sensation were localized to vertical columns running from the surface of the brain to underlying white matter. All cells in an individual column responded to selective sites on the skin and to either superficial or deep pres- sure (Mountcastle, 1957). This columnar organization is now appreciated as a universal organizing principle of brain function. At about the same time that Mountcastle was doing his pioneering work in the Physiology Department, Ste- phen Kuffler spent 12 years in a laboratory in the base- ment of the Ophthalmology Department. In one body of work, he characterized synaptic inhibition in stretch receptor neurons of crustacea, which led to subsequent work of his later colleagues David Potter and Edward Kravitz establishing GABA as the principal inhibitory neurotransmitter. Perhaps Kuffler’s most important con- tribution was his discovery of center-surround inter- actions in the retina (Kuffler, 1952). Utilizing a multibeam ophthalmoscope that had been developed in the Ophthalmology Department, he recorded from single retinal ganglion cells and observed diametrically oppo- site responses depending on whether light impacted the central or peripheral field. In 1959, Kuffler moved Figure 1. Johns Hopkins’ Neuroscience Greats to Harvard where in 1966 he established a Department (A) Harvey Cushing (left), the first head of Neurosurgery, provided of Neurobiology. the definitive characterization of hypo- and hyperpituitarism. Walter Torsten Wiesel and David Hubel joined Kuffler at Hop- Dandy (right), his successor, developed ventriculography, inaugu- kins in the mid-1950s, initially working on the retina and rating the field of clinical brain imaging. then turning their attention to the visual cortex. They dis- (B) Philip Bard (left) localized brain areas mediating ‘‘rage’’ and em- covered center-surround and other organizational prin- ployed evoked potentials to map sensory sites in the brain. Vernon Mountcastle (right), using microelectrode recordings, discovered ciples in the cortex (Hubel and Wiesel, 1959). Most the columnar organization of brain function. importantly, they detected parallel receptive fields for (C) Ross Harrison (left) inaugurated the field of tissue culture using neighboring cells in the visual cortex, pointing to a uni- frog embryonic spinal cord. David Bodian (right) employed culture versal role for Mountcastle’s concept of columnar orga- to differentiate diverse types of polio virus, laying the groundwork nization of the cerebral cortex. They moved with Kuffler for the polio vaccine. to
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