Editorial

Editorial ‘A Colledge for the promoting of Physico-Mathematicall Experimental Learning’ was founded on 28 November 1660 by 12 individuals who met after a lecture by Christopher Wren (1632–1723) at Gresham College in London. They suggested a further 41 names for inclusion of whom 15 were physicians. On 12 December 1660, it was agreed that the membership be limited to 45 but with barons, Fellows of the Royal College of Physicians, and professors of mathematics, physic and natural philosophy based in Oxford or Cambridge being eligible as supernumeraries. John Wilkins (1614–72) acted initially as chairman. The ‘Colledge’ received its Royal Charter from Charles II on 15 July 1662, being renamed the ‘Royal Society for improving Natural Knowledge’. These events were the culmination of activities that had begun in the 1640s. But where and to whom the credit lies is disputed. John Wallis (1616–1703) who, as one of the founding Fellows of the Royal Society was directly involved, writes that in about 1645, at a time when academic life was disrupted in ‘both Universities’ (Oxford and Cambridge), he became involved with a group interested in natural philosophy. They met each week to discuss and carry out experiments. Mention of divinity, state-affairs and current news was prohibited. The situation changed in 1648–9 when Wallis moved to Oxford where a dozen men, four of whom were physicians and ‘many other of the most inquisitive persons’, had been meeting at Trinity College since around 1648 to discuss natural philosophy. They and their successors gathered under various names: the Invisible College, the Experimental Club, and the Philosophical Society of Oxford. Amongst those who participated was Thomas Willis (1621–75), arguably the first clinical neurologist. The Invisible College set rules: membership was by majority vote in a secret ballot that required a quorum of 11; members paid subscriptions that included provision for ‘instruments in stock’; meetings were held every Thursday before 2 pm; those who failed to attend for a period of 6 weeks were deemed to have forfeited their membership; and the person appointed for the day was expected to carry out an experiment and fined 2 s 6 d if he did not. Anthony Wood (1632–95) wrote that the group ‘gave themselves the name of Vertuosi and pretended to go beyond all others in the University for knowledge’, a stance that earned some local disapproval. In The history of the Royal-Society of London for the improving of natural knowledge (1667), Thomas Sprat (1635–1713) rehearsed success and failure in ancient and modern philosophy so ‘we may better shew, what is to be expected from these new Undertakers, and what mov’d them, to enter upon a way of Inquiry, different from that, on which the former have proceeded’; gave a narrative of what happened in the first few years; and defended the ‘Advantage and Innocence’ of the Society and its work in the eyes of all professions and of religion. His version of events ran: ‘Some space after the end of the Civil Wars at Oxford, in Dr Wilkins his lodgings, in Wadham College, which was then the place of Resort for Vertuous and Learned Men, that the first meetings were made, which laid the foundation of all this that follow’d … The principal, and most consistent of them, were Doctor Seth Ward, the present Lord Bishop of Exeter, Mr. Boyl, Dr. Wilkins, Sir William Petty, Mr. Mathew Wren, Dr. Wallis, Dr. Goddard, Dr. Willis, Dr. Bathurst, Dr. Christopher Wren, Mr. Rook: besides several others, who joyn’d themselves to them, upon occasions … For such a candid, and unpassionate company, as that was, and for such a gloomy season, what could have been a fitter subject to pitch upon, than Natural Philosophy’. In documenting the various bodies that had endorsed the founding and activities of the Royal Society, Sprat mentions physicians: ‘Of our Physicians, many of the most judicious, have contributed their purses, their bands, their judgments, their writings. This they have done, though they have also in London, a Colledge peculiar to their Profession; which ever since its first foundation, for the space of a hundred and fifty years, has given the world a succession of the most eminent Physicians of Europe. In that they confine themselves to the advancement of Physick: But in this, they have also with great zeal, and ability, promoted this universal inspection, into all Natural knowledge. For without danger of flattery, I will declare of the English Physicians, that no part of the world exceeds them, not only in the skill of their own Art, but in general Learning’. Against this historical preamble, readers of Brain will be delighted to learn that, at their meeting on 8 May 2018, being quorate, the Fellows elected Dimitri Kullmann, editor of this journal, to the Royal Society. He is the 12th of the 17 people who have edited Brain since 1878 to hold that distinction, starting with a run of 88 years to 1966, and with a further presence over the last 21 years to 2018. Dimitri’s career began in Oxford where he studied physiology completing his DPhil (1984) working with Julian Jack FRS on central actions of muscle receptors. Subsequently trained in clinical medicine and now professor of neurology at the UCL Institute of Neurology, his work on the physiology and pharmacology of synapses and small circuits in the mammalian central nervous system is distinguished for several discoveries: long-term potentiation and depression involve more than all or none transmitter release and activation of postsynaptic receptors but include dynamic changes which engage silent synapses; transmitter release and receptor sensitivity change with activity; the business of one synapse spills over to others; long-term potentiation occurs in the small interneuronal circuits that determine regional inhibition and facilitation; and the complexity of these molecular events involves oscillations as the systems adjust during learning and plasticity. As a clinician scientist, Professor Kullmann has also characterized, with others, the role of ion-channel genetic mutations in human disorders that include epilepsy; and evaluated preclinical modelling of gene therapy for treatment of focal epilepsies. Members of the 17th century Invisible College in Oxford thought about epilepsy. In his lectures given around 1660, the year in which the Royal Society was founded, Willis used the term ‘convulsion’ to denote turbulence and expansion of the nervous juice in the brain transmitted as ‘raging’ activity to the nerves leading, in turn, to ‘leapings and contractions’ of the muscles with failure of antagonist muscles to relax when the agonist contracts. Convulsions might become generalized, their severity depending on the duration and speed of movement of the unruly nervous spirit. Epilepsy might follow formation of a cicatrix from meningeal disease constricting the nerve juice and forcing it down nerves with sudden falling to the ground and convulsions of the eyes, lips or face. Alternatively, it could result from admixture of vitriolic material in the blood causing the nervous juice to boil over in the cerebral cortex and swamp the nerves and muscles. Congestion caused the cerebrum and cerebellum, responsible for voluntary and involuntary movements, respectively, to respond by contractions of the limbs and abdominal muscles, and alteration in the pulse and respiration with incontinence. Undigested vitriolic material in the brain was responsible for loss of awareness during, and altered memory after, the paroxysm. Recovery occurred when the vitriolic matter dissipated or was excreted in the foaming mouth of the person with epilepsy. In the present issue, Arjune Sen, Valentina Capelli and Masud Husain, from Oxford, review the complex relationship between epilepsy, age and dementia asking whether seizures promote dementia, and dementia causes seizures. They conclude, not unexpectedly, that both statements are true and that seizures and dementia share common underlying pathophysiological vascular mechanisms. Anna Fassio and colleagues from Genoa, Florence and Pisa (Italy), Tokyo, Hamamatsu, Yokohama and Osaka (Japan), Denizli (Turkey) and Phoenix (USA) identify mutations of ATP6V1A, encoding the A subunit of v-ATPase, in developmental encephalopathy with epilepsy. They model the functional consequences of four alterations, differing in their clinical impact, that either perturb subunit interaction, destabilize protein folding, affect catalytic function, or impair proton transport but collectively alter lysosomal homeostasis and synaptic connectivity. Smriti Patodia, and investigators from groups in London (UK) including that led by Dimitri Kullmann at the UCL Institute of Neurology, and involving Ingrid Scheffer from Melbourne (Australia), who was also elected FRS on 8 May 2018, study neuronal populations in the human brainstem in the context of sudden unexpected death in epilepsy (SUDEP). They find alteration, compared to controls, in medullary neuromodulatory neuropeptidergic and mono-aminergic systems, including those for galanin, and serotonin suggesting that prior epileptic activity leads to structural neuronal changes, which compromise respiratory homeostasis during subsequent seizures. Brain is not the first journal to publish papers on epilepsy. Dr William Cole (1635–1716) wrote on convulsions in Philosophical Transactions of the Royal Society on 1 January 1685, in issue 174, describing a ‘lady of wit and beauty’ who had a miscarriage followed by uncontrollable seizures, which occurred at the same intervals as quartan fever suggesting to Dr Cole that they might be cured by Peruvian bark; and they were. In the same issue he describes Dorothy Cook, who kept a coffee house in Worcester, two of whose children also had seizures, who suffered convulsions for 30 years yet (pace Masud Husain and colleagues) ‘her Intellectuals, and other animal Functions, were not sensibly affected, but she dispatched her Family Affairs with as much Dexterity, considering her Age, as if she had been in perfect Health’. (Later Cole wrote a monograph on epilepsy: Consilium aetiologicum de casu quodam epileptico, etc., 1702). In issue 280, on 1 January 1703, Dr Charles Leigh (1662–1701: FRS 1685) described John Pownel, aged 13, caught in an epidemic fever resulting in obstructive jaundice and large purple spots, who developed seizures causing him to ‘bark in the usual Notes of a Dog, and at last howling like a Hound … roared like a Bull, made a noise like a Hog, and sometimes like that of a Gosling … from different contractions of the Lungs, variously forcing out the Air … as they were differently convulsed’; but happily all was well and Leigh was able to report that, after a while, ‘the boy is very chearful’. In issue 399, on 1 January 1728, Dr Walterius Rhætus (nk) reported three autopsies in people who died with epilepsy, one with meningeal adhesion over the Crista Galli (cribriform plate) and two others with accumulation in the ventricles of turgid fluid and white pellucid bodies that resembled very elegant pearls leaving them ‘ready to burst’. These papers were written in Latin (translated by Samuel Mihles, Medical essays and observations relating to the practice of physic and surgery abridg’d from the Philosophical Transactions etc., 1745) but there is no requirement on Dimitri Kullmann and Ingrid Scheffer to maintain that tradition. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Oxford University Press

Editorial

Brain , Volume Advance Article (6) – May 25, 2018

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Oxford University Press
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© The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com
ISSN
0006-8950
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1460-2156
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10.1093/brain/awy130
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Abstract

‘A Colledge for the promoting of Physico-Mathematicall Experimental Learning’ was founded on 28 November 1660 by 12 individuals who met after a lecture by Christopher Wren (1632–1723) at Gresham College in London. They suggested a further 41 names for inclusion of whom 15 were physicians. On 12 December 1660, it was agreed that the membership be limited to 45 but with barons, Fellows of the Royal College of Physicians, and professors of mathematics, physic and natural philosophy based in Oxford or Cambridge being eligible as supernumeraries. John Wilkins (1614–72) acted initially as chairman. The ‘Colledge’ received its Royal Charter from Charles II on 15 July 1662, being renamed the ‘Royal Society for improving Natural Knowledge’. These events were the culmination of activities that had begun in the 1640s. But where and to whom the credit lies is disputed. John Wallis (1616–1703) who, as one of the founding Fellows of the Royal Society was directly involved, writes that in about 1645, at a time when academic life was disrupted in ‘both Universities’ (Oxford and Cambridge), he became involved with a group interested in natural philosophy. They met each week to discuss and carry out experiments. Mention of divinity, state-affairs and current news was prohibited. The situation changed in 1648–9 when Wallis moved to Oxford where a dozen men, four of whom were physicians and ‘many other of the most inquisitive persons’, had been meeting at Trinity College since around 1648 to discuss natural philosophy. They and their successors gathered under various names: the Invisible College, the Experimental Club, and the Philosophical Society of Oxford. Amongst those who participated was Thomas Willis (1621–75), arguably the first clinical neurologist. The Invisible College set rules: membership was by majority vote in a secret ballot that required a quorum of 11; members paid subscriptions that included provision for ‘instruments in stock’; meetings were held every Thursday before 2 pm; those who failed to attend for a period of 6 weeks were deemed to have forfeited their membership; and the person appointed for the day was expected to carry out an experiment and fined 2 s 6 d if he did not. Anthony Wood (1632–95) wrote that the group ‘gave themselves the name of Vertuosi and pretended to go beyond all others in the University for knowledge’, a stance that earned some local disapproval. In The history of the Royal-Society of London for the improving of natural knowledge (1667), Thomas Sprat (1635–1713) rehearsed success and failure in ancient and modern philosophy so ‘we may better shew, what is to be expected from these new Undertakers, and what mov’d them, to enter upon a way of Inquiry, different from that, on which the former have proceeded’; gave a narrative of what happened in the first few years; and defended the ‘Advantage and Innocence’ of the Society and its work in the eyes of all professions and of religion. His version of events ran: ‘Some space after the end of the Civil Wars at Oxford, in Dr Wilkins his lodgings, in Wadham College, which was then the place of Resort for Vertuous and Learned Men, that the first meetings were made, which laid the foundation of all this that follow’d … The principal, and most consistent of them, were Doctor Seth Ward, the present Lord Bishop of Exeter, Mr. Boyl, Dr. Wilkins, Sir William Petty, Mr. Mathew Wren, Dr. Wallis, Dr. Goddard, Dr. Willis, Dr. Bathurst, Dr. Christopher Wren, Mr. Rook: besides several others, who joyn’d themselves to them, upon occasions … For such a candid, and unpassionate company, as that was, and for such a gloomy season, what could have been a fitter subject to pitch upon, than Natural Philosophy’. In documenting the various bodies that had endorsed the founding and activities of the Royal Society, Sprat mentions physicians: ‘Of our Physicians, many of the most judicious, have contributed their purses, their bands, their judgments, their writings. This they have done, though they have also in London, a Colledge peculiar to their Profession; which ever since its first foundation, for the space of a hundred and fifty years, has given the world a succession of the most eminent Physicians of Europe. In that they confine themselves to the advancement of Physick: But in this, they have also with great zeal, and ability, promoted this universal inspection, into all Natural knowledge. For without danger of flattery, I will declare of the English Physicians, that no part of the world exceeds them, not only in the skill of their own Art, but in general Learning’. Against this historical preamble, readers of Brain will be delighted to learn that, at their meeting on 8 May 2018, being quorate, the Fellows elected Dimitri Kullmann, editor of this journal, to the Royal Society. He is the 12th of the 17 people who have edited Brain since 1878 to hold that distinction, starting with a run of 88 years to 1966, and with a further presence over the last 21 years to 2018. Dimitri’s career began in Oxford where he studied physiology completing his DPhil (1984) working with Julian Jack FRS on central actions of muscle receptors. Subsequently trained in clinical medicine and now professor of neurology at the UCL Institute of Neurology, his work on the physiology and pharmacology of synapses and small circuits in the mammalian central nervous system is distinguished for several discoveries: long-term potentiation and depression involve more than all or none transmitter release and activation of postsynaptic receptors but include dynamic changes which engage silent synapses; transmitter release and receptor sensitivity change with activity; the business of one synapse spills over to others; long-term potentiation occurs in the small interneuronal circuits that determine regional inhibition and facilitation; and the complexity of these molecular events involves oscillations as the systems adjust during learning and plasticity. As a clinician scientist, Professor Kullmann has also characterized, with others, the role of ion-channel genetic mutations in human disorders that include epilepsy; and evaluated preclinical modelling of gene therapy for treatment of focal epilepsies. Members of the 17th century Invisible College in Oxford thought about epilepsy. In his lectures given around 1660, the year in which the Royal Society was founded, Willis used the term ‘convulsion’ to denote turbulence and expansion of the nervous juice in the brain transmitted as ‘raging’ activity to the nerves leading, in turn, to ‘leapings and contractions’ of the muscles with failure of antagonist muscles to relax when the agonist contracts. Convulsions might become generalized, their severity depending on the duration and speed of movement of the unruly nervous spirit. Epilepsy might follow formation of a cicatrix from meningeal disease constricting the nerve juice and forcing it down nerves with sudden falling to the ground and convulsions of the eyes, lips or face. Alternatively, it could result from admixture of vitriolic material in the blood causing the nervous juice to boil over in the cerebral cortex and swamp the nerves and muscles. Congestion caused the cerebrum and cerebellum, responsible for voluntary and involuntary movements, respectively, to respond by contractions of the limbs and abdominal muscles, and alteration in the pulse and respiration with incontinence. Undigested vitriolic material in the brain was responsible for loss of awareness during, and altered memory after, the paroxysm. Recovery occurred when the vitriolic matter dissipated or was excreted in the foaming mouth of the person with epilepsy. In the present issue, Arjune Sen, Valentina Capelli and Masud Husain, from Oxford, review the complex relationship between epilepsy, age and dementia asking whether seizures promote dementia, and dementia causes seizures. They conclude, not unexpectedly, that both statements are true and that seizures and dementia share common underlying pathophysiological vascular mechanisms. Anna Fassio and colleagues from Genoa, Florence and Pisa (Italy), Tokyo, Hamamatsu, Yokohama and Osaka (Japan), Denizli (Turkey) and Phoenix (USA) identify mutations of ATP6V1A, encoding the A subunit of v-ATPase, in developmental encephalopathy with epilepsy. They model the functional consequences of four alterations, differing in their clinical impact, that either perturb subunit interaction, destabilize protein folding, affect catalytic function, or impair proton transport but collectively alter lysosomal homeostasis and synaptic connectivity. Smriti Patodia, and investigators from groups in London (UK) including that led by Dimitri Kullmann at the UCL Institute of Neurology, and involving Ingrid Scheffer from Melbourne (Australia), who was also elected FRS on 8 May 2018, study neuronal populations in the human brainstem in the context of sudden unexpected death in epilepsy (SUDEP). They find alteration, compared to controls, in medullary neuromodulatory neuropeptidergic and mono-aminergic systems, including those for galanin, and serotonin suggesting that prior epileptic activity leads to structural neuronal changes, which compromise respiratory homeostasis during subsequent seizures. Brain is not the first journal to publish papers on epilepsy. Dr William Cole (1635–1716) wrote on convulsions in Philosophical Transactions of the Royal Society on 1 January 1685, in issue 174, describing a ‘lady of wit and beauty’ who had a miscarriage followed by uncontrollable seizures, which occurred at the same intervals as quartan fever suggesting to Dr Cole that they might be cured by Peruvian bark; and they were. In the same issue he describes Dorothy Cook, who kept a coffee house in Worcester, two of whose children also had seizures, who suffered convulsions for 30 years yet (pace Masud Husain and colleagues) ‘her Intellectuals, and other animal Functions, were not sensibly affected, but she dispatched her Family Affairs with as much Dexterity, considering her Age, as if she had been in perfect Health’. (Later Cole wrote a monograph on epilepsy: Consilium aetiologicum de casu quodam epileptico, etc., 1702). In issue 280, on 1 January 1703, Dr Charles Leigh (1662–1701: FRS 1685) described John Pownel, aged 13, caught in an epidemic fever resulting in obstructive jaundice and large purple spots, who developed seizures causing him to ‘bark in the usual Notes of a Dog, and at last howling like a Hound … roared like a Bull, made a noise like a Hog, and sometimes like that of a Gosling … from different contractions of the Lungs, variously forcing out the Air … as they were differently convulsed’; but happily all was well and Leigh was able to report that, after a while, ‘the boy is very chearful’. In issue 399, on 1 January 1728, Dr Walterius Rhætus (nk) reported three autopsies in people who died with epilepsy, one with meningeal adhesion over the Crista Galli (cribriform plate) and two others with accumulation in the ventricles of turgid fluid and white pellucid bodies that resembled very elegant pearls leaving them ‘ready to burst’. These papers were written in Latin (translated by Samuel Mihles, Medical essays and observations relating to the practice of physic and surgery abridg’d from the Philosophical Transactions etc., 1745) but there is no requirement on Dimitri Kullmann and Ingrid Scheffer to maintain that tradition. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

BrainOxford University Press

Published: May 25, 2018

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