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J R Soc Med. 2004 January; 97(1): 34–36.
PMCID: PMC1079269

Charles Scott Sherrington’s Integrative Action: a centenary notice

One hundred years ago Charles Scott Sherrington (1857–1952), Holt professor of physiology in the University of Liverpool, chose as his subject for the Silliman Lectures for 1904 at Yale University ‘The Integrative Action of the Nervous System’; two years elapsed before they were published.1 The yearly series honoured a professional chemist, Benjamin Silliman (1779–1864), who lectured in mineralogy and geology and for his wide interest in natural history had been given an honorary MD. The lectures introduced the term integration into scientific neurology. Sherrington pointed out that reflexes had to be goal-directed, and that ‘the purpose of a reflex serves as legitimate and urgent an object for natural inquiry as the purpose of colouring of an insect or blossom’. His work and his emphasis was on spinal reflexes for he recognized that the spinal cord provides the simplest portion of the mammalian nervous system and yet displays examples of all its synaptic functions.

Information, he realized, is transmitted between nerve cells by contact, for which he had introduced the term synapse in 1897 when Michael Foster invited him to revise the chapters on the nervous system for the seventh edition of his Textbook of Physiology. Santiago Ramón y Cajal (1852–1934) ‘solved at a stroke the great question of the direction of the nerve currents in their travel through the brain and spinal cord’, showing that it was unidirectional. In the reflex arc, the ‘wiring diagram’ of the spinal reflexes, afferent (sensory) and efferent (motor) elements were related at centres in the grey matter by synaptic contacts between the neurons.

Sherrington concentrated on the mechanisms whereby excitatory and inhibitory processes, initiated by different inputs, interact to grade the output of a pool of motoneurons for different purposes. The central issue in the classic experiments he had made with isometric muscle preparations in spinal animals concerned the interaction between excitation and inhibition. That reflex contraction of knee extensor muscle in the decerebrate preparation could be immediately and dramatically cut short by sensory stimulation he found particularly impressive. Excitation and inhibition were shown to be graded states of opposite character, capable of what looked like algebraic summation of opposites (plus and minus signs) when they clashed on the same neuronal membrane, a prophecy proved to be true when the intracellular microelectrode invented by Ling and Gerrard was inserted into spinal motoneurons. Synaptic excitation and inhibition, as produced by appropriate reflexes, were shown to elicit opposite changes in membrane potential of the cell, excitation depolarizing it, inhibition repolarizing or hyperpolarizing it. Changes in ionic permeabilities are now known to explain these electrical changes brought about by synaptic action, which Sherrington felt assured were electrical rather than chemical in nature—as was proved by Otto Loewi (1873–1961) and Henry Dale (1875–1968), who shared the Nobel Prize in 1936.

The spinal reflex, in Sherrington’s words, is a very elementary ‘item of behaviour’, but it had to be elementary to allow detailed examination and to inspire the subsequent analysis that led to his understanding of synaptic action. The stretch reflex might be a ‘convenient fiction’ but it and its fellow spinal reflexes provided the platform from which to examine how motor mechanisms are progressively organized, how the different cortical, subcortical, cerebellar and spinal centres interact in initiating and controlling movement, how sensory receptors operate reflexes, and how neuronal programmes—old and new—are used by higher centres.

Reviewing the ‘physiological and psychical signs of nervous activity’ Sherrington argued that ‘physiology and psychology, instead of prosecuting their studies, as some now recommend, more strictly apart one from another than at present, will find it serviceable for each to give to the results achieved by the other even closer heed than has been customary hitherto.’ In a foreword when the book was reprinted in 1947 ‘without any change whatsoever in the text’, the author returned to the realization that ‘the biological function of the physico-psychical liaison enhances the organism’s power of disposing of its acts’, remarking that ‘each of the two achieves its aim only by reason of a contact utile between them. And this liaison can rank as the final and supreme integration completing the individual. But the problem how that liaison is effected remains unsolved; it remains where Aristotle left it more than 2000 years ago in De Anima’. The duel continues. Sherrington’s obituarist in the British Medical Journal in March 1952 perceptively remarked that The Integrative Action of the Nervous System provided above all a set of concepts by which the nervous system could be understood.2 E D Adrian (1889–1977) elaborated:

‘... he is the scientist’s philosopher because he had advanced natural knowledge himself by skilled observation and experiment, by 50 years’ unremitting work in the laboratory, and because his own interpretation of his discoveries had given a new extension to the biologist’s outlook. Physiologists will know this well enough. To those who have had to struggle with the mass of detailed material about the brain and cord Sherrington’s Integrative Action of the Nervous System brings order out of chaos; it is hard reading at first, because every sentence is charged with meaning, some of it direct enough, but some reaching out to half formed pictures of wider landscape. Though it was published in 1906 it is still as refreshing as it was then. It has needed no revision, but Sherrington’s experimental work went on at high pressure for another 30 years, filling in the gaps and strengthening the framework....’2

It is heartening to discover that Adrian, a professor of physiology in the University of Cambridge who shared with Sherrington the Nobel Prize in 1932, found it hard reading at first, for most of us have had to add later readings in order to struggle through the author’s elaborate prose style with its evocation of the metaphysical poets. Sherrington never lost the elaborate style, though it was favourably diluted by co-authorship with R S Creed, D Denny-Brown, J C Eccles and E G T Liddell in ‘the little red book’ in 1932 (Box 1).

Box 1 Sherrington’s other books

The Assaying of Brabantius and other Verse. Oxford University Press, 1925; enlarged 1940

Reflex Activity of the Spinal Cord (co-authored). Clarendon Press, 1932

Man on His Nature. Cambridge University Press, 1940; 2nd edition 1951

Goethe on Nature and on Science. Cambridge University Press, 1942

The Endeavour of Jean Fernel. Cambridge University Press, 1946

A full bibliography is given in the 1947 reprint1

The Queen Square neurologist F M R Walshe (1885–1973) believed he detected the inspirational influence of clinical neurology:

‘... There is something singularly appropriate in this, for it was from a clinical neurologist, Hughlings Jackson, that Sherrington himself derived no little inspiration. The very phrase, “Integration keeps pace with differentiation,” that we associate with Sherrington, and that we find implied in the title of his classic work, The Integrative Action of the Nervous System, he took from Jackson, and he has returned to neurological medicine in overflowing measure the gift he got from its most distinguished exponent.’2

But according to Sherrington himself in his Nobel Lecture,3 it was the phenomenon of ‘inhibition as a co-ordinative factor’ which fascinated him and enticed him sufficiently to try to unravel its mysteries:

‘That a muscle on irritation of its nerve contracts had already long been familiar to physiology when the nineteenth century found a nerve which when irritated prevented its muscle from contracting. This observation seemed for a time too strange to be believed...

The role of inhibition in the working of the central nervous system has proved to be more and more extensive and more and more fundamental as experiment has advanced in examining it... Its role as a coordinative factor comprises [reflex inhibition] and goes far beyond it. In the working of the central nervous machinery inhibition seems as ubiquitous and as frequent as excitation itself. The whole quantitative grading of the operation of the spinal cord and brain appears to rest upon mutual interactions between the two central processes “excitation” and “inhibition”, the one no less important than the other... Excitation and inhibition are both present from the very stimulus onset and are pitted one against another. The central circumstances may favour one at one time, the other another.’3

And he concluded his lecture with a reference to clinical significance (as if, in very modern mode, he were applying for a research grant):

‘The admixture of inhibition and excitation as a mechanism for co-ordination thus provides a means of understanding the remarkable “compensations” which restore in course of time, and even quickly, the muscular competence for exertion of an act which has been damaged by central nervous lesions. More than one way for doing the same thing is provided by the natural constitution of the nervous system. This luxury of means of compassing a given combination seems to offer the means of restitution of an act after its impairment or loss in one of its several forms.’3

Of the Integrative Action it was said that ‘it showed how through careful analysis of his observations’, Sherrington had built up constructive hypotheses and gradually converted them into what are now recognized physiological principles.4 But, as one of my teachers Donald Henry Barron (1905–1993) pointed out to me many years ago, although there were no new experiments described in the Integrative Action, every page showed how thoroughly acquainted its author was with the wealth of experiments made in previous centuries by astute observers. Writing the chapters on Spinal Cord, Parts of the Brain below the Cerebral Cortex, Cutaneous Sensation, and The Muscular Sense for E A Schäfer’s Textbook of Physiology (1900) made him fully aware of all that had gone before. This odyssey gave him the carefully referenced, encyclopaedic knowledge of experimental neurophysiology which prepared the ground for his own idiosyncratic powers of integration.5 The Integrative Action of the Nervous System provided above all a set of concepts by which the nervous system could be understood.2

Sherrington focused on the ‘simple’ nervous arrangement of the spinal cord to illustrate the elaborate networks in the cerebral cortex. As Homer’s ghost whispered to Patrick Kavanagh, writing ‘Epic’ on parish rivalry in 1949,

I made the Iliad from such

A local row. Gods make their own importance.


Dr John Moynihan critically read a first draft of the paper.


1. Sherrington C S. The Integrative Action of the Nervous System. New York: Charles Scribner’s Sons, 1906. Reprinted by Cambridge University Press 1947 (with a new preface and full bibliography), and by Yale University Press 1961 (paperback)
2. Anonymous. BMJ 1952;i: 606–9 [PMC free article] [PubMed]
3. Sherrington C S. Inhibition as a co-ordinative factor. In Nobel Lectures, Physiology or Medicine 1922–1941. Amsterdam: Elsevier, for the Nobel Foundation, 1965: 278–89
4. Anonymous. Lancet 1952;i: 569–71
5. Schäfer E A. Textbook of Physiology, Vol. 2. Edinburgh: Young J Pentland, 1900: 698–1002

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press