Ramón y Cajal: a century after the publication of his
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1. d 4 Figure 4 Ram n y Cajal s family A His wife Silveria Fa an s Garcia33 c 1880 B Portrait of Silveria holding in her arms their two younger daughters Enriqueta and Paula as an allegory of maternity 1886 C Portrait of Enriqueta4 1886 D Self portrait of Ram n y Cajal with four of his children in 1888 From left to right they are Fe J orge Cajal Paula and Santiago E Family portrait in 1897 From left to right the sitters are Luis Pilar J orge Paula Santiago Silveria and Fe F Family portrait c 1906 From left to right the sitters are Paula Cajal Silveria Fe Pilar Santiago35 and Luis G Self portrait c 1920 All photographs by Ram n y Cajal Art had an important place in Ram n y Cajal s life Painting and drawing were two passions that led him to create some of the most beautiful scientific illustrations ever made Figures 2 3 In collaboration with his father he also painted a colour atlas of human anatomy that was unfortu nately never published25 Cajal was an enthusiast of the art of photography and an accomplished photographer 26 He took hundreds of photographs portraits landscapes and scientific photographs Figure 4 He had a laboratory where he used to develop and sometimes to manufacture the photographic films Ram n y Cajal was one of the pioneers of colour photography in Spain In 1912 he published La fotografia de los colores Fundamentos cient ficos y reglas pr2. cticas a book entirely dedicated to this subject2 Politics and popularity As well as being very prolific Ram n y Cajal was a popu lar author He wrote a variety of books intended for a broad public including Recuerdos de mi vida Charlas de caf 4 and El mundo visto a los 80 a os 5 I take into con sideration that I am not writing exclusively for specialists but for a cultured public of varied interests Always inter ested in popularizing science he adopted the pseudonym Doctor Bacteria and wrote articles about the marvels of histology and science fiction tales 28 Ramon y Cajal was always willing to give advice to e ee Spanish political leaders about national education and Figure5 Cajal 1924 This statue in marble of Santiago Ram n y Cajal by the sculptor Mariano Benlliure was inaugurated in his honour at the School of Medicine of the newspapers with editorials about a variety of issues relevant University of Zaragoza science issues Furthermore he regularly contributed to Endeavour Vol 25 1 2001 15 16 to his country He was appointed a senator for life and was offered the position of Minister at the Spanish Ministerio de Instrucci n Publica the current Ministry of Education and Culture which he did not accept Of the countless honours that Ramon y Cajal did receive the one that he might have cherished most is the gratitude and affection of his fellow countrymen Figure 5 Ram n
3. 1889 Dolores del parto considerablemente atenuados por la sugesti n hipn tica Gaceta M dica Catalana 12 484 486 23 Turning suggestion to the therapeutic field I succeeded in performing prodigies which would be envied by the most skilful of the miracle workers I may cite the radical transformation of the emotional condition of patients an almost instantaneous step from sadness to joy the restoration of appetite in hysteroepileptics who would not eat and were extremely emaciated the cure by a simple command of diverse kinds of chronic paralysis of a hysterical nature the sudden cessation of attacks of hysteria with loss of consciousness the complete forgetting of painful and distressing occurrences the total abolition of the pains of childbirth in normal women and finally surgical anaesthesia etc 24 Ramon y Cajal s sensibility to art might have been encouraged by his mother Antonia Cajal Puente a beautiful and robust highland woman As Justo Ram n Casastis she was born in the village of Larr s in the region of Aragon 25 At that time Justo Ram n Casasus had a professorship of dissection at the School of Medicine of the University of Zaragoza In spite of the fact that he repressed the artistic vein of his son for many years he was on this occasion very proud of Ramon y Cajal s anatomical watercolours Ram n y Cajal was then at the School of Medicine and was willing to put his artistic aptitudes to th
4. Director of the Instituto Nacional de Higiene Alfonso XIII The National Institute of Hygiene the Laboratorio de Investigaciones Biol gicas The Lab oratory of Biological Research and the Instituto Cajal The Cajal Institute and was President of the Junta para Ampliaci n de Estudios e Investigaciones Cient ficas the current Consejo Superior de Investigaciones Cientificas CSIC He was a dedicated teacher and mentor for more than 50 years offering advice to students young researchers and colleagues In 1897 he wrote Reglas y consejos sobre la investigaci n biol gica in his own words Some rules and counsels designed to awaken the taste and passion for scientific investigation in our young teachers 1 12 This book recently translated into English has been broadly acclaimed Ram n y Cajal s scientific excellence and devoted teachings 3 led to the establishment of the so called Spanish school of neurohistology a large group of outstanding pupils that continued his work and had an enormous influence on generations of Spanish scientists Endeavour Vol 25 1 2001 Figure 3 Ram n y Cajal s drawing of neuroglia in the white matter of the adult human brain using the gold method 2 In some cells the fibrillary apparatus is clearly visible A whereas in other cells the strong cytoplasmic staining prevents its visualization B C Labels a b d perivascular feet Literary works Ramon y Cajal s litera
5. Pll SO160 9327 00 01334 X Figure 1 Self portrait of Ram n y Cajal at the microscope c 1910 1912 Scientific books The first volume of Textura del Sistema Nervioso del Hombre y de los Vertebrados was published in 1899 This is a three volume work that Ram n y Cajal finished in 1904 and considered the principal work of his life The final version of this book updated by Ram n y Cajal and translated to French by his friend Leon Azoulay was published in 1909 and 1911 as Histologie du Syst me Nerveux de l Homme et des Vert br s this remains the definitive work on the morphology of the vertebrate nervous system In Textura and Histologie Ram n y Cajal summarized his work over two decades In these books in addition to describing the structure and or ganization of virtually all parts of the nervous system Ramon y Cajal discussed his theories among them the neuron doctrine gt and the law of functional or dynamic polarization which are the cornerstones of neurobiology and the natural foundation for the study of the nervous system Figure 2 Ramon y Cajal made countless contributions to the neurosciences many of which can be found in his books and have been translated to English Textura Histology Les Nouvelles Id es sur la Structure du Syst me Nerveux chez l Homme et chez les Vert br s a work that sum marizes his revolutionary view of the nervous system Estudios sobre la Degeneraci n y Regeneraci n de
6. Ramon y Cajal a century after the publication of his masterpiece Pedro J Andres Barquin Santiago Ram n y Cajal published the first of the three volumes of his principal life s work in 1899 and published the last volume in 1904 This book remains the definitive work on the morphology of the vertebrate nervous system In it Ram n y Cajal describes the structure and organization of virtually all parts of the nervous system and discusses his theories including the neuron doctrine and the law of functional polarization which are the cornerstones of modern neurobiology A century later Ram n y Cajal s work is still fundamental to understanding the nervous system Countless modifications during evolution have provided living matter with an instrument of unparalleled com plexity and remarkable function the nervous system the most highly organized structure in the animal kingdom The dominant role played by the nervous system is obvious From its inception this system mediated ever increasing coordination between the various elements of multicellular organisms which were essentially un structured disorganized and subject to all the vagaries of the surrounding environment early on The nervous system provided these animals with the necessary mechanisms for nutrition and defense and the number precision power and coordination of these mechanisms steadily increased Furthermore in the highest echelons of life it also provided optim
7. Vertebrates translated by N Swanson and L W Swanson Oxford University Press Endeavour Vol 25 1 2001 on A declaration of the unity and independence of the neuron and all its processes Nerve cells always remain free independent and individual and are the fundamental unit of the nervous system as a whole Nerve impulse transmission from neuron to neuron is by contact rather than continuity 6 The law of functional dynamic or axipetal polarization of electrical activity in neurons Normally the dendrites and cell body show axipetal conduction that is electrical activity is conducted toward the axon Conversely the axon shows somatofugal and dendrifugal conduction that is it transmits activity arriving from the parent cell body or dendrites and does so from its origin to its terminals 7 Ramon y Cajal S 1894 Les Nouvelles Id es sur la Structure du Syst me Nerveux chez l Homme et chez les Vert br s French edition reviewed and enlarged by the author and translated from the Spanish by L Azoulay Reinwald Paris France This book was published in English in 1990 as New Ideas on the Structure of the Nervous System in Man and Vertebrates translated by N Swanson and L W Swanson MIT Press Cambridge MA USA 8 Ram n y Cajal S 1913 1914 Estudios sobre la Degeneraci n y Regeneraci n del Sistema Nervioso Moya Madrid Spain This book was published in English in 1928 as Degeneration and Regenera
8. al means for survival feelings thought and will Santiago Ramon y Cajal Santiago Ram n y Cajal 1852 1934 Figure 1 is ac knowledged as the founder of neuroscience Born on 1 May 1852 in the Spanish village of Petilla de Aragon in a very modest family Santiago enjoyed a childhood in close contact with nature Very early in his life he showed an ability to unravel nature s secrets and a strong liking for painting and drawing aptitudes that would later be of great importance in his scientific career Ramon y Cajal s precocious artistic vein was repressed by his father a man with a strong character who persuaded him to enter medical school at Zaragoza This was the starting point of an extraordinary scientific adventure which led him to explore the organization and function of the nervous system and to publish the most profound body of work by a single scientist in the history of neuroscience Pedro J Andres Barquin DVM PhD MPH Is Head of Laboratory and Project Leader at the Department of CNS F Hoffmann La Roche Basel Switzerland He was born in Zaragoza Spain and received his DVM and PhD from the University of Zaragoza and his MPH from the Spanish National School of Public Health He has been a fellow at INSERM Paris and at the School of Medicine of the University of California San Francisco e mail pedro_j andres roche com 0160 9327 01 see front matter 2001 Elsevier Science Ltd All rights reserved
9. e service of medicine 26 A number of Ram n y Cajal s photographs can be found in Alvarez J et al eds 1984 Ramon y Cajal Fotografia Aragonesa Vol 1 Diputaci n Provincial de Zaragoza Zaragoza Spain 27 Ramon y Cajal S 1912 La Fotografia de los colores Fundamentos cient ficos y reglas pr cticas Moya Madrid Spain A 1994 edition is currently available from Libros Clan Madrid Spain 28 Ram n y Cajal S 1905 Cuentos de vacaciones Narraciones pseudocientificas Imprenta Fortanet Madrid Spain This book was written in 1885 1886 A 1999 edition is currently available from Colecci n Austral Espasa Calpe Madrid Spain 29 Swanson L W et al 1999 Organization of Nervous Systems In Fundamental Neuroscience Zigmond M J et al eds pp 10 11 14 Academic Press 30 Albright T D et al 2000 Neural science a century of progress and the mysteries that remain Cell 100 and Neuron 25 joint suppl S1 S55 31 For a list of Ram n y Cajal s publications prizes and honours see Ref 1 32 Ram n y Cajal s discovery in 1913 of the gold sublimate method for the staining of neuroglia was an important step forward to the study of glial cells and primary tumours in the central nervous system 33 Ram n y Cajal married Silveria Fa an s Garcia in 1879 and had seven children In Cajal s words I should be unjust if out of mistaken discretion I should fail to say that during my first years as a profess
10. eire Mallo and Mabel Garz n for their thoughtful comments Notes and references 1 Ram n y Cajal S 1901 1917 Recuerdos de mi vida Vol 1 Mi infancia y juventud Vol 2 Historia de mi labor cientifica Moya Madrid Spain This book was first published in English in 1937 as Recollections of My Life translated by E Horne Craigie with the assistance of J Cano American Philosophical Society Philadelphia PA USA a 1989 MIT Press edition is currently available MIT Press Cambridge MA USA 2 Ram n y Cajal s father Justo Ram n Casas s a pure blooded Aragonese was a modest surgeon at the time He was a man of great energy an extraordinarily hard worker and full of noble ambition 3 Ramon y Cajal S 1899 1904 Textura del Sistema Nervioso del Hombre y de los Vertebrados Moya Madrid Spain The first and second volumes of this book were published in English in 1999 and 2000 as Texture of the Nervous System of Man and the Vertebrates translated and edited with addition from the French version by P Pasik and T Pasik Springer Verlag The publication in English of the third volume is due in 2001 4 Ram n y Cajal S 1909 1911 Histologie du Syst me Nerveux de l Homme et des Vert br s French edition reviewed and updated by the author translated from Spanish by L Azoulay Maloine Paris France This book was published in English in 1995 as Histology of the Nervous System of Man and
11. l Sistema Nervioso a monumental study containing his works and Endeavour Vol 25 1 2001 13 14 SE on gt x fanams sum aar AN TAN A i TN Figure 2 Ram n y Cajal s drawing of neurons in layers 5 7 of the 15 day old human infant visual cortex using the Golgi method A Layer 5 B layer 6 C layer 7 Labels a giant pyramidal cell b medium sized pyramidal cell with a long descending axon c small pyramidal cell with an arcuate ascending axon d pyramidal cell with an axon that bifurcates into two arcuate branches e pyramidal cell with an axon that gives rise to several ascending arcuate fibres f h stellate cells with an ascending axon ramifying in layers 5 and 6 i k pyramidal cells with an arcuate ascending axon ramifying in layers 7 and 8 ideas relating to neurogenesis neuronal plasticity and nerve degeneration and regeneration Neuronismo 6 Reticula rismo his posthumous work devoted to the defence of the neuron doctrine and his writings about the cerebral cortex contain seminal investigations and ideas that are as relevant today as they were when they first appeared 100 years ago Teaching Ram n y Cajal was appointed Auxiliary Professor of Anatomy and Director of the Anatomical Museum at the University of Zaragoza Professor of Anatomy at the University of Valencia and Professor of Histology and Pathology at the Universities of Barcelona and Madrid He also was the
12. mal y T cnica Microgr fica 1889 Manual de Anatom a Patol gica General 1890 Elementos de Histolog a Normal y de T cnica Microgr fica 1897 and Manual T cnico de Anatom a Patol gica 1918 Several editions of these books were published in Spain between 1889 and 1953 14 Ram n y Cajal S 1921 Charlas de caf Pensamientos an cdotas y confidencias J Pueyo Madrid Spain Reprinted in Santiago Ram n y Cajal Obras Selectas 2000 Espasa Calpe Madrid Spain 15 Ram n y Cajal S 1934 El mundo visto a los 80 a os Impresiones de un arterioscler tico Tipograf a Art stica Madrid Spain Reprinted in Santiago Ram n y Cajal Obras Selectas 2000 Espasa Calpe Madrid Spain 16 Rodr guez E L 1977 As era Cajal Espasa Calpe Madrid Spain 17 Lorenzo Lizalde C 1991 El pensamiento de Cajal Instituci n Fernando el Cat lico Zaragoza Spain 18 Ibarz Serrat V 1994 La Psicolog a en la obra de Santiago Ram n y Cajal Instituci n Fernando el Cat lico Zaragoza Spain 19 Calvo Roy A 1999 Cajal Triunfar a toda costa Alianza Editorial Madrid Spain 20 Ram n y Cajal S 1885 Estudios sobre el microbio v rgula del c lera y las inoculaciones profil cticas Tipograf a del Hospicio Provincial Zaragoza 1 108 21 Ram n y Cajal S 1885 Contribuci n al estudio de las formas involutivas y monstruosas del comabacilo de Koch La Cr nica M dica Valencia 9 197 204 22 Ramon y Cajal S
13. or only the unsurpassable self abnegation of my wife made my scientific work possible So much so that a certain highly talented lady used to say Half of Cajal is his wife Silveria and Santiago spent the rest of their lives together She died in 1930 two years before him 34 Enriqueta died when she was seven years old 35 Santiago died when he was 29 years old Endeavour Vol 25 1 2001 17
14. ry books and particularly his autobiography have been instrumental in gaining a deep understanding of his character and the tenor of his life In addition to being a passionate neuroscientist he was also interested in bacteriology psychology philosophy astronomy drawing and painting photography litera ture politics and more 9 At the request of the pro vincial government of Zaragoza in 1885 Ram n y Cajal carried out a comprehensive study of an outbreak of cholera in Valencia and described for the first time the experimental proof of the formation of antibodies that is to say of the possibility of protecting animals from the toxic effects of the most virulent bacillus by previously injecting hypodermically a certain quantity of a culture which has been killed by heat 2021_ The prize he was awarded by the Diputaci n Provincial de Zaragoza for this study was a magnificent Zeiss microscope which placed him on a level technically with the best equipped foreign microscopists At that period of his life he also conducted in vestigations into suggestion and hypnosis and their usefulness for improving some clinical conditions and decreasing pain 3 The understanding of the human mind and the search for a link between neurobiology and consciousness are leitmotifs in the work of Ram n y Cajal In his writings one can find frequent thoughts about the transcendence of his discoveries for psychology and philosophy 8
15. tion of the Nervous System translated and edited by R M May Oxford University Press The translation was reprinted in 1991 as Cajal s Degeneration and Regeneration of the Nervous System edited with an introduction and additional translations by J DeFelipe and E G Jones Oxford University Press 9 Ram n y Cajal S 1933 Neuronismo Reticularismo Las pruebas objetivas de la unidad anat mica de las c lulas nerviosas Arch Neurobiol Madrid 13 217 291 and 579 646 Published in English in 1954 as Neuron Theory or Reticular Theory Objective Evidence of the Anatomical Unity of the Nerve Cells translated by M Ubeda Purkiss and C A Fox CSIC Madrid Spain 10 An English translation of Ram n y Cajal s writings about the cerebral cortex 1890 1935 can be found in Cajal on the Cerebral Cortex 1988 translated and edited with extensive annotations by J DeFelipe and E G Jones Oxford University Press 11 Sanchez Ron J M 1999 Cincel martillo y piedra Historia de la ciencia en Espa a Siglos XIX y XX Taurus Madrid Spain 12 Ram n y Cajal S 1897 Reglas y consejos sobre la investigaci n biol gica L Aguado Madrid Spain A later edition of this book was published in English in 1999 as Advice for a Young Investigator translated by N Swanson and L W Swanson MIT Press Cambridge MA USA 13 Ram n y Cajal also wrote a number of textbooks of histology and pathology including Manual de Histolog a Nor
16. y Cajal enjoyed enormous popularity in Spain that some how remains today In fact almost every city and village in Spain has a street or square named in his honour and he is widely known among the population The Cajal Insti tute of Neurobiology and many medical centres around the country have also been named in his honour Ram n y Cajal died in Madrid on 17 October 1934 and Spanish citizens from every social class attended his funeral An incredible scientist Ram n y Cajal laid firm found ations for the study of the nervous system 3 He pub lished more than 300 major works many of them book length monographs He was awarded many scientific prizes among them the Moscow Prize by the executive committee of the International Medical Congress of Paris 1900 the Helmholtz Gold Medal by the Imperial Academy of Science of Berlin 1905 and the Nobel Prize in Physiology or Medicine 1906 3 Santiago Ram n y Cajal is probably the most prominent neuroscientist of all time A century after the publication of his masterpiece Ram n y Cajal s work is still fundamental to understand ing the nervous system Acknowledgements I thank Dr Ricardo Martinez Murillo Director of the Cajal Institute CSIC Madrid Spain and Dr Miguel A Freire Mallo Scientist In Charge of the Legado Cajal at the Cajal Institute for the permission to reproduce Ram n y Cajal s drawings and photographs I thank Dr Maria Clemencia Hernandez Dr Miguel A Fr
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