John Raymond Smythies
John Raymond Smythies (30 November 1922 – 28 January 2019) was a British neuropsychiatrist, neuroscientist and neurophilosopher. Biography. Smythies was born on 30 November 1922 in Nainital, United Provinces, British India, where his father, Evelyn Arthur Smythies, a philatelist, was employed by the Department of Forests. His brother Bertram Evelyn (“Bill”) Smythies became an ornithologist. His cousins on the Smythies side include Yorick Smythies, Richard Dawkins (a first cousin once removed), Graham Greene and Christopher Isherwood. In 1932 Smythies enrolled at Cheltenham College Junior School, transferred to Rugby School in 1936, and thence to Christ's College, Cambridge , in 1940 (18) and to University College Hospital, London in 1942 where he studied medicine (19). He graduated M.B., B.Chir. (Cantab) in 1945. After two years as a Surgeon-Lieutenant in the R.N.V.R. as ship's doctor on based in Bermuda, he completed his basic medical postgraduate training at Addenbrooke's Hospital, Cambridge, before selecting neuropsychiatry for a speciality. Two weeks into his first psychiatric residency at St. George's Hospital, London (20), noting the close chemical relation between the psychotomimetic drug mescaline and the neurotransmitter catecholamines, he suggested that schizophrenia might be caused by some abnormality in catecholamine metabolism  that produced a mescaline-like substance in the brain. In collaboration with the organic chemist John Harley-Mason and Humphry Osmond, his psychiatric colleague at St. George's, he developed this idea, into the first specific biochemical theory of schizophrenia—the transmethylation hypothesis (5). Inspired by the fact that mescaline produces such remarkable effects on all human mental faculties and by the interdisciplinary work of Albert Schweitzer, in the same year Smythies decided to tackle the mind-brain problem in a systematic way i.e. by undertaking a rigorous training in neuroscience, experimental psychology and philosophy. He first worked for one  year as a resident in the EEG Department at the National Hospital, Queen Square, London (21). He then took an M.Sc. degree in neuroanatomy, philosophy and cultural anthropology with the neuroanatomist William C. Gibson at the University of British Columbia (22). The neuroanatomical research involved was a study of the synaptic structure in human cortex as revealed by silver staining and was awarded a post-graduate M.D degree by Cambridge (23). His teacher in philosophy was the distinguished American philosopher Avrum Stroll, who became a lifelong mentor and friend. This was followed during the tenure of a Nuffield Fellowship by  six months with the Nobel Laureate Sir John Eccles in neurophysiology and 18 months at the Psychological Laboratory in Cambridge with Oliver Zangwill studying the stroboscopic patterns (the complex geometrical hallucinations induced by looking at a flickering light). This work has been extensively reviewed by John Geiger. Then Smythies worked a further two years in neuropharmacology with Harold E. Himwich in Galesburg, Illinois and with Hudson Hoagland at the Worcester Foundation, before returning to London where he completed his formal clinical psychiatric training with Sir Aubrey Lewis at the Maudsley Hospital (25). He then joined the Faculty of the University  of Edinburgh for twelve years, first as senior lecturer then reader (26), before being invited to a personal chair at the University of Alabama at Birmingham, funded by the Ireland family, where he stayed for eighteen years (27). In 1956 Smythies published his first book "Analysis of Perception" (28) on the mind-brain problem in which he presented a new theory — extended materialism — based on an analysis of fundamental flaws in the current orthodox theory (mind-brain identity) and previous work by Joseph Priestley, C.D. Broad, H.H. Price and Bertrand Russell. A second book, "The Walls of Plato’s Cave , followed in 1994 (17) on the same topic. Robert Almader's (29) described the work as This is certainly one of the four or five most arresting and compelling books written on the nature of consciousness, the mind-brain problem, and human personality." The theory extends our concepts of consciousness and analyses possible geometrical and topological relations between phenomenal space and physical space linked to brane theory in physics. In 2008, the distinguished British physicist Bernard Carr (30), following a different line of research, presented a very similar theory as the basis for a necessary new paradigm shift in cosmology . In 1998 he wrote "Every Person's Guide to Antioxidants" (37). Smythies gives an account of his work on synaptic plasticity in his book "The Dynamic Neuron" (2002) (8). Smythies served as president of the International Society of Psychoneuroendocrinology from 1970 to 1974 (31), consultant to the World Health Organization from 1963 to 1968 (32), and editor of the "International Review of Neurobiology" from 1958 to 1991. He was elected a member of the Athenaeum in 1968 (33). He published over 200 scientific papers and 16 books. He made extensive contributions to knowledge in a number of fields including the  neurochemistry of schizophrenia (5,6) and the neuropharmacology of psychedelic drugs (7); the functional neuroanatomy of synapses with particular regard to the role of synaptic plasticity, endocytosis and redox factors (8,9); the role in the brain of orthoquinone metabolites of catecholamines (10); the role of virtual reality mechanisms in visual perception (11) and, in particular, theories of brain-consciousness relations (12–17). Smythies held positions as the Charles Byron Ireland Professor Emeritus of Psychiatric Research at the University of Alabama Medical Center at Birmingham, visiting scholar at the Center for Brain and Cognition, University of California, San Diego, and senior research fellow  at the Institute of Neurology, University College London. Aldous Huxley, in his work "The Doors of Perception", which details the effects of mescaline, credits Smythies with having inspired him to take the subject. For the last two decades of his life, Smythies worked with Professor Ramachandran's Center for Brain and Cognition at UCSD, latterly on the function of the claustrum as well as the epigenetics of neurocomputation, exosomes and telocytes (37–54). Personal life and death. On 2 December 1950 Smythies married Vanna Gattorno of Trieste, Italy. John and Vanna published their joint autobiography "Two Coins in the Fountain" in  2006 (34). Smythies is also the author of a book of poems entitled "Poems from the Edge of Time" (35), and a satirical play "The Trial of God" (36). He died in January 2019 at the age of 96. References. 1. Smythies J.R. Schizophrenia: Chemistry, Metabolism and Treatment. Springfield, Illinois, Charles C. Thomas, 1963. 2. Smythies J.R (with H.E. Himwich and S.S. Kety, editors) Amines and Schizophrenia. New York, Pergamon Press. 1966. 3. Smythies J.R. Biological Psychiatry. London, Heinemann, 1968. German edition, 1971. 4. Smythies J.R and Corbett L.C. Psychiatry for Students of Medicine. London, Heinemann, 1976. Spanish edition, 1984 . 5. Smythies J.R & Osmond H. (1952) Schizophrenia. A New Approach. J Ment Sci., pp. 98, 309–316. 6. Smythies J. (Editor) Schizophrenia. A disorder of synaptic plasticity. Special volume (59) in The International Review of Neurobiology, San Diego, Elsevier, 2004. 7. Smythies J. R. "Hallucinogenic Drugs", Chapter 18 in Modern Trends in Neurology, Dennis Williams, editor. 3rd edition. London, Butterworth, 1962. 8. Smythies J. R. The Dynamic Neuron. Cambridge MA., MIT Press, 2002. 9. Smythies J. The Neuromodulators. International Review of Neurobiology, San Diego, Elsevier, 2005. 10. Smythies J. R. The role of free radicals in the brain in health and  disease in relation to synaptic plasticity. In: Free Radicals in Brain Pathophysiology. (G. Poli, E. Cadenas & L. Packer, eds.) New York, Dekker. 11. Smythies J. 2009, "Philosophy, perception, and neuroscience" Perception, pp. 38, 638–651. 12. Smythies J.R. Brain and Mind, London, Routledge & Kegan Paul, editor and contributor of essay "The representative theory of perception", 1965. 13. Smythies J. R. The Neurological Foundations of Psychiatry. Oxford, Blackwell. 1966. 14. Smythies J. Science and ESP. London, Routledge & Kegan Paul, 1967. 15. Smythies J.R. (with Arthur Koestler, editors). Beyond Reductionism. London, Macmillan, 1969. 16. Smythies J. Brain Mechanisms and Behaviour. Oxford, Blackwell, 1970 . Japanese edition, 1973. 17. Smythies J. The Walls of Plato's Cave. Aldershot, Avebury Press, 1994. 18. Records of Christs's College, Cambridge. 19. Records of University College Hospital, London. 20. Records of St. George's Hospital, London 21. Records of the National Hospital, Queen Square, London. 22. Records of the University of British Columbia. 23. Smythies J. R., Gibson W.C., & Purkis V.A. (1957) The distribution and morphology of boutons termineaux in the human cerebrum. J Comp Neur., pp. 108, 175. 25. Records of the Institute of Psychiatry, University of London. 26. Records of the University of Edinburgh. 27. Records  of the University of Alabama at Birmingham. 28. Smythies, J. R. Analysis of Perception. London, Routledge & Kegan Paul, 1956. 29. Almader, R. (1997) Journal for Scientific Exploration, pp. 10, 314–318. 30. Carr, B. (2008) "Worlds apart?" Proc.Soc.Psychical Research, pp. 59, 1–96. 31. Records of the International Society for Neuropsychopharmacology. 32. Records of the World Health Organization. 33. Records of the Athanaenum Club, Pall Mall, London. 34. Smythies J. & Smythies V. Two Coins in the Fountain. (joint autobiography). Amazon.com (Booksurge) 2006. 35. Smythies J. Poems from the Edge of Time. Pulborough, Ellis, 2002. 36. Smythies J. The Trial of  God. (satirical play) Amazon.com (Booksurge) 2006. 37. Smythies J. Every Person's Guide to Antioxidants. Rutgers University Press 1998. 38. Smythies JR. The Dynamic Neuron. Cambridge MA. MIT Press, 2002. 39. Smythies, J., Edelstein, L., Ramachandran, V. The Claustrum: Structural, Functional and Clinical Neuroscience. San Diego. Academic Press (Elsevier). 2014. 40. Smythies J, Edelstein L, Ramachandran V. (2012) Hypotheses relating to the function of the claustrum. Frontiers in Integrative Neuroscience. 2012;6:53. doi: 10.3389/fnint.2012.00053. Epub 2012 Aug 2. 41 Smythies J, Edelstein L. (2013) Transsynaptic modality codes in the brain: possible involvement of synchronized spike timing, microRNAs, exosomes and epigenetic  processes. Frontiers in Intregrative Neuroscience. 2012;6:126. doi: 10.3389/fnint.2012.00126. Epub 2013 Jan 4. 42. Smythies J. (2013) Schizophrenia: one coat of many colors. Frontiers in Psychiatry, 27 May 2013 | doi: 10.3389/fpsyt.2013.00043. 43. Edelstein L, Smythies J. (2013) Spike dynamic and epigenetic malfunctions in epilepsy: a tale of two codes. Frontiers in Epilepsy: 27 May 2013. doi: 10.3389/fneur.2013.00063. 44. Smythies J. Edelstein L. (2013) Interactions between the spike code and the epigenetic code during information processing in the brain. Frontiers in Molecular Neuroscience. 8 July doi: 10.3389/fnmol.2013.00017 45. Smythies J, Edelstein L. (2013) Telocytes, exosomes, gap junctions  and the cytoskeleton: the makings of a primitive nervous system? Front. Cell. Neurosci. | doi: 10.3389/fncel.2013.00278. 46. Smythies J, Edelstein L, Ramachandran V (2014). Hypotheses relating to the function of the claustrum II: instructional oscillations and dendritic integration. Front. Integr. Neurosci. 8:7. doi: 10.3389/fnint.2014.00007. 47. Smythies J, Edelstein L. (2013) Hypotheses concerning how Otx2 makes its incredible journey: a hitchhiker on the road to Rome. Front. Mol. Neurosci. 6, 55. doi: 10.3389/fnmol.2013.00055. eCollection 2013. 48. Edelstein L, Fuxe K and Smythies J (2014). Life without glutamate: the epigenetic effects of glutamate deletion. Front. Mol. Neurosci. 7:14. doi : 10.3389/fnmol.2014.00014. 49. Smythies LE, Smythies JR. (2014) Exosomes in the gut. Front Immunol. 2014 Mar 17;5:104. eCollection 2014. 50. Edelstein L, Smythies J (2014). Epigenetic aspects of telocytes/cordocytes: jacks of all trades, masters of most. Front Cell. Neurosci. 8:32. doi: 10.3389/fncel.2014.00032. 51. Edelstein L, Smythies J. (2014) The role of telocytes in morphogenetic bioelectrical signaling: once more unto the breach. Front Mol Neurosci. 2014 May 13;7:41. doi: 10.3389/fnmol.2014.00041. eCollection 2014. 52. Smythies J, Edelstein L. (2014) The desferrioxamine-prochlorperazine coma—clue to the role of dopamine-iron recycling in the synthesis of hydrogen peroxide in the  brain. Front.Mol.Neurosci. 53. Smythies J, Edelstein L, Ramachandran V. (2014) Molecular mechanisms for the inheritance of acquired characteristics-exosomes, microRNA shuttling, fear and stress: Lamarck resurrected? Front. Genet. 2014 May 15;5:133. doi: 10.3389/fgene.2014.00133. eCollection 2014. 54. Edelstein L, Smythies J. The role of epigenetic-related codes in neurocomputation: dynamic hardware in the brain. in Edelstein L, Smythies J, Noble D. (Editors) Epigenetic information-processing mechanisms in the brain. Phil.Trans.R.Soc.B. Theme Issue vol. 369, No. 1652, 26 September 2014.