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Neurosciences - A neurosurgeon's perspective.
The advancements in the field of science in the past fifty years have highlighted the need to integrate all fields of human endeavours and have emphasised interdependency of various disciplines. The separation of humanities, therefore, from neurosciences is a preposterous practical joke on all thinking men. With the human genome project on the anvil, biotechnology is making significant headway holding out promise for organ regeneration. Macro evolution is over, but micro-evolution continues in the brain. Neural Darwinism thus, continues to evolve as long as individual remains conscious and has memory. In the milieu of widely varying internal physiological mechanisms and external stimuli, an alternative theory to preprogrammed directionalism is proposed by three mechanisms namely developmental variation and selection, experiential selections and reentrant signalling. Reentrant signalling reorients and correlates the external inputs leading to psychic development preceding the development of consciousness. The cholinergic and aminergic neuro-modelling systems are well suited to serve as value systems. The main achievement of consciousness is to bring together the many categorizations involved in perceptions into a SCENE. Another part of evolution involved capacity of reentrant signalling to be guided by a value system where it is provided with a lot of choices. With 10(13) neurons and 10(16) connections, freedom of choice may manifest into a 'Buddha' or a 'Hitler'. As part of the evolutionary process, it was interesting how capacity to categorize the need to worship by referring to environment outside evolved into a search within our minds. As the next stage of evolution, neuroscience may, thus, serve as the next gateway to understanding the mind and soul.
The advancements in the field of science in the past fifty years have highlighted the need to integrate all fields of human endeavours and have emphasised interdependency of various disciplines. The separation of humanities, therefore, from neurosciences is a preposterous practical joke on all thinking men. With the human genome project on the anvil, biotechnology is making significant headway holding out promise for organ regeneration. Macro evolution is over, but micro-evolution continues in the brain. Neural Darwinism thus, continues to evolve as long as individual remains conscious and has memory. In the milieu of widely varying internal physiological mechansims and external stimuli, an alternative theory to preprogrammed directionalism is proposed by three mechanisms namely developmental variation and selection, experiential selections and reentrant signalling. Reentrant signalling reorients and correlates the external inputs leading to psychic development preceding the development of consciousness. The cholinergic and aminergic neuro-modelling systems are well suited to serve as value systems. The main achievement of consciousness is to bring together the many categorizations involved in perceptions into a SCENE. Another part of evolution involved capacity of reentrant signalling to be guided by a value system where it is provided with a lot of choices. With 1013 neurons and 1016 connections, freedom of choice may manifest into a Buddha or a Hitler. As part of the evolutionary process, it was interesting how capacity to categorize the need to worship by referring to environment outside evolved into a search within our minds. As the next stage of evolution, neuroscience may, thus, serve as the next gateway to understanding the mind and soul. This is the most exhilarating of times to live in. It is said that the quantum of growth in knowledge and human accomplishment in the last 50 years, has no parallel in the whole history of mankind. This is true not only of medical sciences but in all aspects of human endeavour. What an excellent time to bring to a close the year 1999, the `decade of the brain.' The momentum generated by such explosive intellectual activity will ensure that the new millenium will have many more spectacular achievements awaiting revelation. It would be apt to designate the next decade as the `decade of the mind' , and dedicate the following decade to `the mind in search of its soul'! I already seem to be anticipating my thesis. The department of biotechnology, Government of India held an interactive session on `Vision of Neurosciences in the Next Millennium' in March 1998. There were, I believe, 50 active participants and 20 observers. The participants were drawn from practically all neuroscience disciplines, both basic and clinical. In addtition, some leaders in the field of genetics, structural biology, biophysics, biochemistry, computer sciences and mathematical modelling, provided insight into the possible contributions of these disciplines to neuroscience research. Dr. Tandon, as chairman of the task force on Medical Biotechnology and Neurosciences steering committee, was very much there; and we hope, that the proposed `Brain Research Centre', will soon become a reality which we could all be proud of. The role played by physicists, cosmologists and mathematicians in pioneering this tremendous upsurge of intellectual motivity should be acknowledged and lauded. Their contributions have revolutionized and transformed our understanding of nature almost to the degree when Copernicus changed our idea of `earth centering universe' into being just a planet of an ordinary, average size, near the inner edge of one of the spiral arms of our galaxy. Newtonian physics was superseded by Einstein's theory of relativity, the quantum theory of the atom and Stephen Hawking's elaboration of the `Big Bang'. Time became a dimension and miloniums later, the sense of time became a conscious event for an individual, what a fascinating thought! A point being made by some physicists is that, there is also a cosmological natural selection which makes our relationship to the cosmos and to each other a very basic ingredient in our understanding of nature. To quote a professor of Physics, "human society, like space and time, is not absolute or eternal; it is determined by the relationships among the individuals who are a part of it. If we seek to understand how a complex and beautiful system can come into existence through self organisation, we are not only talking about biology or cosmology we are also talking about our evolving understanding of ourselves". While missing the essential point of purposefulness, he atleast, emphasizes the all important fact of inter-dependency of various disciplines. From physics to an understanding of ourselves! The neuroscientists must acknowledge that all scientific disciplines are closely interrelated and dependent; and that physics, mathematics and the arts have completely outstripped us neurobiologists in the intellectual surge of the last few decades. To the neuron or the atom it matters little whether its pursuer is a biochemist, physicist, poet or philosopher. Therefore, we must consider neurosciences not as a thing apart to be studied, admired or ignored. It is a vital part of our culture and its separation from what is fondly called `the humanities' is a preposterous practical joke on all thinking men. (apologies to W.S.Beck). In other words, we neuroscientists failed to see the woods because of the trees, by persisting in artificially separating the brain and the mind. This practice is one of the intellectual absurdities whilch calls for introspective analysis of attitudes of the past and stout resolve for the future, so that history will not repeat itself. If we as a society have to take our rightful place as leaders in the scientific community, we have to lay aside once and for all as an aberration of the past, the practice of mindless neurology and brainless psychiatry. We barbers, on the other hand, continued to ply our merry trade without impediments, undisturbed by any metaphysical dichotomies, perfecting our navigation through the brain, eagerly becoming robots in human guise. All science and arts have a commonalilty of endeavour, a closeness in striving for truth and any artificial separation is blatantly anti intellectual. Let me illustrate this with parallelism. I quote, "people like us, who believe in physics know that the distinction between past, present and future is only a stubbornly persistent illusion". This was written by Albert Einstein a short time before his death. Compare this to the following poem written by famous poet T.S. Elliot. Time present and time past, Are both perhaps present in time future, And time future contained in time past. If all time unredeemable, What might have been is an abstraction, Remaining a perpetual possibility BR> What an amazing similarity of thought between a scientist and a poet. As one group of scientists are celebrating the landing of voyager on Mars or finding ice capped areas on the moon, another equally devoted group has been unraveling the mysteries of inner space. The molecular biologists and geneticists are in the lead. The whole scientific community was thrilled when `Dolly' appeared on the scene last year followed by `Fredrlich' in USA this year, `Cumulina' and fifty genetically identical mice in Hawaii. A group of enthusiastic, optimistic, researchers connected to the human genome project are striving to map the genome and identify all of its estimated 75-100,000 genes by the year 2005. 25-30% of all genetic diseases are diseases of the brain. The genes responsible for over 40 disorders of the brain including Alzheimers, Huntingtons disease, amyotrophic lateral sclerosis, and ataxia telangectasia, to mention a few, have been identified. Interestingly, carriers of the last gene i.e. about 1% of the population may be at an increased risk for cancer. What is still more fascinating is that Hedgehog genes hold out promise of organ regeneration. Unfortunately, the genes required in regenerating damaged organs are very difficult to catch in adults. Given the implications of being able to repair, say, a damaged heart, it is small wonder that developmental biology is attracting a growing number of researchers and biotechnology companies are not far behind ! One firm has caught and patented three of these elusive genes, dubbbed hedgehogs, because of their spiky appearance under the microscope. The Genes are named Sonic, Indian and Desert. Sonic creates brain and nerve cells. It has already been used to create dopaminergic neurons! Human trials on Parkinson's disease patients, I understand will be started soon. Before we leave the wonders of molecular biology, we should, perhaps note that in a few laboratories on either side of the Atlantic, headless tadpoles and headless mice have been created. I now quote a very responsible scientist in this field, "It would almost certainly be possible to produce a human body without a forebrain. These human bodies without semblance of consciousness would not be considered persons, and thus it would be perfectly legal to keep them alive as a future source of organs". It won't be long before scientific bodies like ours will serve to make clear our ethical, social and moral views in regard to situations like these. One will have to be careful when making decisions, because we should not throw out the baby with the bath water, nor, bottle the bath water and sell it as `Holy water'. As a background for a neuroscientist's perspective of time scales involved in the evolution of consciousness and brain mind relationship, it would be useful to study Carl Sagan's cosmological calendar. He compresses the 15 billion year life time of our universe to a single year. The `Big Bang' was on January 1; Earth condenses out of interstellar matter in early September; Dinosaurs emerge on December 24 Christmas eve, flowers on December 28 and men and women at 10.30 p.m. on December 31. All of recorded human history occupies the last 10 seconds of the year. Despite the insignificance of the instant we have occupied in cosmic time, it is incredibly exciting to note that man is the only intelligent possibility evolved who could not only ask `How', but also the still more important question `Why'. In the last 100 years, which according to the cosmic calendar would amount to 1/100th of a second, there has been a tremendous ferment in our understanding of the `inner world', especially as it relates to the nervous system and more particularly the brain. Historically, this understanding is based on the concept of `localization' as proposed by Jean Fernel in the 16th century, that all diseases are localized to solid organs, in contrast to Gallenic Humours. Once this concept of function and dysfunction was established and localised to anatomic parts; and Hitzig and Fritsch in 1870 localized motor function in the brain; the brain was no longer an organ in search of a function. Listen to William Shakespere, late 16th century, as he makes Portia, in The Merchant of Venice, say, "Where does the quality of mercy reside, in the heart, or in the mind?" The idea that the heart is the seat of the mind probably originated in India and was accepted by Aristotle and became a part of Greek thinking. Finally, as late as Sir Charles Sherrington, writing his book `Man on his nature' says, "of Man we know even more confidently that his mind is co-related with his brain. Evolution in this pure natural-selection-Darwinian mould seems to be over for all intents and purposes, whereas mental processes are continuously evolving. Macro-evolution is over, but micro- evolution continues in the brain on an individual basis. It is in respect to the brain's micro-evolution that I would like to introduce the concept of `Neural Darwinism' or the brain as a selectional system as propounded by Gerald Edelman. Edelman was awarded the noble prize in physiology and medicine in 1972 and is currently Director of the Neuroscience Institute at the Scripps Research Institute. Classical Darwinism operates upon the final product, whereas Neural Darwinism, is continuously and ceaselessly evolving as long the individual is conscious and having a memory. The selectional system of the brain works for and by the individual's initiative and lifts the concept of evolution onto another plane of purposiveness other than procreation and maintenance of the species and also provides, the physical basis of the mind. This thesis is based on two observations; one, the individual variation among people of the same species is so great, inspite of a commonality in outward configuration of the brain, that the idea of the brain being wired like a machine, though an attractive proposition, is totally untenable. Just consider for a moment the number and diversity of neuro-transmitters, receptors, channels, signalling system; such diversity would be totally redundant and totally against any kind of mechanistic law, if the brain were following a pre-programmed pattern. Whereas if there is to be a selectional system of functioning, then unlimited combinations would be necessary - and that is indeed what is available. Secondly, the external stlimuli, i.e., the environment both external and internal, is so totally varied and unpredictable from hour to hour and day to day, that to survive, the organism from time of its inception to its death is called upon to `create criteria for categorisation of these stimuli'. Even if the brain was a computational masterpiece the only answer it could give to such varied inputs would be, `not programmed to handle chaos'. Therefore, an alternative to instructionism or pre-programmed directionalism is required and is contained in `the theory of neuronal group selection' (TNGS), which postulates a continuing generation of diversity with selection occuring at various levels. The three mechanisms identified in a TNGS are i) Developmental, ii) Eperiential and iii) Re-entrant signallling. i) Developmental variation and selection : The structural diversity of the nervous system, arises during development. The process of cell division, adhesion, migration, death, synapse formation and loss, results in an unavoidable generation of diversity of ramifications, despite the fact that grossly, any particular area in human brain is similar from individual to individual. ii) Experiential selections : Here functioning neuronal groups continue to be selected by ongoing synaptic connections, some being amplified, others weakening, driven by behaviour and experience. iii) Re-entrant signalling : Serves the purpose of re-orienting and correlating the external spatio-temporal properties of inputs/signals/stimuli to neuronal groups in the primary and associated regions of the brain, as maps. These mapped regions exchange and correlate signals by re-entering, i.e. by ongoing parallel signalling between separate neuronal groups. It may take place via reciprocal connections between and within maps, eg, cortico-cortical, cortico-thalamo-cortical or more complex like cortico-basal ganglia-cerebellum etc. In the maps themselves space and time are correlated. Gradually, the number of inter-related maps may increase and take precedence over other signals. The construction of perceptual categorizations and maps, the capacity for generalization made possible by reentrant signalling, is the beginning of psychic development, and far precedes the development of consciousness or mind, or of attention or concept formation, yet it is a pre-requisite for all of these; it is the beginning of an enormous upward path and it can achieve remarkable power even in relatively primitive animals like birds- Oliver Sacks. The next element in the selectional system is a value system built into it. This value system is a learnt experience acquired during evolution because they contribute to appropriate behaviour and fitness of the individual in society. The cholinergic and aminergic neuro modulatory systems, seem particularly well suited to serve as value systems. According to the TNGS, value dependent learning is essential in the selection of adaptive behaviour in a somatic time frame. Edelman distinguishes two degrees of consciousness `primary' and `higher order consciousness'. Primary consciousness is defined as the state of being mentally aware of things in the world, of having mental images in the present only. The essential achievement of consciousness, is to bring together the many categorizations involved in perception, into a SCENE". The scene is not an image, not a picture, but a correlation between different kind of categorizations which makes `sense' to that individual only. The ability to create `SCENES' in the mind depends on neuronal circuits which allow continual re-entrant signalling between areas of memory of value categories and the ongoing global mappings that categorize perception as they actually take place. At this transcedental moment in evolution, memory became the substrate and servant of consciousness. Memory in living organisms unlike computers, takes through activity and continual recategorisation. Only in man and to some extent in apes does a `higher order consciousness' emerge. Higher order consciousness arises from primary consciousness; it supplements it, it does not replace it. It is dependent on the evolutionary development of language and all that it implies culturally, so that finally self-consciousness is achieved; a consciousness of being a self in the world with human experience and imagination to draw on. The acquisition of a new memory leads to a conceptual explosion, the result being consciousness of being conscious. Or as somebody said "I am because I am. That is the function of the mind. Palaentological evidence points to higher order consciousness developing in a very short space of time, perhaps hundreds or thousands of years, whereas, classical Darwinian evolution would have taken millions of years. Proof for this theory is available upto a point. High performance super computers linked together and programmed to function as if they were a selectional system, has shown that value systems with an infinite number of choices functioned just like a child learning from experience. Incredibly clever, these gadgets are named Darwin III and Nomad. The tasks they perform requires a good amount of discrimination. Unfortunately, I do not know enough of this science to interpret the findings. There are, however, a number of instances encountered by neurologists or neurosurgeons which cannot be explained by classical neurology. I quote Dr. Sack's own experience. "After sustaining a nerve injury to one leg and when for a period of two weeks it lay immobile and senseless, I found it alien, not mine, not me, not real. I was astonished when this happened, my neurological knowledge could not assist me, the situation was clearly neurological, but classical neurology has nothing to say about the relation of sensation to knowledge and to self, or about how normally the body is owned; and how, if the flow of neural information is impeded, it may be lost to consciousness and disowned! I remember most vividly the case of a teenager, who following a fall down the stairs, became completely paraplegic. She used to insist that she did not have any legs, except perhaps some stump-like thing at the thighs, gradually she noticed that the stumps were growing in size, this coincided with some sensory recovery though the motor function was still negligible. Now it is clear to me, mapping of the body image in this girl was not fixed, but quite plastic and depended among other things, on sensory input. Stranger still are some of the cases of anosognosia or autopagnosia where the patients are so totally unaware of part or parts of their body that they may even insist that it definitely belongs to somebody else. We can now explain it by Edelman's theory as a total break-down of high level re-entrant signalling and mapping in one hemisphere allowing a radical reorganization of consciousness. You may remember the case history of Dr. P as recorded in the book etitled "The man who mistook his wife for a hat." Dr. P while not consciously able to indentify any body could often guess the identity correctly. You may have come across cases of `blind sight'. People with total cortical blindness consequent to massive bilateral damage to visual areas, while asserting that they cannot see a thing are still able to walk across a room without bumping into any furniture. In all these cases you find that perceptual categorization has been preserved but divorced from consciousness of the here and now. In such cases it appears to be only the final process in which the re-entrant loop combining memory current perceptual categorization that breaks down. Another sophisticated mutation which occurred in our brains is the capability of re-entrant signalling to be guided by a value system of a higher order. This becomes the basic requirement of a mind that responds to historic `cues' and which can have infinite choices. The choices made may be required to "veto" basic human drives and lower order value system. For this drive of re-entrant signalling to occur one has to have connections in the order of what human brains have. A total unpredictability is an absolute prerequisite in freedom of choice. This is indeed what we have. Now one need not wonder why the human brain should have 10[13] neurons and 10[16] connections. The reason seems apparent, the infinity of possible connections is not for primary level consciousness or even a higher order consciousness, it is for freedom of choice. It was this freedom of choice that produced Adolph Hitler and Guatam Buddha. They were endowed with the same hardware but given the freedom of choice, therefore a `sinner' or `saint' is made by freedom of choice, not by a pre-determined wiring system. At a given time in our past a highest order value system was put in place where the mind could categorize and differentiate good from evil. When did it occur? Perhaps the first time when humans felt the need to worship powers greater than them, be they Sun, Moon or Spiritual beings, the capacity to categorize the need to worship, not necessarily by turning to the environment, but inwards into their minds may have been the end point of all these millions of years of evolution. What a sophisticated way for the evolutionary process to culminate! This capability was recognised and so clearly put into words by William Blake. To see the world in a grain of sand And heaven in a wild flower To hold eternity in the palm of your hand and infinity in an hour Or as the great Urdu poet Mirza Ghalib put it. Na tha kuch to khuda tha, Kuch Na tha to khuda hota, Duboya mujhko honi ne, na hota main to kya hota? (God existed when nothing else did God would have existed if nothing else did all my sufferings arise from my human existence had I not existed then what would I have been?) So this is the last perspective I leave with you, An urdu poet giving a lucid exposition of Vedantic wisdom quoted by a Christian in a neurology conference, to honour an outstanding neuroscientist. We hope for a second enlightenment soon. If such a second coming occurs, its major scientific underpinning will be neuroscience, not physics. This brings me to the end of my lecture and the idea briefly mentioned at the beginning that we should be more than excited about neuroscience being the gateway to understanding the mind and the soul. Neuroscience may not solve the ultimate mystery of Nature, because, we ourselves, are part of the mystery we are trying to solve.
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