Caltech News 28(3), 11 Ered, Ro Regenerate Cormecrions to Their Roger Sperry with His Work." Sperry Was Also an Avid Original Targets

Home , Michael Gazzaniga, Roger Wolcott Sperry, Thought, Torsten Wiesel

specificity of neural reconnection—that 1981 interview. "He soilpted phe• is, by the ability of neurons, when sev• nomenally. The Sperrys' home is filled Caltech News 28(3), 11 ered, ro regenerate cormecrions to their Roger Sperry with his work." Sperry was also an avid original targets. This work led in the paleontologist, with an extensive col• early 19(50s to a new theory explaining lection of prehistoric moUusks. 1913-1994 how neurons grow, assemble, and orga• "He was one of the premier experi• nize themselves in the brain by means mental neurobiologists of his time," Roger W. Spetiy, 1981 Nobel laure• of amazingly intricate, genetically said Norman Davidson, the Norman ate in physiology or medicine and the determined chemical codes. Chandler Professor of Chemical Biol• Institute's Board of Trustees Professor Sperry is best known for his "left- ogy, Emeritus, and executive oflScer for of Psychobiology, Emeritus, <;lied on brain/right-btain" research, work that biology at Caltech. "Those of us who April 17,1994, of a heart attack and of has had an incalculable impact on fields have kpown him since those early years complications associated with a neuro• ranging fimm neurophysiology to psy• will always remember the courage and muscular degenerative disease from chology to education. Working in the tenacity with which he continued to which he had suffered for many years. 1950s and early 1960s with patients carry on his work in later years in spite He was 80. who had had their corpus callosum— of a debilitating degenerative disease. A native of Hartford, Connecticut, the bundle offibers connecting the left It was an inspiration ro all who knew Sperry earned his bachelor's degree in and right cerebral hemispheres—surgi• him." English literature from Oberlin College cally cut in an effort to control epilep• The late Caltech professor is sur• in 1935, then focused his attention on tic seizures, he demonstrated how the vived by his wife of 45 years. Norma psychology, earning his master's in that two hemispheres function, indepen• Deupree Sperry, of Pasadena; his dently and in concett. The most strik• brother, Russell L Sperry, of Bend, ing of his discoveries and the one with Oregon; his son, Glenn Tad Sperry, of which his name continues to be most Philadelphia; his daughrer, Janeth widely associated is the finding that Hope Sperry, of Cleveland; and two under certain conditions, each hemi• grandchildren. sphere has the seeming capacity to The fiunily asks that donations in behave like a separate consciousness, Sperry's memory be made to rhe Mus• with the left side of the brain generally cular Dystrophy Association, or ro the more specialized for verbal and analyti• Children's Lung Fund, Qeveland, cal* thinking, and the right side for Ohio. spatial and visual thought. In latet years, Sperry's own ever- active brain turned increasingly to philosophy, particularly to issues asso• ciated with the mind—brain question— that is, the relarionship between the observable physiological structure of the brain and the quality of subjective, conscious thought that characterizes the mind. In pondering these ques• tions, Sperry broke with the behaviorist school, which then dominated psychol• ogy and the behavioral sciences, and advocated a new approach that placed far greater emphasis on the role of men• tal states and experiences in influencing field in 1937, also 6om Oberlin. For the physiological functioning of the his doctorate, he studied zoology, earn• brain. Hefirst se t out these ideas in ing his degree from the University of 1965 in what the January 1994 issue of Chicago in 1941. HumaMnd Advajicmg, which was dedi• Sperry's academic career was as cated to Sperry, described as "a remark• diverse as his educational background. able series of philosophical After graduaring from Chicago, he held papers"; and he continued to write and fellowships at Harvard from 1941 to publish provocative and influential 1946, where he worked in the Yerkes writings on the nature of consciousness Laboratories of Primate Biology, and he up until the time of his death. It was performed military service from 1942 for this work, more than for his studies to 1945 by taking part in the federal of vision, neuronal growth, or split- government's Medical Research Project brain parients, that Sperry wished most on Nerve Injuries. After the war he to be remembered. taught as an assistant professor in the For his work on hemispheric special• University of Chicago's department of ization, Sperry was awarded the 1981 anatomy until 1952. During 1952 and Nobel Prize in physiology or medicine, 1953, he served as associate professor of along with David H. Hubel and psychology at the same institution Torsten N. Wiesel. He also received while simultaneously serving as the the National Medal of Science in 1989 section chief for neurological diseases from President Bush, the Wolf Prize in and blindness at the National Institutes Medicine and the Albert Lasker Medi• of Health. In 1954 he became the cal Research Award in 1979, and the Hixon Professor of Psychobiology at California Scientist of the Year Award Caltech, where he remained for the in 1972, among many other honors. next forty years. He retired from teach• In addition to his talents as a re• ing as professor emeritus In 1984. searcher, Sperry was "the most artistic Among Sperry's many accomplish- person I've ever known," said long-time menrs is research he carried out in the laboratory assistant Lois MacBird in a early 1950s showing the nervous sys• tem to be characterized by a very high Chicago nH6unc

April 23, 1994 Saturday, NORTH SPORTS FINAL EDITION

ROGER SPERRY, 80 STUDIED FUNCTIONS OF HUMAN BRAIN

By Kenan Heise, Tribune Staff Writer. Through study of animals and human patients who had had the connections be• Roger W. Sperry, 80, a Nobel laureate tween the right and left sides of their and professor emeritus of psychobiology at brains severed, he demonstrated the the California Institute of Tech• functions of the two hemispheres of the nology, was honored for his research in brain. His research and observations right-side, left-side brain functions and helped establish concepts now regularly learning. He was a former professor at the taught in the areas of art, education and University of Chicago, where he had re• philosophy. ceived his doctorate in zoology. Other work he did explained how neurons A resident of Pasadena, Calif., he died use chemical codes to grow, assemble and Sunday in Huntington ^ylemorial Hospital organize themselves following hereditary in Pasadena. patterns.

Professor Sperry, a native of Hartford, Professor Sperry shared the 1981 Conn., received his bachelor's and mas• Nobel Prize in physiology or medicine ter's degrees from Oberlin College. He with David Hubel and Torsten Wiesel. He earned his doctorate at the U. of C. in also received the National Medal of Sci• 1941. During World War II, his military ence, the Wolf Prize in Medicine and the duty involved medical research on nen/e Albert Lasker Medical Research Award. injuries. Survivors include his wife, Norma; a He taught after the war, first as an as• son, Glenn; a daughter, Janeth; a brother; sistant professor and then an associate and two grandchildren. professor at the U. of C. He then was sec• tion chief for neurological diseases and Services are pending. blindness at the National Institute of Health and was a professor at Cal Tech GRAPHIC: PHOTO; PHOTO: Roger W. Sperry from 1954 to 1984. in 1979. Date: 4/19/94 IpZ--; Page: Al ^^"d^" Pasadena Star-News Jump: A5 "~—-——

Brain research

pioneer Sperry

dead at 80 Nobel winner taught at Caltech

By Roberto Ceniceros sidered nearly useless. STAFF WBTTER Sperry's results substantiated that analytic process and higher PASADENA — Retired Caltech verbal skills tend to be located in professor Roger Wolcott Sperry. a the left hemisphere, while the 1381 Nobel Prize winner for dis• right side is more holistic arid coveries- iiliowing that the two copes better with spatial relation• hemispheres of the brain function ships. independently, has died of a heart Sperry also received the Na• attack. tional Medal of Science in 1989 Sperry, a Pasadena resident, from then-President George Bush. was 80 when he died Sunday at In the 1940s, Sperry researched Huntington- Memorial Hospital in the functions of brain cells and PasadeiEi Memorial services were vision. In the 196(3s he infroduced pending. groundwork for a theory explain• Sperry's work ethic drove him ing how neurons grow, assemble to research and write until his and organize themselves in the hospitalization April 11," friends brain by- means of chemical codes . and relatives said yesterday. For confroUed by heredity. the last 25 years, he suEfered from Before his death, Sperry had a degenerative nerve disease. been studying the role of con• sciousness and its importance in "He was so single-minded that preserving values, said Norma if he was working, that was all he Deupree Sperry, his wife of 45 thou^t about," said his assistant, years. Mary JpfFriPs "I would say, 'See you tomorrow,' and he would He was concerned about the very meticulously put his middle earth's condition and population finger over his index finger. I growth His wife said he beUeved guess he was saying, 'With any people should set values that pre• luck.' " serve the quahty of life. , Sperry won the Nobel Prize in Sperry continued working at medicine-physiology for his pio• Caltech as a professor emeritus of neering research involving "spht- psychobiology after his ofBcial re• brain" patients whose left and tirement in 1984. right brain hemispheres were siir- About six months ago, he began gicaHy cut He showed how the using a Walker Jeffiles said Sperry two brain hemispheres function held a pencil with great difficulty independently and together. but pressed on with his work. His discovery revolutionized The illness forced Sperry to give the way doctors, psychologists up the Baja California fishing vaca• and scientists understood the tions that he had purchased a brain. Before Sperry's work, the camper to enjoy. He was in Baja right hemisphere had been con• when the 1981 Nobel Prize was Pasadena Star News cont.

awarded and learned about it over the radio. "From the tune we got the camper, in about 1973, we were down there several times a year until two years ago," Npnna Deu• pree Sperry said "We were unable to go after that It was too difBcult for him to get around." Sperry's list of accomplishments • extended beyond science. Friends knew him for his square dancir^, sculpture and fos• sil collection. His wife said he once held the Connecticut state high-school re• cord in the javelin throw. He was captain of the basketball team dur• ROGER W. SPERRY ing his days at Oberlin College in Ohio. I Birthplace: Hartford, Conn., He earned his doctorate degree Aug. 20; 1913 in zoology in 1941 from the Uni• • Education: Bachelor's degree versity of Chicago. in English literature, Oberlin Col• In addition to his widow, Sperry lege, 1935; master's degree in is survived by his son, Glenn Tad psychology, Oberlin College, Sperry of Philadelphia; daughter, 1937; tioctorate in zoology, Uni• Janeth Hope Sperry of Cleveland; versity |f Chicago, 1941 brother, Russell L. Sperry, of Bend, • M^pr awards Nobel Prize in _ :• Ore.; and two grandchildren. medicine-physiology, 1981; fJa- - tionai "-Medal of Science, 1989; >• Wolf Prize in Medicme, Albert".;, Lasker Medical Research Award, .;• -. both in 1979; California Scientist of the Year Award, 1972 . . -Z • Occupation: Among other.po- C sitions, joined Caltech in 1954 as -i:: Hixon Professor of Psychobioloa'- Retired in 1984 • " " : I Family: Mam'ed Nonna Deu^' pree on Dec. 28, 1949; brother Russell Sperry of Bend, Ore.; son • Glenn Tad Sperry of Philadelphia; • • daughter Janeth Hope Sperry of- : Cleveland; two grandchildren . obi-tuary

were extended to monkeys, which RogerW. Sperry (1913-1994)als o failed to recede the aberrant neuromuscular connections; but, Colwyn oger Wolcott Sperry, bom in eminent neuro-embryologist Paul unlike rats, they quickly learned to Trevarthen RHartford, Connecticut on 20 A. Weiss at the University of suppress maladaptive movements Dept of Psychology, August 1913, died 17 April 1994 Chicago^. Analysis of the disordered and to substitute effective acts The University of in Pasadena. He was Emeritus movement patterns following sur• performed by intact parts of the Edinburgh, Professor of Psychobiology at the gical transposition of the insertions motor apparatus. Evarts^ explains Edinburgh, UK. California Institute of Technology of extensor and flexor muscles or the significance of this work on (Caltech), where he had been excliange of motor nerves showed animals of differing evolutionary Hixon Professor from 1954 to 1984. that the rat's motor system was grade for the development of Sperry received the 1981 Nobel 'hard-wired' and resistant to re• Sperry's ideas of the role of the Prize for Physiology and Medicine education. Experiments on the cerebral neocortex in voluntary for research on the functions of the effects of surgical rearrangements motor co-ordination, perceptual cerebral hemispheres, sharing the of peripheral nerves continued control of movement and con• honour with Torsten Wiesel and firom 1941 to 1946 with Kari Lashley sciousness (Sperry, 1952). The David Hubel, whose research on at Harvard and at the Yerkes work led Sperry, in 1945, to advise visual mechanisms was inspired by Laboratories of Primate Biology neurosurgeons that the human Sperry's eariy studies of visual in Orange Paric, Florida (Sperry, brain could not readily adapt to embryology and the functional 1945). Sperry confirmed exper• rearrangements of peripheral motor anatomy of visual cortex. iments by Leon Stone and Robert nerves. From 1942 to 1945, Sperry Matthey showing that a newt's eye performed military service on Sperry devoted his scientific life dissected fi-om the head, and re• the Medical Research Project on to exploration of the innate powers placed so that the optic nerve could Nerve Injuries. of the mind, and he became the regrow, would establish normal leading nativist and most articulate Returning to Chicago in 1946 as vision. He added the important mentalist in beiiavioural and brain Assistant Professor of Anatomy, experiment of a rearrangement of science. He believed totally in the Sperry continued nerve-growth the eye in the body, changing the scientific method but fearlessly ex-, experiments on other sensory and relation of the retinal array with tended his experimental under• motor systems and began work respect to the motor system. standing of the neural machinery of with small tropical fish at the When the eye was rotated 180° intentions and awareness into a Lemer Marine Laboratory at before regeneration of the optic philosophical theory of values and a Bindni, British West Indies, show• nerve, the recovered vision was scientific ethic [Sperry, 1952,1983, ing that nerves from eye to brain also rotated. The animal never 1988 (Details of references are and from brain to fin muscles regained the ability to move in the given in Box 1)]. He pioneered obeyed the law of innate specifi• correct direction to seize food. research into experimental embry• cation of regenerated connections-^. This showed that the nerves were ology of brain circuits^ perception In these studies he was assisted by guided to re-establish the same and learning in the mamrnalian Norma Deupree, who became his retina-brain connections as before cerebral cortex, and specializations wife in 1949. hi 1950 he reported the operation, and, moreover, it of consciousness in the human that fish and amphibians with sur• ruled out learning as the mech• cerebral hemispheres. He was first gically inverted vision consistently anism for recovery of function recognized as an extremely skilled displayed compulsive drding when• (Sperry, 1963). and imaginative researcher in the ever they moved. Sperry showed early 1940s when he published the At Yerkes, experiments on the that the midbrain was the site of a findkigs of his PhD thesis with the effects of rearranging motor nerves predictive adjustment of vision in• side the brain, triggered by the motor impulse, and anticipating the Box 1. Key publications of R. W. Sperry sensory displacement caused by movement Instead of stabilizing The problem of central nervous reorganization after nerve regeneration and muscle the perceived world, the input transposition. (1945) Quart. Rev. Biol. 20, 311-369 Neural basis of the spontaneous optokinetic response produced by visual inversion. (1950) from the inversed eye had the J. Comp. Physiol. Psychol. 43, 482-489 reverse effect generating an il• Neurology and the mind-brain problem. (1952) Am. Sd. 40, 291-312 lusory drift of surroundings in the Chemoaffinity in the orderly grovv^ of nerve fiber patterns and connections. (1963) Proc. same direction as the movement^. Natl Acad. Sd. USA 50, 703-710 Sperry postulated a 'corollary dis• Split-brain approach to learning problems. (1967) in G. C. Quarton, T. Melnechuk and F. O. charge from efference' or 'central Schmitt (eds), The Neurosciences: A Study Program, pp. 714-722, Rockefeller University kinetic factor' that explained per• Press ception of self-movement and con• Some effects of disconnecting the cerebral hemispheres (Nobel Lecture). (1982) Sc/ence 217, stancy of perceived surroundings 1223-1226 during movement (Sperry, 1950). Science and Moral Priority (1993), Columbia University Press The same perceptual-constancy Psychology's mentalist paradigm and the religion/science tension. (1988) Am. Psychol. 43, 607-613 mechanism was discovered simul• The impact and promise of the cognitive revolution. (1993) Am. Psychol. 48, 878-885 taneously by Erik von Hoist and Horst Mttelstaedt and named by

402 TINS, Vol. 17, No. 10, 199^- them 'the reafference principle' At Caltech, Myers and a grow• using an 'efference-copy' signal. ing group of Sperr5''s post-graduate At Chicago, Sperr}' experimented students and \'isiting scientists de• •R-ith cats to test theories of veloped the split-brain experiments Wolfgang Kohler and Lashley that with cats, and extended these form recognition is mediated by experiments to monkeys, enabling electrical or magnetic 'field' effects a classical series of studies of the in grey matter, or interference mechanisms of eye-hand co• patterns generated by waves of ordination (Sperry, 1967). The activity in random cortical fibre division of visual learning was con• feltworks. With Nanc\ Miner and firmed and extended to touch, and Ronald Myers he then tested the the role in visual awareness of the %'isual discrimination to the limit intention to respond with one or and found that the animals' acuity other hand was explored. The and form recognition were not monkey experiments confirmed affected. They concluded that per• that commissurotomy had truly ception depends on information divided consciousness in two. passing vertically into and out of Then, in 1960, Joseph Bogen, the cortex by axons looping below a Los Angeles neurosurgeon, the grey matter. The behavioural- proposed that the split-brain ex• test apparatus later served to periments justified a re-examination study learning in cats and monkeys of commissurotomy as a treatment with split-brains. The theories that for epilepsy. Split-brain monkeys Sperry discredited with these ex• retained intelligence and co-ordi• periments resemble current ideas nation, and it was thought that of emergent integrations in dy• disconnection of the cerebral cor• namic neural assemblies, wliich tices might reduce seizures, and also take insufficient accotmt of prevent their propagation. motivation (Sperrj^ 1952). In 1962, a paratrooper with pro• At Lashley's laboratory, Sperry gressively worsening seizures was shared discussions of the functions operated on by Bogen and Philip of the corpus callosum, the func• VogeL Psychological tests per• tions of which were a mysterj'. formed by Michael Gazzaniga, concluded that consciousness and Ronald Myers undertook PhD re• under the direction of Sperry and its communication should be viewed search with Sperrj' on this Bogen, determined the effects of as a causal and explanatory prin• problem He sectioned the optic commissurotomy on perception, ciple, not a metaphysical epiphen- chiasma and corpus callosum of speech and motor control The omenon In 1965, Sperry published cats, and then proceeded to show startling findings of divided aware• the first of a series of ptiilosophical that visual learning was divided in ness and the lateralization of the papers. Under the titie Mind, two by the surgerj', and that- the capadt}' of speech to the left Brain and Humanist Values, he corpus callosum coiild transfer per• hemisphere, revealed by com• proposed a new mentalistic monist ceptual learning from one hemi• missurotomy, in Bogen's patient theory of mind that broke with sphere to the other. Thus, what were' then published. Sperrj''s behaviourist traditions in giving Sperry later called the 'split-brain' laboratory became the source of a subjective experience a prime con• was created (Sperry, 1967). stream of pathfinding papers on the trolling role in brain function and In 1952, Sperry was appointed functional differences in the two behaviour (Sperry, 1983, 1988). Section Chief at the National Insti• separated hemispheres of a small Sperry portrays consciousness as tute for Neurological Diseases and group of patients who had accepted a special example of a general Blindness. Then, in 1954, he ac• the operation, and benefited by principle, 'macrodeterminism', in- cepted the Hixon Chair at Caltech. reduction of epilepsy. The hitherto •Rtich the higher, more evolved In the Biology division, Sperry's littie-known functions of the so- forces throu^out nature exert laboratory became a centre for called 'minor' hemisphere were control over their lower compo• new research on nerve regener• fully explored and demonstrated to nents. Conversely, the highest of ation in amphibia and fish, adding be iai more elaborate than had human motives are constrained by evidence for nerve guidance by been believed. The now accepted inherent cerebral design. Sperry's 'intricate chemical codes under view of the human brain as com• renunciation of the traditional genetic control' (Sperry, 1963)''. prising laterally specialized and science-values dichotomy stimu• Sperry suggested that learning complementary realms of con• lated some hostile criticism inidaBy, would prove to be by modification, sciousness and cognition is sum• but after the mid-1970s, gained of the same process that creates marized in Sperry's Nobel Address ^\^de acceptance in what is now adaptive nerve circuits in the em• published in 1982. seen as a new era in value phil• osophy- Sperry had always ad• bryo. In 1955, he published a Sperry considered the role of vocated objective scientific enquiry prophetic paper on the nature of consciousness in daily experience as the brain's most reliable basis the conditioned response, empha• and education in his writings on for arriving at belief, and now sizing the role of transitory fadli- the mental life of commissurotomy argued that the same applies to tatory motor sets and 'perceptual patients. In line with comments he vahie judgements, which he held expectancy'. made as early as the 1950s, he were the true causes of human Award (1979) and The National dog Chadwick, stranded by a hurri• action and in need of scientific Medal of Science (1989). He was cane and out of touch with Caltech examination and methodical im• also elected to many national for days. Sperry was an indus• provement if hunoanity was to societies including the National trious artist and sdentific illus• avoid ecological, economic and Academy of Sciences of the United trator, filling his home with sculp• social catastrophies, the signs of States of America, and Foreign tures and ceramics, induding busts which have become increasingly Membership of the Royal Society of of his family, and life drawings. apparent to all thoughtful and the United Kingdom. Later, a pro• His students remember him as well-informed persons in recent gressive neuromotor impairment an inspiring teacher and perceptive decades. He sought both a new from primary lateral sclerosis critic with a predse, ironic sense ethics for science, and a new forced him to forego participation in of humour tempered by gentle scientific examination of the source ceremonies. kindness^. of ethics in the workings of con• Sperry was a tadtum, socially sciousness (Sperry, 1993). Sperry's reticent person with a rich and Selected references efforts to explain the emergence of creative private life. Something of 1 hunt, R.K. and Cowan, W.M. (1990) dynamic order and purpose in the a maverick, he shunned formalities in Brain Circuits and Functions of the psychological field and of motives and preferred to vacation in Mind (Trevarthen, C, ed.), pp. 19-74, Cambridge University Press in consciousness lead to the ques• remote, wild places. With the 2 Hamburger, V. (1979) Neurosd. tion: how do human populations company and help of his wife Newsletter 5-6 guide their increasingly powerful Norma and children Tad and Jan, 3 Evarts, E. V. (1990) in Brain Circuits dominion over one another and he discovered giant fossil dinosaur and Functions of the Mind (Trevarthen, over every other element of natural bones and record-breaking am• C, ed.), pp. xiii-xxvi, Cambridge University Press order on earth? Writing on this monites in the deserts and canyons 4 Levi-Montalcini, R. (1990) in Brain global problem actively occupied of the southwestern states of the Circuits and Functions of the Mind him at the time of his death. USA, and caught big fish off the (Trevarthen, C, ed.), pp. 3-18, Roger Sperry received many shores of Baja California. When the Cambridge University Press high honours in addition to the announcement of his Nobel Prize 5 Trevarthen, C, ed. (1990) in Brain Orcuits and Functions of the Mind, Nobel Rrize, including The Albert came, he and Norma were camping pp. xxvii-xxxvii, Cambridge Univer• Lasker Basic Medical Research alone on a beach in Baja with their sity Press persp-ect:2V3s on d^saa-sa Synuclein proteins and Alzheimer's disease

Anthony J. Brookes and David St Clair

AnthonyJ. Brookes In Alzheimer's disease, synuclein/NAC (non-amyloid^ component of defined in order to understand the molecular path• and David St Clair are Alzheimer's disease amyloid) proteins are found in presynaptic ology of AD. Therefore, the cloning of a cDNA for attheMRCHuman cholinergic nerve temiinals that degenerate early in Alzheimer's an unrecognized component of AD amyloid Genetics Unit, disease, and they are also found dosely linked to ^-amyloid fibrils In deposits was noted with great interest^. This cDNA Western General senile plaques. Synudein/NACproteins provide a potential molecular was given the name NAG; its precursor was called Hospital, Crewe link between the degeneration of cholinergic nerve temiinals, and the NACP. Immunochemical analyses of AD brains, with Road, Edinburgh, formation of plaques, and might have a primary role in their antibodies raised against two separate fragments of UKEH42XU. development NAG peptide, showed staining of amyloid on diffuse, primitive and mature plaques, as well as on Our understanding of the molecular aetiology of cerebral blood vessels. Electron microscopy reveals Alzheimer's disease (AD) is currently incomplete. localization of NAG peptide on amyloid fibrils Evidence suggests that both genetic and environ• spedfically. In this respect, NAG peptide differs from mental factors can contribute to the development of most other components of plaques where co- this disorder''. With respect to the genetic basis of association with amyloid is demonstrable using light AD, significant recent advances include: microscopy only; this suggests that NAG peptide and amyloid are especially tightiy linked. By search• (1) the demonstration that the gene for the ing the database with the gene for NAGP, we amyloid precursor protein (APP - the precursor of p observed a highly significant match to rat 'synudein' amyloid, the primary component of the amyloid sequences^. When the 423-nudeotide coding 'plaques' deposited in AD brains) can be the site of domain of the human NAGP gene was aligned with causative mutation, albeit in a minority of cases^; rat synuclein, the overall identity was 90% with 32 (2) the determination that a gene of major in• of the 42 differences being in third codon positions. fluence for familial AD (FAD) lies on chromosome 14 The proteins translated from these sequences were (Ref. 3); 95% identical, indicating that these are equivalent (3) the discovery that possessing the £4 isoform of genes within different species. By mapping the gene apolipoprotein E predisposes at least to the late for synudein/NAG to chromosome 4 using mono- onset form of AD (Ref. 4). chromosome hybrids, it has been shown that this- Although important, these are probably only the gene is not the FAD-predisposing locus on chromo• first of many components that will need to be some 14 (A.J.B. and D.StG., unpublished obser-

what it hears. It could even be shown that . RogerW. Sperry (1913-1994) certain specific functions are better done by the right hemisphere than the left; for ROGER Sperry, co-winner of the 1981 lum plates or metal wires, which should example tiie left hand (hence the right Nobel Prize in Physiology or Medicine with have profoundly disturbed or short- hemisphere) could carry out some Torsten Wiesel and myself, died on 17 April circuited any such currents. In the second, visuospati'al tasks far better than tiie right in Pasadena, California, of a heart attack. he diced up the cortex with radially In one marvellous passage we find a For many years he had suffered from a arranged pieces of insulating mica. In description of the right hand coming neuromuscular degenerative disease, but- neither experiment was cortical function across and messing up what until then had until recently had continued to be active in seriously disturbed. This was before Ver• been a successful three-dimensional thinking and writing about the brain, con• non Mountcastie's discovery of cortical drawing of a cube by the left hand. In these sciousness and the mind. His contributions columns, but Sperry did know of the pre- papers we learned that one person could to neurobiology were titania. have, literally at one and the same time, two consciousnesses. I first came across Sperry in the fail of 1953, when I heard him speak at an Many of these ideas became dis• international physiological congress torted when they percolated down to in Montreal. I had just begun my the public, and one could easily get training in clinical neurology, and had the impression that the right hemis• not yet done any research. Spertys phere was for" emotions and art, and talk came as a revelation. that the left was for' reasoning and It is hard today to recapture our other dry intellectual pursuits. The state of knowledge of the nervous original papers in Brain are the best system in the early 1950s, a time antidote to such simplifications. They when it was widely thought that the are highly readable and well within wiring of the brain came about largely the grasp of a high-school student. through experience, in his talk, Sperry in later life, Sperry became in• described the simple experiment of creasingly interested in theories of surgically interchanging the tendi• mind and consciousness, concentrat• nous insertions of flexor and extensor ing on the relationship between mind muscles, or the nerves that supplied and consciousness and ethical them, in a limb of a rat, to see whether values. Many of his fellow neuro• the nervous system would releam to biologists could not easily follow his use the muscles properly. The re- arguments, which seemed to come learning never took place. Even the closer to philosophy than to neurol• circuits responsible for spinal re• ogy. But one could sympathize with flexes such as limb withdrawal in his contenti'on that brain mechanisms response to a painful stimulus to the would never be understood solely on Speny: titanic contributions to neurobiology. foot remained quite unchanged. a basis of the chemistry and biophys• A similar simplicity and lucidity charac• dominance of radial cortical connections ics of single nerve cells. The revolution in terized all of Sperry's work on neural from the vyork of Santiago Ramon y Cajal these areas in the past generation has development during that era. One of his and Lorente de No, and realized that the made it abundantiy clear that without such best known developmental studies estab• inserts should leave these connections a basis brain mechanisms are totally out of lished that in a fish the fibres of a severed relatively intact. reach. Sperry's point was that more than optic nerve grew back precisely to their My next encounter with Roger Sperry chemistry and biophysics is required, ft former targets in the brain, even if at the was again indirect; in 1955 I found myself is like the relationship between chemistry time of severing the nerve the eye was in the army and posted to Walter Reed of bricks and mortar, and the finished rotated 180° in its socket. Here no adaptive Army Institute of Research, sharing a suite cathedral relearning or rewiring of the circuits re• of laboratory cubicles with Ronald Myers, Our week together in Stockholm, in sponsible for normal visual behaviour who had just got his PhD under Sperry at December 1981, with Torsten Wiesel, was seemed to occur, so thatthefish continued the University of Chicago. Myers's thesis' marvellous fun. Our family and his were to snap downwards at bait placed above it. topic involved behavioural studies of de- next-door neighbours at the Grand Hotel. Such experiments suggested that when ficrts resulting from severing the corpus In one lovely incident, just before the first individual nerve fibres in a growing nerve callosum in cats. Up to that time, no one banquet, a knock came at our door. It was trunk find their proper targets they do so had any idea of the function of this huge Roger Sperry's son, holding an untied by specific chemical cues that somehow bundle of nerve fibres, which connects the white bow tie in his hand. "Does anyone recognize complementary cues in the two hemispheres; together, Myers and have any idea what to do with this?", he targets. These ideas have still not been Sperry showed that it had a very specific asked. I, of course, had no idea, because I proven directiy, but they have had a pro• function in vision, and this was the begin• have too littie sense of style to use anything found influence on the entire experimental ning of the split-brain studies. but the already-tied kind. But our youngest field of neurodevelopment, today one of In the 1960s, Sperry, along with Joseph son, who plays the trumpet, had had to the most active branches of neurobiology.' Bogen, Michael Gazzaniga and others, ex• wear formal attire so often at concerts that In the 1950s the nervous system, and in tended this line of research to humans. The he had become an expert in the difficult particular the cerebral cortex, was sup• workappearedfirstintwo beautiful papers procedure. So Paul went next door and tied posed by some (who were taken seriously) in Brain, in 1965 and 1967. Almost over• all the Sperry family's bowties. to function not by nerve conduction and night a wealth of facts and concepts be• David Hubel synapses but by a pooriy spelled out came available. The left hemisphere was process of electrical fields or waves in a' known to be largely responsible for David Hubel is in the Department of Neuro• volume conductor. Two experiments speech, but the new observations showed biology, Harvard Medical School, 220 cleanly disposed of these ideas. In one, that the right hemisphere has language LongwoodAvenue, Boston, Massachusetts Sperry inserted into the cortex many tanta• capabilities too, comprehending much of 02115, USA.

186 NATURE - V0L369 - 19 MAY 1994 Q(? 4

OCHI giomi fa 6 scompar- ideale diventa non meno causa• so Roger Wolcott Speny, NEUROSCIENZE le di queUa di una molecola, di P professore emerito di psi- ima cellula o di un impulse ner• cobiologia al California Institu• voso... L'errore ormai secolare te of Technology di Pasadena, del. materialjsmo ' scientifico una delle figure piil significati• Addio g SperiY/ esploratore del due cervelli consiste precisamente neU'ave- ve fra gU studiosi del sistema re ignorato questa seconda for• nervoso di tutti i tempi. Nato a Scoperse la specializzazione degU emisferi cerebrali edebbe il Nobel ma di causazione*. Hartford nel Connecticut nel Il paradigma «macromenta- 1913, aveva ricevuto il Premio le» di Sperry sostiene dunque Nobel nel 1981 per i suoi fonda- gio sottendono tuttavia forme ti. separate sotto la stessa volta mente fino alia sua scompcusa. che tutte le different! e riccbe mentali studi suUa specializza- elaborate di ideazione e di ra- cranica. Si tratta di cuna nuova forma di quality dell'esperienza e tutte zione ftumonale degU emisferi gionamento, (juaHtativamente A Sperry va anche ricono• monismo in cui le entity men- le forze vitali e mentali del- del cerveUo umano. diverse, ma non inferiori a sciuto il merito di aver rivelato tali hanno un ruolo emergente I'individuo e deUa society, le• • •- • , ' 'tV•„':•; Sperry ha fomito un contri- quelle dell'emisfero sinistro. nei suoi studi giovanai, degni e causale, in cui non h data gate a multiforml interessi, buto decisivo al cambiamento Gli esperimenti cbe banno anch'essi del Nobel, alcuni esperienza cosciente al di fuori propositi ed. impegni personali deUe concezioni sull'asinune- portato a queste nuove concezio^ principi fondamentah che rego- del cêrvello, n6 vi 6 posto per e coUettivi, devono acquistare txia funzionale degH emisferi ni sono stati eseguid su pazienti lano lo sviluppo del sistema un'entiti disincamata, la si vo- agli occhi deUa scienza una di• cerebrali. Fin dalle scoperte con cerveUo «diviso», doh con nervoso. Le complesse connes- glia chiamare coscienza, mente gnity ontologica ed un potere anatomo-cliniche di Dax, Broca sezione del corpo caHoso forma-: sioni selettive fra le miriadi di o spirito». . •• causale paragonabili a queUi e Wernicke nel secolo scorso, to da fibre cbe collegano i due neuroni del cerveUo adulto si Per citare un siio esempio: la degli atomi e delle particeUe queste concezioni erano im- emisferi cerebrali. Precedenti orânizzano gia prima deUa na- geometria di una ruota emerge subatomiche e deUe loro inte- prontate alia dottrina della do- esperimenti su gatti e scimmie scita sulla base di complessi co- da una particolare disposizione razioni. Se a'ccettismiq (êsta minanza assoluta dell'emisfero avevano provato che il corpo cal- dici chimici sotto il controUo di delle molecole che compongono impostazione, U mondo m cui sinistro, riconosciuto come il loso 6 necessario per trasferire a istruzioni geneticbe. Su queste la ruota stessa, ma a sua volta viviamo e U nostro stesso esse- substrate fondamentale deUe dascun emisfero infonnazioni di rimo liveUo di organizzazione cohdizibna la traiettoria cbe le re ci appariranno govematl funzioni cerebrali per il Hn- senso inviate selettivamente al- Famhiente esercita poi le sue molecole percorrono durante il non solo «dal basso», ciofe dalle guaggio e per i processi cogniti- I'altro emisfero, permettendo importanti azioni di raffina- movimento della ruota: tdRi- leggi della fisica e della chimi- vi. Le licerche di Sperry banno cosi I'unificazione cognitiva dei mento e di mantenimento del- terina,, quando nessun segnale spetto agU eventi intemi alia ca, ma anche govemabUi, e in inveoe dimostrato cbe entram- due emisferi. Con tecnicbe ana- I'organizzazione cerebrale. In luminoso raggitmge gU occhi. ruota, le molecole sono guidate modo assai piil influente e bi gli emisferi cerebrali parteci- logbe a quelle applicate sugK accordo con le idee di Sperry, La grandezza di Roger Sperry dalle consuete leggi fisico-cbi- denso' di significati trascen- | pano aH'attiviti mentale, pur animah, egh dimostrft che nei David Hubel e Tomsten Wiesel, non si Umita alle sue fonda- micbe. Rispetto al resto del denti, «daU'alto», ciofe daUa con specializzazioni fimzionali pazienti con cervello diviso le in- con lui vincitori del premio No• mentali scoperte scientifiche. mondo, il comportamento deUe forza dei valori umani. diverse e complementari. An- formaziom sensoriah hmitate ad bel, hanno dimostrato che I'or- Gik dagli Annl 60 era divenuto molecole h dettato, per lo pii, cbe remisfero destro possiede im solo emisfero davano origine ganizzazione della parte visiva famoso come neurofilosofo per dalle macroproprieti della ruo• Giovanni Berlucchi J un'ampia gamma di capacity ad esperienze cosdenti inacces- del cervello h silmeno in parte aver sostenuto un'ipotesi di ta presa n?! suo insieme». Gii University dl Verona ' cognitive che pur non espri- sibih all'altro emisfero, tanto da predisposta aUe funzioni della monismo emergentista che nel 1965 egli scriveva: «La po- Piergiorgio Strata mendosi attraverso il linguag- suggerire I'esistenza di due men- vista gik durante la vita intrau- aveva perfezionato successiva- tenza causale di un'idea o di un Unlversiti di Torino A REMEMBRANCE OF ROGER W. SPERRY

Ronald Meyer, Developmental and Cell Biology, University of California, Irvine

In the era of modern science, it is seldom that anyone ventures far from their field of expertise, and nearly unheard of for someone to make major contributions in such diverse disciplines as psychology and developmental biology. Roger Sperry, who passed away In April of this year, was one of these rare individuals. Sperry received a Nobel prize In 1981 for his "split brain" studies on cortical hemispheric specialization, but there were many who felt he also deserved one for his earlier work on the formation of nerve connections. The 60's and 70's were a transition time in which both areas were being actively pursued in his laboratory at Caltech and, for those of us In the lab, it was a remarkable experience in scientific cultural diversity. In the "human wing," split brain patients were being tested with everything from exotic image stabilization devices to tinker toys. The rest of the lab contained a veritable zoo. There was a colony of monkeys and cats, mostly with split brains, being tested with elaborate electromechanical devices. There was a room full of newly-hatched chicks pecking bad-tasting beads to study memory formation; and various frogs and fish were having nerves cut to study selective nerve growth using electrophysiological and neuroanatomical methods. Sperry was happy to let us work on whatever we wanted as long as we could convince him that we were asking an important question. Although he was happy to give general advice about what to do, it was largely up to us to figure out how to do the experiments, and we did so with a great deal of independence. Writing up the experiments, however, was a different reality. Sperry, who majored in English literature as an undergraduate, was an excellent writer and expected every paper that came from his lab to be well written, down to the choice of the best synonym for every word. For those of us who were less gifted writers, this was a traumatic ordeal of endless revisions which could easily last a year or more. The papers and our writing skills, but not our egos, were the better for it. Generously, Sperry did not put his name on most of our papers. Sperry's contribution to developmental neurobiology was fundamental, but to really appreciate this one has to go back to the late 1930's and early 1940's when he did his work. At that time. It was generally believed that individual nerve fibers were essentially identical in the way they responded to their local environment during axonal growth. Tissue culture studies seemed to show that axons were guided solely by mechanical structures, and a number of in vivo studies had purportedly shown that fibers would form connections with whatever targets they were made to encounter. Astoundingly, these misconnected fibers even appeared to support normal function. The conclusion was that nerve fibers were intrinsically identical and that neuronal function depended on learning, not on specific neuronal connections. Sperry tested this then current wisdom by rotating the eye of a frog by 180 degrees and then cutting and scrambling the optic nerve. When the nerve grew back, he tested the frog's vision by presenting it with a fly on the end of a wire. When the fly was in front of the frog, the frog turned 180 degrees, and when the fly was behind it, the frog snapped as if the fly were in front. The frog saw a visual world upside down, never learning to see correctly. It would have starved if left on its own. From this simple experiment, Sperry concluded that optic fibers from different parts of the retina must

8 have grown to specific locations in the brain and therefore fibers must possess chemical identities that allow them to differentially respond to different chemospecific cues in the brain. The experiment also showed that specific connections, not just learning, were fundamental for neuronal function. As a young assistant professor when this pioneering work was done, Sperry showed remarkable courage, considering that his thesis advisor and colleague at the University of Chicago, Paul Weiss, was the major proponent of mechanical guidance. Perhaps too much courage, because in spite of having published a number of papers extending and confirming his early findings in several different systems, he was denied tenure. (Chicago later gave him an honorary degree.) At Caltech, Sperry continued this work, culminating in the early 60's with direct anatomical evidence for the directed growth of optic fibers and the elaboration of his chemoaffinity hypothesis. Today, the idea that growing axons differentially respond to chemical cues in their environment to form specific connections during development and that specific connections are actually important for neuronal function is hardly controversial. It is a fact of life for developmental neurobiologists. Many examples of selective growth have been reported in diverse systems from mammalian cortex to Drosophila nervous system, and a few guidance molecules have now been identified. It is good to remember that there was a time that we did not know about chemospecificity and that it was Roger Sperry who told us about it.

Note: Ron Meyer was one of Roger Sperry's last graduate students

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