(1) The History of Brain Science in a Nutshell

1 brainwhoa...the mind is THERE!
2brain regionsmegascopic
3brain cells (neurons)microscopic
4neurotransmittersbetween neurons
5receptorsin neural membrane
6second messengers inside neuron
7gene regulators inside nucleus


1bodieshuman & animal
2paperfor anatomical drawings
4heavy chemicals stains to trace nerves
5drugsrandom discovery-->bioengineered
6electrical gearvoltage clamps, EEG
8X-rays/nuclear magnetismCAT, MRI,3D molecular imaging [X-ray crystallography/protein NMR]
9bioinformatic computer systemsautomated gene/protein sequencing

(note: brain technology has long been restricted to highly trained researchers. However, we are approaching the age of inexpensive noninvasive imaging and PC-based neural nets and brain models. EEG and ANS monitoring equipment is already available to hobbyists, and $1 MRIs, gene chips, and MBIs (mind-brain interfaces) are on the horizon.)


dark blue=anatomy of braingray=technology
light blue=microanatomy of neuronorange=observation of behavior
pink=drugs, transmitterspurple=study of consciousness
green=DNA, genesyellow=holism, emergence

-1700Imhotep (Egypt)first use of word “brain,” with description of distal symptoms of brain damage from 30 clinical cases
-500Alcmaeon of Crotona locates vision and senses in localized brain regions
-370Hippocrates locates epilepsy, sensation, all mental processes in brain
-360Plato locates mental processes in brain
-350Aristotledescribes memory formation as the association of simple ideas (mistakenly thinks thought occurs in heart)
-300Herophilus of Alexandria father of anatomy, locates human intelligence in brain, distinguished sensory and motor nerves, first anatomical drawings
-280Erasistratus of Chios describes origin of nerves in brain, divisions of the brain
-150Poseidonus of Byzantiumreported effects of localized brain damage (though incorrect)
177Galenlocalized mental processes in solid brain matter (not ventricles), traced sensory nerve system
1021Ibn al-Haytham (Iraq)discovers that vision occurs in brain, not eyes
1504Leonardo da Vinci modern anatomical drawing, wax injection of ventricles
1543Andreas Vesalius father of modern anatomy, realistic drawings
1550Bartolomeo Eustachio locates origin of optic nerves in brain
1590Zacharias Janssen invents the compound microscope
1611Lazarus Riverius describes impaired states of consciousness
1621Robert Burton describes depression
1637Descartesproposes that mind+body interact in brain
1665Robert Hooke develops microscopes
1673Joseph DuVerneyperforms experimental ablation in pigeons
1684Raymond Vieussens uses boiling oil to harden the brain
1690Lockeproposes that mind is a blank slate that develops through sense data--eliminates a lot of nonscientific psychological BS, but ignores DNA
1695Humphrey Ridley anatomy text -- first describes peduncles, mamillary bodies, etc
1709George Berkeley describes how concepts like distance are constructs of the brain, based on past experience
1717Antony van Leeuwenhoekdescribes nerve fiber in cross section
1740Emanuel Swedenborgtheorizes motor cortex map, neurons, neuroendocrine system, etc -- ideas ignored b/c not a professor
1749David Hartley the first English work using the word "psychology"
1755J.B. Le Roy uses electroconvulsive therapy for mental illness
1760Charles Lorry demonstrates that damage to the cerebellum affects motor coordination
1772John Walsh conducts experiments on torpedo (electric) fish
1781Kantargues we are born with built-in templates of a priori knowledge (more neuroscientifically sound than Locke)
1791Luigi Galvanidiscovers nervous system = electrical
1800Franz Joseph Gallproposes that brain has special regions for all mental functions, even emotion
1800Humphrey Davy synthesizes nitrous oxide
1801Adam Friedrich Wilhelm Serturner crystalizes opium and obtains morphine
1809Johann Christian Reil uses alcohol to harden the brain
1809Luigi Rolando uses galvanic current to stimulate cortex
1811Julien Jean Legallois discovers respiratory center in medulla
1812Benjamin Rush father of american psychiatry, promotes asylums, treatment for alcoholism
1820Johann Shweiggerinvents galvanometer (precursor to voltage clamps, EEGs to study neurons)
1822Pierre Flourenslocates movement in cerebellum, shows brain has regions for mental functions but NOT memory: finds that memory is distributed; also describes ablation for studying behavior
1825Jean Baptiste Bouillaudpresents cases of loss of speech after frontal lesions
1825Robert B. Todd discusses the role of the cerebral cortex in mentation, corpus striatum in movement and midbrain in emotion
1826Johannes Muller proposes theory of "specific nerve energies" (early notion of electrical transmission by nerves)
1827E. Merck & Company markets morphine
1832Justus von Liebig discovers chloral hydrate
1832Jean Pierre Robiquet isolates codeine
1832Sir Charles Wheatstone invents the stereoscope
1833Philipp L. Geiger isolates atropine
1836Marc Dax descrives effects on speech from left hemisphere damage
1836Gabriel Gustav Valentin identifies neuron nucleus and nucleolus
1838Eduard Zeis studies dreams in people who are blind
1838Robert Remak suggests that nerve fiber and nerve cell are joined
1838Jean Esquirol promotes asylums
1839Theodor Schwann, Mattias Jakob Schleidendiscovers CELLS, which make up all living things
1840Adolph Hannover uses chromic acid to harden nervous tissue
1842Crawford W. Long uses ether on man
1847James Young Simpson uses chloroform anesthesia
1848John Harlowpatient Phineas Gage loses moral judgment with damage to ventromedial cortex
1849Hermann von Helmholtzmeasures speed of frog nerve impulses= 90 feet per second, slowly actively propagated
1850Emil Du Bois Reymond invents nerve galvanometer
1853William Benjamin Carpenter proposes "sensory ganglion" (thalamus) as seat of consciousness
1855Bartolomeo Panizza shows the occipital lobe is essential for vision
1855Richard Heschl describes the transverse gyri in the temporal lobe (Heschl's gyri)
1856Albrecht von Graefe describes homonymous hemianopia
1859Darwindescribes how humans evolved from animals
1860Gustav Theodor Fechner develops "Fechner's law"--intensity of perception is logarithm of sense stimuli (i.e. progressively less sensitive)
1860Albert Niemann purifies cocaine
1864Pierre Paul Brocadescribes how expressive (speech) aphasia is caused by frontal lobe damage
1865Gregor Mendeldescrobes jpw hereditary information is passed in units (genes)
1867Theodore Meynert performs histologic analysis of cerebral cortex
1873Gustav Fritsch, Eduard Hitzigshows that a dog moves when motor cortex stimulated
1873Camillo Golgi discovers silver nitrate staining of nerves, used by Cajal (below)
1874Roberts Bartholow electrically stimulates human cortical tissue
1875Richard Caton records electrical activity from the brain
1878Paul Broca publishes work on the "great limbic lobe"
1878Harmon Northrop Morse synthesized acetaminophen
1878Claude Bernard describes nerve/muscle blocking action of curare
1879Carl Wernickesensory aphasia caused by temporal lobe damage
1879Wilhelm Wundt sets up lab devoted to study human behavior
1879Mathias Duval introduces an improved method of embedding tissue using collodion
1879William Crookes invents the cathode ray tube
1881Hermann Munk reports on visual abnormalities after occipital lobe ablation in dogs
1883Emil Kraepelin coins the terms neuroses and psychoses, discovers schizophrenia
1885Paul Ehrlich notes that intravenous dye does not stain brain tissue : blood-brain barrier
1885Hermann Ebbinghausdetermines that people can memorize 7 nonsense words one session, forget most in 1 hour (short-term), rest in 1 month (long-term)
1885Carl Weigert introduces hematoxylin to stain myelin
1889Santiago Ramon y Cajaldescribes how brain = network of unique neurons which fire in one direction
1890John Hughlings Jacksondescribes how temporal seizures elicit dreamy states
1890William Jamesdescribes how memory can be short-term, long-term, habitual, or autonomic (unconscious)
1895William His first uses the term hypothalamus, dendrite
1895Wilhelm Konrad Roentgen invents the X ray
1895Heinrick Quincke performs lumbar puncture to study cerebrospinal fluid
1897Felix Hoffmann synthesizes aspirin
1897Karl Ferdinand Braun invents the oscilloscope
1897Ferdinand Blum uses formaldehyde as brain fixative
1899Francis Gotch describes a "refractory phase" between nerve impulses
1900Georg Muller, Alfons Pilzeckerlongterm memory blocked by disruption within 1 hour
1900Sigmund Freud describes mental illnesses as unconscious neurobiological processes, observed through dreams, free association, slips
1902Julius Bernsteincalculates nerve impulse = 70 millivolt ionic shift across membrane of neuron
1903Ivan Pavlovshows in dogs hows training creates direct connections between sense and motor nerves
1905John Newport Langley introduces the concept of receptor molecules , describes "parasympathetic nervous system" –
1906Charles Sherringtoncat reflexes = senses integrated by excitatory/inhibitory interneurons to single motor output
1907Ross Granville Harrison describes tissue culture methods
1908Richard Goldschmidtneurons in animals are always in the same place
1908Victor Alexander Haden Horsley,Robert Henry Clarke design stereotaxic instrument
1908Willem Einthoven makes string galvanometer recordings from the vagus nerve
1909Harvey Cushing first to electrically stimulate human sensory cortex
1911George Barger,Henry Dale discover norepinephrine
1913Edwin Ellen Goldmann finds blood brain barrier, impermeable to large molecules
1913Santiago Ramon y Cajal develops gold chloride mercury stain to show astrocytes
1913Walter Samuel Hunter devises delayed response test
1914Henry H. Dale isolates acetylcholine
1915J.G. Dusser De Barenne describes activity of brain after strychnine application
1915Thomas Hunt Morganeach gene in fruit fly is located in certain place on chromosomes
1919Gordon Morgan Holmes localizes vision to striate area
1919Walter E. Dandy introduces air encephalography
1920Stephen Walter Ranson demonstrates connections between the hypothalamus and pituitary
1920Otto Loewi, Henry Dalefluid from frog vagus nerve directly slows heart of another frog
1921Hermann Rorschach develops the inkblot test
1921John Augustus Larsen, Leonard Keeler develop the polygraph
1927Chester William Darrow studies galvanic skin reflex
1928Philip Bard suggests the neural mechanism of rage is in the diencephalon
1928Walter Rudolph Hess reports "affective responses" to hypothalamic stimulation
1928Lord Edgar Douglas Adriannerve impulses are all identical, with 1 millisecond upstroke + downstroke
1928John Fulton observes sounds of blood flowing over the human visual cortex
1929Walter B. Cannon coins the term homeostasis
1929Hans Berger first human electroencephalogram
1929Karl Lashleyremoving parts of rat brains does not eliminate memory
1930Carlyle Jacobsenfrontal lobe in monkeys controls short-term memory
1931Ulf Svante von Euler,J.H. Gaddum discover substance P
1932Smith, Kline first amphetamine, Benzedrine
1932Max Knoll, Ernst Ruska invent the electron microscope
1932Jan Friedrich Tonnies develops multichannel ink writing EEG machine, differential amplifier
1933Ralph Waldo Gerard describes first experimental evoked potentials
1934S. Howard Bartley performs studies on cortical visual evoked potentials in rabbits
1935Frederic Bremer uses cerveau isole preparation to study sleep
1936Egas Moniz publishes work on the first human frontal lobotomy
1936Walter Freeman performs first lobotomy in the United States
1936Wade Marshall, Wilder Penfieldsensory nerves connect to neurons arranged in shape of body
1937James Papez describes limbic circuit, visceral theory of emotion
1937Heinrich Kluver, Paul Bucy describe bilateral temporal lobectomies
1938Albert Hofmann synthesizes LSD
1938Ugo Cerletti, Lucino Bini treat human patients with electroshock
1939Alan Hodgkin, Andrew Huxleynerve impulse of squid = 110 millivolts
1942Stephen Kuffler develops the single nerve muscle fiber preparation
1943John Raymond Brobeck describes hypothalamic hyperphasia
1948Wilder Penfieldelicits memories/auras from 8% patients with temporal lobe stimuli
1948Jerzy Kornorskineuron voltage drops after excitation (refractory period)
1949Giuseppi Moruzzi, Horace Winchell Magoun discover reticular activating system: cutting a cat's sense nerves does not affect wakefulness, but cuttin RAS does
1949John Cade discovers that lithium is an effective treatment for bipolar depression
1949Kenneth Cole develops the voltage clamp
1949D.O. Hebbreverbatory circuits are responsible for short-term memory
1949CP Duncanlongterm memory blocked by seizures within 1 hour
1950Steven Kufflerretinal cells signal contrast, not brightness
1950Vernon Mountcastleplace cells = cortical neurons that respond to stimuli from certain directions
1950B.F. Skinner, Jerome Brunerpigeon training creates direct connections between sense and motor nerves
1950Eugene Roberts, J. Awapara independently identify GABA in the brain
1950Henri Laboritantihistamine chlorpromazine tranquilizes patients, also antipsychotic, with Parkinsonism side-effect
1951John Ecclesneurotransmitters can modulate neuron potential (excite to -55mV or inhibit to +75mV)
1952Alan Lloyd Hodgkin, Andrew Fielding Huxley describes action potential in mathematical terms, by using voltage clamp on squid neurons
1953Eugene Aserinski , Nathaniel Kleitman describe rapid eye movements (REM) during sleep
1953H. Kluver, E. Barrera introduce Luxol fast blue MBS stain
1953James Watson, Francis Crick discover double helix of DNA, with 4 nucleotides=copying mechanism
1954James Olds describes rewarding effects of hypothalamic stimulation
1954John Lilly invents the "isolation tank"
1955Kandel, PurpuraLSD increases (not stops) serotonin inhibition of visual cortex exposed to flashes of light
1956DW Woolley, EN ShawLSD stops serotonin contractions of rat uterus
1956Rita Levi Montalcini, Stanley Cohen isolate and purify nerve growth factor
1956L. Leksell uses ultrasound to examine the brain
1957Brenda Milner, William ScovilleH.M. hippocampectomy, loss of long-term memory encoding
1958Harry Harlowmonkeys isolated from mother devastated behaviorally, partially reversed by cloth-covered wooden dummy and a few hours with normal infant monkey
1958Arvid Carlssondiscovers dopamine in brain, lack causes Parkinsonism, L-Dopa causes schizoid
1958Haloperidol introduced as a neuroleptic
1959David Hubel, Torsten Wieselvisual thalamus responds to contrast, visual cortex responds to contours with specific orientation
1959P. Karlson,M. Lusher describe pheromones
1960Louis Flexnerprotein inhibitors block consolidation during and shortly after learning, but not short-term memeory
1960Geoffrey WatkinsGA is main transmitter, with 2 hippocampal receptors, rapid AMPA depolarizes cell 20mV-->opens NMDA-->Ca+-->kinase-->additional AMPA receptors
1960Aaron Beckcognitive behavioral therapy (CBT) = short-term psychological treatment
1961Robert Dotyclassical conditioning by stimulus to dog visual cortex and motor cortex
1961Earl Sutherlanddescribes how cells may learn from environment: epinephrine at metabotropic receptors on fat/muscle membrane-->binds adenylyl cyclase which makes 1000 molecules of cAMP for minutes second-messenger changes cell
1961Brenner and Cricktriplets of 4 nucleotides yield 20 amino acids
1962Eldon Foltz performs the first cingulotomy to treat chronic pain
1962Francois Jacob, Jacques Monoddiscover how genes are switched on/off: regulatory gene-->regulatory protein-->(in absence of lactose) binds to promoter-->frees effector gene-->protein/enzymes
1965Ronald Melzack,Patrick D. Wall gate control theory of pain
1966Ed Evarts, Robert Wurtz, Michael Goldbergsingle cell recordings from behaving and attentive monkeys
1968Ed KrebscAMP-->binds regulatory units on protein kinase A, freeing catalytic units to phosphorylate proteins
1969D.V. Reynolds describes the analgesic effect of electrical stimulation of the periaqueductal gray
1969Bernard Katznerve impulse opens voltage-gated ion channel at synapse, releasing neurotransmitters
1970Paul Greengarddopamine receptor in brain-->cAMP, activates protein kinase
1970Walter Gilbert, Frederick Sangerrapid DNA sequencing, recombinant DNA (snip out gene, clone it, stitch to bacterial DNA)
1971John O’Keefeplace cells in hippocampus respond to any sense from certain direction
1972Godfrey N. Hounsfield develops x ray computed tomography
1973Terje Lomo, Tim Blisshippocampal cells strengthened for days after rapid stimuli
1973Candace Pert,Solomon Snyder discover opioid receptors in brain
1973Paul Bergfirst recombinant DNA molecule
1973Herbert Boyer, Stanley Coheninvents gene cloning
1973Konrad Z. Lorenz, Nikolaas Tinbergen, Karl von Frisch discover imprinting in animals (=postnatal gene regulation)
1974Alan Baddeleyworking memory = moment-to-moment memory for executing complex behavior
1974Thomas Nagel, John Searlebinding/NCC, subjectivity—what are the elements of subjective consciousness
1974John Hughes,Hans Kosterlitz discover enkephalin
1974M.E.Phelps, E.J.Hoffman,M.M.Ter Pogossian develop first PET scanner
1974First NMR image (a mouse) is taken
1974Seymour Benzermutatogenic chemicals on drosophila, flies with defective gene for disposing of cAMP have no short-term memory
1976Choh Hao Li,David Chung describe beta endorphins
1976Erwin Neher ,Bert Sakmann invents the patch clamp, which can record from individual membrane channels
1980Richard Morrisblocking NMDA blocks longterm potentiation--shows how a short-term transmitter can affect longterm neural activity (memory)
1980Gerald Klerman, Myran Weissmandevelops interpersonal psychotherapy = CBT for mistaken beliefs about others
1981Roger Wolcott Sperry shows how sense data is filled out by brain, by observing patients with split hemispheres
1982Bengt Ingemar Bergstrom, John Robert Vane, Sune K. Bergstrom discovers of prostaglandins
1983Benjamin Libetdiscovers readiness potential in EEG 1 second before movement, 200 ms before “willing”
1987Larry Squire, Daniel Schacterdescribes how implicit/procedural (conditioning motor skills) versus explicit/declarative memory are recorded by different modules of the brain
1987Gerald Edelmanproposes that consciousness is widely distributed throughout the cortex and thalamus
1987Eli Lillyprozac introduced as treatment for depression
1989Colin McGinnproposes that consciousness cannot be studied by limited mind
1990Thomas Ebertdiscovers that musicans' cortical finger maps expand 5-fold
1990Crick and Kochproposes neural correlates of consciousness, perhaps claustrum
1990Michael Merzenichdiscovers that cortical maps vary among monkeys and expands with use
1990Eric Lumerdescribes binocular rivalry-- the prefrontal and posterior pariental regions of the cortex seem to relay the decision regarding which image is to be enhanced to the visual system, which then brings the image into consciousness
1992Craig Baileydiscovers long-term memory in aplysia based on new axon terminals
1992Daniel Dennettproposes that consciousness is function of neural computation, nothing else
1994Alfred G. Gilman,Martin Rodbell discovers G protein coupled receptors, key part of nerve signalling and memory
1996Lewis Baxter, Jeffrey Schwartzproves CBT for OCD=SSRI=inhibit caudate; psychotherapy for depression=SSRI=shift in activity from dorsal to ventral PFC
1996Anthony Movshon, William Newsomeperforms single cell recordings from behaving and attentive monkeys -- reveals consciousness on a cellular level
1999Patricia Goldman-Rakicfinds that removing monkey PFC destroys working (not all short-term) memory
2004Rene Henmouse dentate gyrus lesion abolishes effect of antidepressants

Note:This timeline is based on Kandel's summary, plus this timeline and other web sources. Obviously the two last entries do not begin to suggest the huge explosion of research in the last 10 years. The timeline as a whole leans toward Kandel's interest in memory.

The timeline is almost all white males from a few Western nations, comprising an exclusive old-boy network. Kandel describes this vividly in his book. His career, in fact, probably coincides with the peak of the old-boy system.

This system is phasing out for several reasons--the PC/Internet Revolution, China, the changing nature of science itself. Most discoveries of the past were made by men puttering around with tangible equipment such as microscopes. Future research will be done by software; what human involvement remains will be spread among a global network of researchers from private enterprise as well as university labs--as well as late-night hackers. The age of the lone researcher who stumbles almost randomly into a celebrated place in scientific history is over.

Thankfully, the age of unethical and crude experimentation on animals and the mentally ill is also phasing out. Kandel describes how one of the seminal anatomical texts was based on dissections of Holocaust victims. The entirety of brain research history, though including some of the most fascinating and profound revelations about the nature of human experience, is a ghastly and chaotic tale of dissections and intoxications and horrifying injuries. The future may not provide such a riveting story, but it will be fundamentally better in almost every respect.

As Kandel told an interviewer in 2004, looking back on his career, "We've had a wonderful run on cellular molecular biology. The time has now come to use more synthetic approaches."


-500-1853humoralismGalen4 humors: black bile - yellow bile -phlegm - bloodwild speculation
1858-1900sstructuralismWundt (father of psychology)3 elements: sensation -affection-perceptionsemi-controlled introspection
1903-1950sbehaviorismPavlovstimulus-->responsecontrolled animal studies
1900-1960sFreudianismFreud3 divisions: ego - id - superegosemi-controlled talk therapy
1950-1980shumanismMaslow5 needs: physiological-->safety-->love-->esteem-->self-actualization" " (more sensitive, respectful; less dogmatic)
1960-2000scognitivismBeck3 modalities: cognition-->emotion-->behaviorcontrolled human studies
1980-2000scomputationalismMinsky3 quantities: input-->nodes-->outputhighly controlled simulations, AI


1247institutionalized psychiatry (Bedlam=first asylum, London)confinement, restraint, lobotomy, electroshock, insulin shock
1900psychoanalysistalk therapy
1960sspecific therapiescognitive behavioral therapy (CBT), interpersonal therapy, music therapy, etc.

Note: Although cognitive and computational neuroscience have gradually become more rigorous and falsifiable, and psychiatry has moved towards short-term, empirically based specific therapies, all psychological theories and treatments are essentially reductionistic and their purported "elements" and "structures" are all vulnerable to criticism on the basis of the distributed, emergent, and holistic nature of the brain and mind. In general psychiatry is a grand reification "signifying nothing" and is widely assumed to be gradually yielding to more empirical neurology, perhaps as a subspecialty, "neuropsychiatry."